Publications
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Brandal, Siri Helene Bertelsen; Mo, Torgeir; Fangberget, Anne; Nilsen, Line Brennhaug; Geier, Oliver Marcel & Bjørndal, Hilde
[Show all 11 contributors for this article]
(2026).
MRI for Predicting Response and 10-Year Outcome of Neoadjuvant Chemotherapy with or Without Additional Bevacizumab Treatment in HER2-Negative Breast Cancer.
Cancers.
18(3).
doi:
10.3390/cancers18030393.
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Objectives: To explore if MRI can monitor treatment and predict outcome in patients with human epidermal growth factor 2 (HER2)-negative breast cancer receiving neoadjuvant chemotherapy (NACT) with or without bevacizumab. Methods: Multiparametric MRI was performed at baseline and after 12 and 25 weeks of NACT. MRI assessment included tumour size, apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI), and signal intensity–time curves and vascular volume transfer constant (KTRANS) from dynamic contrast-enhanced MRI (DCE). The reference standards were pathological complete response (pCR) at the time of surgery, and 10-year recurrence-free survival. Receiver operating characteristics analyses were performed to assess the predictive value of the MRI parameters. MRI findings and outcomes were compared between the treatment groups. Results: Seventy women were included from November 2008 to July 2012, with a median age of 49.5 years and median tumour diameter of 47 mm. Fourteen patients (20.0%) achieved pCR, while eleven (15.7%) had recurrence during the 10-year follow-up. The treatment significantly reduced tumour size, increased ADC, decreased KTRANS, and shifted the signal intensity–time curves towards more benign shapes. The DCE parameters changed significantly more in the bevacizumab group. In the bevacizumab group, baseline KTRANS predicted pCR (Area under curve (AUC) = 0.73), but the difference in pCR-rates between the treatment groups was not significant (p = 0.07). Only tumour size and shrinkage at 12 weeks predicted pCR (AUC = 0.71–0.85) regardless of size measuring method. No MRI parameters predicted survival. Conclusions: All MRI parameters reflected treatment response, but no parameter predicted survival or benefit from adding bevacizumab to chemotherapy.
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Qvigstad, Lars Fredrik; Aas, Kirsti; Tulipan, Andreas Julius; Hole, Knut Håkon; Storås, Anne Marie Holck & Hammarström, Clara Louise
[Show all 9 contributors for this article]
(2025).
Clinical Trial Protocol for prePSMA: A Multicenter, Randomized, Noninferiority Trial of Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as Triage for Extended Pelvic Lymph Node Dissection in Patients Scheduled for Robot-assisted Laparoscopic Radical Prostatectomy.
European Urology Focus.
11(6),
p. 915–920.
doi:
10.1016/j.euf.2025.07.010.
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Switlyk, Marta Daniela; Dale, Einar; Tafjord, Svetlana; Willumsen, Lise Haldorsen; Hole, Knut Håkon & Hompland, Tord
(2025).
Reduced field-of-view DWI outperforms conventional DWI in assessing tumor heterogeneity and HPV status in head and neck cancer.
Scientific Reports.
15(1).
doi:
10.1038/s41598-025-17284-8.
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Reduced field-of-view diffusion-weighted imaging (reduced-FOV DWI) is a promising technique for assessing tumor heterogeneity and microstructure. In this study, we evaluated the ability of reduced-FOV DWI to identify specific patterns associated with human papillomavirus (HPV) exposure in head and neck squamous cell carcinoma (HNSCC). Whole-lesion analysis of the tumor was performed on reduced-FOV and conventional DWI using a multi b value sequence. The extracted parameters included the 10th-90th percentile of the apparent diffusion coefficient (ADC) and fractional blood volume (fBV), skewness, and kurtosis. The differences between HPV-negative and HPV-positive tumors were greater for reduced-FOV DWI. ADC was significantly lower in HPV-positive tumors (reduced-FOV DWI: p < 0.001, r90th = 0.50; conventional DWI: p < 0.001, r10th = 0.49). The fBV was significantly lower in HPV-positive tumors on reduced-FOV DWI (reduced-FOV DWI: p90th < 0.001, r90th = 0.47; conventional DWI: not statistically significant). Moreover, there were significant differences between parameters derived from reduced-FOV and conventional DWI (ADC: p10th−90th < 0.001, fBV: p10th−50th < 0.001; skewnessADC, fBV: p < 0.001, kurtosisADC: p = 0.008; kurtosisfBV: p < 0.001). In conclusion, DWI parameters varied depending on HPV status and the differences between HPV-positive and HPV-negative tumors were greater for reduced-FOV DWI. The reduced-FOV DWI better reflected histopathology than did conventional DWI
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Frich, Pål Stefan; Sigstad, Eva; Berstad, Audun Elnæs; Opsahl, Else Marie; Fagerlid, Kristin Holgersen & Kotanska-Grøholt, Krystyna
[Show all 9 contributors for this article]
(2025).
Ethanol Ablation of Metastatic Lymph Nodes in Patients With Papillary Thyroid Carcinoma—Predictors of Clinical Outcome.
Journal of Clinical Endocrinology and Metabolism (JCEM).
ISSN 0021-972X.
doi:
10.1210/clinem/dgaf298.
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Context
Ethanol ablation (EA) is a treatment option in recurrent or persistent metastatic lymph nodes (MLNs) from papillary thyroid carcinoma.
Objective
This work aimed to assess whether ultrasonographic characteristics of the MLN, history of lymph node surgery, aggressive histological subtype, or BRAFV600E mutation in the primary tumor predict long-term response from EA.
Methods
Seventy-five patients who received EA at a tertiary referral center were included. We evaluated treatment response from the most recent clinically indicated examination, or a study-specific examination. BRAFV600E analysis and review of histological subtypes in the primary tumor were conducted.
Results
Median interval from initial surgery to follow-up was 119 months (range, 39-471 months). Pure cystic MLN had a better outcome than the solid and partially cystic MLN (13/13, 100% vs 90/121, 74%; P = .039). Small MLNs (≤0.5 mL) had a higher response rate compared to larger lesions (71/92, 77% vs 10/19, 53%; P = .045). We observed no difference in EA response between patients with or without the BRAFV600E mutation (80/99, 81% vs 17/25, 68%; P = .181) or an aggressive subtype (22/24, 92% vs 75/100, 75%; P = .099) in their primary tumors. EA achieved similar rates of locoregional disease control in neck regions with or without previous lymph node surgery (66% vs 63%, P = .825).
Conclusion
EA was highly effective in pure cystic MLNs. Partially cystic or noncystic MLNs over 0.5 mL were less responsive, though many of these MLNs still showed a lasting response. BRAFV600E mutation, aggressive histological subtype, or absence of prior lymph node surgery did not negatively affect EA response.
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Ramberg, Håkon; Zucknick, Manuela; Barletta, Francesco; Davik, Petter; Nybøen, Åsmund & Eri, Lars Magne
[Show all 15 contributors for this article]
(2025).
Development and evaluation of a lymph node invasion risk prediction model in intermediate- and high-risk prostate cancer patients.
Acta Oncologica.
ISSN 0284-186X.
64,
p. 1446–1454.
doi:
10.2340/1651-226x.2025.43970.
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Background and purpose:
Many prostate cancer patients undergoing pelvic lymph node dissection (PLND) have no sign of lymph node invasion (LNI) during final pathological assessment. To improve preoperative staging accuracy, we developed the Oslo model, which estimates the risk of LNI based on clinical, histopathological, and magnetic resonance imaging (MRI) variables.
Patients/materials and methods:
We utilized data from 903 prostate cancer patients treated at Oslo University Hospital (OUS) to develop the model using Bayesian logistic regression. The Oslo model was validated with data from 189 patients at IRCCS Ospedale San Raffaele (HRS), 157 from St. Olav’s Hospital, and 231 from OUS. We assessed its performance against the Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti 2019 nomograms using metrics like AUC, R², decision curve analysis, and calibration plots.
Results:
The Oslo model outperformed Briganti 2019, demonstrating a higher net benefit and a 10% reduction in interventions at a 7% cutoff. Key variables included clinical T stage on MRI, Prostate Specific Antigen (PSA), prostate volume, International Society of Urological Pathology grade group, and maximum lesion length on MRI. Validation showed strong reliability in the OUS and HRS cohorts but weaker performance in the St. Olav’s cohort. The AUCs were 77% for the Oslo model, 74% for Briganti 2019, and 66% for MSKCC. Limitations include small and heterogeneous validation cohorts.
Interpretation:
The Oslo model enhances predictive performance in intermediate- and high-risk patients using easily accessible clinical and MRI data, potentially reducing unnecessary PLND interventions and assisting clinicians in treatment decision-making.
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Ryg, Una; Lilleby, Wolfgang; Nilsen, Line Brennhaug; Hellebust, Taran Annette Paulsen; Seierstad, Therese & Hole, Knut Håkon
(2025).
Image-Based Recurrence Patterns After Reirradiation in Prostate Cancer with Long-Term Follow-Up.
Advances in Radiation Oncology.
ISSN 2452-1094.
10(12).
doi:
10.1016/j.adro.2025.101900.
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Purpose
Local failure of prostate cancer after definitive radiation therapy is associated with poor prognosis. Studies on reirradiation have primarily focused on toxicity and oncologic outcome and only partially reported recurrence patterns. Investigating the recurrence pattern may help guide future therapy decisions.
Methods and Materials
Thirty-three men with local recurrence of prostate cancer after primary definitive radiation therapy were enrolled between 2012 and 2018 (median age 69.8 years [IQR: 6.8], median prostate-specific antigen 4.1 ng/mL [IQR: 3.8]). Twenty-three patients received reirradiation with focal high dose-rate brachytherapy, and 10 received stereotactic body radiation therapy to the prostate with (8/10) or without (2/10) a simultaneous integrated boost to the recurrent tumor. The sites of recurrences were examined with multiparametric magnetic resonance imaging and compared with the dose distribution maps.
Results
During the median 99 months (IQR: 56) follow-up, 25 patients had biochemical rerecurrence. Twenty had adequate imaging. Five patients had rerecurrences solely inside the high-dose region, and 7 had both inside and outside the high-dose region. Two patients with a prostatic recurrence received whole-gland stereotactic body radiation therapy without a boost to the tumor. Four had a combination of rerecurrence within the prostate as well as regional lymph node metastases. One patient had a prostatic rerecurrence and a single bone metastasis. One patient had prostatic rerecurrence, lymph node metastases, and bone metastases. No patients had only regional or distant metastases.
Conclusions
After reirradiation of prostate cancer, the tumor frequently recurred within the prostate, both inside and outside the high-dose region. About 1 in 3 patients also had regional or distant metastatic disease at rerecurrence.
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Skingen, Vilde Eide; Salberg, Unn Beate; Hompland, Tord; Fjeldbo, Christina Sæten; Helgeland, Hanna & Frikstad, Kari-Anne
[Show all 11 contributors for this article]
(2024).
Spatial analysis of microRNA regulation at defined tumor hypoxia levels reveals biological traits of aggressive prostate cancer.
Journal of Pathology.
ISSN 0022-3417.
264(3),
p. 270–283.
doi:
10.1002/path.6344.
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Mechanisms regulating the gene expression program at different hypoxia severity levels in patient tumors are not understood. We aimed to determine microRNA (miRNA) regulation of this program at defined hypoxia levels from moderate to severe in prostate cancer. Biopsies from 95 patients were used, where 83 patients received the hypoxia marker pimonidazole before prostatectomy. Forty hypoxia levels were extracted from pimonidazole-stained histological sections and correlated with miRNA and gene expression profiles determined by RNA sequencing and Illumina bead arrays. This identified miRNAs associated with moderate (n = 7) and severe (n = 28) hypoxia and predicted their target genes. The scores of miRNAs or target genes showed prognostic significance, as validated in an external cohort of 417 patients. The target genes showed enrichment of gene sets for cell proliferation and MYC activation at all hypoxia levels and PTEN inactivation at severe hypoxia. This was confirmed by RT-qPCR for MYC and PTEN, by Ki67 imm
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Mo, Torgeir; Brandal, Siri Helene Bertelsen; Geier, Oliver; Engebråten, Olav; Nilsen, Line & Kristensen, Vessela N.
[Show all 10 contributors for this article]
(2023).
MRI Assessment of Changes in Tumor Vascularization during Neoadjuvant Anti-Angiogenic Treatment in Locally Advanced Breast Cancer Patients.
Cancers.
15(18).
doi:
10.3390/cancers15184662.
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Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy regimen in breast cancer patients are not well studied. Understanding the effects of the anti-vascular treatment on tumor vasculature may provide a selection of patients that can benefit. The aim of this study was to study the vascular effect of bevacizumab using clinical dynamic contrast-enhanced MRI (DCE-MRI). A total of 70 women were randomized to receive either chemotherapy alone or chemotherapy with bevacizumab for 25 weeks. DCE-MRI was performed at baseline and at 12 and 25 weeks, and in addition 25 of 70 patients agreed to participate in an early MRI after one week. Voxel-wise pharmacokinetic analysis was performed using semi-quantitative methods and the extended Tofts model. Vascular architecture was assessed by calculating the fractal dimension of the contrast-enhanced images. Changes during treatment were compared with baseline and between the treatment groups. There was no significant difference in tumor volume at any point; however, DCE-MRI parameters revealed differences in vascular function and vessel architecture. Adding bevacizumab to chemotherapy led to a pronounced reduction in vascular DCE-MRI parameters, indicating decreased vascularity. At 12 and 25 weeks, the difference between the treatment groups is severely reduced.
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Lilleby, Wolfgang; Seierstad, Therese; Inderberg, Else Marit & Hole, Knut Håkon
(2023).
Impact of human telomerase reverse transcriptase peptide vaccine combined with androgen deprivation therapy and radiotherapy in de novo metastatic prostate cancer: Long-term clinical monitoring.
International Journal of Cancer.
ISSN 0020-7136.
152(10),
p. 2166–2173.
doi:
10.1002/ijc.34448.
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Reijnen, Jeroen Sebastiaan; Ryg, Una; Marthinsen, Jon Bache; Schönhardt, Irina; Seierstad, Therese & Hole, Knut Håkon
(2023).
Monoparametric high-resolution diffusion weighted MRI as a possible first step in an MRI-directed diagnostic pathway for men with suspicion of prostate cancer.
Frontiers in Oncology.
13,
p. 1–11.
doi:
10.3389/fonc.2023.1102860.
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Purpose To explore if a high-resolution diffusion weighted MRI sequence (DWI-only) could be used as a first step in an MRI-directed diagnostic pathway. Methods Prospective single center study that between December 2017 and August 2018 included 129 consecutive patients with suspicion of prostate cancer into a PI-RADS-based MRI-directed diagnostic pathway. All patients had multiparametric MRI (mpMRI). Based on only the transversal high-resolution DWI images two consultant radiologists prospectively categorized the findings as positive, equivocal, or negative for clinically significant cancer. The radiologists then interpreted the mpMRI and assigned a PI-RADS score. A third independent reader retrospectively categorized the DWI-only exams without access to the mpMRI. The interpretations of DWI-only were compared to the PI-RADS classification from mpMRI and the histopathology from the biopsies. Non-biopsied patients were followed in a safety net monitoring for 56 months. Results Based on DWI-only, 29 (22.5%) of the exams were categorized as negative, 38 (29.5%) as equivocal and 62 (48.1%) as positive. Of the 56 patients with PI-RADS 4-5 at mpMRI, 55 were also categorized as positive at DWI-only. All patients diagnosed with clinically significant cancer were identified using DWI-only. 56 months of safety net monitoring did not reveal any clinically significant cancers among patients with exams categorized as negative or equivocal. There was high inter-reader agreement on positive findings, but less agreement on negative and equivocal findings. Conclusions In this concept study, the monoparametric DWI-only identified all patients with clinically significant cancer in a mpMRI-directed diagnostic pathway.
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Switlyk, Marta Daniela; Hopland, Olav Andreas; Reitan, Edmund; Sivanesan, Shivanthe; Brennhovd, Bjørn & Axcrona, Ulrika
[Show all 7 contributors for this article]
(2023).
Multiparametric Magnetic Resonance Imaging of Penile Cancer: A Pictorial Review.
Cancers.
15(22).
doi:
10.3390/cancers15225324.
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The role of multiparametric magnetic resonance imaging (mpMRI) in assessing penile cancer is not well defined. However, this modality may be successfully applied for preoperative staging and patient selection; postoperative local and regional surveillance; and assessments of treatment response after oncological therapies. Previous studies have been mostly limited to a few small series evaluating the accuracy of MRI for the preoperative staging of penile cancer. This review discusses the principles of non-erectile mpMRI, including functional techniques and their applications in evaluating the male genital region, along with clinical protocols and technical considerations. The latest clinical classifications and guidelines are reviewed, focusing on imaging recommendations and discussing potential gaps and disadvantages. The development of functional MRI techniques and the extraction of quantitative parameters from these sequences enables the noninvasive assessment of phenotypic and genotypic tumor characteristics. The applications of advanced techniques in penile MRI are yet to be defined. There is a need for prospective trials and feasible multicenter trials due to the rarity of the disease, highlighting the importance of minimum technical requirements for MRI protocols, particularly image resolution, and finally determining the role of mpMRI in the assessment of penile cancer
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Switlyk, Marta Daniela; Hopland, Ola Andreas; Sivanesan, Shivanthe; Brennhovd, Bjørn; Ottosson, Fredrik & Berner, Kjetil
[Show all 8 contributors for this article]
(2023).
Multi-parametric MRI without artificial erection for preoperative assessment of primary penile carcinoma: A pilot study on the correlation between imaging and histopathological findings.
European Journal of Radiology Open (EJR Open).
10.
doi:
10.1016/j.ejro.2023.100478.
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Purpose We aimed to evaluate the diagnostic potential of non-erectile multi-parametric magnetic resonance imaging (mpMRI) for preoperative assessment of primary penile squamous cell carcinoma (SCC). Method Twenty-five patients who underwent surgery for penile SCC were included. Preoperative mpMRI without artificial erection was performed in all patients. The preoperative MRI protocol consisted of high-resolution morphological and functional sequences (diffusion-weighted imaging and dynamic contrast-enhanced MRI perfusion) covering the penis and lower pelvis. T and N staging, according to the 8th edition of the Union for International Cancer Control TNM classification, as well as the largest diameter and thickness/infiltration depth of the primary lesions were determined in all patients. Imaging data were retrospectively collected and compared with the final histopathology reports. Results Very good agreement was observed between MRI and histopathology for the involvement of corpus spongiosum (p = 0.002) and good agreement was observed for the involvement of penile urethra and tunica albuginea/corpus cavernosum (p < 0.001 and p = 0.007, respectively). Good agreement was observed between MRI and histopathology for overall T staging and weaker, but still good agreement was observed for N staging (p < 0.001 and p = 0.002, respectively). A strong and significant correlation was observed between MRI and histopathology for the largest diameter and thickness/infiltration depth of the primary lesions (p < 0.001). Conclusions Good concordance was observed between MRI and histopathological findings. Our initial findings indicate that non-erectile mpMRI is useful in preoperative assessment of primary penile SCC.
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Skingen, Vilde Eide; Hompland, Tord; Fjeldbo, Christina Sæten; Salberg, Unn Beate; Helgeland, Hanna & Ragnum, Harald Bull
[Show all 11 contributors for this article]
(2023).
Prostate cancer radiogenomics reveals proliferative gene expression programs associated with distinct MRI-based hypoxia levels.
Radiotherapy and Oncology.
ISSN 0167-8140.
188.
doi:
10.1016/j.radonc.2023.109875.
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Background and purpose: The biology behind individual hypoxia levels in patient tumors is poorly understood. Here, we used radiogenomics to identify associations between magnetic resonance imaging (MRI)-based hypoxia levels and biological processes derived from gene expression data in prostate cancer.
Materials and methods: For 85 prostate cancer patients, MRI-based hypoxia images were constructed by combining diffusion-weighted images reflecting oxygen consumption and supply. The ability to differentiate hypoxia levels in these images was verified by comparison with matched biopsy sections stained for the hypoxia marker pimonidazole. For MRI-defined hypoxia levels, corresponding hypoxic fractions were calculated and correlated with biopsy gene expression profiles. Biological processes were predicted by gene set enrichment analysis (GSEA) and validated by immunohistochemistry (Ki67 proliferation marker, reactive stroma grade) and RT-PCR (MYC).
Results: Genes with correlation between expression level and hypoxic fraction were identified for 56 MRI-based hypoxia levels. At all levels, GSEA identified proliferation as the predominant biological process enriched among the correlating genes. Two independent proliferative gene signatures were developed. The Peak1 signature, upregulated at moderate/severe hypoxia, reflected MYC upregulation and high Ki67-proliferation index of cancer cells in pimonidazole-positive regions. The Peak2 signature, upregulated at mild to non-hypoxic levels, was associated with fibroblast gene signature and reactive stroma grade. High scores of both Peak1 and Peak2 indicated elevated risk of biochemical recurrence in multiple cohorts.
Conclusion: Radiogenomics identified two gene expression programs activated at different hypoxia levels, reflecting proliferation of cancer cells and stroma cells. Genes involved in these programs could be candidate targets for intervention.
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Ryg, Una; Seierstad, Therese; Nilsen, Line; Hellebust, Taran Annette Paulsen; Djupvik, Linda Holth & Gustafson, Hilde
[Show all 10 contributors for this article]
(2022).
A prospective study of high dose-rate brachytherapy or stereotactic body radiotherapy of Intra-prostatic recurrence: Toxicity and long term clinical outcome.
Frontiers in Oncology.
12:861127,
p. 1–10.
doi:
10.3389/fonc.2022.861127.
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Background Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy. Methods and Material Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival. Results Median follow-up time was 81 months (range 21–115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years. Conclusion The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.
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Salberg, Unn Beate; Skingen, Vilde Eide; Fjeldbo, Christina Sæten; Hompland, Tord; Ragnum, Harald Bull & Vlatkovic, Ljiljana
[Show all 9 contributors for this article]
(2022).
A prognostic hypoxia gene signature with low heterogeneity within the dominant tumour lesion in prostate cancer patients.
British Journal of Cancer.
ISSN 0007-0920.
127,
p. 321–328.
doi:
10.1038/s41416-022-01782-x.
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Background: Gene signatures measured in a biopsy have been proposed as hypoxia biomarkers in prostate cancer. We assessed a previously developed signature, and aimed to determine its relationship to hypoxia and its heterogeneity within the dominant (index) lesion of prostate cancer.
Methods: The 32-gene signature was assessed from gene expression data of 141 biopsies from the index lesion of 94 patients treated with prostatectomy. A gene score calculated from the expression levels was applied in the analyses. Hypoxic fraction from pimonidazole immunostained whole-mount and biopsy sections was used as reference standard for hypoxia.
Results: The gene score was correlated with pimonidazole-defined hypoxic fraction in whole-mount sections, and the two parameters showed almost equal association with clinical markers of tumour aggressiveness. Based on the gene score, incorrect classification according to hypoxic fraction in whole-mount sections was seen in one third of the patients. The incorrect classifications were apparently not due to intra-tumour heterogeneity, since the score had low heterogeneity compared to pimonidazole-defined hypoxic fraction in biopsies. The score showed prognostic significance in uni-and multivariate analysis in independent cohorts.
Conclusions: Our signature from the index lesion reflects tumour hypoxia and predicts prognosis in prostate cancer, independent of intra-tumour heterogeneity in pimonidazole-defined hypoxia.
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Hopland, Ola Andreas; Fosså, Sophie Dorothea; Ottosson, Fredrik; Brennhovd, Bjørn; Svindland, Aud & Hole, Knut Håkon
[Show all 10 contributors for this article]
(2021).
Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience.
Scandinavian Journal of Urology.
ISSN 2168-1805.
55(4).
doi:
10.1080/21681805.2021.1946135.
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Objectives To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND) Material and Methods Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Results Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10–27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1 Conclusion Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.
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Hernes, Eivor; Rootwelt-Revheim, Mona Elisabeth; Hole, Knut Håkon; Tulipan, Andreas Julius; Strømme, Hilde & Lilleby, Wolfgang
[Show all 7 contributors for this article]
(2021).
Prostate-Specific Membrane Antigen PET for Assessment of Primary and Recurrent Prostate Cancer with Histopathology as Reference Standard: A Systematic Review and Meta-Analysis.
PET Clinics.
ISSN 1556-8598.
16(2),
p. 147–165.
doi:
10.1016/j.cpet.2020.12.001.
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Prostate-specific membrane antigen PET is a promising diagnostic tool in prostate cancer. The gold standard for the detection of prostate tumor and lymph node metastases is histopathology. The aim of the present review was to investigate accuracy measures of 68Ga/18F-labeled prostate-specific membrane antigen PET tracers in primary and recurrent prostate cancer with systematic sector-based histopathology as the reference standard. A systematic literature search was performed and 34 studies were included. Overall, prostate-specific membrane antigen PET showed high specificity, but variable sensitivity to localize known prostate cancer and detect pelvic lymph node metastases.
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Seierstad, Therese; Hole, Knut Håkon; Tulipan, Andreas Julius; Strømme, Hilde; Lilleby, Wolfgang & Rootwelt-Revheim, Mona Elisabeth
[Show all 7 contributors for this article]
(2021).
18F-Fluciclovine PET for Assessment of Prostate Cancer with Histopathology as Reference Standard: A Systematic Review.
PET Clinics.
ISSN 1556-8598.
16(2),
p. 167–176.
doi:
10.1016/j.cpet.2020.12.012.
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Abstract
The PET tracer 18F-fluciclovine (Axumin) was recently approved in the United States and Europe for men with suspected prostate cancer recurrence following prior treatment. This article summarizes studies where systematic sector-based histopathology was used as reference standard to assess the diagnostic accuracy of the tracer 18F-fluciclovine PET in patients with prostate cancer.
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Rootwelt-Revheim, Mona Elisabeth; Hole, Knut Håkon; Mo, Torgeir; Bruland, Øyvind; Reitan, Edmund & Julsrud, Lars
[Show all 7 contributors for this article]
(2021).
Multimodal functional imaging for early response assessment in patients with gastrointestinal stromal tumor treated with tyrosine kinase inhibitors.
Acta Radiologica.
ISSN 0284-1851.
63(8),
p. 995–1004.
doi:
10.1177/02841851211027389.
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Background: Several imaging modalities are used in the early work-up of patients with gastrointestinal stromal tumor (GIST) receiving tyrosine kinase inhibitor (TKI) treatment and there is a need to establish whether they provide similar or complimentary information.
Purpose: To compare 18F-fluorodeoxyglucose positron emission tomography (FDG PET), computed tomography (CT) and magnetic resonance imaging (MRI) as early predictors of three-month outcomes for patients with GIST receiving TKI treatment.
Material and methods: Thirty-five patients with advanced GIST were prospectively included between February 2011 and June 2017. FDG PET, contrast-enhanced CT (CECT), and MRI were performed before and early after onset of TKI treatment (range 8-18 days). Early response was categorized according to mRECIST (CT), the Choi criteria (CECT), and PERCIST (FDG PET/CT). For MRI, volumetry from T2-weighted images and change in apparent diffusion coefficient (ADC) from diffusion-weighted imaging was used. The reference standard for early assessment was the three-month mRECIST evaluation based on CT. At three months, both stable disease (SD) and partial response (PR) were categorized as response. Clinical usefulness was defined as agreement between early and three-month assessment.
Results: At the three-month assessment, 91% (32/35) were responders, 37% (13/35) PR, 54% (19/35) SD, and 9% (3/35) had progressive disease (PD). Early assessment correctly predicted three-month response in 93% (27/29) for MRI, 80% (28/35) for PERCIST, 74% (26/35) for Choi, and 23% (8/35) for mRECIST. Six patients had non-FDG-avid tumors. For the FDG-avid tumors, PET/CT correctly predicted three-month response in 97% (28/29).
Conclusion: MRI was superior to CECT for early assessment of TKI-treatment response in GIST. If the tumor was FDG-avid, PET and MRI were equally good. Changes in functional parameters were superior to changes in longest tumor diameter (mRECIST).
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Tulipan, Andreas Julius; Salberg, Unn Beate; Hole, Knut Håkon; Vlatkovic, Ljiljana; Aarnes, Eva-Katrine & Rootwelt-Revheim, Mona Elisabeth
[Show all 8 contributors for this article]
(2021).
Amino acid transporter expression and 18F-FACBC uptake at PET in primary prostate cancer.
The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI).
11(4),
p. 250–259.
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Abstract
Little is known about the transport mechanism of anti-3-18F-fluorocyclobutane-1-carboxylic acid (FACBC) into prostate tumors. Because of the structural similarity to natural amino acids, FACBC is anticipated to cross the cell membrane via amino acid transporters, and preclinical studies have suggested that ASCT2, LAT1 and SNAT2 are involved. In 16 patients with intermediate or high-risk prostate cancer we matched the FACBC uptake from clinical PET to the location of punch biopsies from resected prostatectomy specimens and compared maximum standardized uptake value (SUVmax) with the gene expression of 40 amino acid transporters. The study also included immunohistochemistry for the three amino acid transporters ASCT2, LAT1 and SNAT2. Furthermore, we performed global gene expression analysis of the biopsies to investigate biological processes associated with FACBC uptake. Several amino acid transporters had a higher gene expression level than the others, but we found no significant correlations between SUVmax and the gene expression levels of any of 40 different amino acid transporters. In the immunohistochemical analyses, ASCT2 and SNAT2 were highly expressed, but not correlated to SUVmax. LAT1 had low gene- and protein expression. Global gene expression analyses identified 153 unique genes that were positively correlated to SUVmax. These genes were found to be associated with gene sets reflecting intracellular transport and high metabolic activity. Based on the study findings we propose that the uptake mechanism of FACBC is more complex than mediated by a few amino acid transporters.
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Hole, Knut Håkon; Tulipan, Andreas Julius; Reijnen, Jeroen Sebastiaan; Hernes, Eivor; Vlatkovic, Ljiljana & Lie, Kathrine
[Show all 8 contributors for this article]
(2021).
Localization of primary prostate cancer: FACBC PET/CT compared with multiparametric MRI using histopathology as reference standard.
The American Journal of Nuclear Medicine and Molecular Imaging (AJNMMI).
11(5),
p. 387–394.
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FACBC (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid) is a FDA-approved PET-tracer in patients with suspected recurrent prostate cancer. In the diagnostic work-up of primary prostate cancer, accurate localization of the index tumor is needed for image-guidance of biopsies. We therefore assessed the performance of FACBC PET/CT to detect and localize the index tumor and compared it to multiparametric MRI (mpMRI) using whole-mount histopathology as reference standard. Twenty-three patients with biopsy-proven prostate cancer had FACBC PET/CT and mpMRI within two weeks prior to prostatectomy. FACBC PET/CT was acquired as 14 minutes list-mode and re-binned into seven 2-minutes intervals. Static FACBC was the acquired data from 4-6 minutes, whereas the dynamic FACBC included all seven intervals. Two radiologists and two nuclear medicine physicians independently interpreted the images and consensus was reached in case of discrepancy. Static PET detected 15 of 23 (65%) of the index tumors, dynamic PET detected 14 of 22 (64%), and MRI detected 20 of 23 (87%). To assess the extent of the tumor, the interpreters delineated the tumor in a 12-regions sector-based template. True positive, true negative, false positive and false negative sectors were recorded based on the template drawings and whole-mount histopathology. Both static and dynamic FACBC PET had sensitivity of 40% and specificity of 99%, whereas MRI had sensitivity of 81% and specificity of 100%. Our data indicate that FACBC PET/CT may be useful but that mpMRI is better for localizing the index tumor in patients with prostate cance
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Knuth, Franziska Hanna; Adde, Ingvild Askim; Huynh, Bao Ngoc; Grøndahl, Aurora Rosvoll; Winter, René & Negård, Anne
[Show all 15 contributors for this article]
(2021).
MRI-based automatic segmentation of rectal cancer using 2D U-Net on two independent cohorts.
Acta Oncologica.
ISSN 0284-186X.
61(2),
p. 255–263.
doi:
10.1080/0284186X.2021.2013530.
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Background Tumor delineation is time- and labor-intensive and prone to inter- and intraobserver variations. Magnetic resonance imaging (MRI) provides good soft tissue contrast, and functional MRI captures tissue properties that may be valuable for tumor delineation. We explored MRI-based automatic segmentation of rectal cancer using a deep learning (DL) approach. We first investigated potential improvements when including both anatomical T2-weighted (T2w) MRI and diffusion-weighted MR images (DWI). Secondly, we investigated generalizability by including a second, independent cohort. Material and methods Two cohorts of rectal cancer patients (C1 and C2) from different hospitals with 109 and 83 patients, respectively, were subject to 1.5 T MRI at baseline. T2w images were acquired for both cohorts and DWI (b-value of 500 s/mm2) for patients in C1. Tumors were manually delineated by three radiologists (two in C1, one in C2). A 2D U-Net was trained on T2w and T2w + DWI. Optimal parameters for image pre-processing and training were identified on C1 using five-fold cross-validation and patient Dice similarity coefficient (DSCp) as performance measure. The optimized models were evaluated on a C1 hold-out test set and the generalizability was investigated using C2. Results For cohort C1, the T2w model resulted in a median DSCp of 0.77 on the test set. Inclusion of DWI did not further improve the performance (DSCp 0.76). The T2w-based model trained on C1 and applied to C2 achieved a DSCp of 0.59. Conclusion T2w MR-based DL models demonstrated high performance for automatic tumor segmentation, at the same level as published data on interobserver variation. DWI did not improve results further. Using DL models on unseen cohorts requires caution, and one cannot expect the same performance.
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Reijnen, Jeroen S.; Marthinsen, Jon Bache; Tysland, Alf Ole; Muller, Christoph Rainer; Schönhardt, Irina & Andersen, Erlend K F
[Show all 8 contributors for this article]
(2021).
Results from a PI-RADS-based MRI-directed diagnostic pathway for biopsy-naive patients in a non-university hospital.
Abdominal Radiology.
ISSN 2366-004X.
46,
p. 5639–5646.
doi:
10.1007/s00261-021-03249-8.
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Abstract Purpose To assess the safety and performance of a MRI-directed diagnostic pathway for patients with first-time suspicion of prostate cancer in a non-university hospital. Methods Between May 2017 and December 2018 all biopsy-naive patients examined in our hospital followed a MRI-directed diagnostic work-up algorithm based on PI-RADS score. In short, PI-RADS 1–2 was generally not biopsied and PI-RADS 3–5 was reviewed by a multidisciplinary team. Patients with PI-RADS 4-5 were all referred to biopsy, either transrectal ultrasound-guided biopsy or MRI in-bore biopsy for small tumors and for sites difficult to access. PI-RADS scores were compared to the histopathology from biopsies and surgical specimens for patients who had prostatectomy. Non-biopsied patients were referred to a safety net monitoring regimen. Results Two hundred and ninety-eight men were enrolled. 97 (33%) had PI-RADS 1–2, 44 (15%) had PI-RADS 3, and 157 (53%) had PI-RADS 4–5. 116 (39%) of the patients avoided biopsy. None of these were diagnosed with significant cancer within 2–3.5 years of safety net monitoring. Almost all high ISUP grade groups (≥ 3) were in the PI-RADS 4–5 category (98%). Prostatectomy specimens and systematic biopsies from MRI-negative areas indicated that very few clinically significant cancers were missed by the MRI-directed diagnostic pathway. Conclusion Our findings add to evidence that a MRI-directed diagnostic pathway can be safely established in a non-university hospital. The pathway reduced the number of biopsies and reliably detected the site of the most aggressive cancers. Graphic abstract
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Bains, Simer Jit; Abrahamsson, Hanna Josefine; Flatmark, Kjersti; Dueland, Svein; Hole, Knut Håkon & Seierstad, Therese
[Show all 9 contributors for this article]
(2019).
Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer.
Cancer Immunology and Immunotherapy.
ISSN 0340-7004.
doi:
10.1007/s00262-019-02458-x.
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Objective High rates of systemic failure in locally advanced rectal cancer call for a rational use of conventional therapies to foster tumor-defeating immunity. Methods We analyzed the high-mobility group box-1 (HMGB1) protein, a measure of immunogenic cell death (ICD), in plasma sampled from 50 patients at the time of diagnosis and following 4 weeks of induction chemotherapy and 5 weeks of sequential chemoradiotherapy, both neoadjuvant modalities containing oxaliplatin. The patients had the residual tumor resected and were followed for long-term outcome. Results Patients who met the main study end point—freedom from distant recurrence—showed a significant rise in HMGB1 during the induction chemotherapy and consolidation over the chemoradiotherapy. The higher the ICD increase, the lower was the metastatic failure risk (hazard ratio 0.26, 95% confidence interval 0.11–0.62, P = 0.002). However, patients who received the full-planned oxaliplatin dose of the chemoradiotherapy regimen had poorer metastasis-free survival (P = 0.020) than those who had the oxaliplatin dose reduced to avert breach of the radiation delivery, which is critical to maintain efficient tumor cell kill and in the present case, probably also protected the ongoing radiation-dependent ICD response from systemic oxaliplatin toxicity. Conclusion The findings indicated that full-dose induction oxaliplatin followed by an adapted oxaliplatin dose that was compliant with full-intensity radiation caused induction and maintenance of ICD and as a result, durable disease-free outcome for a patient population prone to metastatic progression.
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Meltzer, Sebastian; Bakke, Kine Mari; Rød, Karina Lund; Negård, Anne; Flatmark, Kjersti & Solbakken, Arne Mide
[Show all 19 contributors for this article]
(2019).
Sex-related differences in primary metastatic site in rectal cancer; associated with hemodynamic factors?
Clinical and Translational Radiation Oncology.
21,
p. 5–10.
doi:
10.1016/j.ctro.2019.11.006.
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Background and purpose We investigated how features relating to pelvic cavity anatomy and tumor hemodynamic factors may influence systemic failure in rectal cancer. Materials and methods Rectal cancer patients (207 women, 343 men), who had been prospectively enrolled onto six cohorts and given curative-intent therapy, were analyzed for the first metastatic event. In one of the cohorts, the diameter of the inferior mesenteric vein (IMV) was assessed on diagnostic abdominal computed tomography images (n = 113). Tumor volume (n = 193) and histologic response to neoadjuvant therapy (n = 445) were recorded from diagnostic magnetic resonance images and surgical specimens, respectively. Results More women than men developed lung metastasis (p = 0.037), while the opposite was the case for liver metastasis (p = 0.040). Wider IMV diameter correlated with larger tumor volume (r = 0.481, p < 0.001) and male sex (p < 0.001). Female sex was the only adverse prognostic factor for lung metastasis. When sex, tumor volume, and histologic response were taken into consideration, poor tumor response remained the only determinant for liver metastasis (p = 0.002). Conclusions In a diverse rectal cancer population given curative-intent treatment, women and men had different outcome with regard to the primary metastatic site. Tumor hemodynamic factors should be considered in rectal cancer risk stratification.
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Abrahamsson, Hanna Josefine; Porojnicu, Alina Carmen; Lindstrøm, Jonas Christoffer; Dueland, Svein; Flatmark, Kjersti & Hole, Knut Håkon
[Show all 11 contributors for this article]
(2019).
High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer.
BMC Cancer.
19(1).
doi:
10.1186/s12885-019-5724-z.
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Background:Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastaticprogression is still dominant. We investigated if patients’circulating 25-hydroxyvitamin D [25(OH)D] levels wereassociated with outcome.Methods:Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samplescollected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation beforesurgery, and analyzed with respect to season, disease presentation, and treatment effects.Results:In the cohort of patients residing at latitude 58–62°N, baseline 25(OH)D differed significantly over theseasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, andchanged over the three-month neoadjuvant period till response evaluation solely owing to season. The patientsubgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to theneoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases withresponse (ypT0–3) and T2–3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L,regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk ofdisease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment forage, sex, body mass index, and season.Conclusion:Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levelswere insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse thanpatients with T2–3 disease when 25(OH)D was sufficient.
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Tulipan, Andreas Julius; Vlatkovic, Ljiljana; Malinen, Eirik; Brennhovd, Bjørn; Hole, Knut Håkon & Lie, Kathrine
[Show all 9 contributors for this article]
(2018).
Comparison of time curves from dynamic 18F-fluciclovine positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging for primary prostate carcinomas.
Physics and imaging in radiation oncology (PIRO).
7,
p. 51–57.
doi:
10.1016/j.phro.2018.09.003.
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Background and purpose: Multimodal imaging is increasingly included in the assessment of prostate cancer patients, and there is a need to study whether different techniques provide similar or complementary information. In the initial perfusion phase contrast agents and radioactive labelled tracers act as blood-pool agents and may show similar characteristics. The purpose of the current work was to compare time-activity- and time-concentration-curves (TCs) of dynamic 18F-fluciclovine (18F-anti-1-amino-2-[F]-fluorocyclobutane-1-carboxylic acid, FACBC) positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Materials and methods: Dynamic FACBC PET and DCE MRI were performed on 22 patients with intermediate or high-risk prostate cancer within 23 days prior to robot-assisted laparoscopic prostatectomy. Index tumour was delineated in the images using whole mount tissue sections as reference standard. Tumour TCs from PET and MRI were compared visually and quantitatively by calculating correlation coefficients between the curves at different time points after injection. Results: For the first minute post injection, the mean correlation coefficient between the TCs from PET and MRI was 0.92 (range; 0.75–0.99). After the first minute, MRI showed washout while PET showed plateau kinetics. Conclusion: Dynamic FACBC and DCE MRI showed similar wash-in time curve characteristics. At later time points, FACBC plateaued whereas MR contrast medium washed out. In DCE MRI, the usefulness of wash-in information is well documented. Whether wash-in information from dynamic FACBC can provide added value remains to be documented.
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Kalanxhi, Ert; Meltzer, Sebastian; Schou, Jakob Vasehus; Larsen, Finn Ole; Dueland, Svein & Flatmark, Kjersti
[Show all 12 contributors for this article]
(2018).
Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer.
British Journal of Cancer.
ISSN 0007-0920.
118(10),
p. 1322–1328.
doi:
10.1038/s41416-018-0085-y.
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Background Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.
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Bakke, Kine Mari; Hole, Knut Håkon; Dueland, Svein; Kotanska-Grøholt, Krystyna; Flatmark, Kjersti & Ree, Anne Hansen
[Show all 8 contributors for this article]
(2017).
Diffusion-weighted magnetic resonance imaging of rectal cancer: tumour volume and perfusion fraction predict chemoradiotherapy response and survival.
Acta Oncologica.
ISSN 0284-186X.
56(6),
p. 813–818.
doi:
10.1080/0284186X.2017.1287951.
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Background: In locally advanced rectal cancer (LARC), responses to preoperative treatment are highly heterogeneous and more accurate diagnostics are likely to enable more individualised treatment approaches with improved responses. We investigated the potential of diffusion-weighted magnetic resonance imaging (DW MRI), with quantification of the apparent diffusion coefficient (ADC) and perfusion fraction (F), as well as volumetry from T2-weighted (T2W) MRI, for prediction of therapeutic outcome. Material and methods: In 27 LARC patients receiving neoadjuvant chemotherapy (NACT) before chemoradiotherapy (CRT), T2W- and DW MRI were obtained before and after NACT. Tumour volumes were delineated in T2W MRI and ADCs and Fs were estimated from DW MRI using a simplified approach to the intravoxel incoherent motion (IVIM) model. Mean tumour values and histogram analysis of whole-tumour heterogeneity were correlated with histopathologic tumour regression grade (TRG) and 5-year progression-free survival (PFS). Results: At baseline, high tumour F predicted good tumour response (TRG1-2) (AUC = 0.79, p = 0.01), with a sensitivity of 69% and a specificity of 100%. The combination of F and tumour volume (Fpre/Vpre) gave the highest prediction of poor tumour response (AUC = 0.93, p < 0.001) with a sensitivity of 88% and a specificity of 91%, and also predicted PFS (p < 0.01). Baseline tumour ADC was not significantly related to therapeutic outcome, whereas a positive change in ADC from baseline to after NACT, ΔADC, significantly predicted good tumour response (AUC = 0.83, p < 0.01, 83% sensitivity, 73% specificity), but not PFS. Conclusions: The MRI parameter F/V at baseline was a remarkably strong predictor of both histopathologic tumour response and 5-year PFS in patients with LARC.
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Goscinski, Mariusz Adam; Hole, Knut Håkon; Tønne, Elin; Ryder, Truls; Kotanska-Grøholt, Krystyna & Flatmark, Kjersti
(2016).
Fibromatosis in vertical rectus abdominis myocutaneous flap imitating tumor recurrence after surgery for locally advanced rectal cancer: Case report.
World Journal of Surgical Oncology (WJSO).
14.
doi:
10.1186/s12957-016-0818-4.
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Flatmark, Kjersti; Sælen, Marie Grøn; Hole, Knut Håkon; Abrahamsen, Torveig Weum; Fleten, Karianne Giller & Hektoen, Helga
[Show all 10 contributors for this article]
(2016).
Individual tumor volume responses to short-course oxaliplatin containing induction chemotherapy in locally advanced rectal cancer – Targeting the tumor for radiation sensitivity?
Radiotherapy and Oncology.
ISSN 0167-8140.
119(3),
p. 505–511.
doi:
10.1016/j.radonc.2016.02.020.
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Background
Neoadjuvant treatment of locally advanced rectal cancer (LARC) involves chemoradiotherapy (CRT), which may cause significant toxicity, and the potential role and sequential placement of neoadjuvant chemotherapy (NACT) relative to CRT is under debate.
Patients and methods
In a non-randomized study of 72 LARC patients, short-course oxaliplatin-containing NACT was administered prior to CRT. Tumor volumes were calculated from magnetic resonance images before and after NACT, and four weeks after CRT, and associations between tumor volume responses and outcome were analyzed. Additionally, the impact of oxaliplatin exposure on radiosensitivity was examined in colorectal carcinoma cell lines.
Results
All tumors except one responded to NACT, with better responses in T3 than T4 cases, and 69/72 patients obtained additional tumor volume reduction after subsequent CRT. However, no associations were found between tumor volume reduction and long-term outcome. Of note, oxaliplatin-resistant cells were significantly more radiosensitive than the oxaliplatin-sensitive counterparts.
Conclusions
Oxaliplatin-containing NACT led to substantial tumor volume reduction with particularly good responses in T3 cases. NACT did not impede subsequent CRT response, and experimental results rather suggested enhanced radiosensitivity in oxaliplatin-exposed cells, encouraging studies to explore the administration of NACT prior to CRT. Data are still lacking to support omitting radiation in LARC management.
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Seierstad, Therese; Hole, Knut Håkon; Kotanska-Grøholt, Krystyna; Dueland, Svein; Ree, Anne Hansen & Flatmark, Kjersti
[Show all 7 contributors for this article]
(2015).
MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer.
British Journal of Radiology (BJR).
ISSN 0007-1285.
88:20150097(1051).
doi:
10.1259/bjr.20150097.
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Objective: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT followed by CRT (VCRT). VPRE, VNACT and tumour volume changes relative to VPRE, ΔVNACT and ΔVCRT were calculated and correlated to histological tumour regression grade (TRG). Results: 61% of good histological responders (TRG 1–2) to NACT followed by CRT were correctly predicted by combining VPRE < 10.5 cm3, ΔVNACT > −78.2% and VNACT < 3.3 cm3. The highest accuracy was found for VNACT, with 55.1% sensitivity given 100% specificity. The volume regression after completed NACT and CRT (VCRT) was not significantly different between good and poor responders (TRG 1–2 vs TRG 3–5). Conclusion: MRI-assessed small tumour volumes after NACT correlated with good histological tumour response (TRG 1–2) to the completed course of NACT and CRT. Furthermore, by combining tumour volume measurements before, during and after NACT, more good responders were identified.
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Hole, Knut Håkon; Axcrona, Karol; Lie, Kathrine; Vlatkovic, Ljiljana; Geier, Oliver & Brennhovd, Bjørn
[Show all 9 contributors for this article]
(2013).
Routine pelvic MRI using phased-array coil for detection of extraprostatic tumour extension: accuracy and clinical significance.
European Radiology.
ISSN 0938-7994.
23(4),
p. 1158–1166.
doi:
10.1007/s00330-012-2669-x.
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Objectives To determine the accuracy and assess the clinical significance of surface-coil 1.5-T magnetic resonance imaging (MRI) for the detection of locally advanced prostate cancer (PCa). Methods Between December 2007 and January 2010, we examined 209 PCa patients (mean age = 62.5 years) who were consecutively treated with robot-assisted laparoscopic prostatectomy and prospectively staged by MRI. One hundred and thirty-five patients (64.6 %) had locally advanced disease. Conventional clinical tumour stage and MRI-assessed tumour stage were compared with histopathological tumour stage (pT). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) were calculated using pT as the “gold standard”. Overstaged and understaged cases at MRI were reviewed. Results Sensitivity, specificity, PPV, NPV and OA for the detection of locally advanced disease were 25.9, 95.9, 92.1, 41.2 and 50.5 % and 56.3, 82.2, 85.4, 50.4 and 65.4 % for clinical staging and MRI, respectively. Among patients understaged at MRI, the resection margins were free in 64.4 % of the cases (38/59). Conclusions Although the accuracy was limited, the detection of locally advanced disease improved substantially when MRI was added to routine clinical staging. The majority of the understaged patients nevertheless achieved free margins. When assessing the clinical significance of MRI staging the extent of extraprostatic extension has to be considered. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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Hole, Knut Håkon; Larsen, Stein Gunnar; Kotanska-Grøholt, Krystyna; Giercksky, Karl-Erik & Ree, Anne Hansen
(2013).
Magnetic resonance-guided histopathology for improved accuracy of tumor response evaluation of neoadjuvant treatment in organ-infiltrating rectal cancer.
Radiotherapy and Oncology.
ISSN 0167-8140.
107(2),
p. 178–183.
doi:
10.1016/j.radonc.2013.03.017.
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Dimmen, Magne; Vlatkovic, Ljiljana; Hole, Knut Håkon; Nesland, Jahn M; Brennhovd, Bjørn & Axcrona, Karol
(2012).
Transperineal prostate biopsy detects significant cancer in patients with elevated prostate-specific antigen (PSA) levels and previous negative transrectal biopsies.
BJU International.
ISSN 1464-4096.
110(2 Pt 2),
p. E69–75.
doi:
10.1111/j.1464-410x.2011.10759.x.
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Andersen, Erlend K F; Hole, Knut Håkon; Lund, Kjersti Vassmo; Sundfør, Kolbein; Kristensen, Gunnar S Balle & Lyng, Heidi
[Show all 7 contributors for this article]
(2012).
Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance.
International Journal of Radiation Oncology, Biology, Physics.
ISSN 0360-3016.
82(3),
p. E485–E492.
doi:
10.1016/j.ijrobp.2011.05.050.
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Hjortland, Geir Olav; Meza, Leonardo Zepeda; Beiske, Klaus; Ree, Anne Hansen; Tveito, Siri & Høifødt, Hanne Kleppe
[Show all 12 contributors for this article]
(2011).
Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma.
BMC Cancer.
11.
doi:
10.1186/1471-2407-11-455.
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Background Metastatic progression due to development or enrichment of therapy-resistant tumor cells is eventually lethal. Molecular characterization of such chemotherapy resistant tumor cell clones may identify markers responsible for malignant progression and potential targets for new treatment. Here, in a case of stage IV adenocarcinoma of the gastroesophageal junction, we report the successful genome wide analysis using array comparative genomic hybridization (CGH) of DNA from only fourteen tumor cells using a bead-based single cell selection method from a bone metastasis progressing during chemotherapy. Case presentation In a case of metastatic adenocarcinoma of the gastroesophageal junction, the progression of bone metastasis was observed during a chemotherapy regimen of epirubicin, oxaliplatin and capecitabine, whereas lung-, liver and lymph node metastases as well as the primary tumor were regressing. A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes. Further intrapatient tumor heterogeneity of these highlighted gene copy number changes was analyzed by fluorescence in situ hybridization (FISH) in all available primary and metastatic tumor biopsies, and ErbB2 protein expression was investigated by immunohistochemistry. ERBB2 was heterogeneously amplified by FISH analysis in the primary tumor, as well as liver and bone metastasis, but homogenously amplified in biopsy specimens from a progressing bone metastasis after three initial cycles of chemotherapy, indicating a possible enrichment of erbB2 positive tumor cells in the progressing bone marrow metastasis during chemotherapy. A similar amplification profile was detected for wild-type KRAS, although more heterogeneously expressed in the bone metastasis progressing on chemotherapy. Correspondingly, the erbB2 protein was found heterogeneously expressed by immunohistochemical staining of the primary tumor of the gastroesophageal junction, while negative in liver and bone metastases, but after three initial cycles of palliative chemotherapy with epirubicin, oxaliplatin and capecetabine, the representative bone metastasis stained strongly positive for erbB2. Conclusion Global analysis of genetic aberrations, as illustrated by performing array-CGH analysis on genomic DNA from only a few selected tumor cells of interest sampled from a progressing bone metastasis, can identify relevant therapeutic targets and genetic aberrations involved in malignant progression, thus emphasizing the importance and feasibility of this powerful tool on the road to more personalized cancer therapies in the future.
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Fangberget, Anne; Nilsen, Line; Hole, Knut Håkon; Holmen, Marit Muri; Engebråten, Olav & Naume, Bjørn
[Show all 9 contributors for this article]
(2011).
Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging.
European Radiology.
ISSN 0938-7994.
21(6),
p. 1188–1199.
doi:
10.1007/s00330-010-2020-3.
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Objective To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Methods Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37–72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Results Before NAC, HER2 overexpression was the single significant predictor of pCR (p=0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42×10−3 mm2/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. Conclusion ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR.
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Seierstad, Therese; Hole, Knut Håkon; Sælen, Erik; Ree, Anne Hansen & Flatmark, Kjersti
(2009).
MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy.
Radiotherapy and Oncology.
ISSN 0167-8140.
93(2),
p. 279–284.
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Conclusions: Tumor volume reduction for rectal cancer patients following neoadjuvant chemotherapy allows for increased tumor dose using a SIB strategy without increased OAR toxicity. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 93 (2009) 279-289
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Seierstad, Therese; Hole, Knut Håkon; Sælen, Erik; Ree, Anne Hansen; Flatmark, Kjersti & Malinen, Eirik
(2009).
MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy.
Radiotherapy and Oncology.
ISSN 0167-8140.
93(2),
p. 279–284.
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Lillleby, Wolfgang; Axcrona, Karol; Alfsen, G. Cecilie; Urnes, Thomas & Hole, Knut Håkon
(2007).
Diagnosis and treatment of primary signet-ring cell carcinoma of the prostate.
Acta Oncologica.
ISSN 0284-186X.
46,
p. 1195–1197.
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Hoff, Geir; Wiig, Johan N.; Reed, Wenche; Hole, Knut Håkon; Scheistrøen, Marit & Henriksen, Halvor
(2005).
Short stricture of the rectum regressing on discontination of hormone replacement therapy: Endoscopic appearance, multiple biopsies and clinical improvement insufficient for diagnosis.
Scandinavian Journal of Gastroenterology.
ISSN 0036-5521.
40(3),
p. 365–367.
doi:
10.1080/00365520510011614.
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Goscinski, Mariusz Adam; Hole, Knut Håkon; Tønne, Elin; Ryder, Truls; Kotanska-Grøholt, Krystyna & Flatmark, Kjersti
(2016).
Fibromatosis in vertical rectus abdominis
myocutaneous flap imitating tumor recurrence after surgery for locally advanced rectal cancer: case report.
World Journal of Surgical Oncology (WJSO).
14(63).
doi:
10.1186/s12957-016-0818-4.
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Bakke, Kine Mari; Seierstad, Therese; Hole, Knut Håkon; Ree, Anne Hansen & Redalen, Kathrine Røe
(2015).
Histogram analysis of apparent diffusion coefficients from diffusion-weighted MRI during neoadjuvant treatment of locally advanced rectal cancer predicts histologic tumor response and survival.
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Seierstad, Therese; Hole, Knut Håkon; Grøholt, Krystyna Kotanska; Dueland, Svein; Ree, Anne Hansen & Flatmark, Kjersti
[Show all 7 contributors for this article]
(2015).
Prediction of response to neoadjuvant chemotherapy followed by chemoradiotherapy in rectal cancer by MRI volumetry.
Radiotherapy and Oncology.
ISSN 0167-8140.
115,
p. S350–S350.
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Raabe, Nils Kristian; Sundfør, Kolbein; Hole, Knut Håkon; Djupvik, Linda Holth; Larsen, Stein Gunnar & Dueland, Svein
(2014).
Høydoserate brakyterapi mot residiverende endetarmskreft etter konvensjonell residivbehandling.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
134(20),
p. 1929–1920.
doi:
10.4045/tidsskr.14.1162.
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Andersen, Erlend K F; Hole, Knut Håkon; Lund, Kjersti Vassmo; Kristensen, Gunnar S Balle; Lyng, Heidi & Malinen, Eirik
(2012).
IMPACT OF TUMOR DELINEATION ERRORS ON OUTCOME PREDICTION BASED ON DCE-MRI OF CERVICAL CANCER PATIENTS RECEIVING RT.
Radiotherapy and Oncology.
ISSN 0167-8140.
103,
p. 72–72.
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Revheim, Mona-Elisabeth; Hole, Knut Håkon; Bruland, Øyvind Sverre; Haugland, Hans Kristian; Hall, Kirsten Sundby & Seierstad, Therese
(2011).
DW MRI for evaluation of treatment response to imatinib in a rectal gastrointestinal stromal tumour.
Acta Oncologica.
ISSN 0284-186X.
50(1),
p. 148–150.
doi:
10.3109/0284186X.2010.516273.
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Larsen, Stein Gunnar; Hole, Knut Håkon; Kotanska-Grøholt, Krystyna; Dueland, Svein & Giercksky, Karl-Erik
(2010).
THE PRE-TREATMENT MRI PREDICTS THE NEED FOR EXTENDED TOTAL MESORECTAL EXCISION (ETME) IN T4A RECTAL CANCER.
Annals of Oncology.
ISSN 0923-7534.
21,
p. 60–60.
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Published
Jan. 16, 2019 12:32 PM
- Last modified
Feb. 11, 2019 11:30 AM