Publications
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Cooley, Victoria; Trewin-Nybråten, Cassia Bree; Lindemann, Kristina Yvonne Kathe; Zivanovic, Oliver; Kaaks, Rudolf & Fortner, Shannon Renee Turzanski
(2026).
Ovarian cancer survival in Germany: a nationwide analysis by stage and histotype.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
36(4).
doi:
10.1016/j.ijgc.2026.104509.
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Slørdahl, Kathinka Schmidt; Puco, Katarina; Falk, Ragnhild Sørum; Dyvik, Ingrid; Brabrand, Sigmund & Niehusmann, Pitt
[Show all 19 contributors for this article]
(2026).
Clinical outcomes of genomically guided trametinib monotherapy across cancer types: results from the IMPRESS-Norway trial.
Acta Oncologica.
ISSN 0284-186X.
65,
p. 90–96.
doi:
10.2340/1651-226X.2026.45086.
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Background and purpose: Molecular profiling guides cancer treatment, by identifying actionable genomic alterations. The IMPRESS-Norway trial (NCT04817956) is a nation-wide precision medicine trial evaluating the efficacy of approved cancer drugs on a novel indication in patients with advanced cancers harbouring potentially actionable alterations. Trametinib, a selective MEK1/2 inhibitor targeting the Mitogen-Activated Protein Kinase (MAPK) signalling pathway, is approved for BRAF V600 mutant melanoma but may also show activity in tumours with other alterations. This sub-study aimed to assess the efficacy of trametinib monotherapy across tumour types with alterations activating the MAPK signalling pathway.
Patient/material and methods: In the IMPRESS-Norway trial patients are screened with the TruSight Oncology 500 panel or circulating tumour DNA profiling. Eligible patients are offered biomarker matched targeted therapies. In this subgroup analysis, we identified patients treated with trametinib monotherapy. Primary endpoints were disease control rate (DCR) after 16 weeks and safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Results: DCR after 16 weeks of treatment was 39% in 52 response evaluable patients, with four patients (8%) experiencing partial response, and 16 (31%) stable disease. Responses were seen in tumours harbouring BRAF fusions, GNA11, GNAQ, KRAS, NF1, and NRAS alterations, most frequently in low-grade serous ovarian cancer, central nervous system tumours, and uveal melanoma. Forty-eight percent of patients experienced treatment-related adverse events, including two treatment related deaths. Median PFS and OS were 4 and 9 months, respectively.
Interpretation: Trametinib monotherapy achieved a 39% DCR in patients lacking standard options, supporting further studies to confirm efficacy and identify predictive biomarkers for treatment response.
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Skrede, Ole-Johan; Pradhan, Manohar; Isaksen, Maria; Hveem, Tarjei Sveinsgjerd; Vlatkovic, Ljiljana & Nesbakken, Arild
[Show all 23 contributors for this article]
(2026).
Generalisation of automatic tumour segmentation in histopathological whole-slide images across multiple cancer types.
NPJ precision oncology.
10.
doi:
10.1038/s41698-026-01311-6.
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Deep learning is expected to aid pathologists in tasks such as tumour segmentation. We developed a general tumour segmentation model for histopathological images and examined its performance in different cancer types. The model was developed using over 20,000 whole-slide images from over 4000 patients with colorectal, endometrial, lung, or prostate carcinoma. Performance was validated in pre-planned analyses on external cohorts with over 3000 patients across six cancer types. Exploratory analyses included over 1500 additional patients from The Cancer Genome Atlas. Average Dice coefficient was over 80% in all validation cohorts with en bloc resection specimens and in The Cancer Genome Atlas cohorts. No performance loss was observed when comparing the general model with single-cancer models specialised in cancer types from the development set. In conclusion, extensive and rigorous evaluations demonstrate that generic tumour segmentation by a single model is possible across cancer types, patient populations, sample preparations and slide scanners.
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Kalsnes, Joakim; Isaksen, Maria; Julbø, Frida Marie Ihle; Pradhan, Manohar; Kleppe, Andreas & Raedt, Sepp de
[Show all 33 contributors for this article]
(2026).
Applicability of mitotic figure counting by deep learning: a development and pan‐cancer validation study.
FEBS Open Bio.
16(7),
p. 1259–1270.
doi:
10.1002/2211-5463.70210.
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Mitotic figure counting is an established measure of cell proliferation that is included in grading systems. We developed a deep learning method for mitotic figure counting and evaluated its prognostic impact in multiple external validation datasets. The deep learning method was trained in whole slide images of tissue sections stained with haematoxylin and eosin from a publicly available breast cancer dataset where mitotic figures have been annotated by expert pathologists. The final model was externally validated according to a protocol with predefined analyses of 14 571 patient samples from 13 patient cohorts from seven different cancer types. The predefined primary analysis was univariable Cox survival analysis of the number of mitotic figures detected per mm 2 . Automatic mitotic figure counting correlated well with known proliferation rates, and patients with more mitotic figures per mm 2 had significantly worse patient outcome in all the studied cancer types except colorectal cancer. This study demonstrates the practical potential of automated, deep learning‐based mitotic figure counting, both by automating pathology work and by suggesting expanded use in more cancer types, such as prostate cancer.
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Harter, Philipp; Marmé, Frederik; Redondo, Andrés; Reuss, Alexander; Lindemann, Kristina Yvonne Kathe & Kurzeder, Christian
[Show all 30 contributors for this article]
(2025).
Atezolizumab With Bevacizumab and Nonplatinum Chemotherapy for Recurrent Ovarian Cancer: Final Results From the Placebo-Controlled AGO-OVAR 2.29/ENGOT-ov34 Phase III Trial.
Journal of Clinical Oncology.
ISSN 0732-183X.
44(2),
p. 116–116.
doi:
10.1200/jco-25-01210.
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PURPOSE To evaluate atezolizumab combined with bevacizumab and non–platinum-based chemotherapy for recurrent ovarian cancer. METHODS The double-blind randomized phase III AGO-OVAR 2.29/ENGOT-ov34 trial (ClinicalTrials.gov identifier: NCT03353831 ) enrolled patients with first or second relapse of ovarian cancer ≤6 months after completing platinum-based chemotherapy (or third relapse regardless of treatment-free interval). PD-L1 status was tested centrally (VENTANA SP142 assay) in recent (<3 months) biopsies before random assignment. All patients received bevacizumab and investigator-selected chemotherapy (once weekly paclitaxel or pegylated liposomal doxorubicin) until disease progression or toxicity, plus either atezolizumab 840 mg or placebo once every 2 weeks until progression (maximum 2 years), randomly assigned 1:1, and stratified by number of previous lines, planned chemotherapy, previous bevacizumab, and PD-L1 status. Primary end points were overall survival (OS) and progression-free survival (PFS) in the intention-to-treat population. RESULTS Among 574 patients randomly assigned between September 2018 and July 2022, 72% were bevacizumab-pretreated, 36% had received three previous treatment lines, 26% had PD-L1–positive tumors, and 54% received paclitaxel with study therapy. After 418 patients had died, the hazard ratio for OS was 0.83 (95% CI, 0.68 to 1.01; P = .06; median 14.2 months with atezolizumab and 13.0 months with placebo) and the hazard ratio for PFS was 0.87 (95% CI, 0.73 to 1.04; P = .12; median 6.4 v 6.7 months, respectively). OS hazard ratios were similar regardless of PD-L1 status. Grade ≥3 adverse events occurred in 72% of atezolizumab-treated and 69% of placebo patients. CONCLUSION Combining atezolizumab with bevacizumab and chemotherapy did not significantly improve OS or PFS in patients with recurrent ovarian cancer ineligible for platinum. The safety profile was as expected from previous experience with these drugs.
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Ebner, Christoph; Lindemann, Kristina Yvonne Kathe; Kristensen, Gunnar S Balle; Frosch, Alice; Askautrud, Hanne Arenberg & Santo, Gianpaolo Di
[Show all 9 contributors for this article]
(2025).
Are brain metastases a special issue in POLE-mutated endometrial cancer? a case report series.
Frontiers in Oncology.
15.
doi:
10.3389/fonc.2025.1568137.
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POLE-mutated endometrial cancers have repeatedly shown to harbor an excellent prognosis. Recurrences or primary advanced disease are rare events in this subgroup. We report three cases of POLE-mutated endometrioid ECs with brain metastases. While patients with CNS metastases from endometrial cancers are very uncommon and generally confer a poor prognosis and limited survival, all cases presented here survived substantially longer than the median survival time of patients with brain metastasis published in the literature. All patients responded well to systemic therapy or radiotherapy. Additionally, we present one case with complete response to only four cycles of pembrolizumab monotherapy. These cases suggest that, even in the setting of brain metastases or recurrent disease, a pathogenic POLE mutation remains a marker for excellent clinical outcome. The question of why these tumors metastasized to the brain in the first place remains to be answered by further research.
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Lindemann, Kristina Yvonne Kathe; Kildal, Wanja; Kleppe, Andreas; Tobin, Kari Anne Risan; Pradhan, Manohar & Mascialino, Barbara
[Show all 11 contributors for this article]
(2025).
Real-world outcomes in molecular subgroups for patients with advanced or recurrent endometrial cancer treated with platinum-based chemotherapy.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
35(5).
doi:
10.1016/j.ijgc.2024.101618.
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Objective
There is scarce real-world evidence on patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy. We assessed the oncological outcome in groups by molecular classification.
Methods
This retrospective cohort study included patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy after hysterectomy at The Norwegian Radium Hospital, Oslo University Hospital, Norway, between January 2006 and December 2017. Patients were molecularly classified as pathogenic POLE mutated, mismatch repair deficient, p53 abnormal, or no specific molecular profile. Time-to-recurrence and cancer-specific survival were calculated.
Results
We identified 264 advanced-stage patients (stage III/IV) and 96 patients with recurrent disease. The molecular classification was prognostic for time-to-recurrence (p < .0001) and cancer-specific survival (p < .0001) in patients with advanced disease, but the outcome did not differ significantly by molecular groups in recurrent patients. In all molecular groups, patients with stage III disease had longer time-to-recurrence and cancer-specific survival compared to patients with stage IV disease. The worst outcome was observed in patients with p53 abnormal tumors with an HR of 1.57 (95% CI 1.07 to 2.30) for time-to-recurrence and HR of 1.78 (95% CI 1.19 to 2.65) for cancer-specific survival in stage III/IV disease and an HR of 1.45 (95% CI 0.83 to 2.52) for time-to-recurrence and HR of 1.60 (95% CI 0.99 to 2.68) for cancer-specific survival in patients with recurrent disease. The few patients with POLE mutated tumors had favorable outcomes despite the advanced/recurrent disease status.
Conclusions
Oncological outcomes differ by molecular groups, in particular among patients with advanced disease. Patients with p53 abnormal tumors have the worst outcome, while patients with POLE mutated tumors have favorable outcomes even with recurrent disease. Implementation of the addition of immunotherapy to chemotherapy is expected to lead to substantial improvement of outcome, particularly in patients with mismatch repair deficient advanced/recurrent disease. There is still a high unmet need in advanced/recurrent patients with p53 abnormal and no specific molecular profile tumors.
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Hillemanns, Peter; Zikan, Michal; Forget, Frédéric; Denys, Hannelore; Baurain, Jean-Francois & Rob, Lukas
[Show all 17 contributors for this article]
(2025).
Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study.
Journal for ImmunoTherapy of Cancer (JITC).
13(1).
doi:
10.1136/jitc-2024-010827.
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Støer, Nathalie Charlotte; Botteri, Edoardo; Lindemann, Kristina Yvonne Kathe; Langseth, Hilde & Fortner, Shannon Renee Turzanski
(2025).
Low-dose aspirin and non-aspirin non-steroidal anti-inflammatory drugs and epithelial ovarian cancer survival: a registry-based cohort study in Norway.
BMC Cancer.
25,
p. 1–10.
doi:
10.1186/s12885-025-14168-y.
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Background Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAID) have been associated with improved survival in individuals with epithelial ovarian cancer (EOC); however, findings to date are inconsistent. Methods We conducted a registry-based cohort study evaluating survival following an incident invasive EOC diagnosis including individuals diagnosed between 2004–2018 (n = 4325; n = 2206 deaths; n = 1973 EOC deaths). Evaluated exposures were low-dose aspirin and NA-NSAIDs. Two primary post-diagnosis exposure windows were evaluated: fixed post-diagnostic baseline exposure ≤ 305 days after diagnosis (use, non-use) and updated “time-varying” exposure (never, past, current use; cumulative defined daily dose (DDD)). Pre-diagnostic exposure (use, non-use) was further evaluated. Multivariable Cox-proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals [95% CIs]. The primary outcome was cause-specific survival. Restricted mean survival time (RMST) in exposure groups was estimated at 5 years following start of follow-up. Results Baseline post-diagnosis aspirin use was not associated with survival following an EOC diagnosis (e.g., use vs. no use: aspirin, HR = 1.02 [95% CI = 0.84–1.24]). Inverse associations were observed between current aspirin use post-diagnosis and survival in the time-varying exposure models (HR 0.68 [0.57–0.81]), and with higher post-diagnosis cumulative DDD of aspirin. Findings for NA-NSAIDs were less consistent. No associations were observed for pre-diagnostic use. Results for overall survival were similar to those for cause-specific survival. Compared to never use, post-diagnosis low-dose aspirin use was associated with a longer RMST (e.g., ever vs. never use, difference in RMST = 2.67 months). Conclusions This study provides further evidence of a potential beneficial effect of post-diagnosis low-dose aspirin use for ovarian cancer survival.
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Skipar, Kjersti Øvrum; Hompland, Tord; Lund, Kjersti Vassmo; Fjeldbo, Christina Sæten; Lindemann, Kristina Yvonne Kathe & Hellebust, Taran Annette Paulsen
[Show all 8 contributors for this article]
(2025).
Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study.
Acta Oncologica.
ISSN 0284-186X.
64,
p. 439–447.
doi:
10.2340/1651-226X.2025.43045.
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Background and purpose: Locally advanced cervical cancer is treated with chemoradiotherapy. The treatment-related morbidity is high. Tumor hypoxia has prognostic impact and represents a valid, interventional target. This phase II study investigated efficacy of the antidiabetic drug metformin to modify hypoxia according to established biomarkers. Preliminary results including tolerability, safety and feasibility are reported here.
Patients and methods: Patients were included in a 1:1 randomized, open-label design, comparing standard chemoradiotherapy ± metformin. Metformin 850 mg twice daily was administered 1 week before and during chemoradiotherapy. Magnetic resonance images (MRI) and tumor biopsies were collected at baseline, after 1 week of metformin treatment, and at brachytherapy for biomarker assessments. Tolerability and safety were determined by treatment completion rates and frequency of adverse events (AEs). Safety was further evaluated by possible increase in MRI-based hypoxia during the first week of metformin. Feasibility was determined by proportion of completed study interventions and imaging and biopsy procedures.
Results: In total, 18 and 23 patients were allocated to the intervention and control arm, respectively. Eighteen and 15 patients completed metformin treatment for 1 and 5 weeks. Frequency of AEs ≥ grade 3 was not significantly different between study arms. Most AEs were gastrointestinal toxicities. Tumors with increase in hypoxia during the first week were all below the defined safety limit. A total of 98% of scheduled MR series and biopsies were collected with satisfactory quality.
Interpretation: Addition of metformin to chemoradiotherapy is tolerable and safe. Serial sampling of MRI and tumor biopsies for hypoxia biomarker assessment is feasible.
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Mirza, Mansoor R.; Bjørge, Line; Marmé, Frederik; Christensen, René DePont; Gil-Martin, Marta & Auranen, Annika
[Show all 20 contributors for this article]
(2025).
Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial.
Gynecologic Oncology.
ISSN 0090-8258.
192,
p. 128–136.
doi:
10.1016/j.ygyno.2024.12.003.
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Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer.
Patients and methods: This placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endometrial cancer that was primary metastatic or had relapsed after ≥1 prior systemic therapy. Patients were randomized in a 1:1 ratio, stratified by number of prior chemotherapy lines, measurable versus evaluable non-measurable disease, and prior medroxyprogesterone/megestrol acetate treatment, to receive oral letrozole 2.5 mg on days 1–28 plus either oral palbociclib 125 mg or placebo on days 1–21, repeated every 28 days until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS).
Results: Among 77 patients randomized between February 16, 2017, and December 21, 2018, 73 were treated (36 with palbociclib–letrozole, 37 with placebo–letrozole). Median follow-up was 21.9 (95 % CI, 16.7 to 22.3) months. Median PFS was 8.3 (95 % CI, 4.6 to 11.2) versus 3.1 (95 % CI, 2.7 to 6.8) months, respectively. In a landmark analysis at 12 months the PFS hazard ratio was 0.57 (95 % CI, 0.32 to 0.99; P = .044). Grade ≥ 3 adverse events were more common with palbociclib–letrozole (67 %) than placebo–letrozole (30 %), most commonly neutropenia (44 % v 0 %, respectively).
Conclusion: These results support a potential role of the palbociclib–letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned.
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Lindemann, Kristina Yvonne Kathe; Siegenthaler, Franziska; Johannesen, Karin Teien; Arozamena, Carlos Casas; Nebdal, Daniel Johan Hammer & Rau, Tilman T.
[Show all 13 contributors for this article]
(2025).
Prognostic value of assessing ctDNA in patients with endometrial carcinoma - an international multicenter study.
Gynecologic Oncology.
ISSN 0090-8258.
195,
p. 98–105.
doi:
10.1016/j.ygyno.2025.03.002.
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Objective: At present, no reliable blood-based biomarkers have been established for patients with endometrial cancer. Liquid biopsies, which can detect circulating tumor DNA (ctDNA), provide a non-invasive way to assess prognosis, monitor tumor evolution and treatment response. We aimed to examine the feasibility and performance of ctDNA as a prognostic tool in a multi-center cohort of EC patients with matched tumor samples.
Methods: Blood plasma samples were collected preoperatively from 83 patients at three European cancer centers. Circulating cell-free DNA (cfDNA) was isolated and analyzed using the Oncomine™ Pan-Cancer cell-free assay. Tumor tissue from 56 of the 83 patients was subjected to whole-exome sequencing, and clinical data were collected for oncological outcome assessment.
Results: The mean input of cfDNA was 8.17 ng (range 1.47–29.12 ng). Sixteen (19.3 %) patients were considered ctDNA positive with mutations in one or more genes. Most alterations detected in plasma were concordant with mutations found in the matched tumor for the paired cases. The preoperative presence of ctDNA was associated with a significantly higher rate of recurrence (37.5 % vs 11.9 %, P = 0.024). Although eight of the 14 (57 %) patients with recurrence were negative for ctDNA at diagnosis, positive ctDNA status remained an independent predictor of recurrence also when controlling for other known histopathologic risk factors (HR 5.49, 95 % CI 1.5–20, P = 0.010).
Conclusions: Our results demonstrated the feasibility of using an off-the-shelf gene panel to detect ctDNA in patients with endometrial cancer. ctDNA positivity was significantly associated with worse oncological outcomes.
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Vistad, Ingvild; Skorstad, Mette; Berntsen, Sveinung; Demmelmaier, Ingrid; Bjørge, Line & Poll-Franse, Lonneke V. Van De
[Show all 17 contributors for this article]
(2025).
Empowerment and quality of life in gynecological cancer survivors: Outcomes from a multicenter quasi-experimental cohort study from Norway (the LETSGO trial).
Cancer.
ISSN 0008-543X.
131(16).
doi:
10.1002/cncr.70040.
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Background: Increasing outpatient demands and unmet patient needs necessitate personalized follow-up care for cancer survivors. This study investigated whether a self-management–focused follow-up model improves empowerment and quality of life (QoL) in gynecological cancer survivors compared to standard follow-up.
Methods: Twelve Norwegian hospitals participated in this cohort study. Patients initiating routine follow-up after primary treatment were eligible and allocated to either intervention or standard care follow-up groups based on their treatment hospital. The intervention included nurse-led consultations using coaching techniques for education on symptom monitoring and healthy lifestyle, alternated with physician-led consultations and access to a mobile app. Standard follow-up consisted of physician-led consultations only. The primary outcome was change in patient empowerment over 12 months, measured with the self-monitoring and insight domain of the Health Education Impact Questionnaire (heiQ). Secondary outcomes included changes in remaining heiQ domains and QoL. Data were analyzed according to intention-to-treat principles using linear mixed effects models.
Results: Among 741 participants (intervention: 378, standard: 363), baseline characteristics were comparable. At 12 months, no significant differences were observed in self-monitoring and insight (Δ = 0.02 [95% confidence interval (CI), –0.04 to 0.08]; effect sizes [ES] = 0.29). However, health-directed activity (Δ = 0.15 [95% CI, 0.04–0.25]; ES = 0.15), emotional well-being (Δ = 0.12 [95% CI, 0.02–0.20]; ES = 0.15), social functioning (Δ = 5.2 [95% CI, 1.1–9.3]; ES = 0.41), and physical functioning (Δ = 2.5 [95% CI, 0.0–5.0]; ES = 0.20) were significantly more improved in the intervention group.
Conclusion: Lifestyle and Empowerment Techniques in Survivorship of Gynaecologic Oncology follow-up did not significantly impact self-monitoring and insight, but positively influenced other survivorship domains, indicating its potential for enhancing self-management and QoL in gynecological cancer survivors.
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Haug, Ala Jabri; Støer, Nathalie Charlotte; Langseth, Hilde; Siafarikas, Franziska; Botteri, Edoardo & Fortner, Shannon Renee Turzanski
[Show all 7 contributors for this article]
(2025).
Non-steroidal anti-inflammatory medication use and endometrial cancer survival: A population-based Norwegian cohort study.
International Journal of Cancer.
ISSN 0020-7136.
157(2),
p. 277–287.
doi:
10.1002/ijc.35363.
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While nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to improve survival in certain cancers, data in patients with endometrial cancer (EC) is conflicting. This study investigated use of aspirin and nonaspirin NSAIDs (NA-NSAIDs) and EC-specific—and all-cause death. This nationwide cohort study linked data from the Cancer Registry of Norway with The Norwegian Prescription database. Patients diagnosed with EC from 2004 to 2018 were included. Post-diagnosis exposure to aspirin and NA-NSAIDs was defined as ≥3 consecutive prescriptions ≥30 days after EC diagnosis, with pre-diagnosis use as ≥2 filled prescriptions <6 months prior to diagnosis. Follow-up started 10 months after diagnosis. Hazard ratios for the risk of death were calculated with multivariable Cox-regression models. Our study population included 7751 individuals with EC, 685 (9%) were aspirin users and 620 (8%) were NA-NSAIDs users. The median follow-up time was 5.0 years, with 1518 (20%) deaths observed (n = 728 (9%) EC-specific). In multivariable analysis, aspirin use was significantly associated with a 19% higher risk of all-cause death compared to non-users (HR = 1.19, 95% CI [1.01–1.41]). The association was stronger among combined pre- and postdiagnosis use (HR = 1.35 [1.12–1.64]). NA-NSAIDs use increased risk of cancer-related death (HR = 1.25 [0.99–1.58]) and there was a dose–response association with significantly higher risk of cancer-specific death with higher cumulative doses (HR = 1.33 [1.02–1.75]). We found a higher risk of cancer-specific—and all-cause death among patients that used aspirin and NA-NSAIDs after a diagnosis of EC. Further studies on the biological mechanisms underlying these associations are needed.
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Skipar, Kjersti Øvrum; Hompland, Tord; Lund, Kjersti Vassmo; Lindemann, Kristina Yvonne Kathe; Hellebust, Taran Annette Paulsen & Bruheim, Kjersti
[Show all 7 contributors for this article]
(2024).
MRI-guided dynamic risk assessment in cervical cancer based on tumor hypoxia at diagnosis and volume response at brachytherapy.
Radiotherapy and Oncology.
ISSN 0167-8140.
195,
p. 1–7.
doi:
10.1016/j.radonc.2024.110263.
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Background and purpose: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification.
Material and methods: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HFpre) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HFpre. In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. C
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Kleppe, Andreas; Lindemann, Kristina Yvonne Kathe; Kildal, Wanja; Tobin, Kari Anne Risan; Pradhan, Manohar & Vlatkovic, Ljiljana
[Show all 10 contributors for this article]
(2024).
Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer.
Gynecologic Oncology.
ISSN 0090-8258.
192,
p. 80–88.
doi:
10.1016/j.ygyno.2024.11.005.
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Introduction. The role of molecular classification and L1CAM in high-risk endometrial cancer is uncertain. We aimed to determine the association of molecular profiling and L1CAM with patterns of relapse and survival.<p> <p>Material and methods. This retrospective cohort study included patients referred to Department for Gynecologic Oncology, Oslo University Hospital between January 1, 2006 and December 31, 2017. L1CAM expression and molecular profiling according to ProMisE was performed. Main outcome was time to recurrence (TTR) and cancer specific survival (CSS). <p>Results. Of 489 patients, 486 could be molecular classified. Thirty-seven (8 %) had POLE mutated tumors, 148 (30 %) had MMRd tumors, 189 (39 %) had p53 abnormal tumors, and 112 (23 %) had NSMP tumors. High L1CAM expression was observed in 256 (53 %), low in 227 (46 %) tumors (6 (1 %) missing). ProMisE was significant for TTR but not for CSS in multivariable analysis. L1CAM was significant in multivariable analysis for both TTR and CSS. In a multivariable model with ProMisE and L1CAM expression in the same multivariable model, ProMisE lost significance while L1CAM remained significant. Patients with POLE mutated tumors entailed an excellent prognosis while patients with p53 abnormal or L1CAM overexpressing tumors entailed a poor prognosis with a high frequency of distant recurrences. Patients with MMRd tumors, NSMP and p53 abnormal tumors with low L1CAM had an intermediate prognosis. <p>Conclusions. L1CAM is an additional adverse factor in the p53 abnormal and NSMP groups. These groups need special attention in studies intensifying adjuvant treatment.
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Lindemann, Kristina Yvonne Kathe; Kildal, Wanja; Kleppe, Andreas; Tobin, Kari Anne Risan; Pradhan, Manohar & Isaksen, Maria
[Show all 10 contributors for this article]
(2024).
Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer.
European Journal of Cancer.
ISSN 0959-8049.
200.
doi:
10.1016/j.ejca.2024.113584.
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Introduction - The role of molecular classification in patients with low/intermediate risk endometrial cancer (EC) is uncertain. Higher precision in diagnostics will inform the unsettled debate on optimal adjuvant treatment. We aimed to determine the association of molecular profiling with patterns of relapse and survival.<p> <p>Material and methods - This retrospective cohort study included patients referred to The Norwegian Radium Hospital, Oslo University Hospital from 2006–2017. Patients with low/intermediate risk EC were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP). The main outcomes were time to recurrence (TTR) and cancer-specific survival (CSS).<p> <p>Results - Of 626 patients, 610 could be molecularly classified. Fifty-seven patients (9%) had POLE-mutated tumors, 202 (33%) had MMRd tumors, 34 (6%) had p53 abnormal tumors and 317 (52%) had NSMP tumors. After median follow-up time of 8.9 years, there was a statistically significant difference in TTR and CSS by molecular groups. Patients with p53 abnormal tumors had poor prognosis, with 10 of the 12 patients with relapse presenting with para-aortic/distant metastases. Patients with POLE mutations had excellent prognosis. In the NSMP group, L1CAM expression was associated with shorter CSS but not TTR.<p> <p>Conclusions - The differences in outcome by molecular groups are driven by differences in relapse frequency and -patterns and demand a higher precision in diagnostics, also in patients with low/intermediate risk EC. Tailored adjuvant treatment strategies need to consider systemic treatment for patients with p53 abnormal tumors and de-escalated treatment for patients with POLE mutated tumors.
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Gorp, Gorp Van; Cibula, D.; Lv, W.; Backes, F.; Ortaç, F. & Hasegawa, K.
[Show all 30 contributors for this article]
(2024).
ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer.
Annals of Oncology.
ISSN 0923-7534.
35(11),
p. 968–980.
doi:
10.1016/j.annonc.2024.08.2242.
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Davidson, Ben; Lande, Karin Teien; Nebdal, Daniel J.H.; Nesbakken, Anne Jorun; Holth, Arild & Lindemann, Kristina Yvonne Kathe
[Show all 8 contributors for this article]
(2024).
Endometrial carcinomas with ambiguous histology often harbor TP53 mutations.
Virchows Archiv.
ISSN 0945-6317.
0(0),
p. 1–9.
doi:
10.1007/s00428-024-03912-7.
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The objective of the present study was to characterize the molecular features of endometrial carcinomas with ambiguous histology. Eighteen carcinomas that could not be conclusively typed based on morphology and immunohistochemistry underwent analysis of mismatch repair (MMR) status, microsatellite status, and whole-exome sequencing. None of the tumors had pathogenic POLE mutation. Twelve tumors (67%) were microsatellite stable, and 6 (33%) had microsatellite instability. Fourteen tumors (78%) harbored TP53 mutations, and 2 (11%) had mutations in MMR genes. Eleven carcinomas (61%) were classified as copy number high and 7 (39%) as MSI-hypermutated, the latter including 3 tumors with TP53 mutation who concomitantly had MSI or mutation in a MMR gene. Other mutations that were found in > 1 tumor affected MUC16 (7 tumors), PIK3CA (6 tumors), PPP2R1A (6 tumors), ARID1A (5 tumors), PTEN (5 tumors), FAT1 (4 tumors), FAT4 (3 tumors), BRCA2 (2 tumors), ERBB2 (2 tumors), FBXW7 (2 tumors), MET (2 tumors), MTOR (2 tumors), JAK1 (2 tumors), and CSMD3 (2 tumors). At the last follow-up (median = 68.6 months), 8 patients had no evidence of disease, 1 patient was alive with disease, 8 patients were dead of disease, and 1 patient died of other cause. In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive.
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Luijten, Maartje M. W.; Weelden, Willem Jan van; Lalisang, Roy I.; Bulten, Johan; Lindemann, Kristina Yvonne Kathe & Beekhuizen, Heleen J. van
[Show all 23 contributors for this article]
(2024).
Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.
Cancers.
16(11).
doi:
10.3390/cancers16112084.
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Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0–10%, 10–50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.
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Davidson, Ben; Holth, Arild; Lindemann, Kristina Yvonne Kathe; Eriksson, Ane Gerda Zahl; Nilsen, Thale Andrea & Kristensen, Annette Torgunrud
(2024).
Molecular characteristics of tubo-ovarian carcinosarcoma at different anatomic locations.
Virchows Archiv.
ISSN 0945-6317.
485(6),
p. 1053–1061.
doi:
10.1007/s00428-024-03821-9.
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Carcinosarcoma (CS) is an uncommon and clinically aggressive malignancy. The objective of the present study was to characterize the molecular features of CS at various anatomic locations, including serous effusions. Specimens (n = 32) consisted of 25 biopsies/surgical resection specimens and 7 serous effusions (6 peritoneal, 1 pleural) from 25 patients. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. A total of 31 mutations were found in 25 of the 32 tumors studied, of which 1 had 3 mutations, 4 had 2 different mutations, and 20 had a single mutation. The most common mutations were in TP53 (n = 25 in 24 tumors; 1 tumor with 2 different mutations), with less common mutations found in RB1 (n = 2), MET (n = 1), KRAS (n = 1), PTEN (n = 1), and KIT (n = 1). Patient-matched specimens harbored the same TP53 mutation. Tumors with no detected mutations were more common in serous effusion specimens (3/7; 43%) compared with surgical specimens (4/25; 16%). In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain.
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Os, Silje Skjelsvik; Skipar, Kjersti Øvrum; Skovlund, Eva; Hompland, Ivar; Hellebust, Taran Annette Paulsen & Guren, Marianne
[Show all 8 contributors for this article]
(2024).
Survival prediction in patients with gynecological cancer irradiated for brain metastases.
Acta Oncologica.
ISSN 0284-186X.
63,
p. 206–212.
doi:
10.2340/1651-226X.2023.34899.
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ackground and purpose: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers.
Material and methods: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS.
Results: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001), Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively.
Interpretation: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.
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Mirza, M.R.; Tandaric, Luka; Henriksen, J.R.; Mäenpää, J.; Christensen, R.D. & Waldstrøm, M.
[Show all 14 contributors for this article]
(2024).
NSGO-OV-UMB1/ENGOT-OV30: A phase II study of durvalumab in combination with the anti-CD73 monoclonal antibody Oleclumab in patients with relapsed ovarian cancer.
Gynecologic Oncology.
ISSN 0090-8258.
188,
p. 103–110.
doi:
10.1016/j.ygyno.2024.06.017.
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Objectives In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. Methods In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. Results This trial included 25 patients with a median age of 66 years (47–77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2–4.2) and the median overall survival was 8.4 months (95% CI: 5.0–13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. Conclusions Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
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Casey, Nicholas Paul; Kleinmanns, Katrin; Forcados, Christopher; Gelebart, Pascal Francois; Joaquina, Sandy & Lode, Martine Rott
[Show all 21 contributors for this article]
(2024).
Efficient CAR T cell targeting of the CA125 extracellular repeat domain of MUC16.
Journal for ImmunoTherapy of Cancer (JITC).
12:e008179(4),
p. 1–14.
doi:
10.1136/jitc-2023-008179.
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Background Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies in the Western world. Contributing factors include a high frequency of late-stage diagnosis, the development of chemoresistance, and the evasion of host immune responses. Currently, debulking surgery and platinum-based chemotherapy are the treatment cornerstones, although recurrence is common. As the clinical efficacy of immune checkpoint blockade is low, new immunotherapeutic strategies are needed. Chimeric antigen receptor (CAR) T cell therapy empowers patients’ own T cells to fight and eradicate cancer, and has been tested against various targets in OC. A promising candidate is the MUC16 ectodomain. This ectodomain remains on the cell surface after cleavage of cancer antigen 125 (CA125), the domain distal from the membrane, which is currently used as a serum biomarker for OC. CA125 itself has not been tested as a possible CAR target. In this study, we examined the suitability of the CA125 as a target for CAR T cell therapy. Methods We tested a series of antibodies raised against the CA125 extracellular repeat domain of MUC16 and adapted them to the CAR format. Comparisons between these candidates, and against an existing CAR targeting the MUC16 ectodomain, identified K101 as having high potency and specificity. The K101CAR was subjected to further biochemical and functional tests, including examination of the effect of soluble CA125 on its activity. Finally, we used cell lines and advanced orthotopic patient-derived xenograft (PDX) models to validate, in vivo, the efficiency of our K101CAR construct. Results We observed a high efficacy of K101CAR T cells against cell lines and patient-derived tumors, in vitro and in vivo. We also demonstrated that K101CAR functionality was not impaired by the soluble antigen. Finally, in direct comparisons, K101CAR, which targets the CA125 extracellular repeat domains, was shown to have similar efficacy to the previously validated 4H11CAR, which targets the MUC16 ectodomain. Conclusions Our in vitro and in vivo results, including PDX studies, demonstrate that the CA125 domain of MUC16 represents an excellent target for treating MUC16-positive malignancies.
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Cun, Han T.; Bernard, Laurence; Lande, Karin Teien; Lawson, Barrett C.; Nesbakken, Anne Jorun & Davidson, Ben
[Show all 11 contributors for this article]
(2024).
Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.
Gynecologic Oncology.
ISSN 0090-8258.
189,
p. 138–145.
doi:
10.1016/j.ygyno.2024.07.677.
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Objective The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes. Methods Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures. Results 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%). Conclusions This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.
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Lorusso, Domenica; Xiang, Yang; Hasegawa, Kosei; Scambia, Giovanni; Leiva, Manuel & Ramos-Elias, Pier
[Show all 34 contributors for this article]
(2024).
Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.
The Lancet.
ISSN 0140-6736.
403(10434),
p. 1341–1350.
doi:
10.1016/S0140-6736(24)00317-9.
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Lorusso, Domenica; Xiang, Yang; Hasegawa, Kosei; Scambia, Giovanni; Leiva, Manuel & Ramos-Elias, Pier
[Show all 34 contributors for this article]
(2024).
Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.
The Lancet.
ISSN 0140-6736.
doi:
10.1016/S0140-6736(24)01808-7.
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Areklett, Elisabeth Wang; Andersson, Stein; Fagereng, Elisabeth; Bruheim, Kjersti; Stubberud, Jan Egil & Lindemann, Kristina Yvonne Kathe
(2024).
Cognitive impairment in cervical cancer survivors—Exploring the discrepancy between subjective and objective assessment.
Psycho-Oncology.
ISSN 1057-9249.
33(2).
doi:
10.1002/pon.6300.
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Objective Cancer-related cognitive impairment has severe implications for the quality of life and societal participation of cervical cancer survivors (CCS). However, there is no research on the association between subjective and objective cognitive impairment (CI) in cervical cancer. This cross-sectional study aimed to examine the frequency and severity of objective CI in CCS reporting significant subjective CI and explore the discrepancy between subjective and objective CI. Methods Sixty-five CCS reporting significant subjective CI, defined as 1.5 SD below the normative mean, underwent neuropsychological (NP) assessment covering attention, verbal memory, processing speed, verbal fluency, and executive functions. CCS were compared to healthy age-matched controls (n = 74). A subjective versus objective discrepancy score was calculated based on the standardized scores within each group. Results The CCS group performed significantly poorer across all NP tests compared to healthy controls (all p-values <0.001) and 81.5% had scores below cut-off as defined by the International Cognition and Cancer Task Force. However, compared to published normative data, most CCS performed within the clinically normal range. Processing speed and verbal memory were the most affected cognitive domains. By calculating a discrepancy score, both groups on average displayed a quite accurate concordance between subjective and objective cognitive functioning. Conclusion Although CI is evident in CCS, our results confirm that objective and subjective CI represent different constructs and highlight the limitations of normative data. Differentiating subjective and objective CI is important when tailoring effective interventions in the survivorship care of CCS.
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Areklett, Elisabeth Wang; Hagen, Bjørn Ole Ingulfsvann; Stubberud, Jan Egil; Fagereng, Elisabeth; Andersson, Stein & Lindemann, Kristina Yvonne Kathe
(2024).
Digital goal management training for cognitive impairment in cervical cancer survivors—a randomized comparison study.
Journal of cancer survivorship.
ISSN 1932-2259.
doi:
10.1007/s11764-024-01701-4.
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Purpose Cognitive impairment (CI) is a common late effect after cancer treatment, for which effective interventions are lacking. Goal management training (GMT) is a validated cognitive training protocol reported to improve cognition, including executive functioning. The purpose of this study was to examine the feasibility and acceptability of digital GMT in cervical cancer survivors (CCS) experiencing CI and compare it to computerized cognitive training (CCT). Methods Thirty-five CCS with significant subjective CI were randomized in a 1:1 ratio between digital GMT (N = 18) and CCT (N = 17). The primary endpoint was attendance, and participants attending ≥ 80% of the sessions were categorized as completers. Acceptability was evaluated post-intervention using the Client Satisfaction Questionnaire-8 (CSQ-8). Secondary outcomes included self-reported and performance-based cognitive functioning. Results The completion rate in both groups was 88%. Participants in both groups reported high levels of satisfaction (CSQ-8; GMT: M = 25.2, SD 3.7, range 18–31, and CCT: M = 24.6, SD 3.1, range 19–30). Exploratory analyses showed improvements in both groups over time in attention and memory as well as self-reported cognitive functioning. Conclusion Digital GMT is feasible with a high level of compliance and satisfaction in CCS. Preliminary efficacy data shows promising cognitive improvement over time, and the results are comparable to CCT and warrant further investigation in a larger-scale trial. Implications for Cancer Survivors If deemed effective in a larger study, digital cognitive training, such as GMT, is a low-cost, low-staff intensive intervention that is easily implemented and available to cancer survivors experiencing CI.
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Krakstad, Camilla; Berg, Hege Fredriksen; Lindemann, Kristina Yvonne Kathe & Halle, Mari Kyllesø
(2024).
Frequency of ERBB2-Low Expression in Endometrial Cancer.
JAMA Oncology.
ISSN 2374-2437.
10(11).
doi:
10.1001/jamaoncol.2024.3660.
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The epidermal growth factor receptor 2 (ERBB2, formerly HER2)–targeting antibody drug conjugates (vic-)trastuzumab duocarmazine and trastuzumab deruxtecan have recently been tested in endometrial cancer (EC), including patients with ERBB2 immunohistochemistry score 1+ and 2+–expressing tumors. Interim results1 show response rates in patients with cervical (50.0%), endometrial (57.5%), and ovarian cancer (45.0%). These response rates suggest practice-changing efficacy and support further investigation in phase 3 trials in EC. We therefore reanalyzed ERBB2 data previously reported2 and added information on all ERBB2 scoring categories and molecular subtype, aiming to characterize patient subgroups also with ERBB2-low tumors (1+ and 2+).
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Pujade-Lauraine, E.; Selle, F.; Scambia, G.; Asselain, B.; Marmé, F. & Lindemann, Kristina Yvonne Kathe
[Show all 23 contributors for this article]
(2023).
Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.
Annals of Oncology.
ISSN 0923-7534.
doi:
10.1016/j.annonc.2023.09.3110.
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Background Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. Patients and methods This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. Results Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan–Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan–Meier estimates). No new safety signals were identified with olaparib rechallenge. Conclusions In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.
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Valstad, Hanna; Eyjólfsdóttir, Brynhildur; Wang, Yun; Kristensen, Gunnar S Balle; Jensen, Tone Skeie & Lindemann, Kristina Yvonne Kathe
(2023).
Pelvic exenteration for vulvar cancer: Postoperative morbidity and oncologic outcome – A single center retrospective analysis.
European Journal of Surgical Oncology.
ISSN 0748-7983.
49(9).
doi:
10.1016/j.ejso.2023.06.010.
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Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell’s biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy—a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H2O2) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.
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Corbaux, Pauline; You, Benoit; Glasspool, Rosalind M.; Yanaihara, Nozomu; Tinker, Anna V. & Lindemann, Kristina Yvonne Kathe
[Show all 19 contributors for this article]
(2023).
Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis.
European Journal of Cancer.
ISSN 0959-8049.
191.
doi:
10.1016/j.ejca.2023.112966.
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Background In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. Methods The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. Results KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41–0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45–0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. Conclusion KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
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Lindemann, Kristina Yvonne Kathe; Kleppe, Andreas; Eyjólfsdóttir, Brynhildur; Danbolt, Svana Heimisdottir; Wang, Yun Yong & Heli-Haugestøl, Anne Gjertine
[Show all 12 contributors for this article]
(2023).
Prospective evaluation of an enhanced recovery after surgery (ERAS) pathway in a Norwegian cohort of patients with suspected or advanced ovarian cancer.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
33(8),
p. 1279–1286.
doi:
10.1136/ijgc-2023-004355.
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Objective This prospective cohort study evaluated the introduction of an enhanced recovery after surgery (ERAS) pathway in a tertiary gynecologic oncology referral center. Compliance and clinical outcomes were studied in two separate surgical cohorts. Methods Patients undergoing laparotomy for suspected or verified advanced ovarian cancer at Oslo University Hospital were prospectively included in a pre- and post-implementation cohort. A priori, patients were stratified into: cohort 1, patients planned for surgery of advanced disease; and cohort 2, patients undergoing surgery for suspicious pelvic tumor. Baseline characteristics, adherence to the pathway, and clinical outcomes were assessed. Results Of the 439 included patients, 235 (54%) underwent surgery for advanced ovarian cancer in cohort 1 and 204 (46%) in cohort 2. In cohort 1, 53% of the patients underwent surgery with an intermediate/high Aletti complexity score. Post-ERAS, median fasting times for solids (13.1 hours post-ERAS vs 16.0 hours pre-ERAS, p<0.001) and fluids (3.7 hours post-ERAS vs 11.0 hours pre-ERAS, p<0.001) were significantly reduced. Peri-operative fluid management varied less and was reduced from median 15.8 mL/kg/hour (IQR 10.8–22.5) to 11.5 mL/kg/hour (IQR 9.0–15.4) (p<0.001). In cohort 2 only there was a statistically significant reduction in length of stay (mean (SD) 4.3±1.5 post-ERAS vs 4.6±1.2 pre-ERAS, p=0.026). Despite stable readmission rates, there were significantly more serious complications reported in cohort 1 post-ERAS. Conclusions ERAS increased adherence to current standards in peri-operative management with significant reduction in fasting times for both solids and fluids, and peri-operative fluid administration. Length of stay was reduced in patients with suspicious pelvic tumor. Despite serious complications being common in patients with advanced disease undergoing debulking surgery, a causal relationship with the ERAS protocol could not be established. Implementing ERAS and continuous performance auditing are crucial to advancing peri-operative care of patients with ovarian cancer.
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Santos, Margarida Varela dos; Holth, Arild; Lindemann, Kristina Yvonne Kathe; Staff, Anne Cathrine & Davidson, Ben
(2023).
Clinical significance of L1CAM expression in metastatic tubo-ovarian high-grade serous carcinoma.
Gynecologic Oncology.
ISSN 0090-8258.
176,
p. 76–81.
doi:
10.1016/j.ygyno.2023.07.004.
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Objective To analyze the expression and prognostic role of L1CAM in tubo-ovarian high-grade serous carcinoma (HGSC). Methods L1CAM protein expression by immunohistochemistry was analyzed in 644 HGSC (413 effusions, 231 surgical specimens). Expression was analyzed for association with clinicopathologic parameters and survival. Results L1CAM protein expression was found in 401/413 (97%) effusions and 209/231 (90%) surgical specimens, with significantly higher staining extent in effusions (p < 0.001). L1CAM protein expression in effusions was unrelated to clinicopathologic parameters (p > 0.05). In surgical specimens, higher L1CAM expression was significantly related to primary (intrinsic) chemoresistance (p = 0.017). High (>25%) L1CAM expression in HGSC effusions (p = 0.02), older patient age (p = 0.013), FIGO stage IV disease (p < 0.001) and larger residual disease volume (p = 0.001) were significantly associated with shorter overall survival (OS) in univariate analysis. In Cox multivariate analysis, only FIGO stage (p = 0.001) and residual disease volume (p = 0.003) were independent prognosticators of OS. L1CAM expression in effusions was unrelated to progression-free survival (PFS). There was no association between L1CAM expression in surgical specimens and survival. Conclusion L1CAM is overexpressed in HGSC effusions compared to surgical specimens. Its overexpression in effusions is significantly associated with shorter OS, but not independently of established prognostic factors such as FIGO stage and residual disease volume.
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Vilming, Bente; Dahl, Jørgen Fallås; Bentzen, Anne Gry; Ingebrigtsen, Vibeke Anett; Nilsen, Elisabeth Berge & Vistad, Ingvild
[Show all 12 contributors for this article]
(2023).
Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
33(12),
p. 1898–1905.
doi:
10.1136/ijgc-2023-004484.
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Objectives The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer. Methods This retrospective multi-center cohort study included 94 platinum-sensitive recurrent ovarian cancer patients without known gBRCA1/2 mutation treated in an individual patient access program in Norway. The primary outcome was time from start of niraparib treatment to first subsequent treatment. Secondary endpoints included progression-free survival, safety, and tolerability. Results After median follow-up of 13.4 months (95% confidence interval (CI) 10.0 to 16.8), 68.1% had progressed and 22.3% had died. Of the entire cohort, 61.7% had commenced a new line of treatment, and 24.5% were still receiving niraparib. The median duration of niraparib treatment was 5.0 months (range 0.4 to 27.3), and the median time to first subsequent treatment was 10.7 months (95% CI 8.4 to 13.0). Patients with elevated CA125 prior to start of niraparib had shorter time to first subsequent treatment (7.3 months, 95% CI 4.2 to 10.3) than patients with normalized CA125 (12.2 months, 95% CI 10.9 to 13.7 (p=0.002). Patients who started on individual dose based on weight and platelet counts had fewer dose reductions (p<0.001) and interruptions (p=0.02). Conclusion In a real-world setting, niraparib maintenance treatment in patients with non-gBRCA1/2 mutated recurrent platinum-sensitive ovarian cancer showed effectiveness comparable with published phase III studies and acceptable safety. Individualized dosing is essential to minimize adverse events. CA125 levels at start of niraparib treatment may help to estimate the individual prognosis.
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Skaali, Tone Margrethe Olsbu; Blomhoff, Rune; Lindemann, Kristina Yvonne Kathe; Smeland, Sigbjørn; Bruheim, Kjersti & Selland, Mette
[Show all 7 contributors for this article]
(2023).
Self-reported distress and problems after treatment for gynecological cancer – Correlation between a short screening tool and longer measures of anxiety/depression and health-related quality of life.
Acta Obstetricia et Gynecologica Scandinavica.
ISSN 0001-6349.
doi:
10.1111/aogs.14709.
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Abstract Introduction The National Comprehensive Cancer Network (NCCN) distress thermometer and problem list (DTPL) is a brief self‐report screening measure for use in follow‐up cancer care. The aims of this study were to explore the correlations between scores on the DTPL and scores on longer measures of anxiety/depression and health‐related quality of life among women treated for gynecological cancer, and to define a cutoff score on the DT representing high levels of psychological distress in this patient group. Material and methods During outpatient visits, 144 women filled in the DTPL, the Hospital Anxiety and Depression Scale (HADS) and the RAND‐36‐Item Short Form Health Survey (RAND‐36) between October 2019 and March 2020. We assessed the agreement between the DT‐scores and the HADS scores, explored variables associated with high levels of distress on the DT, and studied the associations between DTPL‐scores and scores of health‐related quality of life (HRQoL) from RAND‐36. Results In receiver operating characteristic curve analysis between the distress score from the DT and a HADS total score ≥15 (defining high levels of anxiety/depression symptoms), the area under the curve was 0.81 (95% CI: 0.74–0.89). Using a cutoff of ≥5 on the DT (scale 0–10), we found a balanced level of sensitivity (81%) and specificity (71%) towards a HADS total score of ≥15. The scores of distress and problems reported on the DTPL correlated significantly with the majority of HRQoL function scales from RAND‐36. Conclusions The NCCN DTPL can be used as a screening measure for self‐reported distress and problems after treatment for gynecological cancer. A score of ≥5 on DT may indicate high level of anxiety/depression as measured by HADS. The tool may help identify patients in need of referral to supportive care and rehabilitation facilities.
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Oaknin, Ana; Gladieff, Laurence; Martínez-García, Jerónimo; Villacampa, Guillermo; Takekuma, Munetaka & Giorgi, Ugo De
[Show all 32 contributors for this article]
(2023).
Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial.
The Lancet.
ISSN 0140-6736.
403(10421),
p. 31–43.
doi:
10.1016/S0140-6736(23)02405-4.
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Lindemann, Kristina Yvonne Kathe; Danbolt, Svana Heimisdottir; Ramberg, Lene Kristine Marsby; Eyjólfsdóttir, Brynhildur; Wang, Yun & Heli-Haugestøl, Anne Gjertine
[Show all 15 contributors for this article]
(2023).
Patient-reported nausea after implementation of an enhanced recovery after surgery protocol for gynae-oncology patients.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
33(8),
p. 1287–1294.
doi:
10.1136/ijgc-2023-004356.
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Objectives This study aimed to analyze the adherence to strategies to prevent post-operative nausea and vomiting after implementation of an enhanced recovery after surgery (ERAS) protocol for gynae-oncology patients. Patient-reported nausea before and after ERAS was also studied. Methods This prospective observational study included all patients undergoing laparotomy for a suspicious pelvic mass or confirmed advanced ovarian cancer before (pre-ERAS) and after the implementation of ERAS (post-ERAS) at Oslo University Hospital, Norway. Patients were a priori stratified according to the planned extent of surgery into two cohorts (Cohort 1: Surgery of advanced disease; Cohort 2: Surgery for a suspicious pelvic tumor). Clinical data including baseline characteristics and outcome data were prospectively collected. Results A total of 439 patients were included, 243 pre-ERAS and 196 post-ERAS. At baseline, 27% of the patients reported any grade of nausea. In the post-ERAS cohort, statistically significantly more patients received double post-operative nausea and vomiting prophylaxis (64% pre-ERAS vs 84% post-ERAS, p<0.0001). There was no difference in the need for rescue medication (82% pre-ERAS vs 79% post-ERAS; p=0.17) and no statistically significant difference between pre- and post-ERAS or between the surgical cohorts in patient-reported nausea of any grade on day 2. Patients who reported none/mild nausea on day 2 had significantly less peri-operative fluid administered during surgery than those who reported moderate or severe nausea (median 12.5 mL/kg/hour vs 16.5 mL/kg/hour, p=0.045) but, in multivariable analysis, fluid management did not remain significantly associated with nausea. Conclusion Implementation of an ERAS protocol increased the adherence to post-operative nausea and vomiting prevention guidelines. Nausea, both before and after laparotomy, remains an unmet clinical need of gynae-oncology patients also in an ERAS program. Patient-reported outcome measures warrant further investigation in the evaluation of ERAS.
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Berek, Jonathan S.; Matias-Guiu, Xavier; Creutzberg, Carien; Fotopoulou, Christina; Gaffney, David & Kehoe, Sean
[Show all 9 contributors for this article]
(2023).
FIGO staging of endometrial cancer: 2023.
International Journal of Gynecology & Obstetrics.
ISSN 0020-7292.
162(2),
p. 383–394.
doi:
10.1002/ijgo.14923.
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Abstract Introduction Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. Methods The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. Results Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non‐aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non‐aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low‐grade endometrioid carcinomas limited to the uterus with simultaneous low‐grade endometrioid ovarian involvement; (IB) non‐aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high‐grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non‐aggressive histological types that infiltrate the cervical stroma; (IIB) non‐aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para‐aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification ( POLEmut , MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of “m” for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICm p53abn or IAm POLEmut ). Summary The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence‐based context for treatment recommendations and for the more refined future collection of outcome and survival data.
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Lundberg, Frida E.; Stensheim, Hanne; Ullenhag, Gustav J.; Sahlgren, Hanna Milerad; Lindemann, Kristina Yvonne Kathe & Fredriksson, Irma
[Show all 7 contributors for this article]
(2023).
Risk factors for the increasing incidence of pregnancy-associated cancer in Sweden – a population-based study.
Acta Obstetricia et Gynecologica Scandinavica.
ISSN 0001-6349.
doi:
10.1111/aogs.14677.
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Abstract Introduction The incidence of cancer during pregnancy and within first year post‐delivery, ie pregnancy‐associated cancer (PAC), is increasing in many countries, but little is known about risk factors for these trends. This study quantified incidence of PAC by trimesters and post‐delivery periods, and assessed the role of maternal age, parity, immigrant status, education, smoking and body mass index for the risk and incidence trends of PAC. Material and methods We used data from the national birth and cancer registers in Sweden during 1973–2017 to define a register‐based cohort of women aged 15–44 years. Incidence rates of PAC during pregnancy and up to 1 year post‐delivery were calculated per 100 000 deliveries per year. Poisson regression with multiple imputation estimated incidence rate ratios with 95% confidence intervals adjusted by year, age, previous parity, immigrant status, education, smoking and BMI during 1990–2017, when information on risk factors was available. Results Among 4 557 284 deliveries, a total of 1274 (during pregnancy) and 3355 (within 1 year post‐delivery) cases of PAC were diagnosed, with around 50 cases/year diagnosed during pregnancy and 110 cases/year during the first year post‐delivery in the latest period 2015–2017. The most common cancer types during pregnancy were malignant melanoma, breast and cervical cancer, together accounting for 57% of cases during pregnancy and 53% during the first year post‐delivery. The numbers of PAC were lower during pregnancy than during post‐delivery for all tumor types with lowest numbers during first trimester. The PAC incidence rates increased over calendar time. High maternal age at diagnosis, smoking, nulliparity and non‐immigrant background were associated with significantly higher risks of PAC. The increasing PAC incidence was in part explained by higher maternal age over time, but not by the other factors. Conclusions High maternal age is the strongest risk factor for PAC. We show for the first time that smoking, nulliparity and non‐immigrant background are also contributing risk factors for PAC. However, only high maternal age contributed significantly to the increasing incidence. Further studies on other potential risk factors for PAC are warranted, since our results indicate that age on its own does not fully explain the increase.
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Davidson, Ben; Jensen, Tone Skeie; Holth, Arild; Lindemann, Kristina Yvonne Kathe; Barrameda, Anne Marie Toralba & Lie, Kathrine
[Show all 7 contributors for this article]
(2023).
Lymphovascular invasion and p16 expression are independent prognostic factors in stage I vulvar squamous cell carcinoma.
Virchows Archiv.
ISSN 0945-6317.
484,
p. 951–963.
doi:
10.1007/s00428-023-03670-y.
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Abstract The objective of this study was to identify clinicopathologic parameters associated with disease outcome in FIGO stage I vulvar squamous cell carcinoma (vSqCC). The cohort consisted of 126 patients diagnosed with vSqCC in the period 2006–2016 who underwent primary vulvar surgery and evaluation of groin lymph node status. Tumors were reviewed by an experienced gynecologic pathologist. p16 and p53 protein expression by immunohistochemistry and HPV status were analyzed in 116 tumors. Clinicopathologic parameters, protein expression and HPV status were analyzed for association with progression-free and overall survival (PFS, OS). p16 expression and aberrant p53 were found in 49 (42%) and 61 (53%) tumors, respectively. Sixty-six tumors were HPV-associated (57%). Relapse was diagnosed in 35/126 (28%) of patients, and 23 (18%) died of disease. Tumor diameter > 4 cm ( p = 0.013), lymphovascular space invasion (LVSI; p < 0.001), the presence of lichen sclerosus ( p = 0.019), p16 expression ( p = 0.007), p53 expression ( p = 0.012), HPV status ( p = 0.021), lymph node metastasis ( p < 0.001) and post-operative radiotherapy ( p < 0.001) were significantly related to OS in univariate analysis. Tumor diameter > 4 cm ( p = 0.038), LVSI ( p = 0.003), the presence of lichen sclerosus ( p = 0.004), p16 expression ( p = 0.004), HPV status ( p = 0.039), lymph node metastasis ( p < 0.001) and post-operative treatment ( p < 0.001), were significantly related to PFS in univariate analysis. Age, BMI and surgical resection involvement were not significantly associated with OS or PFS. In multivariate Cox analysis, LVSI and p16 expression were independent prognosticators of OS ( p < 0.001 and p = 0.02, respectively) and PFS ( p = 0.018, p = 0.037). In conclusion, LVSI and p16 expression are independent prognostic factors in stage I vSqCC.
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Siegenthaler, F.; Lindemann, Kristina Yvonne Kathe; Epstein, E.; Rau, T.T.; Nastic, D. & Ghaderi, M.
[Show all 10 contributors for this article]
(2022).
Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification.
Gynecologic Oncology.
ISSN 0090-8258.
165(2),
p. 230–238.
doi:
10.1016/j.ygyno.2022.02.024.
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Objective Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. Methods This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. Results Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12–20); with the shortest median time in MMRd patients, with 13 months (95% CI 5–21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11–76), compared to 39 months (95% CI 21–57) and 10 months (95% CI 7–13) for the NSMP and p53abn cases respectively (log-rank, P = .001). Conclusion Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.
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Poveda, A.; Lheureux, S.; Colombo, N.; Cibula, D.; Lindemann, Kristina Yvonne Kathe & Weberpals, J.
[Show all 18 contributors for this article]
(2022).
Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation: OPINION primary analysis.
Gynecologic Oncology.
ISSN 0090-8258.
164(3),
p. 498–504.
doi:
10.1016/j.ygyno.2021.12.025.
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Objective The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. Methods In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. Results Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6–10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. Conclusion Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.
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Paulsen, Torbjørn; Liland, Heidi; Myklebust, Tor Åge & Lindemann, Kristina Yvonne Kathe
(2022).
Early referral to a palliative team improves end-of-life care among gynecological cancer patients: a retrospective, population-based study.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
32(2),
p. 181–188.
doi:
10.1136/ijgc-2021-002898.
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Objective To assess end-of-life care among patients with gynecological cancer, and to describe the association between timing of palliative care referral and patterns of care.
Methods All women with residence in Oslo, Norway, who died of gynecological cancer between January 1, 2015 and December 30, 2017 (36 months), were identified. Patients were primarily treated at the Norwegian Radium Hospital and clinical data on end-of-life care were retrospectively extracted from the medical records.
Results We identified 163 patients with median age 70.1 years at death (range 26–100) with the following diagnoses: ovarian (n=100), uterine (n=40), cervical (n=21), and vulvar cancer (n=2). 53 (33%) of patients died in a palliative care unit, 34 patients (21%) died in nursing homes without palliative care, and 48 (29%) patients died in hospital. Only 15 (9%) patients died at home. 25 (15%) patients received chemotherapy in the last 30 days before death, especially ovarian cancer patients (n=21, 21%). 103 patients (61%) were referred to a palliative team prior to death. Referral to a palliative team was associated with a significantly reduced risk of intensive care unit admission (OR 0.11, 95% CI 0.02 to 0.62) and higher likelihood of a structured end-of-life discussion (OR 2.91, 95% CI 1.03 to 8.25). Palliative care referral also seemed to be associated with other quality indicators of end-of-life care (less chemotherapy use, more home deaths).
Conclusions End-of-life care in patients with gynecological cancer suffers from underuse of palliative care. Chemotherapy is still commonly used towards end-of-life. Early palliative care referral in the disease trajectory may be an important step towards improved end-of-life care.
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Skipar, Kjersti Øvrum; Hompland, Tord; Lund, Kjersti Vassmo; Løndalen, Ayca; Malinen, Eirik & Kristensen, Gunnar S Balle
[Show all 10 contributors for this article]
(2022).
Risk of recurrence after chemoradiotherapy identified by multimodal MRI and 18F-FDG-PET/CT in locally advanced cervical cancer.
Radiotherapy and Oncology.
ISSN 0167-8140.
176,
p. 17–24.
doi:
10.1016/j.radonc.2022.09.002.
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Background and purpose: MRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence.
Materials and methods: Eighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). Ktrans, reflecting vascular function, apparent diffusion coefficient (ADC), reflecting cellularity, and standardized uptake value (SUV), reflecting glucose uptake,were extracted from DCE-MR, DW-MR and FDG-PET images, respectively. By applying an oxygen consumption and supply-based method, ADC and Ktrans parametric maps were voxel-wise combined into hypoxia images that were used to determine hypoxic fraction (HF).
Results: HF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort.Low HF identified low-risk patients with 95 % precision. Based on the 50th SUV-percentile (SUV50), patients with high HF were divided into an intermediate- and high-risk group with high and low SUV50, respectively. This defined a multimodality biomarker, HF/SUV50. HF/SUV50 increased the precision of detecting high-risk patients from 41% (HF alone) to 57% and showed prognostic significance in multivariable analysis for all endpoints.
Conclusion: Multimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors.
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Marth, Christian; Abreu, Miguel Henriques; Andersen, Klaus Kaae; Aro, Karoliina M.; Batarda, Maria de Lurdes & Boll, Dorry
[Show all 18 contributors for this article]
(2022).
Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).
Cancer.
ISSN 0008-543X.
128(16),
p. 3080–3089.
doi:
10.1002/cncr.34350.
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Background This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). Methods This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III–IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. Results Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42–0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41–0.84; p < .01). Conclusions Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population.
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Gatius, Sonia; Velasco, Ana; Varela, Mar; Cuatrecasas, Miriam; Jares, Pedro & Setaffy, Lisa
[Show all 14 contributors for this article]
(2022).
Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study.
Virchows Archiv.
ISSN 0945-6317.
480(5),
p. 1031–1039.
doi:
10.1007/s00428-022-03291-x.
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Determination of microsatellite instability (MSI) and mismatch repair deficiency (MMRD), respectively, in endometrial carcinomas (ECs) is important for diagnostic and prognostic purposes, identification of Lynch syndrome carriers, and selection of patients for immunotherapy. The Idylla™ MSI assay is fully automated, does not require non-tumoral tissue, and can be performed in about 150 min. Two hundred forty-two formalin-fixed paraffin-embedded (FFPE) EC samples from 7 international centers were tested by the Idylla™ MSI assay and compared to the Promega™ MSI Analysis System and immunohistochemistry (IHC) for MMR proteins. The cases were selected with an enrichment of MSI EC to around 40%. Concordance was 87.5% between the Idylla™ MSI assay and IHC and 88.58% between IHC and Promega™ MSI assay. Concordance between Idylla™ and Promega™ MSI assays was 89.91%. Discordant results occurred more frequently in cases with MSH6 or PMS2 deficiency. Invalid cases occurred with the three techniques (IHC, 7.00%; Promega™ MSI assay, 5.37%; and Idylla™ MSI assay, 2.47%). The concordance rate between Idylla™ MSI assay and the other 2 methods increased to 88.83% for IHC and to 91.22% for the Promega™ MSI assay when the cutoff of instability in the scoring system was moved from 0.5 to 0.3. The Idylla™ MSI assay is a rapid and highly concordant test for MSI in EC. Modification of the Idylla™ scoring system could increase the sensitivity and specificity of the MSI assay for EC analysis.
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Utne, Inger; Stokke, Kjersti; Ritchie, Christine Seel; Løyland, Borghild; Grov, Ellen Karine & Rasmussen, Hege Lund
[Show all 10 contributors for this article]
(2022).
Changes in Subjective Measures of Cognitive Function in Older Adults From the Initiation Through 12 Months After the Receipt of Chemotherapy.
Cancer Nursing.
ISSN 0162-220X.
46(6).
doi:
10.1097/NCC.0000000000001140.
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Background: Cognitive impairment has a negative impact on older patients with cancer. Objective: Evaluate for inter-individual differences in two subjective measures of cognitive function in older patients (n = 112), as well as determine which demographic, clinical, and symptom characteristics, and levels of physical function, were associated with initial levels and with the trajectory of each of these two measures. Methods: Cognitive function was assessed using the cognitive function scale from the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (QLQC30 CF) and the Attentional Function Index (AFI) at the initiation of chemotherapy and at 1, 3, 6, 9, and 12 months after its initiation. Hierarchical linear modeling was used to assess for interindividual differences in and characteristics associated with initial levels and changes in cognitive function. Results: Characteristics associated with decreases in QLQ-C30 CF scores at the initiation of chemotherapy were longer time since the cancer diagnosis and higher depression scores. Characteristics associated with poorer AFI scores at enrollment were lower levels of education and higher depression scores. No characteristics were associated with worse trajectories of either cognitive function measure. Conclusions: Some older patients undergoing chemotherapy experience decrements in cognitive function. Implication for practice: Our findings suggest that clinicians need to assess for depressive symptoms in older patients prior to the initiation of chemotherapy. Evidence-based interventions (e.g., cognitive stimulation, increased physical activity) can be recommended to maintain and increase cognitive function in older oncology patients.
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Utne, Inger; Løyland, Borghild; Grov, Ellen Karine; Rasmussen, Hege Lund; Torstveit, Ann Helen & Paul, Steven M.
[Show all 11 contributors for this article]
(2021).
Age-related differences in self-report and objective measures of cognitive function in older patients prior to chemotherapy.
Nursing Open.
doi:
10.1002/nop2.1141.
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Aim Evaluate for differences in demographic and clinical characteristics and subjective and objective measures of cognitive function (CF) between younger older adults (YOA, 60–69 years) and older adults (OA, ≥70 years). Design Cross-sectional. Methods Older oncology patients (n = 139) completed subjective (Attentional Function Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) CF scale) and objective (Montreal Cognitive Assessment, Trail Making Test (TMT) A & B) measures of CF prior to chemotherapy. Data were analyzed using parametric and nonparametric tests. Results No differences were found between the two groups for any of the subjective or objective CF measures, except that OA patients had higher TMT B scores. Compared with the general population, OAs had significantly higher EORTC CF scores and YOAs had significantly worse scores for all of the objective tests. Clinically meaningful difference between group differences was found for the TMT B test.
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Lindemann, Kristina Yvonne Kathe; Smogeli, Aud Elisabeth Farstad; Småstuen, Milada Cvancarova; Bruheim, Kjersti; Trovik, Jone & Nordberg, Terje
[Show all 9 contributors for this article]
(2021).
Salvage radiation for pelvic relapse after surgically treated endometrial cancer.
Cancers.
13(6),
p. 1–11.
doi:
10.3390/cancers13061367.
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(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome.
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Vistad, Ingvild; Skorstad, Mette; Demmelmaier, Ingrid; Småstuen, Milada Cvancarova; Lindemann, Kristina Yvonne Kathe & Wisløff, Torbjørn
[Show all 8 contributors for this article]
(2021).
Lifestyle and Empowerment Techniques in Survivorship of Gynaecologic Oncology (LETSGO study): A study protocol for a multicentre longitudinal interventional study using mobile health technology and biobanking.
BMJ Open.
11(7).
doi:
10.1136/bmjopen-2021-050930.
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Introduction The number of gynaecological cancer survivors is increasing and there is a need for a more sustainable model of follow-up care. Today’s follow-up model is time-consuming and patients have reported unmet needs regarding information about their cancer and strategies for managing the consequences of treatment. The main aim of this study is to assess health-related empowerment—in terms of patient education, psychosocial support, and promotion of physical activity—in a new follow-up model by comparing it to standard follow-up in a quasi-randomised study involving intervention hospitals and control hospitals. Methods and analysis At the intervention hospitals, patients will be stratified by risk of recurrence and late effects to either 1 or 3 years’ follow-up. Nurses will replace doctors in half of the follow-up visits and focus in particular on patient education, self-management and physical activity. They will provide patients with information and guide them in goal setting and action planning. These measures will be reinforced by a smartphone application for monitoring symptoms and promoting physical activity. At the control hospitals, patients will be included in the standard follow-up programme. All patients will be asked to complete questionnaires at baseline and after 3, 6, 12, 24 and 36 months. Blood samples will be collected for biobanking at 3, 12 and 36 months. The primary outcome is health-related empowerment. Secondary outcomes include health-related quality of life, adherence to physical activity recommendations, time to recurrence, healthcare costs and changes in biomarkers. Changes in these outcomes will be analysed using generalised linear mixed models for repeated measures. Type of hospital (intervention or control), time (measurement point), and possible confounders will be included as fixed factors. Ethics and dissemination The study is approved by the Regional Committee for Medical Research Ethics (2019/11093). Dissemination of findings will occur at the local, national and international levels.
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Kasius, Jenneke C.; Pijnenborg, Johanna M. A.; Lindemann, Kristina; Forsse, David Erik; Zwol, Judith van & Kristensen, Gunnar S Balle
[Show all 9 contributors for this article]
(2021).
Risk stratification of endometrial cancer patients: FIGO stage, biomarkers and molecular classification.
Cancers.
13(22).
doi:
10.3390/cancers13225848.
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Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.
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Skorstad, Mette; Rooij, Belle H. de; Jeppesen, Mette Moustgaard; Bergholdt, Stinne Holm; Ezendam, Nicole Paulina Maria & Bohlin, Tonje
[Show all 10 contributors for this article]
(2021).
Self-management and adherence to recommended follow-up after gynaecological cancer: results from the international InCHARGE study.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
31(8),
p. 1106–1115.
doi:
10.1136/ijgc-2020-002377.
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Objective: To assess the relationship between self-management skills and adherence to follow-up guidelines among gynecological cancer survivors in the Netherlands, Norway, and Denmark, and to assess the relationship between adherence to follow-up programs and use of additional healthcare services.
Methods: For this international, multicenter, cross-sectional study, we recruited gynecological cancer survivors 1-5 years after completion of treatment. Information on follow-up visits, use of healthcare resources, self-management (measured by the Health Education Impact Questionnaire), clinical characteristics, and demographics were obtained by validated questionnaires. Participants were categorized as adherent if they attended the number of follow-up visits recommended by national guidelines, non-adherent if they had fewer visits than recommended, or over-users if they had more visits than recommended.
Results: Of 4455 invited survivors, 2428 (55%) returned the questionnaires, and 911 survivors were included in the analyses. Survivors with high self-management most frequently adhered to recommended follow-up. Non-adherent survivors showed lower self-management in the health-directed activity domain (OR 1.54, 95% CI 1.03 to 2.32) than adherent survivors. No other associations between self-management and follow-up adherence were revealed. Non-adherent survivors tended to have endometrial cancer, surgical treatment only, be older, and be Danish residents. Over-users reported more follow-up visits and also used additional healthcare services more frequently than adherent survivors.
Conclusion: Low self-management appears to reduce the likelihood of adherence to national guidelines for gynecological cancer follow-up. Focusing on patient education for survivors at risk of low self-management to ensure adherence to recommended follow-up may improve personalization of follow-up.
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Weelden, Willem Jan van; Lalisang, Roy I; Bulten, Johan; Lindemann, Kristina Yvonne Kathe; Beekhuizen, Heleen J. van & Trum, Hans
[Show all 26 contributors for this article]
(2021).
Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer.
American Journal of Obstetrics and Gynecology.
ISSN 0002-9378.
225(4).
doi:
10.1016/j.ajog.2021.05.007.
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Background Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. Objective This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. Study Design Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction–based messenger RNA model to measure the activity of estrogen receptor–related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. Results Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9–43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2–64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9–68.9) and 75.0% (95% confidence interval, 62.2–87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1–73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20–48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20–52) with an estrogen receptor pathway activity score of >15 had not progressed. Conclusion The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.
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Areklett, Elisabeth Wang; Fagereng, Elisabeth; Bruheim, Kjersti; Andersson, Stein & Lindemann, Kristina Yvonne Kathe
(2021).
Self-reported cognitive impairment in cervical cancer survivors: A cross-sectional study.
Psycho-Oncology.
ISSN 1057-9249.
doi:
10.1002/pon.5818.
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Objective Cancer-related cognitive impairment (CRCI) is a major obstacle for cervical cancer survivors, preventing the return to their social life. This study assessed the prevalence of CRCI in cervical cancer survivors and studied the association of self-reported cognitive impairment with treatment regimen and the quality of life (QoL) domains depression, anxiety, and fatigue. Methods Six hundred twenty one cervical cancer survivors, treated with combined chemo-radiotherapy (CCRT) (n = 458) or surgery only (n = 163) were invited in this cross-sectional study. Self-reported cognitive function was assessed using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Fatigue and psychological distress were assessed using EORTC-QLQ C30 and Hospital Anxiety and Depression Scale (HADS). Results Data of 254 women (40.9%) was available for the analysis. Of those, 204 (80.3%) women had received CCRT and 50 (19.7%) surgery only. In the whole cohort, 42.5% reported significant cognitive impairment. In both treatment groups cognitive complaints were significantly associated with anxiety, depression, and fatigue (all p < 0.001). CCRT was strongly associated with increased risk of CRCI (OR = 4.02, 95% CI = 1.57–10.25). Anxiety, depression, and fatigue increased the risk of CRCI by 13% (OR: 1.13, 95% CI 1.03–1.23), 16% (OR 1.16, 95% CI 1.04–1.28) and 2% (OR 1.02, 95% CI 1.00–1.03), respectively. Conclusion Almost half of the cervical cancer survivors after CCRT report significant cognitive impairment. CRCI is associated with other indicators of poor QoL, such as depression, anxiety and fatigue. An increased understanding of the specific cognitive domains affected and of the associated late effects like fatigue is crucial to customize successful interventions.
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Selland, Mette; Skrede, Katrine; Lindemann, Kristina Yvonne Kathe; Skaali, Tone Margrethe Olsbu; Blomhoff, Rune & Bruheim, Kjersti
[Show all 8 contributors for this article]
(2021).
Distress, problems and unmet rehabilitation needs after treatment for gynecological cancer.
Acta Obstetricia et Gynecologica Scandinavica.
ISSN 0001-6349.
doi:
10.1111/aogs.14310.
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Introduction - The prevalence of distress, problems and need for rehabilitation among women treated for gynecological cancer is largely unknown. The aims of this study were to examine the prevalence of distress, problems and unmet rehabilitation needs in the first years after treatment for gynecological cancer.<p> <p>Material and methods - Women treated for gynecological cancer within the last 2 years were invited. Participants responded to the National Comprehensive Cancer Network Distress Thermometer and Problem List measuring distress and problems. They also answered a questionnaire regarding physical endurance, muscle strength, and need for rehabilitation services.<p> <p>Results - Of 114 eligible women, 92 (81%) agreed to participate. Mean time since last treatment was 7.6 months (range 0–24.5 months). A total of 57% of the participants reported distress. The four most common problems reported were fatigue (58%), tingling in hands/feet (54%), worry (53%), and problems with memory/concentration (50%). Problems associated with distress were: dealing with partner, all emotional problems (i.e. depression, fears, nervousness, sadness, worry, and loss of interest in usual activities), appearance, memory/concentration, pain, sex, sleep, and problems with physical endurance and muscle strength. Fifty-two per cent reported unmet needs for rehabilitation services. Women with distress reported more unmet rehabilitation needs than those in the non-distressed group.<p> <p>Conclusions - The prevalence of distress in this population of women treated for gynecological cancer was high. Having a high number of problems and having unmet needs for rehabilitation services were both associated with distress. Hence, measurement of distress seems to be helpful when assessing the need for rehabilitation services.
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Kargo, Anette Stolberg; Jensen, Pernille Tine; Lindemann, Kristina Yvonne Kathe; Hjollund, Niels Henrik Ingvar; Lund, Bente & Haee, Mette
[Show all 9 contributors for this article]
(2021).
The PROMova study comparing active and passive use of patient-reported outcome measures in ovarian cancer follow-up: effect on patient-perceived involvement, satisfaction with care, and usefulness.
Acta Oncologica.
ISSN 0284-186X.
60(4),
p. 434–443.
doi:
10.1080/0284186X.2021.1891281.
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Lindemann, Kristina; Martinsson, L.; Kaasa, Stein & Lindquist, David
(2020).
Elderly gynaecological cancer patients at risk for poor end of life care: a population-based study from the Swedish Register of Palliative Care.
Acta Oncologica.
ISSN 0284-186X.
59(6),
p. 636–643.
doi:
10.1080/0284186X.2020.1744717.
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Introduction: Poorer end-of-life (EOL) care for elderly cancer patients has been reported. We assessed the impact of age on 13 indicators for the quality of EOL care as well as adherence to 6 national quality indicators in gynaecological cancer patients. Methods: Age-dependent differences in 13 palliative care quality indicators were studied in gynaecological cancer patients registered in the population-based Swedish Register of Palliative Care. Association between the patient’s age and each quality indicator was analyzed by logistic regression, adjusted for place of death where appropriate. Adherence to six national quality indicators determined by the Swedish National Board of Health and Welfare was estimated in all patients. Results: We included 3940 patients with the following age distribution: 1.6% were 18–39 years of age, 12.3% 40–59 years, 37.2% 60–74 years, 28.9% 75–84 years and 20% were ≥85 years. Age-dependent differences in implementation rate were present for some of the 13 quality indicators. Compared to elderly cancer patients, younger patients were more likely to be cared for by a specialized palliative care service, more often informed about imminent death as well as assessed for pain. For most national quality indicators, the goal level was not met. Only for the ‘on demand prescription for pain’, the goal level was reached. Conclusions: EOL care did not meet national quality indicators in this population-based data from Sweden, in particular in the elderly population. Elderly gynaecological cancer patients are at high risk of poorer EOL care without the involvement of specialized palliative care services. Palliative care services need to be implemented across all institutions of EOL care to ensure good and equal care.
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Harter, Philipp; Pautier, Patricia; Nieuwenhuysen, Els Van; Reuss, Alexander; Redondo, Andres & Lindemann, Kristina
[Show all 18 contributors for this article]
(2020).
Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer - a randomized phase iii trial (ago-ovar 2.29/engot-ov34).
International Journal of Gynecological Cancer.
ISSN 1048-891X.
p. 1–XX.
doi:
10.1136/ijgc-2020-001572.
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Vistad, Ingvild; Lindemann, Kristina; Bentzen, Anne Gry; Dahl, Alv A; Steen, Rita & Kiserud, Cecilie E.
(2020).
Preferences for follow up in long-term survivors after cervical cancer.
Acta Obstetricia et Gynecologica Scandinavica.
ISSN 0001-6349.
69(9),
p. 1253–1259.
doi:
10.1111/aogs.13855.
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Introduction An increasing number of cervical cancer survivors combined with lack of data on the efficacy of long-term surveillance, challenges existing follow-up models. However, before introducing new follow-up models, cervical cancer survivors’ own views on follow up are important. We aimed to explore preferences for follow up in long-term cervical cancer survivors and their associations with self-reported late-effects. Material and methods In 2013, we mailed 974 Norwegian long-term cervical cancer survivors treated during 2000-2007 a questionnaire with items covering preferences for follow up after treatment, clinical variables and validated questionnaires covering anxiety, neuroticism and depression. Results We included 471 cervical cancer survivors (response rate 57%) with a median follow up of 11 years. In all, 77% had FIGO stage I disease, and 35% were attending a follow-up program at the time of survey. Of the patients, 55% preferred more than 5 years of follow up. This was also preferred by 57% of cervical cancer survivors who were treated with conization only. In multivariable analyses, chemo-radiotherapy or surgery with radiation and/or chemotherapy (heavy treatment) and younger age were significantly associated with a preference for more than 5 years’ follow up. Late effects were reported by more than 70% of the cervical cancer survivors who had undergone heavy treatment. Conclusions Our study reveals the need for targeted patient education about the benefits and limitations of follow up. To meet increasing costs of cancer care, individualized follow-up procedures adjusted to risk of recurrence and late-effects in cervical cancer survivors are warranted.
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Lindemann, Kristina; Zalewski, Kamil & Halaska, Michael J.
(2019).
Summary of landmark papers published between August 2018 and May 2019.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
29(1),
p. 1–5.
doi:
10.1136/ijgc-2019-000738.
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Piovano, Elisa; Ferrero, Annamaria; Zola, Paolo; Marth, Christian; Mirza, Mansoor Raza & Lindemann, Kristina
(2019).
Clinical pathways of recovery after surgery for advanced ovarian/tubal/peritoneal cancer: an NSGO-MaNGO international survey in collaboration with AGO-a focus on surgical aspects.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
29(1),
p. 181–187.
doi:
10.1136/ijgc-2018-000021.
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This survey assessed the implementation of enhanced recovery after surgery (ERAS) for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on ERAS pathways in ovarian cancer, because high-level evidence for such interventions is lacking.In July 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, and the Association for Gynecologic Oncology Austria (AGO Austria) (n = 100). The survey covered all aspects of an ERAS pathway including surgery, nursing, and anesthesia. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report.The overall response rate was 62%. Only a third of the centers in Italy and Austria follow a written ERAS protocol compared with 60% of the Scandinavian centers. Only a minority of centers have completely abandoned bowel preparation, with the highest proportion in Scandinavia (36%). Two hours of fasting for fluids before surgery is routinely practiced in Scandinavia and Austria (67–57%, respectively), but not in Italy (5%). Carbohydrate loading is routinely administered only in Scandinavia (67%). Peritoneal drainage is used by 22% routinely and by 61% in cases of bowel resection/lymphadenectomy/peritonectomy. Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia and Austria, but not in Italy.The degree of implementation of ERAS protocols varies across and within cooperative groups. The centralization of ovarian cancer care seems to facilitate standardization of peri-operative protocols. Currently, the high heterogeneity in patterns of care may challenge an international approach to a clinical trial.
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Roncolato, Felicia; Lindemann, Kristina; Willson, Melina L.; Martyn, Julie & Mileshkin, Linda
(2019).
Pi3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer.
Cochrane Database of Systematic Reviews.
2019:CD012160(10),
p. 1–41.
doi:
10.1002/14651858.CD012160.pub2.
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Smogeli, Aud Elisabeth Farstad; Småstuen, Milada Cvancarova; Wang, Yun; Davidson, Ben; Kristensen, Gunnar S Balle & Lindemann, Kristina
(2018).
Clinical Outcome of Patients with High-Risk Endometrial Carcinoma after Treatment with Chemotherapy only.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
28(9),
p. 1789–1795.
doi:
10.1097/IGC.0000000000001356.
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Objectives: Adjuvant treatment of high-risk endometrial cancer (EC) is still controversial. Several studies have tried to clarify the best treatment strategy, and guidelines have been made, but no study to date has shown a survival benefit for radiation over chemotherapy. We aimed to evaluate the outcome of high-risk EC patients treated with adjuvant chemotherapy only in a population where the routine administration of adjuvant radiotherapy was omitted. Methods/Materials: This is a retrospective study including 230 EC patients with FIGO stage I type II, Ib type I/G3, stage II and IIIc treated at the Oslo University Hospital between 2005-2012. Standard treatment was hysterectomy, bilateral salphingo-ooforectomy and at least pelvic lymphadenectomy followed by adjuvant chemotherapy. Results: Of the 230 high-risk patients patients, standard treatment was given to 146 patients (63.5%); 60 patients in stage I, 10 patients in stage II and 76 patients in stage IIIc. Only 10% of patients with stage I disease relapsed, with 3.3% loco-regional relapses and 6.7% distant relapses. Recurrence rate in stage IIIc was 39.5%, with 7.9% isolated vaginal and 31.6% distant relapses. The 3-year DFS was 92% for stage I, 80% for stage II and 60% for stage IIIc disease. In the total population, 55 patients had FIGO stage Ia, 43 Ib, 42 stage II, and 90 IIIc disease. Recurrence rate in the total population was 29.6%, with 9.6% isolated vaginal recurrences, 1.7% recurrences located in the pelvis and 18.3% distant recurrences. Conclusions: Patients with high-risk EC have acceptable vaginal/pelvic control rates after adjuvant chemotherapy. However, prognosis remains poor for patients with stage IIIc disease, also after chemotherapy.
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Lindemann, Kristina; Kok, Peey-Sei; Stockler, Martin; Sykes, Peter & Brand, Alison
(2017).
Enhanced recovery after surgery for suspected ovarian malignancy: A survey of perioperative practice among gynecologic oncologists in Australia and New Zealand to Inform a Clinical Trial.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
27(5),
p. 1046–1050.
doi:
10.1097/IGC.0000000000000982.
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Pradhan, Manohar; Kildal, Wanja; Kleppe, Andreas; Tobin, Kari Anne Risan; Nikolaysen, Filip & Mascialino, Barbara
[Show all 12 contributors for this article]
(2025).
Prognostic Value Of Different Stages Of Maturation Of Tertiary Lymphoid Structures In Molecular Subgroups Of Endometrial Carcinoma.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
35(2),
p. 100104–100104.
doi:
10.1016/j.ijgc.2024.100104.
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Introduction/Background Tertiary lymphoid structures (TLSs) are organized clusters of lymphoid cells at various maturation stages with potential prognostic and predictive impact for response to immunotherapy in several cancer types. We assessed the prognostic significance of TLSs in patients with molecularly classified endometrial carcinoma (EC).
Methodology This retrospective cohort included 1221 patients with molecularly classified EC treated at Oslo University Hospital 2006-2017. Formalin-fixed, paraffin-embedded tissue sections from hysterectomy specimens were immunohistochemically stained for CD21, Ki-67, CD3 and CD20. TLSs were categorized as mature (CD21+/Ki-67+), immature (CD21+/Ki-67–), lymphoid aggregates (CD21–, CD3+, and CD20+), or negative (CD21–/no CD3/CD20+ clusters). Univariable and multivariable analyses were performed to assess the association between TLS stages and time to recurrence (TTR).
Results We identified 517 patients with lymphoid aggregates, 224 with immature TLSs, 138 with mature TLSs, and 342 TLS-negative cases. TLSs were more frequent in POLE-mutated (98%, 94/96) and MMRd (MMR deficient) tumours (87%, 321/368) compared to p53 abnormal (63%, 175/275) and no specific molecular profile (60%, 278/462) tumours (p<0.001). TLS presence of any maturity was significantly associated with longer TTR in univariable (p<0.001) and multivariable analysis (p<0.001). Compared to TLS-negative cases, the hazard ratio was 0.69 (95% confidence interval (95%CI): 0.54-0.89) for lymphoid aggregates, 0.45 (95%CI: 0.31-0.64) for immature TLSs, and 0.27 (95%CI: 0.16-0.44) for mature TLSs in multivariable analyses. In stratified analysis by molecular subgroup, presence of all maturity stages of TLSs remained significantly associated with longer TTR in patients in MMRd and NSMP tumours in multivariable analysis. TLSs is a favourable prognostic marker for EC patients, especially in the MMRd and NSMP subgroups.
Conclusion TLSs were predominantly found in patients with POLE-mutated and MMRd tumours. Prognosis improved progressively with TLS maturation stage, with longest TTR in patients with mature TLSs. Evaluating TLSs may provide additional prognostic information across molecular subgroups.
Disclosures This supported collaborative study was funded by GSK (OSF.IO/JHEVG” title="https://doi.org/10.17605/OSF.IO/JHEVG">https://doi.org/10.17605/OSF.IO/JHEVG).
BM, DS, and HE are full-time employees of GSK and hold stock and/or stock options. HE holds stock/stock options i Abbvie.
KL reports the following conflicts of interest outside the submitted work: Participation on data safety monitoring or advisory boards of Eisai, MSD, Nykode, AstraZeneca, GSK and Karyopharm (honoraria paid to institution); speaker fee from MSD; GSK and Astra Zeneca and research funding paid to institution from GSK. All remaining authors have declared no conflicts of interest.
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Vistad, Ingvild; Skorstad, Mette; Hagen, Milada; Demmelmaier, Ingrid; Bjørge, Line & Poll-Franse, Lonneke V. Van De
[Show all 12 contributors for this article]
(2025).
The Impact Of The LETSGO Personalized Follow-Up Model On Empowerment And Quality Of Life In Gynaecological Cancer Survivors: A Multicenter Quasi-Experimental Study.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
35(2).
doi:
10.1016/j.ijgc.2024.100110.
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Background: Increasing outpatient demands and unmet patient needs necessitate personalized follow‐up care for cancer survivors. This study investigated whether a self‐management–focused follow‐up model improves empowerment and quality of life (QoL) in gynecological cancer survivors compared to standard follow‐up.
Methods: Twelve Norwegian hospitals participated in this cohort study. Patients initiating routine follow‐up after primary treatment were eligible and allocated to either intervention or standard care follow‐up groups based on their treatment hospital. The intervention included nurse‐led consultations using coaching techniques for education on symptom monitoring and healthy lifestyle, alternated with physician‐led consultations and access to a mobile app. Standard follow‐up consisted of physician‐led consultations only. The primary outcome was change in patient empowerment over 12 months, measured with the self‐monitoring and insight domain of the Health Education Impact Questionnaire (heiQ). Secondary outcomes included changes in remaining heiQ domains and QoL. Data were analyzed according to intention‐to‐treat principles using linear mixed effects models.
Results: Among 741 participants (intervention: 378, standard: 363), baseline characteristics were comparable. At 12 months, no significant differences were observed
in self‐monitoring and insight (Δ = 0.02 [95% confidence interval (CI), –0.04 to 0.08]; effect sizes [ES] = 0.29). However, health‐directed activity (Δ = 0.15 [95% CI, 0.04–
0.25]; ES = 0.15), emotional well‐being (Δ = 0.12 [95% CI, 0.02–0.20]; ES = 0.15), social functioning (Δ = 5.2 [95% CI, 1.1–9.3]; ES = 0.41), and physical functioning
(Δ = 2.5 [95% CI, 0.0–5.0]; ES = 0.20) were significantly more improved in the intervention group.
Conclusion: Lifestyle and Empowerment Techniques in Survivorship of Gynaecologic Oncology follow‐up did not significantly impact self‐monitoring and insight, but
positively influenced other survivorship domains, indicating its potential for enhancing self‐management and QoL in gynecological cancer survivors.
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Pradhan, Manohar; Kildal, Wanja; Vlatkovic, Ljiljana; Tobin, Kari Anne Risan; Lindemann, Kristina Yvonne Kathe & Kristensen, Gunnar S Balle
[Show all 8 contributors for this article]
(2025).
Response to correspondence on prognostic value of tertiary lymphoid structures in molecular subgroups of endometrial carcinoma by Pradhan et al.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
35(7),
p. 101970–101970.
doi:
10.1016/j.ijgc.2025.101970.
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Pradhan, Manohar; Kildal, Wanja; Vlatkovic, Ljiljana; Lindemann, Kristina Yvonne Kathe; Tobin, Kari Anne Risan & Kristensen, Gunnar S Balle
[Show all 8 contributors for this article]
(2024).
OFP-02-005 Prognostic value of tertiary lymphoid structures in endometrial carcinoma.
Virchows Archiv.
ISSN 0945-6317.
485(S1),
p. S6–S7.
doi:
10.1007/s00428-024-03880-y.
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Background & objectives: Tertiary lymphoid structures (TLS), organized aggregates of lymphoid cells, are reported as an immunological prognostic marker. We have evaluated the prognostic importance of TLS in patients with endometrial carcinoma using L1 cell adhesion molecule (L1CAM) as a surrogate marker.
Methods: The cohort consists of 1228 endometrial carcinoma patients (880 endometrioid and 348 non-endometrioid) treated at Oslo University Hospital between 2006 and 2017. Formalin-fixed and paraffin- embedded tissue samples from the hysterectomy specimens were sectioned and one section was immunohistochemically stained with antibody against L1CAM to evaluate the presence and number of TLS. Sections with ≥1 TLS were considered as TLS positive.
Results: Out of 1197 evaluable sections, 911 (76%) sections were TLS negative, while 286 (24%) were TLS positive. In TLS positive sections, the median number was 3 (IQR 1-6). TLS positive patients had a significantly lower risk of recurrence (HR 0.60; 95% CI 0.45-0.8, p<0.001) compared to TLS negative patients in univariable analyses. In molecular subgroups,
TLS were more frequently present in tumours with POLE mutation (59%) and MMR deficiency (32%) than in tumours with p53 abnormality (16%) and no specific molecular profile (15%). In patients with MMR deficiency and p53 abnormal tumours, presence of TLS was prognostic with HR of 0.6 (CI 0.37-0.98, p=0.042) and 0.6 (CI 0.68-1.99, p=0.056), respectively.
Conclusion: Evaluation of TLS using L1CAM might provide additional prognostic information for endometrial carcinoma patients with MMR deficiency. A similar indication was observed for patients with p53 abnormality, but further studies are needed to confirm the prognostic value in this subgroup. TLS were predominantly found in POLE mutated and MMR deficient tumours. These findings corroborate with a previous study investigating the correlation and prognostic value of TLS in molecular subgroups using a much smaller patient cohort.
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Lindemann, Kristina Yvonne Kathe; Kildal, Wanja; Kleppe, Andreas; Tobin, Kari Anne Risan; Pradhan, Manohar & Isaksen, Maria
[Show all 10 contributors for this article]
(2024).
259 Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
34(Supplement 1),
p. A167–A168.
doi:
10.1136/ijgc-2024-esgo.317.
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Introduction/Background
The role of molecular classification in patients with low/intermediate risk endometrial cancer (EC) is uncertain. Higher precision in diagnostics will inform the unsettled debate on optimal adjuvant treatment.
Methodology
We retrospectively included patients referred to The Norwegian Radium Hospital, Oslo, Norway (2006–2017). Patients with low/intermediate risk EC were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP). The main outcome was time to recurrence (TTR) and cancer-specific survival (CSS) within the molecular subgroups. We also studied patterns of recurrence in molecular groups.
Results
Of 626 patients, 610 could be molecularly classified and only 24 received adjuvant treatment. Molecular subgroup distribution was: 57 patients (9%) with POLE-mutated tumors, 202 (33%) with MMRd tumors, 34 (6%) with p53 abnormal tumors, and 317 (52%) with NSMP tumors. After a median follow-up time of 8.9 years (95% confidence interval (CI): 6.2–12.6 years), there was a statistically significant difference in TTR (p<0.001) and CSS (p<0.001) by molecular groups. Patients with p53 abnormal tumors had poor prognosis with a 5-year cumulative incidence for recurrence of 32.4% (95% CI: 17.6–48.0) and cancer-specific death (CSD) of 29.4% (95% CI: 15.4–44.9). The majority of these recurrences were para-aortic/distant metastases. Patients with POLE mutations had excellent prognosis with a 5-year cumulative incidence for recurrence of 3.5% (95% CI: 0.7–10.7%) and CSD of 0%. In the NSMP group, L1CAM expression was associated with shorter CSS (HR 12.52, 95% CI: 3.53–44.42, p<0.0001) but not TTR (HR 2.7, 95% CI: 0.95–7.7, p=0.053).
Conclusion
Large differences in prognosis and localization of recurrence by molecular groups demand a higher precision in diagnostics, also in patients with low and intermediate risk EC. Tailored adjuvant treatment strategies need to consider systemic treatment for patients with p53 abnormal tumors and de-escalation of treatment in patients with POLE mutated tumors.
Disclosures
KL: Receipt of grants/research supports: GSK, research funding paid to
Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisa
GK: Stockholder: Novo Nordic
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Lindemann, Kristina Yvonne Kathe; Kildal, Wanja; Kleppe, Andreas; Tobin, Kari Anne Risan; Pradhan, Manohar & Mascialino, Barbara
[Show all 13 contributors for this article]
(2024).
258 Real-world data of patients with stage III/IV endometrial cancer treated with platinum-based chemotherapy after hysterectomy – outcome in molecular subgroups.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
34 (supplement 1),
p. A167–A167.
doi:
10.1136/ijgc-2024-esgo.316.
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Introduction/Background
There is scarce real-world evidence on patients with advanced endometrial cancer (EC) treated with platinum-based chemotherapy in the literature. This study described the oncological outcome in groups by molecular classification.
Methodology
This retrospective cohort study included patients referred to The Norwegian Radium Hospital, Oslo University Hospital (OUH), Norway who were diagnosed or operated for EC at OUH between January 2006 and December 2017. Patients with Stage III/IV EC treated with platinum-based chemotherapy after hysterectomy and with sufficient tumor tissue available at the biobank were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP).
Results
Of 264 patients, 263 were molecularly classified, 10 (4%) as POLE-mutated, 67 (26%) as MMRd, 117 (44%) as p53 abnormal and 69 (26%) as NSMP. One patient could not be molecularly characterized. Median age was 68 (61–74) years with a median follow up time of 5.3 (2.2–10.3) years. Patients with MMRd tumors had significantly longer time to recurrence (HR 0.43, 95% CI: 0.27–0.67, p=0.0001) and longer cancer-specific survival (HR 0.36, 95%CI: 0.22–0.58, p<0.0001) than patients with mismatch repair proficient (MMRp) tumors. Compared to patients with NSMP tumors, patients with p53 abnormal tumors had shorter cancer-specific survival (HR 1.78, 95% CI: 1.19–2.65) while patients with MMRd tumors had longer cancer-specific survival (HR 0.50, 95% CI: 0.29–0.87). Patients with POLE tumors had the longest cancer-specific survival (HR 0.32, 95% 0.08–1.32).
Conclusion
Results show that molecular classification is prognostic in patients with advanced-stage endometrial cancer. Based on the recently reported clinical trials of a checkpoint inhibitor added to platinum-based chemotherapy in advanced and recurrent EC, patients with MMRd, and maybe also p53 abnormal tumors, have a better clinical outcome when treated with this combination treatment
Disclosures
This supported collaborative study was funded by GSK (SCS: 219026)
KL: Receipt of grants/research supports: GSK, research funding paid to
Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisa
BM, DS: Stockholder: GSK, Other: Employee GSK
HE: Other: Employee GSK
GK: Stockholder: Novo Nordic
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Torkildsen, Cecilie Fredvik; Lindemann, Kristina Yvonne Kathe; Bischof, Katharina; Aune, Guro; Vistad, Ingvild & Ingebrigtsen, Vibeke Anett
[Show all 20 contributors for this article]
(2024).
456 Molecular characteristics of gynaecological cancer patients in the IMPRESS-Norway trial – a national prospective, non-randomized clinical trial evaluating the efficacy of anti-cancer drugs on new indications.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
34,
p. A563–A564.
doi:
10.1136/ijgc-2024-ESGO.1105.
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ONDRČKOVA, Camilla Øvrebø; Helland, Åslaug; Blix, Egil Støre; Heinrich, Daniel & Lindemann, Kristina Yvonne Kathe
(2023).
ESMO-kongressen 2023 – dette gleder kreftlegene seg til.
[Journal].
Dagens Medisin.
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Lindemann, Kristina Yvonne Kathe; Zalewski, Kamil; Halaska, Michael J. & Razumova, Zoia
(2020).
Preface.
International Journal of Gynecological Cancer.
ISSN 1048-891X.
30(Suppl 1),
p. 2–2.
doi:
10.1136/ijgc-30-S1.
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Published
May 29, 2017 3:25 PM
- Last modified
Sep. 17, 2019 12:13 PM
