Øyvind Bruland

• Kvassheim, Monika; Hernes, Eivor; Berner, Kjetil; Bruland, Øyvind & Stokke, Caroline (2026). Combining whole-body clearance, blood activity concentrations, and SPECT images to explore the biodistribution of a novel [212Pb]Pb-PSMA-targeting therapy compared to a [177Lu]Lu-PSMA pharmacokinetic model. EANM Innovation. ISSN 3051-2913. 2. doi: 10.1016/j.eanmi.2026.100128. Full text in Research Archive Show summary

  Introduction The recently published phase 0 trial of 212Pb-labelled PSMA-targeting AB001 for metastatic castration-resistant prostate cancer (mCRPC) showed potential for further clinical development. Here we combined blood sample measurement, whole-body (WB) probe measurements, and SPECT/CT images to investigate the biodistribution of AB001. Methods Three mCRPC patients were imaged by SPECT/CT twice post-injection of 10 MBq AB001, and WB activity and whole blood, plasma, and red blood cell (RBC) activity concentrations of 212Pb and 212Bi (measured pre- and post-equilibrium) were sampled at four timepoints. A [177Lu]Lu-PSMA pharmacokinetic (PK) model was adapted to AB001 by changing physical half-lives and combining it with an International Commission on Radiological Protection (ICRP) model for unbound bismuth. The PSMA PK model was also altered by fitting to WB and plasma clearance. 212Pb liver, kidney, parotid gland, and blood activities measured from SPECT were compared to 212Pb in the respective model compartments or to samples. Results Activity concentration was 11 times higher in plasma than RBC. The 212Bi blood activity concentration was consistently lower than 212Pb. The adapted [177Lu]Lu-PSMA PK model indicated similar PK for AB001 in blood, but comparison with SPECT images suggested different biodistributions. Adjusting the excretion rate from the [177Lu]Lu-PSMA-617 PK model by fitting to AB001 WB clearance gave poorer fit between predicted and measured plasma activity than the unaltered model. Adjusting the PK model according to the plasma activities slightly improved the fit of the model to the WB clearance measurements compared to the unadjusted model, but the biodistribution differences compared to SPECT remained. Conclusions High in vivo stability of AB001 was indicated by combination of instant thin-layer chromatography measurements, comparison of plasma and RBC time-activity curves, and modelling of unbound 212Pb. While comparison of biokinetics of AB001 to [177Lu]Lu-PSMA indicated differences in biodistribution, there are considerable uncertainties in the approach, including use of population-based PK models, their applicability to AB001, and SPECT quantification.

• Kristiansen, Sandra Kvarsvik; Dernjani, Nurtene Berisha; Bruland, Øyvind; Edin, Nina Frederike Jeppesen & Juzeniene, Asta (2026). A 3D co-culture model with fibroblast-restricted FAP expression for cancer therapy using [212Pb]Pb-FAPI-46. EJNMMI Radiopharmacy and Chemistry. 11(1). doi: 10.1186/s41181-026-00444-0. Full text in Research Archive
• Fauske, Lena; Bruland, Øyvind; Holtermann, Anne & Larsen, Stein Gunnar (2026). Experiences and Hopes Among Patients with Colorectal Carcinoma and Peritoneal Metastases Who Are Participating in an Early-Phase Clinical Trial. Cancers. 18(2). doi: 10.3390/cancers18020244. Full text in Research Archive
• Larsen, Roy H.; Kolstad, Arne; Fosså, Alexander; Llamazares, Ada Repetto; Smerud, Knut Terje & Illidge, Timothy [Show all 7 contributors for this article] (2026). A Phase II Study of¹⁷⁷Lu–Lilotomab Satetraxetan, a CD37 Antibody–Radionuclide Conjugate, as Third- or Later-Line Treatment of Rituximab-Refractory Follicular B-Cell Lymphoma Patients. Pharmaceuticals. 19(2). doi: 10.3390/ph19020250. Full text in Research Archive Show summary

  Background: CD37, an antigen highly expressed in B-cell malignancies, served as the target in the LYMRIT-37-01 Part B (PARADIGME) and Part C studies employing a single intravenous injection of the radioimmunoconjugate 177Lu-lilotomab satetraxetan (Betalutin®). Methods: Patients with follicular lymphoma (FL), grades I-IIIa, who had received at least two previous lines of therapy and were refractory to at least one previous regimen with rituximab or an anti-CD20 agent, were included. They were randomized to receive either a 40 mg lilotomab pretreatment and an activity dosage of 15 MBq/kg Betalutin ("40/15" regimen) or 100 mg/m2 of lilotomab and 20 MBq/kg of Betalutin ("100/20" regimen). In total, 109 patients were enrolled and received Betalutin, 72 of whom received the 40/15 regimen and 28 received the 100/20 regimen. An additional heavily pretreated "special population" of nine patients received 40/12.5 (i.e., a reduced Betalutin dosage) due to low platelets and/or a previous autologous stem cell transplant. Part C was a small expansion cohort of four patients, all receiving the 40/15 regimen, and was designed to obtain supplementary pharmacokinetic data. Results: The efficacy analysis set comprised a total of 100 patients from the PARADIGME study. The overall response rates were 38.9% and 32.1%, and the complete response rates were 20.8% and 14.3% in the 40/15 and 100/20 groups, respectively. Correspondingly, the median response durations were 8.5 months and 3.4 months in the two groups. Hence, increasing the Betalutin activity dose by using the stronger protective CD37 pre-dosing ("100/20") did not improve the therapeutic benefit. The most common grade ≥ 3 adverse events were hematologic, including neutropenia (11.5%) and thrombocytopenia (8.0%), with nadirs occurring around weeks 5-7 and recovery by week 11. Conclusions: A single-dose administration of Betalutin had a mild toxicity profile with a clinically relevant response rate. It represents a viable treatment alternative in FL patients who are not suitable for more toxic and long-lasting treatments. Trial Registration: This trial was registered at clinicaltrials.gov under #NCT01796171.

• Kristiansen, Sandra Kvarsvik; Shubin, Kirill; Zubrienė, Asta; Matulis, Daumantas; Dernjani, Nurtene Berisha & Juzenas, Petras [Show all 8 contributors for this article] (2026). Radiobiological investigations of a [212Pb]Pb-carbonic anhydrase IX-targeting small-molecule ligand in renal cell carcinoma and colorectal cancer models. International Journal of Radiation Biology. ISSN 0955-3002. 102(2). doi: 10.1080/09553002.2025.2595630. Full text in Research Archive Show summary

  Purpose Carbonic anhydrase IX (CAIX), overexpressed in multiple cancers but limited in normal tissue, is a promising target for radionuclide therapy. This study evaluates [212Pb]Pb-MKV-509, a novel DOTA-conjugated small-molecule ligand, for CAIX-targeted alpha therapy in preclinical renal carcinoma (SK-RC-52) and colorectal (HT-29) cancer models. Materials and methods [212Pb]Pb-MKV-509 was assessed for radiochemical purity and stability. Binding assays determined receptor density and dissociation constants. Clonogenic survival, flow cytometry (viability, DNA damage, cell cycle), and spheroid assays (cross-sectional area, doubling time) evaluated biological responses. An in vivo biodistribution study was performed in SK-RC-52 xenograft-bearing mice, with and without carbonic anhydrase pre-blocking using acetazolamide. Results [212Pb]Pb-MKV-509 exhibited high radiochemical purity (>96%) and stability for up to 48 h. Specific binding was higher in SK-RC-52 than in HT-29 cells. Treatment induced activity-dependent clonogenic inhibition, G2/M arrest, and DNA damage, with greater sensitivity observed in SK-RC-52 cells. Clonogenic survival was reduced by 50% at 3.4 kBq/mL (SK-RC-52) and 7.1 kBq/mL (HT-29). In spheroid models, 2.5–5.0 kBq/mL delayed growth and prolonged doubling time, indicating cross-fire effects. The biodistribution study revealed significant tumor uptake (4.7%IA/g at 2 h), along with high gastrointestinal accumulation. Pretreatment with acetazolamide partially reduced uptake in the stomach and intestines as well as in the tumor. Conclusions These findings highlight the potential of CAIX-targeted alpha therapy. CAIX expression and receptor density impact binding affinity and therapeutic response. The study demonstrates the importance of 3D tumor models in evaluating alpha-particle cross-fire effects. Further ligand optimization is warranted to enhance tumor specificity and minimize off-target uptake.

• Koffi, E.; Padilla, C. S.; Drabbe, C.; Schreuder, W. H.; Zemouri, C. & Hollander, D. den [Show all 26 contributors for this article] (2025). Health-Related Quality of Life in Patients With a Head and Neck Sarcoma: A Mixed-Methods Study. Head and Neck. ISSN 1043-3074. 47(11), p. 3086–3097. doi: 10.1002/hed.28226. Full text in Research Archive
• Berner, Kjetil; Hernes, Eivor; Kvassheim, Monika; Rootwelt-Revheim, Mona-Elisabeth; Bastiansen, Julie Inderberg & Selboe, Silje [Show all 13 contributors for this article] (2025). First-in-Human Phase 0 Study of AB001, a Prostate-Specific Membrane Antigen–Targeted 212Pb Radioligand, in Patients with Metastatic Castration-Resistant Prostate Cancer. Journal of Nuclear Medicine. ISSN 0161-5505. 66(5), p. 732–738. doi: 10.2967/jnumed.124.269299. Full text in Research Archive Show summary

  AB001, a prostate-specific membrane antigen (PSMA)–targeted small molecule labeled with the in vivo–generating α-emitter 212Pb, was investigated in a phase 0 trial in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary objective was to explore the feasibility of γ-camera imaging to assess biodistribution and uptake in metastatic lesions. Methods: Three patients with progressive mCRPC and Eastern Cooperative Oncology Group performance status 1 were included, having prostate-specific antigen levels of 0.44, 0.75, and 15 µg/L. All had at least 3 PSMA-expressing metastatic lesions, with an SUVmax range of 10.1–77.4 on PSMA PET. Each patient received a microdose of 9.4 ± 0.3 MBq of AB001 intravenously. Planar γ-camera and SPECT/CT imaging was scheduled 1–3 h and 16–24 h after administration. Whole-body clearance was assessed with NaI probe measurements. Activity of 212Pb in whole blood and plasma was measured to investigate clearance from blood and in vivo stability of the ligand. Safety, tolerability, and efficacy biomarkers (prostate-specific antigen, alkaline phosphatase) were followed for 28 d. Results: AB001 uptake in the lesion with the highest PSMA expression, a retrocaval lymph node metastasis with a short-axis diameter of 11 mm, was visualized on SPECT. Uptake of AB001 was not clearly demonstrated for other metastatic lesions, possibly because of the lower PSMA expression of these metastases on PSMA PET, combined with the administered AB001 microdose and imaging system limitations. Kidney, urinary bladder with contents, and liver uptake of AB001 were clearly distinguishable from adjacent tissue, and the blood pool content was seen. Salivary glands were not visualized. Blood analyses indicated stability of AB001 after injection, and whole-body probe measurements demonstrated an effective half-life of 8 h. There were no complications related to injection of AB001 or adverse reactions during follow-up. As expected for a phase 0 study, there was no indication of therapeutic effects as assessed by prostate-specific antigen and alkaline phosphatase. Conclusion: The 212Pb-based radioligand AB001 was safely administered to mCRPC patients. γ-camera imaging of AB001 was feasible, even at a microdose, and demonstrated metastatic targeting, albeit for only 1 lesion. The promising biodistribution and clearance encourage further clinical investigation

• Wang, Yun; Nieuwenhuysen, Els Van; Rootwelt-Revheim, Mona-Elisabeth; Deroose, Christophe M.; Eriksson, Ane Gerda Zahl & Eyjólfsdóttir, Brynhildur [Show all 12 contributors for this article] (2025). First experience with intraperitoneal 224Ra-labeled microparticles after cytoreductive surgery in patients with peritoneal recurrence of platinum-sensitive epithelial ovarian cancer. Gynecologic Oncology. ISSN 0090-8258. 204, p. 158–164. doi: 10.1016/j.ygyno.2025.11.018. Full text in Research Archive Show summary

  Objective The aim of this Phase 1 study was to evaluate safety and tolerability of the alpha emitting therapy 224Ra-labeled microparticles (Radspherin®) and to establish the recommended dose for further development. Methods The study was conducted in patients who had undergone complete resection of platinum-sensitive recurrent ovarian cancer. A single dose of Radspherin was administered intraperitoneally one to three days after surgery. Dose escalation (3 + 3 design) was performed at 1, 2, 4 and 7 MBq. Safety and tolerability of Radspherin after 12 months are presented. Results Fourteen patients were enrolled across the 4 dose levels. Median age was 66 (56–77) years. Median peritoneal cancer index at the start of the surgery was 7 (3–16). No dose limiting toxicity (DLT) was observed. A total of 98 treatment emergent adverse events were reported (95 grade 1 or 2, and 3 grade 3). The three grade 3 events were cases of ileus (2) and anaemia (1) and were reported as unrelated to Radspherin by the investigators. One grade 2 serious adverse event of procedural complication (disconnect syringe-catheter) was reported as related to Radspherin. At 12-months, none of the patients had experienced peritoneal disease progression. Conclusions All dose levels were well tolerated, with no DLT observed. The highest activity dose of 7 MBq was selected as recommended dose for an expansion cohort. No grade ≥ 3 adverse events related to Radspherin were reported. Clinical trial information NCT03732768

• Machak, Gennady N.; Bruland, Øyvind; Kovalev, Alexey V. & Rodionova, Svetlana S. (2025). Rethinking the role of bisphosphonates after denosumab treatment in locally advanced or unresectable aneurysmal bone cysts: A metaanalysis. World Journal of Orthopedics (WJO). 16(8). doi: 10.5312/wjo.v16.i8.107083. Full text in Research Archive
• Fauske, Lena; Bruland, Øyvind & Hompland, Ivar (2025). Addressing and supporting the unmet needs of sarcoma survivors: a qualitative study. International Journal of Qualitative Studies on Health and Well-being. ISSN 1748-2623. 20(1). doi: 10.1080/17482631.2025.2597584. Full text in Research Archive
• Tornes, Anna Julie Kjøl; Kvassheim, Monika; Ma, Li-Wei; Wiig, Elisabeth; Hillestad, Tiril & Rootwelt-Revheim, Mona-Elisabeth [Show all 9 contributors for this article] (2025). Therapeutic evaluation of [212Pb]Pb-AB001 and [177Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. 52, p. 4847–4859. doi: 10.1007/s00259-025-07330-y. Full text in Research Archive Show summary

  Background Metastatic castration-resistant prostate cancer (mCRPC) frequently leads to bone and soft tissue metastases, leading to poor prognosis. The beta-emitting radioligand [177Lu]Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA) and may be less efficient against micrometastatic disease. The alpha-emitting radioligand [212Pb]Pb-AB001 could offer enhanced treatment by delivering high energy over a short range. This study compared the efficacy of [212Pb]Pb-AB001 and [177Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. Methods Binding and internalisation of radioligands were evaluated in PC-3 PIP-luc cells. A mouse model was established by intracardiac injection of these cells. Treatments with 0.24‒1.0 MBq [212Pb]Pb-AB001 or 22‒66 MBq [177Lu]Lu-PSMA-617 were initiated 7 d post-cell inoculation. Metastatic burden was measured using bioluminescence imaging, and PSMA-targeted uptake was determined with [18F]F-PSMA-1007 µPET/µCT. Gamma-autoradiography evaluated [212Pb]Pb-AB001 distribution, and bone metastases were identified by radiography. Results Both radioligands displayed comparable in vitro binding. In vivo studies revealed metastatic formation in clinically relevant organs. µPET/µCT demonstrated increased [18F]F-PSMA-1007 uptake in metastases, matching the bioluminescence imaging results. Focal [212Pb]Pb-AB001 distribution in the metastatic xenograft indicated heterogeneously distributed micrometastases in the organs. A median survival up to 47 d was achieved with [212Pb]Pb-AB001, compared to 25 d for controls and 27 d for [177Lu]Lu-PSMA-617. An activity-dependent reduction in bone metastases was observed for [177Lu]Lu-PSMA-617, while no bone lesions were detected in [212Pb]Pb-AB001-treated mice. Conclusion [212Pb]Pb-AB001 showed significant efficacy against micrometastases and advantages over [177Lu]Lu-PSMA-617 in preventing or treating early bone metastases for the investigated injected activities. This implies clinical potential for treating mCRPC, including patients at risk of early metastatic disease, but further studies including dosimetry and toxicity analyses are required with regards to activity levels.

• Machak, Gennady N.; Bruland, Øyvind; Romanova, Tamara N. & Kovalev, Alexey V. (2024). Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal. Journal of Bone Oncology. ISSN 2212-1366. 45. doi: 10.1016/j.jbo.2024.100596. Full text in Research Archive
• Hompland, Ivar; Pedersen, Kjetil Boye; Wiedswang, Anne Marit; Papakonstantinou, Andri; Røsok, Bård Ingvald & Joensuu, Heikki [Show all 7 contributors for this article] (2024). Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study. Acta Oncologica. ISSN 0284-186X. 63, p. 288–293. doi: 10.2340/1651-226X.2024.39851. Full text in Research Archive Show summary

  Introduction: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. Patients: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. Results: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. Interpretation: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

• Larsen, Stein Gunnar; Graf, W.; Larsen, R.H.; Rootwelt-Revheim, Mona-Elisabeth; Mariathasan, Anthony Burton & Sørensen, Olaf [Show all 12 contributors for this article] (2024). Eighteen-Months Safety and Efficacy Following Intraperitoneal Treatment With 224Radium-Labeled Microparticles After CRS-HIPEC in Patients With Peritoneal Metastasis From Colorectal Cancer. Journal of Surgical Oncology. ISSN 0022-4790. 130(6), p. 1395–1402. doi: 10.1002/jso.27897. Full text in Research Archive Show summary

  Background and Objectives Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. Methods A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. Results Eleven patients received 1−4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. Conclusions Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.

• Wal, Deborah van de; Fauske, Lena; Bruland, Øyvind; Jones, Robin L.; Kasper, Bernd & Wilson, Roger [Show all 8 contributors for this article] (2023). Psychological and social challenges of patients with locally advanced and metastatic gastrointestinal stromal tumours (GIST) on long-term treatment with tyrosine kinase inhibitors: a qualitative study with patients and medical oncologists. Supportive Care in Cancer. ISSN 0941-4355. 31(6). doi: 10.1007/s00520-023-07810-7. Full text in Research Archive Show summary

  Abstract Purpose Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of locally advanced and metastatic gastrointestinal stromal tumours (GISTs). Patients are experiencing prolonged survival but often at the expense of their health-related quality of life. It is not only the physical side effects that impact GIST patients’ daily lives but also the psychological and social challenges they have to deal with. This qualitative study aimed to explore the psychological and social life challenges of GIST patients with locally advanced and metastatic disease on ≥ 5 years TKI treatment. Methods Semi-structured interviews with 15 locally advanced and/or metastatic GIST patients and 10 medical oncologists with experience of delivering care to this specific patient group were conducted. Thematic analysis was used to interpret the data. Results Psychological challenges expressed by participants concerned fears, scanxiety, negative change in emotion and mood, doubts about their treatment and follow-up, living with uncertainty, lack of understanding from others or healthcare professionals, and constantly being reminded of their illness. Challenges regarding social health included financial difficulties, challenges in relationships, concerns about fertility and parenting, work, and impact on social activities. Conclusion The reported psychological and social challenges can significantly hamper the overall quality of life of GIST patients. Some challenges were clearly underreported and hardly recognized by medical oncologist, as they may tend to focus on the physical side effects and clinical outcomes of treatment. Therefore, it is essential to take the patient’s perspective into account in research and clinical practice to ensure optimal care for this patient group.

• Larsen, Stein Gunnar; Graf, Wilhelm; Mariathasan, Anthony Burton; Sørensen, Olaf; Spasojevic, Milan & Goscinski, Mariusz Adam [Show all 11 contributors for this article] (2023). First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study). Frontiers in Medicine. 10. doi: 10.3389/fmed.2023.1070362. Full text in Research Archive Show summary

  Background: Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11–12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC. Methods: A first-in-human phase 1 study (EudraCT 2018–002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented. Results: Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28–78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3–30). The peritoneal cancer index was median 7 (3–19), operation time was 395 min (194–515), and hospital stay was 12 days (7–37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution. Conclusion: All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.

• Palmerini, Emanuela; Reichardt, Peter; Hall, Kirsten Sundby; Bertulli, Rossella; Bielack, Stefan S. & Comandone, Alessandro [Show all 18 contributors for this article] (2023). Outcome of rare primary malignant bone sarcoma (RPMBS) treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S). Cancer. ISSN 0008-543X. doi: 10.1002/cncr.34964. Full text in Research Archive Show summary

  Abstract Background Rare primary malignant bone sarcomas (RPMBS) account for 5%–10% of primary high‐grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO‐B.O.S.S) is presented. Methods Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high‐grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m 2 , ifosfamide 9 g/m 2 , and cisplatin 90 mg/m 2 ; postoperative methotrexate 8 g/m 2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan–Meier curves, log‐rank tests, and univariate Cox regression models were used. Results In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40–66 years), and 67 patients were men. Eighty‐eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty‐three of 113 tumors were located in the extremities. Ninety‐five of 113 patients presented with no evidence of metastases. After a median follow‐up of 6.8 years (interquartile range [IQR], 3.5–9.8 years), the 5‐year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%–77.5%), and it was 71.7% (IQR, 58.1%–81.6%) for patients with UPS and 54.9% (IQR, 29.5%–74.5%) for patients with leiomyosarcoma. Grade III–IV hematologic toxicity was reported in 81% patients; 23% had grade II–III neurotoxicity, and 37.5% had grade I–II nephrotoxicity. Five‐year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. Conclusions The survival of patients who had RPMBS in the current series was similar to that of age‐matched patients who had high‐grade osteosarcoma treated according to the same protocol. An osteosarcoma‐like chemotherapy may be proposed in patients who have RPMBS.

• Juzenienne, Asta; Stenberg, Vilde Yuli; Bruland, Øyvind; Rootwelt-Revheim, Mona Elisabeth & Larsen, Roy Hartvig (2023). Dual targeting with 224Ra/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach. Frontiers in Medicine. 9:1051825, p. 1–12. doi: 10.3389/fmed.2022.1051825. Full text in Research Archive Show summary

  Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking 224 Ra and cell-directed complexes of progeny 212 Pb is a promising approach to treat metastatic cancers with bone and soft tissue lesions as well as skeletal metastases of mixed lytic/osteoblastic nature. A novel liquid 224 Ra/ 212 Pb-generator for rapid preparation of a dual targeting solution is described. Cancer cell targeting monoclonal antibodies, their fragments, synthetic proteins or peptides can all be radiolabeled with 212 Pb in the 224 Ra-solution in transient equilibrium with daughter nuclides. Thus, 224 Ra targets stromal elements in sclerotic bone metastases and 212 Pb-chelated-conjugate targets tumor cells of metastatic prostate cancer or osteosarcoma. The dual targeting solution may also be explored to treat metastatic breast cancer or multiple myeloma after manipulation of bone metastases to a more osteoblastic phenotype by the use of bisphosphonates, denosumab, bortezomib or hormone therapy prior to treatment. This may improve targeting of bone-seeking 224 Ra and render an augmented radiation dose deposited within metastases. Our preliminary preclinical studies provide conceptual evidence that the dual 224 Ra-solution with bone or tumor-targeted delivery of 212 Pb has potential to inhibit cancer metastases without significant toxicity. In some settings, the use of a booster dose of purified 212 Pb-conjugate alone could be required to elevate the effect of this tumor cell directed component, if needed, e.g., in a fractionated treatment regimen, where the dual targeting solution will act as maintenance treatment.

• Thorgersen, Ebbe Billmann; Asvall, Jørund; Schjalm, Camilla; Ekholt, Karin; Bruland, Øyvind & Larsen, Stein Gunnar [Show all 7 contributors for this article] (2023). Effect of Intraperitoneal ²²⁴Radium-Labelled Microparticles on Compartmentalized Inflammation After Cytoreductive Surgery and Hypertherm Intraperitoneal Chemotherapy. Technology in Cancer Research & Treatment (TCRT). ISSN 1533-0346. 22. doi: 10.1177/15330338231192902. Full text in Research Archive Show summary

  Despite extensive treatment with surgery and chemotherapy many patients with peritoneal metastases from colorectal cancer experience intraperitoneal disease relapse. The α-emitting 224 radium-labelled microparticle radionuclide therapeutic Radspherin® is being explored as a novel treatment option for these patients. Radspherin® is specially designed to give local radiation to the surface of the peritoneal cavity and potentially kill remaining attached micrometastases as well as free-floating cancer cells, thus preventing future relapse. The effect of Radspherin® on the immune system is not known. Systemic and local inflammatory responses were analyzed in plasma, intraperitoneal fluid and urine collected prospectively as part of a phase 1 dose-escalation study of intraperitoneal instillation of the α-emitting therapeutic radiopharmaceutical Radspherin®, at baseline and the first 7 postoperative days from nine patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. All patients additionally received intraperitoneal instillation of Radspherin® on postoperative day 2. Complement activation products C3bc and the terminal complement complex were analyzed using enzyme-linked immunosorbent assay. Cytokines ( n = 27), including interleukins, chemokines, interferons and growth factors, were analyzed using multiplex technique. The time course and magnitude of the postoperative cytokine response after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy displayed a modest systemic response in plasma, in contrast to a substantial local intraperitoneal response. After administration of Radspherin®, a significant increase ( P < 0.05) in TNF and MIP-1β was observed in both plasma and peritoneal fluid, whereas IL-9 increased only in plasma and IFNγ and IL1-RA only in peritoneal fluid. Only minor changes were seen for the majority of the inflammatory markers after Radspherin® administration. Our study showed a predominately local rather than systemic inflammatory response to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Radspherin® had overall modest impact on the inflammation.

• Mensali, Nadia; Köksal, Hakan; Joaquina, Sandy; Vernhoff, Håkan Patrik; Casey, Nicholas Paul & Romecin, Paola [Show all 27 contributors for this article] (2023). ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma. Nature Communications. 14. doi: 10.1038/s41467-023-39097-x. Full text in Research Archive Show summary

  Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation.

• Fauske, Lena; Jebsen, Nina Louise; Bondevik, Hilde & Bruland, Øyvind (2023). Exploring the Patient Perspective of Bone Sarcoma Survivors Who Have Undergone Particle Radiotherapy Abroad. Anticancer Research. ISSN 0250-7005. 43(5), p. 2031–2039. doi: 10.21873/anticanres.16364. Full text in Research Archive Show summary

  Background/Aim: Sarcoma patients’ experiences of their health-related quality of life and late effects following particle therapy are sparse. Such knowledge is essential to optimize treatment compliance and follow-up care related to this rapidly developing, but still centralized treatment modality. Patients and Methods: This qualitative study has an explorative design and applies a phenomenological and hermeneutical approach based on semi-structured interviews with 12 bone sarcoma patients who had undergone particle therapy abroad. The data were interpreted using thematic analysis. Results: Several of the participants called for more information about how the treatment would be carried out, its acute side effects and late complications. Most participants had positive experiences from the treatment and their stay abroad, but several struggled with late effects and other challenges. Themes that emerged from the analysis were “importance of being prepared”, “treatment and stay abroad”, “basically healthy, but with health problems and challenges”. Conclusion: Oncologists who inform and refer patients to particle therapy abroad must have sufficient experience of this treatment modality, prognoses, acute side effects, and late complications. Findings derived from this study may improve treatment preparation and compliance, enhance understanding of individual patient challenges to reduce stress and worry, and lead to better follow-up care and consequently quality of life of this selected group of bone sarcoma patients.

• Grønningsæter, Simen Rykkje; Blakkisrud, Johan; Selboe, Silje; Rootwelt-Revheim, Mona Elisabeth; Bruland, Øyvind & Bønsdorff, Tina Bjørnlund [Show all 8 contributors for this article] (2023). Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis. Frontiers in Medicine. 10, p. 1–10. doi: 10.3389/fmed.2023.1058914. Full text in Research Archive Show summary

  Aim Two ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles ( 224 Ra-CaCO 3 -MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public. Method Six patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of 224 Ra-CaCO 3 -MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of 224 Ra-CaCO 3 -MP, to estimate the activity concentration of 224 Ra and 212 Pb. Results The patients’ median effective whole-body half-life of 224 Ra-CaCO 3 -MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9–6.8 μSv per patient, and daily contact resulted in 4.3–31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7–83.0 μSv. The highest activity concentrations of 224 Ra and 212 Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for 224 Ra and 628 Bq/g for 212 Pb. Conclusion The number of patients treated with 224 Ra-CaCO 3 -MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200–400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.

• Stenberg, Vilde Yuli; Tornes, Anna Julie Kjøl; Nilsen, Hogne Røed; Rootwelt-Revheim, Mona Elisabeth; Bruland, Øyvind & Larsen, Roy Hartvig [Show all 7 contributors for this article] (2022). Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001. Cancers. 14(11). doi: 10.3390/cancers14112784. Full text in Research Archive Show summary

  This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

• Barnes, David J.; Dutton, Peter; Bruland, Øyvind; Gelderblom, Hans; Faleti, Ade & Bühnemann, Claudia [Show all 26 contributors for this article] (2022). Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial). BMC Cancer. 22(1). doi: 10.1186/s12885-022-09697-9. Full text in Research Archive Show summary

  Abstract The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.

• Boye, Kjetil; Lobmaier, Ingvild Victoria Koren; Kobbeltvedt, Marthe Rosvoll; Thorkildsen, Joachim; Taksdal, Ingeborg & Bjerkehagen, Bodil [Show all 10 contributors for this article] (2022). Real-world evidence on perioperative chemotherapy in localized soft tissue sarcoma of the extremities and trunk wall; a population-based study. Acta Oncologica. ISSN 0284-186X. 61(7), p. 793–800. doi: 10.1080/0284186X.2022.2082259. Full text in Research Archive Show summary

  Background Data from the real-world setting on perioperative chemotherapy in high-risk, localized soft tissue sarcoma (STS) is limited. Real-world data (RWD) includes data derived from patients treated outside clinical trials and often captures long-term follow-up not recorded in clinical trials. The aim of this study was to provide population-based, real-world evidence on perioperative chemotherapy in localized STS. Material and methods Adult patients with localized STS in the extremities or trunk wall treated at Oslo University Hospital, Oslo, Norway from 1998 to 2017 were included in the study. Data were extracted from a prospectively maintained database, supplemented by retrospective review of medical records. Results The total study cohort included 806 patients, of whom 154 (19%) received perioperative chemotherapy. A regimen with anthracycline and ifosfamide was given in 141 of 154 cases (92%). During long-term follow-up two patients developed secondary malignancies, cardiac toxicity was registered in 11 patients (7%) and renal toxicity in 12 patients (8%). Seventy-one of 154 patients (46%) were treated outside of clinical trials and constituted the RWD cohort. The median age at surgery was slightly lower and there were more synovial sarcomas and fewer myxofibrosarcomas in the RWD cohort. No difference in chemotherapy dose intensity was observed. The estimated 5-year metastasis-free survival (MFS) in all patients receiving perioperative chemotherapy was 58%. In the RWD cohort 5-year MFS was 53% and in the clinical study cohort 61% (HR 1.24; 95% CI 0.77–2.00). Conclusion Long-term outcome after perioperative chemotherapy was comparable for patients treated in routine clinical practice to those in clinical trials. Secondary malignancy and cardiac toxicity were observed. The risk of serious late side effects should be included in the decision process on perioperative chemotherapy.

• Tornes, Anna Julie Kjøl; Stenberg, Vilde Yuli; Bruland, Øyvind; Rootwelt-Revheim, Mona Elisabeth; Larsen, Roy H & Juzenienne, Asta (2022). Targeted alpha therapy with the 224Ra/212Pb-TCMC-TP-3 dual alpha solution in a multicellular tumor spheroid model of osteosarcoma. Frontiers in Medicine. 9. doi: 10.3389/fmed.2022.1058863. Full text in Research Archive Show summary

  Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression. We propose a novel dual alpha targeting solution containing two radionuclides from the same decay chain, including the bone-seeking 224 Ra, and cancer cell-surface seeking 212 Pb-TCMC-TP-3 for the treatment of osteoblastic bone cancers, circulating cancer cells and micrometastases. In this in vitro study, the cytotoxic effects of 212 Pb-TCMC-TP-3 (single alpha solution) and 224 Ra/ 212 Pb-TCMC-TP-3 (dual alpha solution) were investigated in a multicellular spheroid model mimicking micrometastatic disease in osteosarcoma. OHS spheroids with diameters of 253 ± 98 μm treated with 4.5, 2.7, and 3.3 kBq/ml of 212 Pb-TCMC-TP-3 for 1, 4, and 24 h, respectively, were disintegrated within 3 weeks. The 212 Pb-TCMC-TP-3 induced a 7-fold delay in spheroid doubling time compared to a 28-times higher dose with the non-specific 212 Pb-TCMC-rituximab. The 224 Ra/ 212 Pb-TCMC-TP-3 completely disintegrated spheroids with diameters of 218–476 μm within 3 and 2 weeks after 4 and 24 h incubation with 5 kBq/ml, respectively. Treatment with 1 kBq/ml of 224 Ra/ 212 Pb-TCMC-TP-3 for 24 h caused an 11.4-fold reduction in spheroid viability compared with unconjugated 224 Ra/ 212 Pb. The single and dual alpha solutions with TP-3 showed cytotoxicity in spheroids of clinically relevant size, which warrant further testing of the dual alpha solution using in vivo osteosarcoma models.

• Schmid, Maximilian P.; Harrabi, Semi; Herfarth, Klaus; Bruland, Øyvind; Welzel, Thomas & Haberer, Thomas [Show all 10 contributors for this article] (2022). Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma—Tumor and Treatment Characteristics and Early Clinical Outcomes. Cancers. 14(24). doi: 10.3390/cancers14246045. Full text in Research Archive
• Fauske, Lena; Wærstad, Pernille Holter; Hompland, Ivar & Bruland, Øyvind (2022). Hope as a Lifeline: Imatinib Discontinuation in Patients With Oligometastatic Gastrointestinal Stromal Tumours. Anticancer Research. ISSN 0250-7005. 42(2), p. 955–963. doi: 10.21873/anticanres.15555. Full text in Research Archive
• Spasojevic, Milan; Mariathasan, Anthony Burton; Frich, Lars Inge; Bruland, Øyvind; Larsen, Stein G. & Stoldt, Stephan (2021). Kreftbehandling med isolert ekstremitetsperfusjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(12), p. 1–6. doi: 10.4045/tidsskr.21.0194. Full text in Research Archive Show summary

  For lokalavanserte bløtvevssarkomer og metastaser fra melanom lokalisert til ekstremitet kan mutilerende kirurgi eller amputasjon være nødvendig for å oppnå lokal kontroll. Isolert ekstremitetsperfusjon med cellegift i høy dose kan være et alternativ til amputasjon for denne pasientgruppen.

• Juzeniene, Asta; Stenberg, Vilde Yuli; Bruland, Øyvind & Larsen, Roy Hartvig (2021). Preclinical and clinical status of psma-targeted alpha therapy for metastatic castration-resistant prostate cancer. Cancers. 13:779(4), p. 1–25. doi: 10.3390/cancers13040779. Full text in Research Archive Show summary

  Bone, lymph node, and visceral metastases are frequent in castrate-resistant prostate cancer patients. Since such patients have only a few months’ survival benefit from standard therapies, there is an urgent need for new personalized therapies. The prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and is a molecular target for imaging diagnostics and targeted radionuclide therapy (theragnostics). PSMA-targeted α therapies (PSMA-TAT) may deliver potent and local radiation more selectively to cancer cells than PSMA-targeted β− therapies. In this review, we summarize both the recent preclinical and clinical advances made in the development of PSMA-TAT, as well as the availability of therapeutic α-emitting radionuclides, the development of small molecules and antibodies targeting PSMA. Lastly, we discuss the potentials, limitations, and future perspectives of PSMA-TAT.

• Eck, Ilse van; Hollander, Dide Den; Lidington, Emma; Hentschel, Leopold; Eichler, Martin & Salah, Samer [Show all 21 contributors for this article] (2021). Health-related quality of life issues experienced by thoracic and breast sarcoma patients: A rare and understudied group. Journal of Clinical Medicine. 10(22). doi: 10.3390/jcm10225334. Full text in Research Archive
• Napoli, Elisa; Bønsdorff, Tina Bjørnlund; Jorstad, Ida Sofie; Bruland, Øyvind; Larsen, Roy H. & Westrøm, Sara (2021). Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use. PLOS ONE. 16(3), p. 1–18. doi: 10.1371/journal.pone.0248133. Full text in Research Archive Show summary

  Alpha-particle emitting radionuclides continue to be the subject of medical research because of their high energy and short range of action that facilitate effective cancer therapies. Radium-224 ( 224 Ra) is one such candidate that has been considered for use in combating micrometastatic disease. In our prior studies, a suspension of 224 Ra-labeled calcium carbonate (CaCO 3 ) microparticles was designed as a local therapy for disseminated cancers in the peritoneal cavity. The progenies of 224 Ra, of which radon-220 ( 220 Rn) is the first, together contribute three of the four alpha particles in the decay chain. The proximity of the progenies to the delivery site at the time of decay of the 224 Ra-CaCO 3 microparticles can impact its therapeutic efficacy. In this study, we show that the diffusion of 220 Rn was reduced in labeled CaCO 3 suspensions as compared with cationic 224 Ra solutions, both in air and liquid volumes. Furthermore, free-floating lead-212 ( 212 Pb), which is generated from released 220 Rn, had the potential to be re-adsorbed onto CaCO 3 microparticles. Under conditions mimicking an in vivo environment, more than 70% of the 212 Pb was adsorbed onto the CaCO 3 at microparticle concentrations above 1 mg/mL. Further, the diffusion of 220 Rn seemed to occur whether the microparticles were labeled by the surface adsorption of 224 Ra or if the 224 Ra was incorporated into the bulk of the microparticles. The therapeutic benefit of differently labeled 224 Ra-CaCO 3 microparticles after intraperitoneal administration was similar when examined in mice bearing intraperitoneal ovarian cancer xenografts. In conclusion, both the release of 220 Rn and re-adsorption of 212 Pb are features that have implications for the radiotherapeutic use of 224 Ra-labeled CaCO 3 microparticles. The release of 220 Rn through diffusion may extend the effective range of alpha-particle dose deposition, and the re-adsorption of the longer lived 212 Pb onto the CaCO 3 microparticles may enhance the retention of this nuclide in the peritoneal cavity.

• Fauske, Lena; Bruland, Øyvind; Dahl, Alv A; Myklebostad, Åse & Reme, Silje Endresen (2021). Does the lightning process training programme reduce chronic fatigue in adolescent and young adult cancer survivors? A mixed-methods pilot study. Cancers. 13(16), p. 1–13. doi: 10.3390/cancers13164076. Full text in Research Archive Show summary

  Chronic fatigue is a common late adverse effect following oncological therapies. No effective treatments exist, although cognitive behaviour therapy has been reported to offer some benefits. The Lightning Process® is a three-day educational training programme with a six-month follow-up comprising elements derived from cognitive behaviour therapy, neurolinguistic programming, and stress theory, which are presented in a condensed form. This pilot intervention study represents the first systematic account of the experience and perceived efficacy of the LP training programme in 13 adolescent and young adult cancer survivors treated for sarcoma or Hodgkin lymphoma. Statistically significant improvements were documented for all the patient-reported outcome measure (PROM) questionnaires comparing the pre- and post-intervention periods. The qualitative findings of the interviews corresponded well with the PROMs findings, as participants emphasised that they now experienced both less fatigue and explicit improvement in their energy level.

• Kerboeuf, Mikael Mathias Kolmannskog; Koppang, Erling Olaf; Haaland, Anita Haug; Lingaas, Frode; Bruland, Øyvind & Teige, Jon [Show all 7 contributors for this article] (2021). Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma. Acta Veterinaria Scandinavica (AVS). ISSN 0044-605X. 63(1), p. 1–10. doi: 10.1186/s13028-021-00608-9. Full text in Research Archive Show summary

  Abstract Background Despite decades of research, the early phases of metastatic development are still not fully understood. Canine osteosarcoma (OS) is a highly aggressive cancer, with a high metastatic rate (> 90%), despite a low overt metastatic prevalence at initial diagnosis (< 15%). Canine OS is generally regarded as a good clinically relevant model for human OS. The aim of this hypothesis-generating study was to evaluate a method to detect pulmonary micrometastases and study their prevalence in dogs with OS without macroscopic metastases. We prospectively enrolled dogs with OS that received no cancer-specific treatment (n = 12) and control dogs without cancer (n = 2). Dogs were necropsied and sampled immediately after euthanasia. The OS dogs were classified as having macroscopic metastases (n = 2) or not (n = 10). We immunohistochemically stained one tissue sample from each of the seven lung lobes from each dog with a monoclonal antibody (TP-3) to identify micrometastases (defined as clusters of 5–50 tumour cells), microscopic metastases (> 50 tumour cells) and TP-3 positive single cells (< 5 tumour cells). Results We showed that pulmonary micrometastases easily overseen on routine histology could be detected with TP-3. Pulmonary micrometastases and microscopic metastases were present in two dogs with OS without macroscopic metastases (20%). Micrometastases were visualised in three (43%) and four (57%) of seven samples from these two dogs, with a mean of 0.6 and 1.7 micrometastases per sample. Microscopic metastases were present in one (14%) and four (57%) of seven samples from the same two dogs, with a mean of 0.14 and 1.0 microscopic metastases per sample. There were four (57%) and two (29%) samples with neither microscopic metastases nor micrometastases for each of these two dogs. The prevalence of pulmonary micrometastases (20%) was significantly lower than expected (> 90%) based on commonly expected metastatic rates after amputation (P < 0.0001). There was no statistically significant difference in the number of TP-3 positive single cells in between groups (P = 0.85). Conclusions Pulmonary micrometastases could be detected with TP-3 immunohistochemistry in a subset of dogs with OS before macroscopic metastases had developed. We propose that dogs with spontaneous OS represent clinically relevant models to study early micrometastatic disease.

• 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. Full text in Research Archive Show summary

  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).

• Stenberg, Vilde Yuli; Larsen, Roy H.; Ma, Li-Wei; Qian, Peng; Juzenas, Petras & Bruland, Øyvind [Show all 7 contributors for this article] (2021). Evaluation of the psma-binding ligand²¹²pb-ng001 in multicellular tumour spheroid and mouse models of prostate cancer. International Journal of Molecular Sciences. ISSN 1661-6596. 22(9). doi: 10.3390/ijms22094815. Full text in Research Archive
• Li, Ruth Gong; Napoli, Elisa; Jorstad, Ida Sofie; Bønsdorff, Tina Bjørnlund; Juzeniene, Asta & Bruland, Øyvind Sverre [Show all 8 contributors for this article] (2021). Calcium carbonate microparticles as carriers of 224Ra: Impact of specific activity in mice with intraperitoneal ovarian cancer. Current Radiopharmaceuticals. ISSN 1874-4710. 14(2), p. 145–153. doi: 10.2174/1874471013666201201102056. Full text in Research Archive Show summary

  Background: Patients with advanced-stage ovarian cancer face a poor prognosis because of recurrent peritoneal cavity metastases following surgery and chemotherapy. Alpha-emitters may enable the efficient treatment of such disseminated diseases because of their short range and highly energetic radiation. Radium-224 is a candidate α-emitter due to its convenient 3.6-day half-life, with more than 90% of the decay energy originating from α-particles. However, its inherent skeletal accumulation must be overcome to facilitate intraperitoneal delivery of the radiation dose. Therefore, 224Ra-labeled CaCO3 microparticles have been developed. Objective: The antitumor effect of CaCO3 microparticles as a carrier for 224Ra was investigated, with an emphasis on the ratio of activity to mass dose of CaCO3, that is, specific activity. Methods: Nude athymic mice were inoculated intraperitoneally with human ovarian cancer cells (ES-2) and treated with a single intraperitoneal injection of 224Ra-labeled CaCO3 microparticles with varying combinations of mass and activity dose, or cationic 224Ra in solution. Survival and ascites volume at sacrifice were evaluated. Results: Significant therapeutic effect was achieved for all tested specific activities ranging from 0.4 to 4.6 kBq/mg. Although treatment with a mean activity dose of 1305 kBq/kg of cationic 224Ra prolonged the survival compared with the control, equivalent median survival could be achieved with 224Ra-labeled microparticles with a mean dose of only 420 kBq/kg. The best outcome was achieved with the highest specific activities (2.6 and 4.6 kBq/mg). Conclusion: Radium-224-labeled CaCO3 microparticles present a promising therapy against cancer dissemination in body cavities.

• Hall, Kirsten Sundby; Bruland, Øyvind; Bjerkehagen, Bodil; Lidbrink, Elisabet; Jebsen, Nina Louise & Hagberg, Hans [Show all 11 contributors for this article] (2020). Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study. Clinical Sarcoma Research. 10. doi: 10.1186/s13569-020-00145-5. Full text in Research Archive Show summary

  Background We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B. Methods Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented. Results Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3–10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7–77.4). The median follow-up time was 5.4 years (range 0.3–10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8–89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3). Conclusions Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis.

• König, Marton; Osnes, Terje; Bruland, Øyvind; Hall, Kirsten Sundby; Bratland, Åse & Meling, Torstein Ragnar (2020). The role of adjuvant treatment in craniofacial malignancy: A critical review. Frontiers in Oncology. 10. doi: 10.3389/fonc.2020.01402. Full text in Research Archive Show summary

  Background: Tumors originating from the craniofacial region usually present in a locally advanced stage with frequent involvement of adjacent sites and have a strong tendency for local recurrence in the absence of adjuvant therapy, even when the original surgical resection was presumed to be radical. In the past decades, several advances in the radiological diagnosis and treatment of craniofacial malignancies have been introduced. There are, however, no randomized trials that define the optimal multimodal treatment of these tumors because of their rarity as well as heterogeneity in both histology and site of origin. The aim of this study was to conduct a critical review of the role of adjuvant therapy in the treatment of craniofacial malignancy. Method: We conducted a critical review of the past and contemporary literature available, focusing on adjuvant oncological treatments of the most common craniofacial malignancies. Results: Preoperative radiotherapy can have a documented role in the treatment of olfactory neuroblastoma and soft tissue sarcoma, while preoperative chemotherapy can be advocated in the treatment of sinonasal undifferentiated carcinoma, neuroendocrine carcinoma, olfactory neuroblastoma, and craniofacial sarcoma (both soft-tissue and high-grade osteosarcoma). Postoperative radiotherapy has a well-established role in the treatment of most craniofacial malignancies. The role of postoperative chemotherapy is unclear in most histologies, but is commonly used during the treatment of well-selected cases of paranasal sinus carcinoma, olfactory neuroblastoma, mucosal melanoma, soft tissue sarcoma and high-grade craniofacial osteosarcoma. Discussion: Alongside developments in surgery, there have also been improvements in diagnostics, radiotherapy, and chemotherapy. Implementation of novel radiation techniques allows delivery of higher radiation doses while minimizing irradiation-related morbidity. Better understanding of tumor biology allows the construction of more complex treatment strategies, incorporating adjuvant chemotherapy either pre- or postoperatively. In the era of personalized targeted therapy, rapid strides are being made to identify specific tumor-targets for use of novel biologic agents, with the potential to change current management paradigms.

• Radaelli, S.; Fossati, Piero; Stacchiotti, S.; Akiyama, T.; Asencio, J.M. & Bandiera, S. [Show all 68 contributors for this article] (2020). The sacral chordoma margin. European Journal of Surgical Oncology. ISSN 0748-7983. 46(8), p. 1415–1422. doi: 10.1016/j.ejso.2020.04.028. Full text in Research Archive Show summary

  Objective Aim of the manuscript is to discuss how to improve margins in sacral chordoma. Background Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. Methods A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. Results En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. Conclusion Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

• Hompland, Ivar; Fauske, Lena; Lorem, Geir F & Bruland, Øyvind (2020). Use of a simple form to facilitate communication on long‑term consequences of treatment in sarcoma survivors. Clinical Sarcoma Research. doi: 10.1186/s13569-019-0124-3. Full text in Research Archive Show summary

  <i>Background</i> - To report on our experience using a simple optional form to facilitate communication on late effects between the patients and the oncologists during outpatient follow-up and to detail on the spectrum of challenges reported by sarcoma survivors.<p> <p><i>Methods</i> - The form was presented for the patients to complete before their consultation and covered topics related to late effects and unmet needs that the patient wished to discuss with the medical personnel. Logistic regression analysis examined how the distribution of the topics varied with age, gender, diagnosis and type of treatment received.<p> <p><i>Results</i> - The form was manageable in a busy outpatient clinic. Of the 265 patients that received the form, 236 (89%) returned it. Patients in a palliative setting and those with other diagnosis than bone sarcoma (BS) and soft-tissue sarcoma (STS) were excluded for subsequent analyses. The final study-cohort comprised 160 patients, 54 (34%) with BS and 106 (66%) with STS. Among these, 140 (88%) had late-effect topics they wanted to discuss with their oncologist. Fatigue was raised by 39% of the patients, pain by 29% and impaired mobility by 23%. BS patients raised fatigue more often (P < 0.005) than those with STS. Patients who had undergone multimodal treatment with chemotherapy raised fatigue more frequently (P < 0.001) than those who had only undergone surgery, radiotherapy or both.<p> <p><i>Conclusions</i> - A simple form on the long-term consequences of sarcoma treatment achieved a high response rate, was feasible to use in an outpatient clinic and facilitated communication on these issues. Fatigue was the most frequent topic raised and it was raised significantly more often in patients who had undergone chemotherapy.

• Lansu, Jules; Bovée, Judith V.M.G.; Braam, Pètra; Boven, Hester van; Flucke, Uta & Bonenkamp, Johannes J. [Show all 24 contributors for this article] (2020). Dose reduction of preoperative radiotherapy in myxoid liposarcoma: A nonrandomized controlled trial. JAMA Oncology. ISSN 2374-2437. p. 1–8. doi: 10.1001/jamaoncol.2020.5865. Full text in Research Archive
• Stenberg, Vilde Yuli; Juzeniene, Asta; Chen, Qingqi; Yang, Xiaoming; Bruland, Øyvind & Larsen, Roy Hartvig (2020). Preparation of the alpha-emitting prostate-specific membrane antigen targeted radioligand [212Pb]Pb-NG001 for prostate cancer. Journal of labelled compounds & radiopharmaceuticals. ISSN 0362-4803. 63(3), p. 129–143. doi: 10.1002/jlcr.3825. Full text in Research Archive Show summary

  Prostate‐specific membrane antigen (PSMA) is the most promising target for radioligand therapy of prostate cancer. The aim of this study was to prepare a small molecular ligand p‐SCN‐Bn‐TCMC‐PSMA (NG001) and compare it with the commonly used DOTA‐based PSMA‐617. The PSMA‐targeting ability of the 212Pb‐labelled ligands was evaluated using PSMA‐positive C4‐2 human prostate cancer cells. Lead‐212 is an in vivo generator of alpha particles by its daughter nuclides 212Bi and 212Po. NG001 was synthesized by conjugating the isothiocyanato group of p‐SCN‐Bn‐TCMC to the amino group of a glutamate‐urea‐based PSMA‐binding entity. Molecular size, chelator unit and chelator linking method are different in NG001 and PSMA‐617. Both ligands were efficiently labelled with 212Pb using a 224Ra/212Pb‐solution generator in transient equilibrium with progeny. Lead‐212‐labelled NG001 was purified with a yield of 85.9±4.7% and with 0.7±0.2% of 224Ra. Compared with [212Pb]Pb‐PSMA‐617, [212Pb]Pb‐NG001 displayed a similar binding and internalization in C4‐2 cells, with comparable tumour uptake in mice bearing C4‐2 tumours, but almost a 2.5‐fold lower kidney uptake. Due to the rapid normal tissue clearance and tumour cell internalization, any significant translocalization of 212Bi was not detected in mice. In conclusion, the obtained results warrant further preclinical studies to evaluate the therapeutic efficacy of [212Pb]Pb‐NG001.

• Stenberg, Vilde Yuli; Juzeniene, Asta; Bruland, Øyvind & Larsen, Roy H. (2020). In situ Generated 212Pb-PSMA Ligand in a 224Ra-Solution for Dual Targeting of Prostate Cancer Sclerotic Stroma and PSMA-positive Cells. Current Radiopharmaceuticals. ISSN 1874-4710. 13(2), p. 130–141. doi: 10.2174/1874471013666200511000532. Full text in Research Archive Show summary

  Background: New treatments combating bone and extraskeletal metastases are needed for patients with metastatic castration-resistant prostate cancer. The majority of metastases overexpress prostate-specific membrane antigen (PSMA), making it an ideal candidate for targeted radionuclide therapy. Objective: The aim of this study was to test a novel liquid 224Ra/212Pb-generator for the rapid preparation of a dual-alpha targeting solution. Here, PSMA-targeting ligands are labelled with 212Pb in the 224Ra-solution in transient equilibrium with daughter nuclides. Thus, natural bone-seeking 224Ra targeting sclerotic bone metastases and 212Pb-chelated PSMA ligands targeting PSMA-expressing tumour cells are obtained. Methods: Two PSMA-targeting ligands, the p-SCN-Bn-TCMC-PSMA ligand (NG001), specifically developed for chelating 212Pb, and the most clinically used DOTA-based PSMA-617 were labelled with 212Pb. Radiolabelling and targeting potential were investigated in situ, in vitro (PSMA-positive C4-2 human prostate cancer cells) and in vivo (athymic mice bearing C4-2 xenografts). Results: NG001 was rapidly labelled with 212Pb (radiochemical purity &gt;94% at concentrations of ≥15 μg/ml) using the liquid 224Ra/212Pb-generator. The high radiochemical purity and stability of [212Pb]Pb-NG001 were demonstrated over 48 hours in the presence of ascorbic acid and albumin. Similar binding abilities of the 212Pb-labelled ligands were observed in C4-2 cells. The PSMA ligands displayed comparable tumour uptake after 2 hours, but NG001 showed a 3.5-fold lower kidney uptake than PSMA-617. Radium-224 was not chelated and, hence, showed high uptake in bones. Conclusion: A fast method for the labelling of PSMA ligands with 212Pb in the 224Ra/212Pb-solution was developed. Thus, further in vivo studies with dual tumour targeting by alpha-particles are warranted.

• Napoli, Elisa; Stenberg, Vilde Yuli; Juzeniene, Asta; Hjellum, Gro E.; Bruland, Øyvind & Larsen, Roy H. (2020). Calibration of sodium iodide detectors and reentrant ionization chambers for 212Pb activity in different geometries by HPGe activity determined samples. Applied Radiation and Isotopes. ISSN 0969-8043. 166:109362, p. 1–9. doi: 10.1016/j.apradiso.2020.109362. Full text in Research Archive Show summary

  Lead-212 is a promising radionuclide for cancer therapy, but no primary 212Pb activity standardization has been published. A need therefore exists for accurate estimation of injected doses of 212Pb activity in equilibrium with progeny, when it comes to preclinical and clinical trials. In this study, 212Pb activity was determined using a high purity germanium (HPGe) detector, which allowed the determination of geometry-specific calibration factors for commercially available reentrant ionization chambers (ICs) and sodium iodide (NaI) detectors.

• Coleman, Robert; Hadji, Peyman; Body, Jean-Jacques; Santini, Daniele; Chow, Edward L.W. & Terpos, Evangelos [Show all 13 contributors for this article] (2020). Bone health in cancer: ESMO Clinical Practice Guidelines. Annals of Oncology. ISSN 0923-7534. p. 1–14. doi: 10.1016/j.annonc.2020.07.019. Full text in Research Archive
• Fauske, Lena; Hompland, Ivar; Lorem, Geir F; Bondevik, Hilde & Bruland, Øyvind (2019). Perspectives on treatment side effects in patients with metastatic gastrointestinal stromal tumour: a qualitative study. Clinical Sarcoma Research. 9(6). doi: 10.1186/s13569-019-0116-3. Full text in Research Archive Show summary

  <i>Background</i>: This study aims to explore how patients with metastatic gastrointestinal stromal tumour (GIST) experience the adverse efects of treatment, as expressed by the individuals themselves.<p> <p><i>Methods</i>: A qualitative, phenomenological and hermeneutic design was applied. Twenty patients with metastatic GIST participated in the study. In-depth and semi-structured interviews were conducted and then analysed by means of an inductive thematic analysis.<p> <p><i>Results</i>: The majority of participants reported experiencing a changed life after being diagnosed with metastatic GIST and commencing systemic medical treatment. More than half of them described partially debilitating self-reported side effects and complaints that had a detrimental impact on their lives. The life-prolonging tyrosine kinase inhibitor treatment prompted the participants to adapt to ‘a new normal’. Several participants also emphasised having an ambivalent relationship with the pill, although most looked upon it as ‘a friend’ because it kept them alive. Paradoxically, while the participants struggled with the side effects of treatment as well as the consequences of living with a chronic cancer, half of them considered themselves to be healthy and, thus, to not actually be cancer patients.<p> <p><i>Conclusions</i>: We observed a gap between the biomedical perspective on disease that health professionals typically adopt and the individual experiences of patients living with metastatic GIST. For those patients who are living in limbo between having metastatic cancer and offered an effective treatment, a holistic view of health on the part of their healthcare providers seems crucial. A vital goal should hence be to improve communication between healthcare professionals and GIST patients so as to secure an individualised follow-up with guidance on coping with, and adapting to, their new normal.

• Berner, Kjetil & Bruland, Øyvind (2019). Prognostic impact of proximal versus distal localization in extremity long bone osteosarcomas. Anticancer Research. ISSN 0250-7005. 39(5), p. 2459–2466. doi: 10.21873/anticanres.13365. Full text in Research Archive
• Jha, Anjani Kumar; Neupane, Pradeep; Pradhan, Manohar; Sharma, Krishna Sagar; Shrestha, Sadina & Sigdel, Padma Raj [Show all 8 contributors for this article] (2019). Ewing Sarcoma in Nepal Treated With Combined Chemotherapy and Definitive Radiotherapy. Journal of Global Oncology (JGO). 2019(5), p. 1–10. doi: 10.1200/JGO.19.00015. Full text in Research Archive Show summary

  To our knowledge, we conducted the first prospective oncologic clinical trial in Nepal aimed at providing state-of-the-art chemotherapy to patients with Ewing sarcoma. The efficacy of external-beam radiotherapy (RT) as the sole local treatment modality was explored and deemed justified as a result of the lack of available advanced tumor-orthopedic services in Nepal. PATIENTS AND METHODS Twenty patients, 11 female and 9 male patients between the ages of 6 and 37 years, with newly diagnosed Ewing sarcoma were enrolled. Neoadjuvant combination chemotherapy, comprising well-established drug combinations, was administered in five courses before external-beam RT, during which one course of etoposide and ifosfamide was given. After RT, six additional chemotherapy courses were scheduled. RT was tolerated well, providing rapid symptom relief and local tumor control, with no pathologic fractures observed among the 15 patients who received such treatment. Eleven patients completed the entire treatment protocol; seven patients were under continued follow-up, with no evidence of disease in six patients at a median follow-up time of 2.3 years (range, 1.3 to 3.1 years) and one patient alive but with a regional recurrence. Four patients experienced metastatic relapse and died as a result of their disease. Three treatment-related deaths linked to toxicity from chemotherapy occurred. Four of the six patients who refused to complete the treatment protocol and were lost to follow-up experienced progressive disease and were assumed dead. This study was feasible with RT as the sole local treatment modality in combination with chemotherapy. As a result of the high number of patients lost to follow-up, no firm conclusions can be drawn, but the majority of the patients who completed treatment obtained durable long-term remissions.

• Berner, Kjetil; Johannessen, Tom Børge; Hall, Kirsten Sundby & Bruland, Øyvind (2019). Clinical epidemiology and treatment outcomes of spindle cell non-osteogenic bone sarcomas - A nationwide population-based study. Journal of Bone Oncology. ISSN 2212-1366. 14. doi: 10.1016/j.jbo.2018.11.002. Full text in Research Archive Show summary

  Purpose: To describe epidemiological and clinical characteristics, as well as long-term treatment outcomes of spindle cell non-osteogenic bone sarcomas (SCS), comprising leiomyosarcoma, fibrosarcoma and undifferentiated pleomorphic sarcoma in bone. Method: We have analysed a nationwide cohort of 104 patients with histologically verified SCS diagnosed between 1975 and 2009, based on registry sources supplemented with clinical records from Norwegian hospitals involved in sarcoma management. Results: In this unselected cohort, a stable annual incidence for SCS patients of slightly below 0.6 per million was observed, with a dominant peak among elderly patients. SCS is mostly a high-grade malignancy (92%) with a male to female ratio of 1.6 for all patients. The axial to appendicular ratio was 0.7, seemingly independent of age. More than one fourth of the patients (29%) had primary metastatic disease. Another 32 patients (46%) developed metastases during follow-up and 12 (17%) experienced local relapses. The five-year sarcoma-specific survival rate was 37%, with no documented improvement over time. Primary metastatic disease was an adverse prognostic factor for survival. Predisposing factors were documented in 19 patients (18%). Negative prognostic factors for overall survival were tumour size >9 cm, age > 40 years, axial tumour localization, FS as subtype and pathologic fracture at time of diagnoses. As expected, patients who received both surgery and chemotherapy as their primary treatment for high-grade SCS (25%) significantly had best sarcoma specific five years survival (62%). Conclusion: We confirm SCS as a rare high-grade bone sarcoma entity, mostly among elderly patients and with a poor overall outcome. The combined treatment of surgery and chemotherapy is essential to achieve optimal long-term survival of SCS.

• Thorkildsen, Joachim; Taksdal, Ingeborg; Bjerkehagen, Bodil; Haugland, Hans Kristian; Johannessen, Tom Børge & Viset, Trond [Show all 9 contributors for this article] (2019). Chondrosarcoma in Norway 1990-2013; an epidemiological and prognostic observational study of a complete national cohort. Acta Oncologica. ISSN 0284-186X. 58, p. 273–282. doi: 10.1080/0284186X.2018.1554260. Full text in Research Archive Show summary

  Background: Knowledge of chondrosarcoma (CS) of bone to date is based on institutional reports and registry publications with limits in reporting, detail and quality of data. Method: We have performed a retrospective search of CS of bone in the National Cancer Registry in Norway from 1990-2013, cross checked against local tumor databases with further quality control and supplementation of all data from clinical files. The time period is defined by the routine use of axial imaging in clinical practice. 311 cases are included. We performed 108 pathological reviews and 223 radiological reviews. The manuscript is prepared according to the STROBE checklist for strengthening of observational studies. We perform uni-/multivariate cox analysis to define independent prognostic variables from the main cohort of central CS of bone. Results: The incidence of CS of bone in Norway is 2.85/million/yr. for both sexes overall, rising to 3.45/million/yr. in the last 5 year period. There is an increase in the most common central CS subtype, stronger for women than for men. Central CS has, in general 10-15% local recurrence rates, all evident by 5 years while metastasis rate increases with location and grade. Exceptions are extremity grade 1 CS which displayed no metastatic events and axial grade 3 disease with high rates (50%) of both local and metastatic relapse. Peripheral CS has limited metastatic potential (2%) but rates of local relapse (13%) continue to appear towards 10 years of follow up. Malignancy grade 3 independently predicts rate of metastasis and presence of soft tissue component predicts local recurrence, metastasis and survival. Conclusion: Rates of local recurrence, metastasis and disease specific survival follow clear patterns depending on subtype, location and grade allowing better tailoring of follow up regimes. Malignancy grade 3 and presence of a soft tissue component independently predict behaviour for central CS of bone.

• Köksal, Hakan; Müller, Elisabeth; Inderberg, Else Marit; Bruland, Øyvind & Wälchli, Sébastien (2019). Treating osteosarcoma with CAR T cells. Scandinavian Journal of Immunology. ISSN 0300-9475. 89:e12741(3), p. 1–8. doi: 10.1111/sji.12741. Full text in Research Archive Show summary

  Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5‐year survival as low as 5%‐10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T‐cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR‐T treatment in a solid tumour. We will discuss the experiences with CAR‐T therapy development and efficacy to combat the clinical challenges in OS.

• Heinrich, Daniel; Bruland, Øyvind; Guise, Theresa A.; Suzuki, Hiroyoshi & Sartor, Oliver (2018). Alkaline phosphatase in metastatic castration-resistant prostate cancer: Reassessment of an older biomarker. Future Oncology. ISSN 1479-6694. 14(24), p. 2543–2556. doi: 10.2217/fon-2018-0087. Full text in Research Archive
• Pedersen, Kjetil Boye; Berner, Jeanne-Marie; Hompland, Ivar; Bruland, Øyvind; Stoldt, Stephan & Hall, Kirsten Sundby [Show all 8 contributors for this article] (2018). Genotype and risk of tumour rupture in gastrointestinal stromal tumour. British Journal of Surgery. ISSN 0007-1323. 105(2), p. e169–e175. doi: 10.1002/bjs.10743. Full text in Research Archive
• Hall, Kirsten Sundby; Bruland, Øyvind; Bjerkehagen, Bodil; Zaikova, Olga; Engellau, Jacob & Hagberg, Oskar [Show all 15 contributors for this article] (2018). Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors—A Scandinavian Sarcoma Group study (SSG XX). European Journal of Cancer. ISSN 0959-8049. 99, p. 78–85. doi: 10.1016/j.ejca.2018.05.011. Full text in Research Archive
• Hompland, Ivar; Hølmebakk, Søren Torben; Pedersen, Kjetil Boye; Stoldt, Stephan; Bjerkehagen, Bodil & Berner, Jeanne-Marie [Show all 11 contributors for this article] (2018). Multimodal kreftbehandling av gastrointestinal stromal tumor. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(15). doi: 10.4045/tidsskr.18.0200. Full text in Research Archive
• Westrøm, Sara; Malenge, Marion Masitsa; Jorstad, Ida Sofie; Napoli, Elisa; Bruland, Øyvind & Bønsdorff, Tina Bjørnlund [Show all 7 contributors for this article] (2018). Ra-224 labeling of calcium carbonate microparticles for internal α-therapy: Preparation, stability, and biodistribution in mice. Journal of labelled compounds & radiopharmaceuticals. ISSN 0362-4803. 61(6), p. 472–486. doi: 10.1002/jlcr.3610. Full text in Research Archive Show summary

  Internal therapy with α‐emitters should be well suited for micrometastatic disease. Radium‐224 emits multiple α‐particles through its decay and has a convenient 3.6 days of half‐life. Despite its attractive properties, the use of 224Ra has been limited to bone‐seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224Ra on the particle surface, resulting in high labeling efficiencies for both 224Ra and daughter 212Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224Ra‐labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224Ra with increasing dose. The results altogether suggest that the 224Ra‐labeled CaCO3 microparticles have promising properties for use as a localized internal α‐therapy of cavitary cancers.

• Hølmebakk, Søren Torben; Hompland, Ivar; Bjerkehagen, Bodil; Stoldt, Stephan; Bruland, Øyvind & Hall, Kirsten Sundby [Show all 7 contributors for this article] (2018). Recurrence-free survival after resection of gastric gastrointestinal stromal tumors classified according to a strict definition of tumor rupture: a population-based study. Annals of Surgical Oncology. ISSN 1068-9265. 25(5), p. 1133–1139. doi: 10.1245/s10434-018-6353-5. Full text in Research Archive
• Parker, Christopher C.; Coleman, Robert Edward; Sartor, Oliver; Vogelzang, Nicholas J.; Bottomley, David & Heinrich, Daniel [Show all 29 contributors for this article] (2018). Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. European Urology. ISSN 0302-2838. 73(3), p. 353–360. doi: 10.1016/j.eururo.2017.06.021. Full text in Research Archive
• Westrøm, Sara; Bønsdorff, Tina Bjørnlund; Bruland, Øyvind & Larsen, Roy H. (2018). Therapeutic effect of α-emitting 224Ra-labeled calcium carbonate microparticles in mice with intraperitoneal ovarian cancer. Translational Oncology. ISSN 1944-7124. 11(2), p. 259–267. doi: 10.1016/j.tranon.2017.12.011. Full text in Research Archive Show summary

  BACKGROUND: Ovarian cancer patients with chemotherapy-resistant residual microscopic disease in the peritoneal cavity have a considerable need for new treatment options. Alpha-emitting radionuclides injected intraperitoneally may be an attractive therapeutic option in this situation as they are highly cytotoxic, while their short range in tissues can spare surrounding radiosensitive organs in the abdomen. Herein we evaluate the therapeutic efficacy of a novel α-emitting compound specifically designed for intracavitary radiation therapy. METHODS: The α-emitter 224Ra was absorbed on calcium carbonate microparticles. Immunodeficient, athymic nude mice with human ovarian cancer cells growing intraperitoneally were treated with different activity levels of 224Ra-microparticles. Tumor growth, survival, and tolerance of the treatment were assessed. Two tumor models based on the cell lines, ES-2 and SKOV3-luc, with different growth patterns were studied. RESULTS: In both models, intraperitoneal treatment with 224Ra-microparticles gave significant antitumor effect with either considerably reduced tumor volume or a survival benefit. An advantageous discovery was that only a few kilobecquerels per mouse were needed to yield therapeutic effects. The treatment was well tolerated up to a dose of 1000 kBq/kg with no signs of acute or subacute toxicity observed. CONCLUSIONS: Intraperitoneal α-therapy with 224Ra-microparticles demonstrated a significant potential for treatment of peritoneal micrometastases in ovarian carcinoma.

• Hesla, Asle Charles; Bruland, Øyvind; Jebsen, Nina Louise; Styring, Emelie; Eriksson, Sigvard & Tsagozis, Panagiotis (2018). Ewing sarcoma of the mobile spine; predictive factors for survival, neurological function and local control. A Scandinavian sarcoma group study with a mean follow-up of 12 years. Journal of Bone Oncology. ISSN 2212-1366. 14, p. 1–9. doi: 10.1016/j.jbo.2018.100216. Full text in Research Archive
• Sartor, Oliver; Coleman, Robert Edward; Nilsson, Sten; Heinrich, Daniel; Helle, Svein Inge & O'Sullivan, Joe M. [Show all 14 contributors for this article] (2017). An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. Annals of Oncology. ISSN 0923-7534. 28(5), p. 1090–1097. doi: 10.1093/annonc/mdx044. Full text in Research Archive
• Hompland, Ivar; Bruland, Øyvind; Hølmebakk, Søren Torben; Poulsen, Jan Peter; Stoldt, Stephan & Hall, Kirsten Sundby [Show all 7 contributors for this article] (2017). Prediction of long-term survival in patients with metastatic gastrointestinal stromal tumor: analysis of a large, single-institution cohort. Acta Oncologica. ISSN 0284-186X. 56(10), p. 1317–1323. doi: 10.1080/0284186X.2017.1330555. Full text in Research Archive
• Barøy, Tale; Chilamakuri, Chandra Sekhar Reddy; Lorenz, Susanne; Sun, Jinchang; Bruland, Øyvind & Myklebost, Ola [Show all 7 contributors for this article] (2016). Genome analysis of osteosarcoma progression samples identifies FGFR1 overexpression as a potential treatment target and CHM as a candidate tumor suppressor gene. PLOS ONE. doi: 10.1371/journal.pone.0163859. Full text in Research Archive
• König, Marton Skog Steinberger; Osnes, Terje; Lobmaier, Ingvild Victoria Koren; Bjerkehagen, Bodil; Bruland, Øyvind & Hall, Kirsten Sundby [Show all 7 contributors for this article] (2016). Multimodal treatment of craniofacial osteosarcoma with high-grade histology. A single-center experience over 35 years. Neurosurgical review. ISSN 0344-5607. p. 1–12. doi: 10.1007/s10143-016-0802-z. Full text in Research Archive Show summary

  High-grade craniofacial osteosarcoma (CFOS) is an aggressive malignancy with a poor prognosis. Our goals were to evaluate treatment outcomes in those treated at a single referral institution over 35 years and to compare our results to the available literature. A retrospective analysis of all 42 patients treated between 1980 and 2015 at Oslo University Hospital, Norway, identified in a prospectively collected database, was conducted. Mean follow-up was 79.6 months. Overall survival at 2 and 5 years was 70.5 and 44.7%, respectively. The corresponding disease-specific survival rates were 73.0 and 49.8%. Treatment was surgery only in eight cases. Additional therapy was administered in 34 patients: chemotherapy in nine, radiotherapy in seven, and a combination of these in 18 cases. Stratified analysis by resection margins demonstrated significantly better survival at 2 and 5 years after radical surgical treatment. Neoadjuvant chemotherapy and subsequent adequate surgery resulted in better survival than surgery alone. Half of the patients either had a primary or familial cancer predisposition. This is the largest single-center study conducted on high-grade CFOS to date. Our experience indicates that neoadjuvant chemotherapy with complete surgical resection significantly improved survival, compared to surgery alone.

• Parker, Christopher; Finkelstein, Steven E.; Michalski, Jeff M.; O'Sullivan, Joe M.; Bruland, Øyvind & Vogelzang, Nicholas J. [Show all 12 contributors for this article] (2016). Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial. European Urology. ISSN 0302-2838. 70(5), p. 875–883. doi: 10.1016/j.eururo.2016.06.002. Full text in Research Archive
• Hompland, Ivar; Bruland, Øyvind; Ubhayasekhera, Kumari; Bergquist, Jonas & Boye, Kjetil (2016). Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour. Clinical Sarcoma Research. 6(21). doi: 10.1186/s13569-016-0062-2. Full text in Research Archive
• Westrøm, Sara; Bønsdorff, Tina B; Abbas, Nasir; Bruland, Øyvind; Jonasdottir, Thora J & Mælandsmo, Gunhild [Show all 7 contributors for this article] (2016). Evaluation of CD146 as target for radioimmunotherapy against Osteosarcoma. PLOS ONE. 11(10). doi: 10.1371/journal.pone.0165382. Full text in Research Archive
• Varghese, Mercy; Bruland, Øyvind; Wiedswang, Anne Marit; Lobmaier, Ingvild Victoria Koren; Røsok, Bård Ingvald & Benjamin, Robert [Show all 7 contributors for this article] (2016). Metastatic mesenteric dedifferentiated leiomyosarcoma: a case report and a review of literature. Clinical Sarcoma Research. 6(2). doi: 10.1186/s13569-016-0042-6. Full text in Research Archive
• Hølmebakk, Søren Torben; Bjerkehagen, Bodil; Pedersen, Kjetil Boye; Bruland, Øyvind; Stoldt, Stephan & Hall, Kirsten Sundby (2016). Definition and clinical significance of tumour rupture in gastrointestinal stromal tumours of the small intestine. British Journal of Surgery. ISSN 0007-1323. 103(6), p. 684–691. doi: 10.1002/bjs.10104. Full text in Research Archive
• Humm, John L.; Sartor, Oliver; Parker, Chris; Bruland, Øyvind & Macklis, Roger (2015). Radium-223 in the treatment of osteoblastic metastases: A critical clinical review. International Journal of Radiation Oncology, Biology, Physics. ISSN 0360-3016. 91(5), p. 898–906. doi: 10.1016/j.ijrobp.2014.12.061. Full text in Research Archive
• Fauske, Lena; Bruland, Øyvind; Grov, Ellen Karine & Bondevik, Hilde (2015). Cured of Primary Bone Cancer, But at What Cost: A Qualitative Study of Functional Impairment and Lost Opportunities. Sarcoma. ISSN 1357-714X. 2015. doi: 10.1155/2015/484196. Full text in Research Archive Show summary

  Purpose. Our study aims to explore how former cancer patients experience physical and psychosocial late effects 3–7 years after they underwent treatment for primary bone sarcoma in the hip/pelvic region. A qualitative, phenomenological, and hermeneutic design was applied. Methods. Sarcoma survivors () previously treated at Oslo University Hospital, Norwegian Radium Hospital were selected to participate. In-depth and semistructured interviews were conducted. The interviews were analysed using inductive thematic analysis. Results. The participants reported that the late effects had three core spheres of impact: “their current daily life,” “their future opportunities,” and “their identity.” They expressed negative changes in activity, increased dependence on others, and exclusion from participation in different areas. Their daily life, work, sports activities, and social life were all affected. Several of their experiences are similar to those described by people with functional impairment or disability. Conclusion. Patients cured of bone cancer in the hip/pelvic region pay a significant price in terms of functional impairment, practical challenges, exclusion from important aspects of life, and loss of previous identity. It is important to appreciate this in order to help bone cancer survivors who struggle to reorient their life and build a secure new identity.

• Hompland, Ivar & Bruland, Øyvind (2015). Can imatinib be safely withdrawn in patients with surgically resected metastatic GIST? Anticancer Research. ISSN 0250-7005. 35(11), p. 5759–5765. Full text in Research Archive
• Fauske, Lena; Bondevik, Hilde; Bruland, Øyvind & Ozakinci, Gozde (2015). Negative and Positive Consequences of Cancer Treatment Experienced by Long-term Osteosarcoma Survivors: A Qualitative Study. Anticancer Research. ISSN 0250-7005. 35(11), p. 6081–6090. Full text in Research Archive
• Anfinsen, Kristin Paaske; Grotmol, Tom; Bruland, Øyvind & Jonasdottir, Thora Johanna (2015). Primary bone cancer in Leonbergers may be associated with a higher bodyweight during adolescence. Preventive Veterinary Medicine. ISSN 0167-5877. 119(1-2), p. 48–53. doi: 10.1016/j.prevetmed.2015.02.003. Full text in Research Archive
• Berner, Kjetil; Johannessen, Tom Børge & Bruland, Øyvind (2015). Clinical epidemiology of low-grade and dedifferentiated osteosarcoma in Norway during 1975 and 2009. Sarcoma. ISSN 1357-714X. 2015:917679. doi: 10.1155/2015/917679. Full text in Research Archive Show summary

  Purpose. To describe epidemiological, clinical characteristics and treatment outcomes of low-grade osteosarcoma (LGOS), including dedifferentiated osteosarcoma (DLGOS). Method. We analysed a nationwide cohort comprised of patients with histologically verified LGOS and DLGOS between 1975 and 2009, based on registry sources supplemented with clinical records from hospitals involved in sarcoma management. Results. Fifty-four patients were identified, 12 of whom had DLGOS. The annual incidence for all patients was 0.3 per million, with the peak incidence in the third decade of the life. Fifteen patients experienced local relapses during follow-up and ten developed metastatic diseases, including three at primary diagnosis. Patients with DLGOS dominated the metastatic relapse group. The five-year sarcoma-specific survival rate was 91%, with no documented improvement over time. Free margin following surgical resection of the primary tumour had a positive impact on survival. As expected, both local relapse and metastasis during follow-up were associated with an unfavourable outcome. Radiotherapy predicted poor survival due to the selection of high-risk patients in need of such treatment. Neither higher age nor axial tumour localisation was adverse prognostic factors. Conclusion. LGOS has an excellent prognosis when surgically resected with a free margin; however, LGOS has the potential to dedifferentiate and metastasize with a poor outcome.

• Berner, Kjetil; Bjerkehagen, Bodil; Bruland, Øyvind & Berner, Aasmund (2015). Extraskeletal osteosarcoma in Norway, between 1975 and 2009, and a brief review of the literature. Anticancer Research. ISSN 0250-7005. 35(4), p. 2129–2140. Full text in Research Archive
• Berner, Kjetil; Hall, Kirsten Sundby; Monge, Odd R; Weedon-Fekjær, Harald; ZAIKOVA, OLGA & Bruland, Øyvind (2015). Prognostic factors and treatment results of high-grade osteosarcoma in Norway: A scope beyond the "classical" patient. Sarcoma. ISSN 1357-714X. 2015. doi: 10.1155/2015/516843. Full text in Research Archive Show summary

  Purpose. A retrospective study of prognostic factors and treatment outcome of osteosarcoma (OS) during modern chemotherapy era with focus on patients with primary metastatic disease, nonextremity localisation, or age >40 years (nonclassical OS). Methods. A nationwide cohort, comprising 424 high-grade Norwegian bone OS patients, was based on registry sources supplemented with clinical records from hospitals involved in sarcoma management between 1975 and 2009. Results. Only 48% were younger patients with tumour in the extremities and without metastasis at diagnosis (classical OS). A considerable discrepancy in survival between classical and nonclassical OS was observed: 61% versus 26% 10-year sarcoma specific survival. Twice as many of the former received both adequate surgery and chemotherapy compared to the latter. This could only partly explain the differences in survival due to inherent chemoresistance in primary metastatic disease and a higher rate of local relapse among patients with axial tumours. Metastasis at diagnosis, increased lactate dehydrogenase, age > 40 years, and tumour size above median value were all adverse prognostic factors for overall survival. Conclusion. We confirm a dramatic difference in outcome between classical and nonclassical high-grade OS patients, but treatment variables could only partly explain the dismal outcome of the latter.

• Berner, Kjetil; Johannesen, Tom Børge; Berner, Aasmund; Haugland, Hans Kristian; Bjerkehagen, Bodil & Bøhler, Per J. [Show all 7 contributors for this article] (2015). Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma. Acta Oncologica. ISSN 0284-186X. 54(1), p. 25–33. doi: 10.3109/0284186X.2014.923934. Full text in Research Archive
• Juzeniene, Asta; Porojnicu, Alina Carmen; Baturaite, Zivile; Lagunova, Zoya; Aksnes, Lage & Bruland, Øyvind [Show all 7 contributors for this article] (2015). Vitamin D levels and dietary intake among patients with benign soft tissue tumors and sarcomas. Anticancer Research. ISSN 0250-7005. 35(2), p. 1171–1180. Full text in Research Archive
• Juzeniene, Asta; Baturaite, Zivile; Lagunova, Zoya; Grigalavicius, Mantas; Porojnicu, Alina Carmen & Bruland, Øyvind [Show all 7 contributors for this article] (2015). Influence of multiple UV exposures on serum cobalamin and vitamin D levels in healthy females. Scandinavian Journal of Public Health. ISSN 1403-4948. 43(3), p. 324–330. doi: 10.1177/1403494815572206. Full text in Research Archive
• Repetto-Llamazares, Ada H.V.; Larsen, Roy H.; Giusti, Anna Maria; Riccardi, Elena; Bruland, Øyvind & Selbo, Pål Kristian [Show all 7 contributors for this article] (2014). 177 Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: A study of toxicity in nude mice. PLOS ONE. 9(7). doi: 10.1371/journal.pone.0103070. Full text in Research Archive Show summary

  Background CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studieswith 177Lu-HH1. Methodology/Principal Findings Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. Conclusions/Significance 177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

• Repetto-Llamazares, Ada H.V.; Abbas, Nasir; Bruland, Øyvind; Dahle, Jostein & Larsen, Roy H. (2014). Advantage of lutetium-177 versus radioiodine immunoconjugate in targeted radionuclide therapy of B-cell tumors. Anticancer Research. ISSN 0250-7005. 34(7), p. 3263–3269. Full text in Research Archive
• Ohnstad, Hege Oma; Bruland, Øyvind; Taksdal, Ingeborg; Bjerkehagen, Bodil; Nenadovic, Maja & Sæter, Gunnar [Show all 8 contributors for this article] (2014). Response to preoperative chemotherapy in patients undergoing resection of pulmonary metastasis from soft tissue sarcoma - A predictor of outcome? Acta Oncologica. ISSN 0284-186X. 53(9), p. 1180–1187. doi: 10.3109/0284186X.2014.899433. Full text in Research Archive
• Sartor, Oliver; Coleman, Robert; Nilsson, Sten; Heinrich, Daniel; Helle, Svein Inge & O'Sullivan, Joe M. [Show all 21 contributors for this article] (2014). Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: Results from a phase 3, double-blind, randomised trial. The Lancet Oncology. ISSN 1470-2045. 15(7), p. 738–746. doi: 10.1016/S1470-2045(14)70183-4. Full text in Research Archive
• Switlyk, Marta Daniela; Bruland, Øyvind; Skjeldal, Sigmund; Hald, John K; Seierstad, Therese & ZAIKOVA, OLGA (2014). Radiotherapy for spinal metastases from breast cancer with emphasis on local disease control and pain response using repeated MRI. Journal of Bone Oncology. ISSN 2212-1366. 3, p. 5–9. doi: 10.1016/j.jbo.2014.02.003. Full text in Research Archive Show summary

  Aims To evaluate metastatic lesions within the radiation field using repeated magnetic resonance imaging (MRI) and to compare the imaging findings with pain response following radiotherapy (RT) in patients with spinal metastases (SM) from breast cancer. Material and methods 32 Patients with SM from breast cancer admitted for fractionated RT were included in this study. MRI examinations of the spine were scored for the extent of bone metastases, epidural disease and the presence and severity of vertebral fractures. Clinical response was defined according to the updated international consensus on palliative RT endpoints. Results At 2 and 6 months after RT, 38% and 44% of the patients were classified as responders. None of the patients developed motor deficits. Importantly, a decrease in the intraspinal tumor volume after RT was reported in all patients. Only 6% of the patients showed bone metastases progression within the RT field, whereas 60% of the patients showed disease progression outside the RT portals. 5 Patients developed new fractures after RT, and fracture progression was observed in 21 of the 38 lesions (55%). The pain response to RT did not correlate with the presence of vertebral body fracture before RT, fracture progression or other recorded MRI features of metastatic lesions. Conclusion RT provided excellent local tumor control in patients with SM. Most patients benefit from RT even in cases of progressive vertebral fracture. Pain response was not associated with imaging findings and MRI cannot be used to select patients at risk of not responding to RT.

• Bjerkehagen, Bodil; Småstuen, Milada C; Hall, Kirsten Sundby; Skjeldal, Sigmund; Bruland, Øyvind & Smeland, Sigbjørn [Show all 8 contributors for this article] (2013). Incidence and mortality of second sarcomas – A population-based study. European Journal of Cancer. ISSN 0959-8049. 49(15), p. 3292–3302. doi: 10.1016/j.ejca.2013.05.017. Full text in Research Archive
• Rusten, Espen; Rødal, Jan; Revheim, Mona Elisabeth; Skretting, Arne; Bruland, Øyvind & Malinen, Eirik (2013). Quantitative dynamic 18 FDG-PET and tracer kinetic analysis of soft tissue sarcomas. Acta Oncologica. ISSN 0284-186X. 52(6), p. 1160–1167. doi: 10.3109/0284186X.2012.728713. Full text in Research Archive
• Revheim, Mona Elisabeth; Kristian, Alexandr; Malinen, Eirik; Bruland, Øyvind; Berner, Jeanne-Marie & Holm, Ruth [Show all 8 contributors for this article] (2013). Intermittent and continuous imatinib in a human GIST xenograft model carrying KIT exon 17 resistance mutation D816H. Acta Oncologica. ISSN 0284-186X. 52(4), p. 776–782. doi: 10.3109/0284186X.2013.770920. Full text in Research Archive
• Lia, K.; Bruland, Øyvind; Randem, H.L.; Aksnes, Liv Hege; Poulsen, Jan Peter & Taksdal, Ingeborg [Show all 7 contributors for this article] (2013). Two cases with fatal outcome following total lung irradiation for metastatic bone sarcoma. Journal of Bone Oncology. ISSN 2212-1366. 2(4), p. 174–179. doi: 10.1016/j.jbo.2013.09.002. Full text in Research Archive

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• Juzeniene, Asta; Baum, Richard Paul; Bruland, Øyvind & Larsen, Roy (2023). Targeted Alpha Particle Therapy in Oncology. Frontiers in Medicine. ISBN 9782832519837. 186 p. Full text in Research Archive

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• Ondrckova, Camilla; Bruland, Øyvind; Tasken, Kjetil & REvheim, Mona E (2023). 15 millioner til forskningsprosjekt: - Bare starten på et kjempestort kapittel innen kreftbehandling. [Internet]. Dagen Medisin. Full text in Research Archive
• Bruland, Øyvind; Larsen, Roy Hartvig; Baum, Richard Paul & Juzenienne, Asta (2023). Editorial: Targeted alpha particle therapy in oncology. Frontiers in Medicine. 10. doi: 10.3389/fmed.2023.1165747. Full text in Research Archive
• Herlofson, Bente Brokstad; Kjølle, Gry Karina; Westgaard, Kristine Løken; Løndalen, Ayca & Bruland, Øyvind (2018). Osteonecrosis of the jaw in a patient with bone metastatic prostate cancer after long-term bisphosphonate treatment with severe deterioration following radium-223. Clinical Genitourinary Cancer. ISSN 1558-7673. p. 1–4. doi: 10.1016/j.clgc.2018.05.003. Full text in Research Archive
• Berner, Kjetil; Zaikova, Olga; Johannessen, Tom Børge; Hall, Kirsten Sundby & Bruland, Øyvind (2018). Validity and completeness of the Scandinavian Sarcoma Group Central Register by comparison with a nationwide cohort of patients with osteosarcoma in Norway. Journal of Surgical Oncology. ISSN 0022-4790. 118(1), p. 246–247. doi: 10.1002/jso.25137. Full text in Research Archive
• König, Marton Skog Steinberger; Osnes, Terje; Lobmaier, Ingvild Victoria Koren; Bjerkehagen, Bodil; Bruland, Øyvind & Hall, Kirsten Sundby [Show all 7 contributors for this article] (2016). Craniofacial Osteosarcoma: A Single-Institution Experience. Full text in Research Archive
• König, Marton Skog Steinberger; Osnes, Terje; Lobmaier, Ingvild Victoria Koren; Bjerkehagen, Bodil; Bruland, Øyvind & Hall, Kirsten Sundby [Show all 7 contributors for this article] (2016). Treatment of Craniofacial Osteosarcoma: a Multidisciplinary Approach. Full text in Research Archive
• Anfinsen, Kristin Paaske; Grotmol, Tom; Bruland, Øyvind; Trangerud, Cathrine & Jonasdottir, Thora Johanna (2015). Corrigendum to "Primary bone cancer in Leonbergers may be associated with a higher bodyweight during adolescence" [Prev. Vet. Med. 119 (2015) 48-53]. Preventive Veterinary Medicine. ISSN 0167-5877. 120(2), p. 252–252. doi: 10.1016/j.prevetmed.2015.03.015. Full text in Research Archive
• Westrøm, Sara; Abbas, Nasir; Larsen, Roy Hartvig; Bruland, Øyvind; Jonasdottir, Thora Johanna & Bønsdorff, Tina Bjørnlund (2014). Initial evaluation of a CD146/MUC18 targeting radioimmunoconjugate. Full text in Research Archive
• Revheim, Mona Elisabeth; Hole, Knut Håkon; Bruland, Øyvind; Reitan, Edmund; Bjerkehagen, Bodil & Julsrud, Lars [Show all 7 contributors for this article] (2014). Multimodal functional imaging for early response assessment in GIST patients treated with imatinib. Acta Oncologica. ISSN 0284-186X. 53(1), p. 143–148. doi: 10.3109/0284186X.2013.798428. Full text in Research Archive

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