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• Heggebø, Liv Cathrine; Fjæra, Lars Fredrik; Garrote, Frank Leonel Bello; Borgen, Ida Maria Henriksen; Blakstad, Hanne Kristin & Hellebust, Taran Annette Paulsen [Show all 14 contributors for this article] (2026). Case Report: Proton beam therapy – friend or foe for patients with IDH-mutated WHO grade 2 and 3 gliomas? Frontiers in Oncology. 16. doi: 10.3389/fonc.2026.1803943. Full text in Research Archive
• Heggebø, Liv Cathrine; Hellebust, Taran Annette Paulsen; Henry, Thomas; Fjæra, Lars Fredrik; Ottestad, Andreas & Rylander, Hillevi [Show all 36 contributors for this article] (2026). Radiotherapy quality assurance in the PRO-GLIO trial: results from a dummy run comparing experts across twelve institutions in two Scandinavian countries. Clinical and Translational Radiation Oncology. 60. doi: 10.1016/j.ctro.2026.101220. Full text in Research Archive
• Huynh, Bao Ngoc; Futsæther, Cecilia Marie; Tomic, Oliver; Liland, Kristian Hovde; Kakar, Manish & Hellebust, Taran Annette Paulsen [Show all 9 contributors for this article] (2026). Direct integration of deep learning–based GTV auto-segmentation into a clinical radiotherapy planning system. Physics and imaging in radiation oncology (PIRO). 38. doi: 10.1016/j.phro.2026.100962. Full text in Research Archive Show summary

  Manual Gross Tumor Volume (GTV) delineation for radiotherapy is time‑consuming and prone to inter‑observer variability. Deep Learning (DL)-based auto‑segmentation offers faster and more consistent solutions, but translation into clinical practice remains limited. This study aimed to bridge this gap by integrating an in‑house GTV auto‑segmentation DL model into a radiotherapy Treatment Planning System (TPS). To demonstrate the integration process, a head‑and‑neck GTV segmentation model was successfully deployed and operated seamlessly within the TPS. In this integration, DL‑generated GTV contours were produced in under three minutes, demonstrating the feasibility of DL‑based GTV segmentation in the TPS without disrupting the radiotherapy workflow.

• Vijande, Javier; Johansen, Jacob G.; Brabandere, Marisol De; Hellebust, Taran Annette Paulsen; Herreros, Antonio & Kirisits, Christian [Show all 13 contributors for this article] (2025). Temporal drift in calibration of Ir-192 brachytherapy sources: A multi-center study on dosimetric discrepancies and metrological consistency. Physics and imaging in radiation oncology (PIRO). 35. doi: 10.1016/j.phro.2025.100801. Full text in Research Archive
• Ryg, Una; Lilleby, Wolfgang; Nilsen, Line Brennhaug; Hellebust, Taran Annette Paulsen; Seierstad, Therese & Hole, Knut Håkon (2025). Image-Based Recurrence Patterns After Reirradiation in Prostate Cancer with Long-Term Follow-Up. Advances in Radiation Oncology. ISSN 2452-1094. 10(12). doi: 10.1016/j.adro.2025.101900. Full text in Research Archive Show summary

  Purpose Local failure of prostate cancer after definitive radiation therapy is associated with poor prognosis. Studies on reirradiation have primarily focused on toxicity and oncologic outcome and only partially reported recurrence patterns. Investigating the recurrence pattern may help guide future therapy decisions. Methods and Materials Thirty-three men with local recurrence of prostate cancer after primary definitive radiation therapy were enrolled between 2012 and 2018 (median age 69.8 years [IQR: 6.8], median prostate-specific antigen 4.1 ng/mL [IQR: 3.8]). Twenty-three patients received reirradiation with focal high dose-rate brachytherapy, and 10 received stereotactic body radiation therapy to the prostate with (8/10) or without (2/10) a simultaneous integrated boost to the recurrent tumor. The sites of recurrences were examined with multiparametric magnetic resonance imaging and compared with the dose distribution maps. Results During the median 99 months (IQR: 56) follow-up, 25 patients had biochemical rerecurrence. Twenty had adequate imaging. Five patients had rerecurrences solely inside the high-dose region, and 7 had both inside and outside the high-dose region. Two patients with a prostatic recurrence received whole-gland stereotactic body radiation therapy without a boost to the tumor. Four had a combination of rerecurrence within the prostate as well as regional lymph node metastases. One patient had a prostatic rerecurrence and a single bone metastasis. One patient had prostatic rerecurrence, lymph node metastases, and bone metastases. No patients had only regional or distant metastases. Conclusions After reirradiation of prostate cancer, the tumor frequently recurred within the prostate, both inside and outside the high-dose region. About 1 in 3 patients also had regional or distant metastatic disease at rerecurrence.

• Svestad, Jørund Graadal; Mikalsen, Stine Gyland; Heydari, Mojgan; Francke, Regine Hjort; Hervani, Maziar & Hellebust, Taran Annette Paulsen (2025). Setup Accuracy and Efficiency of Real-Time Video Assistance for Surface-Guided Positioning in Radiation Therapy of Right-Sided Locoregional Breast Cancer. Advances in Radiation Oncology. ISSN 2452-1094. 10(9). doi: 10.1016/j.adro.2025.101829. Full text in Research Archive
• Heggebø, Liv Cathrine; Garrote, Frank Leonel Bello; Fjæra, Lars Fredrik; Hervani, Maziar; Ramberg, Christina & Ottestad, Andreas [Show all 14 contributors for this article] (2025). Protons or Photons in Pituitary Neuroendocrine Tumors—That Is Not the Question. International Journal of Particle Therapy (IJPT). 17. doi: 10.1016/j.ijpt.2025.101194. Full text in Research Archive Show summary

  Purpose With the long-life expectancy of patients with pituitary neuroendocrine tumors (PitNETs), reducing long-term toxicity is essential to preserve quality of life. We aimed to investigate whether 2- or 3-field proton beam therapy (PBT) plans better spare organs at risks (OARs), including healthy tissue, than volumetric modulated arc photon therapy (VMAT). Materials and Methods Fifteen consecutive patients who had received radiation therapy for PitNETs were included. We made 4 treatment plans for each patient: one 3-field PBT plan (3F), two 2-field PBT plans (2F-L and 2F-IV), and 1 VMAT plan. Dosing was set to 1.8 Gy × 30 to allow for dosimetric comparisons. Results All 4 treatment techniques showed excellent target volume coverage. Compared to VMAT, the 3 PBT techniques had lower doses to OARs. Median D40% to the hippocampi varied from 0.4 to 1.1 Gy (relative biological effectiveness [RBE]) with PBT and was 5.2 Gy for both hippocampi for VMAT. Median mean dose to brain-CTV and head-CTV were lowest for 2F-L (3.1 and 2.3 Gy [RBE]), followed by 3F (3.9 and 2.5 Gy [RBE]), 2F-IV (4.1 and 2.6 Gy [RBE]), and highest for VMAT (4.8 and 4.7 Gy). A relative reduction in integral dose compared to VMAT was seen for all PBT techniques, with a median reduction of 38.5% to 45.9% for head-CTV. Conclusion Proton techniques spared OARs better than VMAT; however, absolute dose sparing was relatively small, and the clinical value remains uncertain. Nonetheless, the dose reduction, especially for the hippocampi and integral dose, is probably clinically meaningful. We argue that head-CTV should be assessed, as much of the volume receiving dose is located outside the brain. The size and location of the target volume impacted which proton plan was preferable. We conclude that individualized planning is more important than a mere question on protons or photons in PitNET patients.

• Skipar, Kjersti Øvrum; Hompland, Tord; Lund, Kjersti Vassmo; Fjeldbo, Christina Sæten; Lindemann, Kristina Yvonne Kathe & Hellebust, Taran Annette Paulsen [Show all 8 contributors for this article] (2025). Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study. Acta Oncologica. ISSN 0284-186X. 64, p. 439–447. doi: 10.2340/1651-226X.2025.43045. Full text in Research Archive Show summary

  Background and purpose: Locally advanced cervical cancer is treated with chemoradiotherapy. The treatment-related morbidity is high. Tumor hypoxia has prognostic impact and represents a valid, interventional target. This phase II study investigated efficacy of the antidiabetic drug metformin to modify hypoxia according to established biomarkers. Preliminary results including tolerability, safety and feasibility are reported here. Patients and methods: Patients were included in a 1:1 randomized, open-label design, comparing standard chemoradiotherapy ± metformin. Metformin 850 mg twice daily was administered 1 week before and during chemoradiotherapy. Magnetic resonance images (MRI) and tumor biopsies were collected at baseline, after 1 week of metformin treatment, and at brachytherapy for biomarker assessments. Tolerability and safety were determined by treatment completion rates and frequency of adverse events (AEs). Safety was further evaluated by possible increase in MRI-based hypoxia during the first week of metformin. Feasibility was determined by proportion of completed study interventions and imaging and biopsy procedures. Results: In total, 18 and 23 patients were allocated to the intervention and control arm, respectively. Eighteen and 15 patients completed metformin treatment for 1 and 5 weeks. Frequency of AEs ≥ grade 3 was not significantly different between study arms. Most AEs were gastrointestinal toxicities. Tumors with increase in hypoxia during the first week were all below the defined safety limit. A total of 98% of scheduled MR series and biopsies were collected with satisfactory quality. Interpretation: Addition of metformin to chemoradiotherapy is tolerable and safe. Serial sampling of MRI and tumor biopsies for hypoxia biomarker assessment is feasible.

• Stewart, A.J.; Chargari, C.; Chyrek, A.; Eckert, F.; Guinot, J.L. & Hellebust, Taran Annette Paulsen [Show all 15 contributors for this article] (2025). Radiobiology and modelling in Brachytherapy: A review inspired by the ESTRO Brachytherapy pre-meeting course. Clinical and Translational Radiation Oncology. 50. doi: 10.1016/j.ctro.2024.100885. Full text in Research Archive
• Wedde, Trude Baastad; Hagen, Milada; Vatne, Kari; Nilsen, Line; Hellebust, Taran Annette Paulsen & Lilleby, Wolfgang (2025). Patient-reported long-term sexual morbidity in prostate cancer survivors treated with external beam radiation therapy alone or combined with high-dose-rate brachytherapy. Scandinavian Journal of Urology. ISSN 2168-1805. 60, p. 14–22. doi: 10.2340/sju.v60.42165. Full text in Research Archive
• Skipar, Kjersti Øvrum; Hompland, Tord; Lund, Kjersti Vassmo; Lindemann, Kristina Yvonne Kathe; Hellebust, Taran Annette Paulsen & Bruheim, Kjersti [Show all 7 contributors for this article] (2024). MRI-guided dynamic risk assessment in cervical cancer based on tumor hypoxia at diagnosis and volume response at brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 195, p. 1–7. doi: 10.1016/j.radonc.2024.110263. Full text in Research Archive Show summary

  Background and purpose: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification. Material and methods: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HFpre) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HFpre. In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. C

• Huynh, Thuy-Tien Maria; Falk, Ragnhild Sørum; Hellebust, Taran Annette Paulsen; Dale, Einar; Astrup, Guro Lindviksmoen & Hjermstad, Marianne Jensen [Show all 12 contributors for this article] (2024). Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy. Radiotherapy and Oncology. ISSN 0167-8140. 195. doi: 10.1016/j.radonc.2024.110231. Full text in Research Archive Show summary

  Background There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). Material and methods In this cross-sectional study we included HNC survivors treated in 2007–2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen’s effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. Results The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82–6.31), comorbidity (OR 2.17, 95 % CI 1.20–3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16–3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. Conclusions CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.

• Chen, Zhe; Li, X. Allen; Brenner, David J.; Hellebust, Taran Annette Paulsen; Hoskin, Peter & Joiner, Michael C. [Show all 11 contributors for this article] (2024). AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy. Medical Physics. ISSN 0094-2405. doi: 10.1002/mp.17062. Full text in Research Archive
• Johansen, J.G.; Jürgenliemk-Schulz, I.M.; Haddad, H.; Hannoun-Levi, J.M.; Hellebust, Taran Annette Paulsen & Guix, B. [Show all 17 contributors for this article] (2024). The current status of brachytherapy in Europe − A GEC-ESTRO Brachy-HERO survey. Clinical and Translational Radiation Oncology. 50. doi: 10.1016/j.ctro.2024.100883. Full text in Research Archive
• Os, Silje Skjelsvik; Skipar, Kjersti Øvrum; Skovlund, Eva; Hompland, Ivar; Hellebust, Taran Annette Paulsen & Guren, Marianne [Show all 8 contributors for this article] (2024). Survival prediction in patients with gynecological cancer irradiated for brain metastases. Acta Oncologica. ISSN 0284-186X. 63, p. 206–212. doi: 10.2340/1651-226X.2023.34899. Full text in Research Archive Show summary

  ackground and purpose: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers. Material and methods: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS. Results: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001), Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively. Interpretation: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

• Gullhaug, Anna; Haakensen, Vilde Drageset; Ruysscher, Dirk De; Simone, Charles B.; Hotca-Cho, Alexandra E. & Chhabra, Arpit M. [Show all 10 contributors for this article] (2024). Lung cancer reirradiation: Exploring modifications to utilization, treatment modalities and factors associated with outcomes. Journal of Medical Imaging and Radiation Sciences. ISSN 1939-8654. 55(2), p. 221–231. doi: 10.1016/j.jmir.2024.02.004. Full text in Research Archive Show summary

  Background: Patients treated for lung cancer (LC) often experience locoregional failure after initial treatment. Due to technological advances, thoracic reirradiation (re-RT) has become a viable treatment option. We sought to investigate the use of thoracic re-RT in LC patients over a time period characterized by technological advances in a large, multi-center cohort.<p> <p>Methods and materials: LC patients treated with thoracic re-RT in two University Hospitals from 2010-2020 were identified. Clinical variables and RT data were extracted from the medical records and treatment planning systems. Overall survival (OS) was calculated from the last day of re-RT until death or last follow up. <p>Results: 296 patients (small cell LC n=30, non-small cell LC n=266) were included. Three-dimensional conformal radiation therapy was the RT technique used most frequently (63%), and 86% of all patients were referred for re-RT with palliative treatment intent. During the second half of the study period, the use of thoracic re-RT increased in general, more patients received curativere-RT, and there was an increased use of stereotactic body radiation therapy (SBRT). Median time between initial RT and re-RT was 18 months (range 1-213 months). Only 83/296 patients had combined treatment plans that allowed for registration of combined doses to organs at risk (OAR). Most of the combined doses to OAR were below recommendations from guidelines. Multivariate analysis showed superior OS (p<0.05) in patients treated with curative intent, SBRT or intensity modulated radiation therapy or had excellent performance status prior to re-RT. <p>Conclusions: The use of re-RT increased in the second half of the study period, although 2020 did not follow the trend. The use of SBRT and IMRT became more frequent over the years, yet the majority received palliative re-RT. Combined dose plans were only created for one third of the patients.

• Huynh, Thuy-Tien Maria; Dale, Einar; Falk, Ragnhild Sørum; Hellebust, Taran Annette Paulsen; Astrup, Guro Lindviksmoen & Malinen, Eirik [Show all 12 contributors for this article] (2023). Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters. Radiotherapy and Oncology. ISSN 0167-8140. 190. doi: 10.1016/j.radonc.2023.110044. Full text in Research Archive Show summary

  Background Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. Methods This cross-sectional study conducted in 2018–2020, included HNC survivors treated in 2007–2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. Results Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03–1.10), female sex (OR 2.75, 95% CI 1.45–5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03–1.09). NTCP models overall underestimated the risk of long-term dysphagia. Conclusions Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.

• Schmid, Maximilian P.; Lindegaard, Jacob C.; Mahantshetty, Umesh; Tanderup, Kari; Jürgenliemk-Schulz, Ina & Haie-Meder, Christine [Show all 33 contributors for this article] (2023). Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study. Journal of Clinical Oncology. ISSN 0732-183X. 41(10), p. 1933–1942. doi: 10.1200/JCO.22.01096. Full text in Research Archive
• Ryg, Una; Seierstad, Therese; Nilsen, Line; Hellebust, Taran Annette Paulsen; Djupvik, Linda Holth & Gustafson, Hilde [Show all 10 contributors for this article] (2022). A prospective study of high dose-rate brachytherapy or stereotactic body radiotherapy of Intra-prostatic recurrence: Toxicity and long term clinical outcome. Frontiers in Oncology. 12:861127, p. 1–10. doi: 10.3389/fonc.2022.861127. Full text in Research Archive Show summary

  Background Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy. Methods and Material Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival. Results Median follow-up time was 81 months (range 21–115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years. Conclusion The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.

• Westerveld, Henrike; Kirchheiner, Kathrin; Nout, Remi A.; Tanderup, Kari; Lindegaard, Jacob C. & Spampinato, Sofia [Show all 15 contributors for this article] (2022). Dose-effect relationship between vaginal dose points and vaginal stenosis in cervical cancer: An EMBRACE-I sub-study. Radiotherapy and Oncology. ISSN 0167-8140. 168, p. 8–15. doi: 10.1016/j.radonc.2021.12.034. Full text in Research Archive
• Svestad, Jørund Graadal; Mojgan, Heydari; Mikalsen, Stine Gyland; Flote, Vidar Gordon; Nordby, Fredrik & Hellebust, Taran Annette Paulsen (2022). Surface-guided positioning eliminates the need for skin markers in radiotherapy of right sided breast cancer: A single center randomized crossover trial. Radiotherapy and Oncology. ISSN 0167-8140. 177, p. 46–52. doi: 10.1016/j.radonc.2022.10.017. Full text in Research Archive
• Huynh, Thuy-Tien Maria; Aass, Hans Christian Dalsbotten; Falk, Ragnhild Sørum; Astrup, Guro Lindviksmoen; Helland, Åslaug & Bjøro, Trine [Show all 14 contributors for this article] (2022). Associations between patient-reported late effects and systemic cytokines in long-term survivors of head and neck cancer treated with radiotherapy. Journal of cancer survivorship. ISSN 1932-2259. doi: 10.1007/s11764-022-01273-1. Full text in Research Archive Show summary

  Purpose Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. Methods In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. Results Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls. Conclusions More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls. Implications for Cancer Survivors This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.

• Karlsson, Astrid Telhaug; Hjermstad, Marianne Jensen; Omdahl, Therese; Aass, Nina Kathrine; Skovlund, Eva & Hellebust, Taran Paulsen [Show all 9 contributors for this article] (2021). Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer. Acta Oncologica. ISSN 0284-186X. 60(8), p. 1054–1060. doi: 10.1080/0284186X.2021.1924399. Full text in Research Archive Show summary

  Background Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. Methods We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006–2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. Results Use of SRT increased during the period, from 19% (2006–2014) to 45% (2015–2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. Conclusion Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

• Pötter, Richard; Tanderup, Kari; Schmid, Maximilian P.; Jürgenliemk-Schulz, Ina; Haie-Meder, Christine & Fokdal, Lars Ulrik [Show all 50 contributors for this article] (2021). MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study. The Lancet Oncology. ISSN 1470-2045. 22(4), p. 538–547. doi: 10.1016/S1470-2045(20)30753-1. Full text in Research Archive Show summary

  Background - The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods - EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings - Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation - Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies.

• Serban, Monica; Kirisits, Christian; Leeuw, Astrid de; Pötter, Richard; Jürgenliemk-Schulz, Ina & Nesvacil, Nicole [Show all 20 contributors for this article] (2020). Ring Versus Ovoids and Intracavitary Versus Intracavitary-Interstitial Applicators in Cervical Cancer Brachytherapy: Results From the EMBRACE I Study. International Journal of Radiation Oncology, Biology, Physics. ISSN 0360-3016. 106(5), p. 1052–1062. doi: 10.1016/j.ijrobp.2019.12.019. Full text in Research Archive Show summary

  Purpose The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose. Methods and Materials Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD210, CTVHR D90% (EQD210), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD23) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis. Results For similar point A doses, mean CTVHR D90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D90% was 2.8 Gy higher, bladder D2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were <.002 for all comparisons. Equivalently, significant differences were derived from the multivariable analysis. Conclusions T&R-IC applicators have better target dose and dose conformity than T&O-IC in this representative patient cohort. IC applicators fail to cover large target volumes, whereas routine application of IC/IS improves target and OAR dose considerably. Patients treated with T&R show a more favorable therapeutic ratio when evaluating target, bladder/rectum doses, and V85Gy. A comprehensive view on technique/applicators should furthermore include practical considerations and clinical outcome.

• Brandal, Petter; Bergfeldt, Kjell; Aggerholm-Pedersen, Ninna; Bäckström, Gloria; Kerna, Irina & Gubanski, Michael [Show all 16 contributors for this article] (2020). A Nordic-Baltic perspective on indications for proton therapy with strategies for identification of proper patients. Acta Oncologica. ISSN 0284-186X. 59(10), p. 1157–1163. doi: 10.1080/0284186X.2020.1817977. Full text in Research Archive
• Sande, Erlend Peter Skaug; Roa, Ana Maria Acosta & Hellebust, Taran Paulsen (2020). Dose deviations induced by respiratory motion for radiotherapy of lung tumors: Impact of CT reconstruction, plan complexity, and fraction size. Journal of Applied Clinical Medical Physics. 21(4), p. 68–79. doi: 10.1002/acm2.12847. Full text in Research Archive Show summary

  A thorax phantom was used to assess radiotherapy dose deviations induced by respiratory motion of the target volume. Both intensity modulated and static, non‐modulated treatment plans were planned on CT scans of the phantom. The plans were optimized using various CT reconstructions, to investigate whether they had an impact on robustness to target motion during delivery. During irradiation, the target was programmed to simulate respiration‐induced motion of a lung tumor, using both patient‐specific and sinusoidal motion patterns in three dimensions. Dose was measured in the center of the target using an ion chamber. Differences between reference measurements with a stationary target and dynamic measurements were assessed. Possible correlations between plan complexity metrics and measured dose deviations were investigated. The maximum observed motion‐induced dose differences were 7.8% and 4.5% for single 2 Gy and 15 Gy fractions, respectively. The measurements performed with the largest target motion amplitude in the superior–inferior direction yielded the largest dosimetric deviations. For 2 Gy fractionation schemes, the summed dose deviation after 33 fractions is likely to be less than 2%. Measured motion‐induced dose deviations were significantly larger for one CT reconstruction compared to all the others. Static, non‐modulated plans showed superior robustness to target motion during delivery. Moderate correlations between the modulation complexity score applied to VMAT (MCSv) and measured dose deviations were found for 15 Gy SBRT treatment plans. Correlations between other plan complexity metrics and measured dose deviations were not found.

• Tan, Li Tee; Tanderup, Kari; Kirisits, Christian; Mahantshetty, Umesh; Swamidas, Jamema & Jürgenliemk-Schulz, Ina [Show all 27 contributors for this article] (2020). Education and training for image-guided adaptive brachytherapy for cervix cancer—The (GEC)-ESTRO/EMBRACE perspective. Brachytherapy. ISSN 1538-4721. 19(6), p. 827–836. doi: 10.1016/j.brachy.2020.06.012. Full text in Research Archive
• Siebert, Frank-Andre; Kirisits, Christian; Hellebust, Taran Paulsen; Baltas, Dimos; Verhaegen, Frank & Camps, Saskia [Show all 9 contributors for this article] (2020). GEC-ESTRO/ACROP recommendations for quality assurance of ultrasound imaging in brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 148, p. 51–56. doi: 10.1016/j.radonc.2020.02.024. Full text in Research Archive
• Bell, Lauren; Holloway, Lois; Bruheim, Kjersti; Petrič, Primož; Kirisits, Christian & Tanderup, Kari [Show all 12 contributors for this article] (2020). Dose planning variations related to delineation variations in MRI-guided brachytherapy for locally advanced cervical cancer. Brachytherapy. ISSN 1538-4721. 19(2), p. 146–153. doi: 10.1016/j.brachy.2020.01.002. Full text in Research Archive
• Swamidas, Jamema; Kirisits, Christian; Brabandere, Marisol De; Hellebust, Taran Paulsen; Siebert, Frank-André & Tanderup, Kari (2019). Image registration, contour propagation and dose accumulation of external beam and brachytherapy in gynecological radiotherapy. Radiotherapy and Oncology. ISSN 0167-8140. p. 1–11. doi: 10.1016/j.radonc.2019.08.023. Full text in Research Archive
• Nilsen, Line; Grøvik, Endre; Digernes, Ingrid; Saxhaug, Cathrine; Latysheva, Anna & Geier, Oliver [Show all 12 contributors for this article] (2019). Vascular responses in normal brain tissue after combined immunotherapy and SRS to brain metastases. Radiotherapy and Oncology. ISSN 0167-8140. 133, p. 551–552. doi: 10.1016/S0167-8140(19)31420-3. Full text in Research Archive
• Svestad, Jørund Graadal; Ramberg, Christina; Skar, Birgitte & Hellebust, Taran Paulsen (2019). Intrafractional motion in stereotactic body radiotherapy of spinal metastases utilizing cone beam computed tomography image guidance. Physics and imaging in radiation oncology (PIRO). 12, p. 1–6. doi: 10.1016/j.phro.2019.10.001. Full text in Research Archive
• Berger, Thomas; Seppenwoolde, Yvette; Pötter, Richard; Assenholt, Marianne Sanggaard; Lindegaard, Jacob C. & Nout, Remi A. [Show all 20 contributors for this article] (2019). Importance of technique, target selection, contouring, dose prescription, and dose-planning in external beam radiation therapy for cervical cancer: Evolution of practice from EMBRACE-I to II. International Journal of Radiation Oncology, Biology, Physics. ISSN 0360-3016. 104(4), p. 885–894. doi: 10.1016/j.ijrobp.2019.03.020. Full text in Research Archive
• Hellebust, Taran Paulsen (2018). Place of modern imaging in brachytherapy planning. Cancer Radiothérapie. ISSN 1278-3218. 22(4), p. 326–333. doi: 10.1016/j.canrad.2018.03.005. Full text in Research Archive
• Serban, Monica; Kirisits, Christian; Pötter, Richard; Leeuw, Astrid de; Nkiwane, Karen & Dumas, Isabelle [Show all 20 contributors for this article] (2018). Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 129, p. 567–574. doi: 10.1016/j.radonc.2018.09.002. Full text in Research Archive
• Wedde, Trude Baastad; Småstuen, Milada Cvancarova; Brabrand, Sigmund; Fosså, Sophie Dorothea; Kaasa, Stein & Tafjord, Gunnar [Show all 9 contributors for this article] (2018). Ten-year survival after High-Dose-Rate Brachytherapy combined with External Beam Radiation Therapy in high-risk prostate cancer: A comparison with the Norwegian SPCG-7 cohort. Radiotherapy and Oncology. ISSN 0167-8140. p. 1–7. doi: 10.1016/j.radonc.2018.10.013. Full text in Research Archive Show summary

  Background: The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT compared to EBRT alone. Methods: HDR-BT boosts were given followed by 50 Gy conformal EBRT to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for median 2 years. The historical control group (N:296), received a median dose of 70 Gy to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group, PCSM and OM were calculated using competing-risk and Kaplan-Meier analyses, respectively. Differences were assessed with the logrank test. OM and PCSM were computed using Cox and Fine & Grey regression. Significance level set to p<0.05. Patient-measured (PM) toxicity were assessed by EPIC-26 questionnaire at 5 years. Results: Median follow-up was 104 and 120 months for the HDR-BT/EBRT and the EBRT group respectively. A 3.6-fold decreased risk of PCSM (p<0.01) and a 1.6-fold decreased risk of OM (p=0.02) in the HDR-BT/EBRT cohort compared to the EBRT-only group were revealed. Ten year OM and PCSM rates were 16 % and 2.5% in the HDR-BT/EBRT group versus 23% and 8.2% in the EBRT-only group respectively. Treatment modality (SHR=3.58, 95%CI 1.40-9.14) and Gleason score (SHR=2.58, 95%CI 1.15 5.78) were associated with PCSM. Only treatment modality (HR=1.63, 95%CI=1.08-2.44) was significantly associated with OM. Conclusions: Men with high-risk PCa have a significantly reduced PCSM and OM rates when treated with dose-escalated radiotherapy achieved by HDR-BT/EBRT compared to EBRT alone (70 Gy). PM toxicity scores were acceptable and similar to the ProtecT study. A Gleason score of 8-10 was independently associated with increased risk of PCSM. Randomized studies in men with high-risk disease treated with dose-escalation are warranted.

• Li, Anna; Andersen, Erlend K F; Lervåg, Christoffer; Julin, Cathinka H.; Lyng, Heidi & Hellebust, Taran Paulsen [Show all 7 contributors for this article] (2017). Dynamic contrast enhanced magnetic resonance imaging for hypoxia mapping and potential for brachytherapy targeting. Physics and imaging in radiation oncology (PIRO). 2(1), p. 1–6. doi: 10.1016/j.phro.2017.03.002. Full text in Research Archive
• Rusten, Espen; Rekstad, Bernt Louni; Undseth, Christine; Al-Haidari, Ghazwan Ahmed Dhia Eldin; Hanekamp, Bettina & Hernes, Eivor [Show all 9 contributors for this article] (2017). Target volume delineation of anal cancer based on magnetic resonance imaging or positron emission tomography. Radiation Oncology. 12(147), p. 1–8. doi: 10.1186/s13014-017-0883-z. Full text in Research Archive Show summary

  Purpose To compare target volume delineation of anal cancer using positron emission tomography (PET) and magnetic resonance imaging (MRI) with respect to inter-observer and inter-modality variability. Methods Nineteen patients with anal cancer undergoing chemoradiotherapy were prospectively included. Planning computed tomography (CT) images were co-registered with 18F–fluorodexocyglucose (FDG) PET/CT images and T2 and diffusion weighted (DW) MR images. Three oncologists delineated the Gross Tumor Volume (GTV) according to national guidelines and the visible tumor tissue (GTVT). MRI and PET based delineations were evaluated by absolute volumes and Dice similarity coefficients. Results The median volume of the GTVs was 27 and 31 cm3 for PET and MRI, respectively, while it was 6 and 11 cm3 for GTVT. Both GTV and GTVT volumes were highly correlated between delineators (r = 0.90 and r = 0.96, respectively). The median Dice similarity coefficient was 0.75 when comparing the GTVs based on PET/CT (GTVPET) with the GTVs based on MRI and CT (GTVMRI). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTVT_PET) with the same volume evaluated by MRI (GTVT_MRI). Margins of 1–2 mm in the axial plane and 7–8 mm in superoinferior direction were required for coverage of the individual observer’s GTVs. Conclusions The rather good agreement between PET- and MRI-based GTVs indicates that either modality may be used for standard target delineation of anal cancer. However, larger deviations were found for GTVT, which may impact future tumor boost strategies.

• Arnesen, Marius Røthe; Hellebust, Taran Paulsen & Malinen, Eirik (2017). Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage - A modelling study. Physics in Medicine and Biology. ISSN 0031-9155. 62(6), p. N107–N119. doi: 10.1088/1361-6560/aa5de2. Full text in Research Archive
• Arnesen, Marius Røthe; Rekstad, Bernt Louni; Stokke, Caroline; Bruheim, Kjersti; Løndalen, Ayca Muftuler & Hellebust, Taran Paulsen [Show all 7 contributors for this article] (2016). Short-course PET based simultaneous integrated boost for locally advanced cervical cancer. Radiation Oncology. 11(1). doi: 10.1186/s13014-016-0612-z. Full text in Research Archive Show summary

  Background Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control. Methods Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans. Results Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation. Conclusions Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours.

• Arnesen, Marius Røthe; Knudtsen, Ingerid Skjei; Rekstad, Bernt Louni; Eilertsen, Karsten; Dale, Einar & Bruheim, Kjersti [Show all 10 contributors for this article] (2015). Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps. Acta Oncologica. ISSN 0284-186X. 54(9), p. 1607–1613. doi: 10.3109/0284186X.2015.1061690. Full text in Research Archive
• Kirisits, Christian; Rivard, Mark J.; Baltas, Dimos; Ballester, Facundo; Brabandere, Marisol De & Laarse, Rob Van Der [Show all 13 contributors for this article] (2014). Review of clinical brachytherapy uncertainties: Analysis guidelines of GEC-ESTRO and the AAPM. Radiotherapy and Oncology. ISSN 0167-8140. 110(1), p. 199–212. doi: 10.1016/j.radonc.2013.11.002. Full text in Research Archive
• Tedgren, Åsa Carlsson; Bjerke, Hans; Grindborg, Jan-Erik; Hetland, Per-Otto; Kosunen, Antti & Hellebust, Taran Paulsen [Show all 8 contributors for this article] (2014). Comparison of high-dose-rate &lt;sup&gt;192&lt;/sup&gt;Ir source strength measurements using equipment with traceability to different standards. Brachytherapy. ISSN 1538-4721. 13(4), p. 420–423. doi: 10.1016/j.brachy.2014.01.002. Full text in Research Archive
• Hellebust, Taran Paulsen; Heikkilä, Ingrid Espe; Frykholm, Gunilla; Levernes, Sverre G.; Johannessen, Dag Clement & Bjerke, Hans [Show all 7 contributors for this article] (2014). Quality assurance in radiotherapy on a national level; Experience from Norway: The KVIST initiative. Journal of Radiotherapy in Practice. ISSN 1460-3969. 13(1), p. 35–44. doi: 10.1017/S1460396912000544. Full text in Research Archive
• Arnesen, Marius Røthe; Bruheim, Kjersti; Malinen, Eirik & Hellebust, Taran Paulsen (2014). Spatial dosimetric sensitivity of contouring uncertainties in gynecological 3D-based brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 113(3), p. 414–419. doi: 10.1016/j.radonc.2014.11.016. Full text in Research Archive
• Onsrud, Mathias; Småstuen, Milada Cvancarova; Hellebust, Taran Paulsen; Kristensen, Gunnar S Balle; Tropé, Claes Gøran & Lindemann, Kristina (2013). Long-Term Outcomes After Pelvic Radiation for Early-Stage Endometrial Cancer. Journal of Clinical Oncology. ISSN 0732-183X. 31(31), p. 3951–3956. doi: 10.1200/JCO.2013.48.8023. Full text in Research Archive
• Hellebust, Taran Paulsen; Tanderup, Kari; Lervåg, Christoffer; Fidarova, Elena; Berger, Daniel & Malinen, Eirik [Show all 8 contributors for this article] (2013). Dosimetric impact of interobserver variability in MRI-based delineation for cervical cancer brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 107(1), p. 13–19. doi: 10.1016/j.radonc.2012.12.017. Full text in Research Archive
• Hoskin, Peter J.; Colombo, Alessandro; Henry, Ann; Niehoff, Peter; Hellebust, Taran Paulsen & Siebert, Frank-André [Show all 7 contributors for this article] (2013). GEC/ESTRO recommendations on high dose rate afterloading brachytherapy for localised prostate cancer: An update. Radiotherapy and Oncology. ISSN 0167-8140. 107(3), p. 325–332. doi: 10.1016/j.radonc.2013.05.002. Full text in Research Archive
• Petrič, Primož; Hudej, Robert; Rogelj, Peter; Blas, Mateja; Tanderup, Kari & Fidarova, Elena [Show all 11 contributors for this article] (2013). Uncertainties of target volume delineation in MRI guided adaptive brachytherapy of cervix cancer: A multi-institutional study. Radiotherapy and Oncology. ISSN 0167-8140. 107(1), p. 6–12. doi: 10.1016/j.radonc.2013.01.014. Full text in Research Archive
• Nesvacil, Nicole; Tanderup, Kari; Hellebust, Taran Paulsen; Leeuw, Astrid De; Lang, Stefan & Mohamed, Sandy [Show all 10 contributors for this article] (2013). A multicentre comparison of the dosimetric impact of inter- and intra-fractional anatomical variations in fractionated cervix cancer brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 107(1), p. 20–25. doi: 10.1016/j.radonc.2013.01.012. Full text in Research Archive
• Siebert, Frank-André; Venselaar, Jack L. M.; Hellebust, Taran Paulsen; Papagiannis, Panagiotis; Rijnders, Alex & Rivard, Mark J. (2012). Dose-rate to water calibrations for brachytherapy sources from the end-user perspective. Metrologia. ISSN 0026-1394. 49(5), p. S249–S252. doi: 10.1088/0026-1394/49/5/S249. Full text in Research Archive
• Balteskard, Lise; Dahl, Olav; Guren, Marianne; Haraldsen, Mathilde; Strickert, Trond & Wanderås, Eva Hoff [Show all 9 contributors for this article] (2011). Faglige anbefalinger for behandling ved analcancer. StrålevernRapport. ISSN 0804-4910. 5, p. 1–34. Full text in Research Archive
• Guedea, Ferran; Venselaar, Jack; Hoskin, Peter; Hellebust, Taran Paulsen; Peiffert, Didier & Londres, Bradley [Show all 11 contributors for this article] (2010). Patterns of care for brachytherapy in Europe: Updated results. Radiotherapy and Oncology. ISSN 0167-8140. 97(3), p. 514–520. doi: 10.1016/j.radonc.2010.09.009. Full text in Research Archive
• Hellebust, Taran Paulsen; Kristensen, Gunnar S Balle & Olsen, Dag Rune (2010). LATE EFFECTS AFTER RADIOTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER: COMPARISON OF TWO BRACHYTHERAPY SCHEDULES AND EFFECT OF DOSE DELIVERED WEEKLY. International Journal of Radiation Oncology, Biology, Physics. ISSN 0360-3016. 76(3), p. 713–718. doi: 10.1016/j.ijrobp.2009.02.024. Full text in Research Archive
• Hellebust, Taran Paulsen; Kirisits, Christian; Berger, Daniel; Perez-Calatayud, José; Brabandere, Marisol De & Leeuw, Astrid De [Show all 11 contributors for this article] (2010). Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group: Considerations and pitfalls in commissioning and applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 96(2), p. 153–160. doi: 10.1016/j.radonc.2010.06.004. Full text in Research Archive
• Tanderup, K; Hellebust, Taran Paulsen; Lang, S; Granfeldt, J; Potter, R & Lindegaard, JC [Show all 7 contributors for this article] (2008). Consequences of random and systematic reconstruction uncertainties in 3D image based brachytherapy in cervical cancer. Radiotherapy and Oncology. ISSN 0167-8140. 89(2), p. 156–163. doi: 10.1016/j.radonc.2008.06.010. Full text in Research Archive
• Hellebust, Taran Paulsen; Tanderup, K; Bergstrand, ES; Knutsen, BH; Roislien, J & Olsen, Dag Rune (2007). Reconstruction of a ring applicator using CT imaging: impact of the reconstruction method and applicator orientation. Physics in Medicine and Biology. ISSN 0031-9155. 52, p. 4893–4904. doi: 10.1088/0031-9155/52/16/012. Full text in Research Archive
• Dale, E; Hellebust, Taran Paulsen; Bruland, Øyvind & Olsen, Dag Rune (2005). Comparative analyses of the dynamic properties of the bladder wall studied by repetitive pelvic CT scans of patients and cryo-sections of cadavers. British Journal of Radiology (BJR). ISSN 0007-1285. 78, p. 528–532. Full text in Research Archive

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• Heggebø, Liv Cathrine; Borgen, Ida Maria Henriksen; Rylander, Hillevi; Kiserud, Cecilie E.; Nordenmark, Tonje Kristin Haug & Hellebust, Taran Annette Paulsen [Show all 44 contributors for this article] (2023). Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH- mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden. BMJ Open. 13(3). doi: 10.1136/bmjopen-2022-070071. Full text in Research Archive Show summary

  Abstract Introduction The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2–3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. Methods and analysis PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18–65 years with IDH-mutated diffuse gliomas grade 2–3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. Ethics and dissemination To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2–3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.

• Serban, Monica; Kirisits, Christian; Leeuw, Astrid de; Pötter, Richard; Jurgenliemk-Schulz, Ina & Nesvacil, Nicole [Show all 20 contributors for this article] (2019). Performance of ring versus ovoids and intracavitary versus intracavitary-interstitial in the EMBRACE study. Full text in Research Archive Show summary

  Purpose: To investigate the influence of brachytherapy (BT) technique and applicator type on target dose coverage, isodose surface volumes, and dose to organs at risk (OARs). Materials and Methods: 949 patients treated with tandem/ovoids (T&O) and tandem/ring (T&R) BT applicators, from 18 centres in the EMBRACE study, were analysed. Patients received external beam radiotherapy with concomitant chemotherapy, followed by MRI guided adaptive brachytherapy with individualised dose prescription. Centres were divided into 4 groups, according to their applicator (T&O vs T&R) and intracavitary (IC) vs intracavitary/interstitial (IC/IS) usage: T&O and T&R IC centres treating mainly with the IC technique; T&O IC/IS and T&R IC/IS centres treating routinely with the IC/IS technique (>20% of patients). V85Gy EQD210, CTVHR D90% as well as bladder, rectum and vaginal (lateral point at 5mm with respect to the applicator) doses were evaluated. Data was analysed as independent samples based on Student's t-test or by multiple linear regression models. Results: Patient characteristics, target and OAR doses for each center group are presented in Table 1. T&R IC compared to T&O IC centres had: mean CTVHR D90% higher by 4.9Gy EQD210 for a CTVHR volume of 30cm3 and no statistically significant difference when > 45cm3 (Fig.1a); mean V85Gy EQD210 smaller by 19.2cm3 at any given target volume (Fig.1b); mean Bladder ICRU and Rectovaginal Point doses (D_(〖2cm〗^3 ) is given in parenthesis) smaller by 9.1 (7.5) and 5.6 (3.3) Gy EQD23, respectively; mean vaginal dose higher by 17.1Gy EQD23. IC/IS compared to IC centres had: significantly improved target coverage and smaller V85Gy EQD2 for intermediate and large CTVHR volumes (Fig. 1c-f); decreased OAR doses, mostly in T&O. T&R IC/IS compared to T&O IC/IS centres had: mean CTVHR D90% higher by 2.7Gy EQD210; mean V85Gy EQD210 smaller by 8.3cm3 at any given CTVHR volume; mean Bladder D_(〖2cm〗^3 ) and Rectovaginal Point doses smaller by 4.3Gy and 4.8Gy EQD23, respectively; mean vaginal dose larger by 22.5Gy EQD23. All above mentioned differences were statistically significant (p<0.01). For patients treated with IC/IS, needles were used for all fractions in 85% and 55% of cases in T&R IC/IS and T&O IC/IS centres, respectively. Average number of needles/patient was 4.9 (SD:2.5) and 3.5 (SD:1.8) in T&R IC/IS and T&O IC/IS centres, respectively. Conclusions: The T&R IC applicator plans show better coverage and dose conformity than the T&O IC applicator plans for CTVHR<45cm3. For large target volumes, both T&R and T&O IC plans fail to ensure adequate target coverage. Bladder and rectum are, in general, better spared with T&R IC, while the 5mm lateral vaginal dose is higher. Routine application of IC/IS improves target coverage and dose conformity and better spares the OARs. With the addition of needles, the differences seen in target/OAR doses and in V85Gy EQD2 between the IC applicators become smaller. These differences are also related to both the number of needles and fractions with needles used.

• Knudtsen, Ingerid Skjei; Rusten, Espen; Grøndahl, Aurora Rosvoll; Furre, Torbjørn; Hellebust, Taran Paulsen & Futsæther, Cecilia Marie [Show all 8 contributors for this article] (2019). The BIORADIANCE project. Full text in Research Archive
• Serban, Monica; Kirisits, Christian; Leeuw, Astrid de; Pötter, Richard; Jurgenliemk-Schulz, Ina & Nesvacil, Nicole [Show all 20 contributors for this article] (2019). Performance of ring versus ovoids and intracavitary versus intracavitary-interstitial in the EMBRACE study. Radiotherapy and Oncology. ISSN 0167-8140. 133, p. 84–85. Full text in Research Archive Show summary

  Purpose: To investigate the influence of brachytherapy (BT) technique and applicator type on target dose coverage, isodose surface volumes, and dose to organs at risk (OARs). Materials and Methods: 949 patients treated with tandem/ovoids (T&O) and tandem/ring (T&R) BT applicators, from 18 centres in the EMBRACE study, were analysed. Patients received external beam radiotherapy with concomitant chemotherapy, followed by MRI guided adaptive brachytherapy with individualised dose prescription. Centres were divided into 4 groups, according to their applicator (T&O vs T&R) and intracavitary (IC) vs intracavitary/interstitial (IC/IS) usage: T&O and T&R IC centres treating mainly with the IC technique; T&O IC/IS and T&R IC/IS centres treating routinely with the IC/IS technique (>20% of patients). V85Gy EQD210, CTVHR D90% as well as bladder, rectum and vaginal (lateral point at 5mm with respect to the applicator) doses were evaluated. Data was analysed as independent samples based on Student's t-test or by multiple linear regression models. Results: Patient characteristics, target and OAR doses for each center group are presented in Table 1. T&R IC compared to T&O IC centres had: mean CTVHR D90% higher by 4.9Gy EQD210 for a CTVHR volume of 30cm3 and no statistically significant difference when > 45cm3 (Fig.1a); mean V85Gy EQD210 smaller by 19.2cm3 at any given target volume (Fig.1b); mean Bladder ICRU and Rectovaginal Point doses (D_(〖2cm〗^3 ) is given in parenthesis) smaller by 9.1 (7.5) and 5.6 (3.3) Gy EQD23, respectively; mean vaginal dose higher by 17.1Gy EQD23. IC/IS compared to IC centres had: significantly improved target coverage and smaller V85Gy EQD2 for intermediate and large CTVHR volumes (Fig. 1c-f); decreased OAR doses, mostly in T&O. T&R IC/IS compared to T&O IC/IS centres had: mean CTVHR D90% higher by 2.7Gy EQD210; mean V85Gy EQD210 smaller by 8.3cm3 at any given CTVHR volume; mean Bladder D_(〖2cm〗^3 ) and Rectovaginal Point doses smaller by 4.3Gy and 4.8Gy EQD23, respectively; mean vaginal dose larger by 22.5Gy EQD23. All above mentioned differences were statistically significant (p<0.01). For patients treated with IC/IS, needles were used for all fractions in 85% and 55% of cases in T&R IC/IS and T&O IC/IS centres, respectively. Average number of needles/patient was 4.9 (SD:2.5) and 3.5 (SD:1.8) in T&R IC/IS and T&O IC/IS centres, respectively. Conclusions: The T&R IC applicator plans show better coverage and dose conformity than the T&O IC applicator plans for CTVHR<45cm3. For large target volumes, both T&R and T&O IC plans fail to ensure adequate target coverage. Bladder and rectum are, in general, better spared with T&R IC, while the 5mm lateral vaginal dose is higher. Routine application of IC/IS improves target coverage and dose conformity and better spares the OARs. With the addition of needles, the differences seen in target/OAR doses and in V85Gy EQD2 between the IC applicators become smaller. These differences are also related to both the number of needles and fractions with needles used.

• Grimstad, Ingeborg; Arnesen, Marius Røthe; Bruheim, Kjersti; Malinen, Eirik & Hellebust, Taran Paulsen (2018). Dose-surface maps as a tool to predict toxicity after radiotherapy for cervical cancer patients. Radiotherapy and Oncology. ISSN 0167-8140. 127, p. 570–570. Full text in Research Archive
• Arous, Delmon; Pettersen, Erik O; Malinen, Eirik & Hellebust, Taran Paulsen (2018). Radiobiological plan evaluation in brachytherapy using two different cell survival models. Radiotherapy and Oncology. ISSN 0167-8140. 127, p. 1233–1233. Full text in Research Archive
• Furre, Torbjørn; Rekstad, Bernt Louni; Ramberg, Christina; Hellebust, Taran Paulsen; Malinen, Eirik & Dale, Einar (2018). A comparison of swallowing sparing IMPT and VMAT for head and neck cancer. Radiotherapy and Oncology. ISSN 0167-8140. 127, p. 489–489. Full text in Research Archive
• Skingen, Vilde Eide; Rekstad, Bernt Louni; Rusten, Espen; Undseth, Christine; Hellebust, Taran Paulsen & Guren, Marianne [Show all 7 contributors for this article] (2017). PET-based dose painting of anal carcinoma and implications for adaptive approaches. Full text in Research Archive
• Støen, Ingvild; Rusten, Espen; Rekstad, Bernt Louni; Undseth, Christine; Al-Haidari, Ghazwan Ahmed Dhia Eldin & Hellebust, Taran Paulsen [Show all 8 contributors for this article] (2017). Optimal threshold for PET-based autocontouring of boost volume for radiotherapy of anal carcinoma. Full text in Research Archive
• Arous, Delmon; Pettersen, Erik O; Malinen, Eirik & Hellebust, Taran Paulsen (2017). Radiotherapy cell survival curves for cervical cancer: Linear quadratic vs universal survival. Full text in Research Archive
• Rusten, Espen; Rekstad, Bernt Louni; Undseth, Christine; Al-Haidari, Ghazwan Ahmed Dhia Eldin; Hanekamp, Bettina & Hernes, Eivor [Show all 9 contributors for this article] (2016). Target delineation of anal cancer based on MR or PET – an inter-observer, inter-modality study. Radiotherapy and Oncology. ISSN 0167-8140. 119, p. 336–337. Full text in Research Archive
• Arnesen, Marius Røthe; Rekstad, Bernt Louni; Waldeland, Einar; Hellebust, Taran Paulsen & Malinen, Eirik (2015). Intensity modulated proton therapy vs. VMAT for standard and dose escalated radiotherapy of locally advanced cervical cancer. Full text in Research Archive
• Rekstad, Bernt Louni; Rusten, Espen; Undseth, Christine; Arnesen, Marius Røthe; Hellebust, Taran Paulsen & Holmboe, Laila Kampen Dajani [Show all 8 contributors for this article] (2015). Anal carcinoma – a candidate for FDG-PET guided high-dose simultaneously integrated boost. Full text in Research Archive
• Arpit, A; Arnesen, Marius Røthe; Rekstad, Bernt Louni; Malinen, Eirik & Hellebust, Taran Paulsen (2015). IMRT and IMPT of cervical cancer and effect of reduced margins. Radiotherapy and Oncology. ISSN 0167-8140. 115, p. s778–s778. doi: 10.1016/S0167-8140(15)41431-8. Full text in Research Archive
• Arnesen, Marius Røthe; Rekstad, Bernt Louni; Hellebust, Taran Paulsen & Malinen, Eirik (2015). Short-course PET based SIB for cervical cancer. Radiotherapy and Oncology. ISSN 0167-8140. 115, p. s450–s450. doi: 10.1016/S0167-8140(15)40871-0. Full text in Research Archive
• Li, Anna; Andersen, Erlend K F; Lervåg, Christoffer; Julin, Cathinka; Lyng, Heidi & Hellebust, Taran Paulsen [Show all 7 contributors for this article] (2015). Hypoxia imaging with dynamic contrast enhanced MRI and focal brachytherapy of cervical cancers. Full text in Research Archive
• Arnesen, Marius Røthe; Hellebust, Taran Paulsen & Malinen, Eirik (2014). Analysis of the spatial dosimetric sensitivity of contouring uncertainties in gynecological brachytherapy. Radiotherapy and Oncology. ISSN 0167-8140. 111, p. 27–27. Full text in Research Archive
• Arnesen, Marius Røthe; Hellebust, Taran Paulsen & Malinen, Eirik (2014). Regional dosimetric analysis of tumor contouring uncertainties in gynecological brachytherapy. Full text in Research Archive
• Hellebust, Taran Paulsen; Li, Anna; Andersen, Erlend K F; Lervåg, Christoffer; Lyng, Heidi & Malinen, Eirik (2013). Hypoxia guided brachytherapy of cervical cancers using dynamic contrast enhanced MRI. Full text in Research Archive
• Li, Anna; Andersen, Erlend K F; Lervåg, Christoffer; Lyng, Heidi; Hellebust, Taran Paulsen & Malinen, Eirik (2013). Biological image guided brachytherapy of hypoxic cervical cancers. Radiotherapy and Oncology. ISSN 0167-8140. 106, p. 57–57. Full text in Research Archive
• Hellebust, Taran Paulsen; Petrič, Primož; Tanderup, Kari; Berger, Daniel; Fidarova, Elena & Pötter, Richard [Show all 8 contributors for this article] (2012). Inter-observer variability in MR-based cervical cancer brachytherapy – target delineation uncertainty and dosimetric impact. Full text in Research Archive
• Hellebust, Taran Paulsen; Petrič, Primož; Tanderup, Kari; Berger, Daniel; Fidarova, Elena & Pötter, Richard [Show all 8 contributors for this article] (2012). SPATIAL DOSIMETRIC SENSITIVITY ANALYSIS OF CONTOURING UNCERTAINTIES IN GYN 3D-BASED BRACHYTHERAPY. Radiotherapy and Oncology. ISSN 0167-8140. 103, p. 34–34. Full text in Research Archive

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