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The effectiveness of abdominal compression for motion management in hepatobiliary-pancreatic (HPB) radiotherapy has not been systematically evaluated. A systematic review was carried out using PubMed/Medline, Cochrane Library, Web of Science, and CINAHL databases up to 1 July 2021. No date restrictions were applied. Additional searches were carried out using the University of Manchester digital library, Google Scholar and of retrieved papers' reference lists. Studies conducted evaluating respiratory motion utilising imaging with and without abdominal compression in the same patients available in English were included. Studies conducted in healthy volunteers or majority non-HPB sites, not providing descriptive motion statistics or patient characteristics before and after compression in the same patients or published without peer-review were excluded. A narrative synthesis was employed by tabulating retrieved studies and organising chronologically by abdominal compression device type to help identify patterns in the evidence. The inclusion criteria were met by 6 studies with a total of 152 patients. Designs were a mix of retrospective and prospective quantitative designs with chronological, non-randomised recruitment. Abdominal compression reduced craniocaudal respiratory motion in the majority of patients, although in four studies there were increases seen in at least one direction. The influence of patient comorbidities on effectiveness of compression, and/or comfort with compression was not evaluated in any study. Abdominal compression may not be appropriate for all patients, and benefit should be weighed with potential increase in motion or discomfort in patients with small initial motion (<5 mm). Patient factors including male sex, and high body mass index (BMI) were found to impact the effectiveness of compression, however with limited evidence. High-quality studies are warranted to fully assess the clinical impact of abdominal compression on treatment outcomes and toxicity prospective in comparison to other motion management strategies. [ABSTRACT FROM AUTHOR]

Introdution: Variation in shape, position and treatment response of both tumor and organs at risk are major challenges for accurate dose delivery in radiotherapy. Adaptive radiotherapy (ART) has been proposed to customize the treatment to these motion/response patterns of the individual patients, but increases workload and thereby challenges clinical implementation. This paper reviews strategies and workflows for clinical and in silico implemented ART for prostate, bladder, gynecological (gyne) and ano-rectal cancers.Material and methods: Initial identification of papers was based on searches in PubMed. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review.Results: The review consisted of 43 clinical studies and 51 in silico studies. For prostate, 1219 patients were treated with offline re-planning, mainly to adapt prostate motion relative to bony anatomy. For gyne 1155 patients were treated with online brachytherapy re-planning while 25 ano-rectal cancer patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape variations. The studies reported sparing of rectum (prostate and bladder cancer), bladder (ano-rectal cancer) and bowel cavity (gyne and bladder cancer) as compared to non-ART.Conclusion: Implementations of ART were dominated by offline re-planning and online brachytherapy re-planning strategies, although recently online plan selection workflows have increased with the availability of cone-beam CT. Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review. Despite this, clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows. [ABSTRACT FROM AUTHOR]

An editorial is presented on the BiGART 2023 symposium, highlighting its multidisciplinary approach to bridging clinical and translational research in radiation oncology. Topics include the state of biology-guided and adaptive radiotherapy, the exploration of automation and artificial intelligence, and the examinations of proton radiotherapy and considerations for the future of radiotherapy.

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14–15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose. [ABSTRACT FROM AUTHOR]

In the Nordic countries, as in the rest of the world, particle therapy as a radiotherapy modality, is evolving, albeit the hard evidence for the clinical benefit still is scarce. However, a common goal for the Nordic countries is to include a minimum of 80% of the patients treated with particle therapy into clinical trials. In this paper, we summarize the current status of clinical trials involving particle therapy in the Nordic countries, with an overview of both active and coming trials. So far, one is closed for inclusion and data are being analyzed, seven trials are actively recruiting patients and several more trials are underway. No common Nordic trial has yet been designed, nor is in the planning phase, and the authors will discuss the obstacles as well as the opportunities a common Nordic platform may represent. [ABSTRACT FROM AUTHOR]

The authors reflect on a working relationship which has developed between the periodical "Acta Oncologica" and the Nordic Association for Clinical Physics. They suggest that "Acta Oncologica" provides an excellent place for the association to publish papers on medical physics. They argue that the working relationship between the periodical and the association is based on mutual respect and understanding.

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpose of this article is to provide guidance for high-quality LINAC based SRS for patients with BM, with a focus on single isocenter non-coplanar volumetric modulated arc therapy (VMAT). Methods: The article is based on a consensus statement by the study coordinators and medical physicists of four trials which investigated whether patients with multiple BM are better palliated with SRS instead of whole brain radiotherapy (WBRT): A European trial (NCT02353000), two American trials and a Canadian CCTG lead intergroup trial (CE.7). This manuscript summarizes the quality assurance measures concerning imaging, planning and delivery. Results: To optimize the treatment, the interval between the planning-MRI (gadolinium contrast-enhanced, maximum slice thickness of 1.5 mm) and treatment should be kept as short as possible (< two weeks). The BM are contoured based on the planning-MRI, fused with the planning-CT. GTV-PTV margins are minimized or even avoided when possible. To maximize efficiency, the preferable technique is single isocenter (non-)coplanar VMAT, which delivers high doses to the target with maximal sparing of the organs at risk. The use of flattening filter free photon beams ensures a lower peripheral dose and shortens the treatment time. To bench mark SRS treatment plan quality, it is advisable to compare treatment plans between hospitals. Conclusion: This paper provides guidance for quality assurance and optimization of treatment delivery for LINAC-based radiosurgery for patients with multiple BM. [ABSTRACT FROM AUTHOR]

Background: Deformable image registration (DIR) is increasingly used in the field of radiation therapy (RT) to account for anatomical deformations. The aims of this paper are to describe the main applications of DIR in RT and discuss current DIR evaluation methods. Methods: Articles on DIR published from January 2000 to October 2018 were extracted from PubMed and Science Direct. Our search was restricted to articles that report data obtained from humans, were written in English, and address DIR methods for RT. A total of 207 articles were selected from among 2506 identified in the search process. Results: At planning, DIR is used for organ delineation using atlas-based segmentation, deformation-based planning target volume definition, functional planning and magnetic resonance imaging-based dose calculation. In image-guided RT, DIR is used for contour propagation and dose calculation on per-treatment imaging. DIR is also used to determine the accumulated dose from fraction to fraction in external beam RT and brachytherapy, both for dose reporting and adaptive RT. In the case of re-irradiation, DIR can be used to estimate the cumulated dose of the two irradiations. Finally, DIR can be used to predict toxicity in voxel-wise population analysis. However, the evaluation of DIR remains an open issue, especially when dealing with complex cases such as the disappearance of matter. To quantify DIR uncertainties, most evaluation methods are limited to geometry-based metrics. Software companies have now integrated DIR tools into treatment planning systems for clinical use, such as contour propagation and fraction dose accumulation. Conclusions: DIR is increasingly important in RT applications, from planning to toxicity prediction. DIR is routinely used to reduce the workload of contour propagation. However, its use for complex dosimetric applications must be carefully evaluated by combining quantitative and qualitative analyses. [ABSTRACT FROM AUTHOR]

Background. Radical prostatectomy (RP) is worldwide probably the most common procedure to treat localized prostate cancer (PC). Due to a more widespread use of Prostate-Specific Antigen (PSA) testing, patients operated today are often younger and have organ confined disease justifying a more preservative surgery. At the same time, surgical technique has improved resulting in lower risk of permanent side-effects. This paper aims to give an overview of results from modern surgery regarding cancer control and side-effects. A brief overview of the history is given. Material and Methods. A literature research identified recently published papers focusing on outcome and side-effects after RP. Results. One large randomized study (SPCG-4) compared RP and watchful waiting (WW). The study showed that RP was superior to WW in preventing local progression (RR 0.36), distant metastasis (RR 0.65) and death from PC (RR 0.65). Observational studies also show a better outcome for men treated with RP compared to WW. Peri-operative mortality after RP is low in most material around 0.1%. The risk of stricture of the vesico-urethral anastomosis has decreased with improved technique from historically 10-20% to a low incidence of around 2-9% today. Also the risk of incontinence has declined with improved technique. However, while the rates of severe incontinence is usually very low, as many as 30% still report light incontinence after long-term follow-up. Erectile dysfunction (ED) is still a frequent side-effect after RP. This risk is dependent on age, pre-operative sexual function, surgical technique and other risk factors for ED such as smoking, diabetes, etc. In selected subgroups the risk of ED is low. Inguinal hernia is a more recently described complication after open retropubic RP with a post-operative incidence of 15-20% within three years of surgery. Conclusion. RP is an effective method to achieve cancer control in selected patients. With modern technique it is a safe procedure with a low risk of permanent side-effects except for ED. [ABSTRACT FROM AUTHOR]

With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers. [ABSTRACT FROM AUTHOR]

The author reflects on changes which have been made to the periodical "Acta Oncologica". He suggests that despite the fact that it appears as if the journal is turning into another radiotherapy/medical physics journal, it is not. He argues that the periodical's editorial board should administer and further develop the increased attractiveness of the periodical.

This study aimed to develop fully automated script-based radiotherapy treatment plans for cervical cancer patients, and evaluate them against clinically accepted plans, as validation before clinical implementation. In this retrospective planning study, treatment plans for 25 locally advanced cervical cancer (LACC) patients with up to three dose levels were included. Fully automated plans were created using an in-house developed Python script in RayStation, and compared to clinically accepted manually made plans. Quantitatively, relevant dose statistics were compared, and average dose volume histograms (DVHs) were analyzed. Qualitatively, a blinded plan comparison was conducted between the clinical and automatic plans. The accuracy of treatment plan delivery was verified with the Delta4 Phantom+. The quantitative evaluation showed that target coverage was acceptable for all the automatic and clinical plans. The automatic plans were significantly more conformal than the clinical plans; median of 1.03 vs. 1.12. Mean doses to almost all organs at risk (OARs) were reduced in the automatic plans, with a median reduction of between 0.6 Gy and 1.9 Gy. In the blinded plan comparison, the automatic plans were the preferred plans or of equal quality as the clinical plans in 99% of the cases. In addition, plan delivery was excellent, with a mean gamma passing rate of 99.8%. Complete script-based plans were generated in 30–45 min; about four to ten times faster than manually made plans. The automatic plans had acceptable target coverage, lower doses to almost all OARs, more conformal dose distributions, and were predominantly preferred by the clinicians. Based on these results, our institution has implemented the script for clinical use. [ABSTRACT FROM AUTHOR]

This Delphi study aimed to assess current perspectives on hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2−) advanced breast cancer (aBC) treatment strategies across the Nordics, and to establish where consensus exists across the Nordics on HR+/HER2− aBC treatment. A modified, three-round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection, and questionnaire development. The questionnaires covered relevant topics on HR+/HER2− aBC treatment: treatment patterns in different lines of therapy (first [1L], second [2L], and third [3L]), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics, and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. In total, 28 experienced BC oncologists participated in the study from all five Nordic countries. Overall, topics reaching consensus included: preferred treatment approach in 1L and 2L therapy, treatment of oligometastatic disease, visceral crisis, brain metastases, and age-related treatment considerations. No consensus was reached for 3L therapy and local treatment for primary tumour in de novo aBC. Endocrine therapy (ET) combined with a cyclin-dependent kinase (CDK)4/6 inhibitor was the treatment of choice for 1L and 2L therapy. Treatment patterns in clinical practice did not always follow recommendations in current Nordic guidelines, as seen in the case of recently approved treatments. ET in combination with a CDK4/6 inhibitor is the preferred frontline treatment for HR+/HER2− aBC in the Nordics. The observed discrepancy between current guidelines and clinical practice could be due to differences in the reimbursement of novel treatments in the Nordics. Collaborative research efforts are warranted for topics that lack consensus. [ABSTRACT FROM AUTHOR]

Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints. Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE. Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively. The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage. [ABSTRACT FROM AUTHOR]

In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 − 0.90] and 0.68 [0.51 − 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 − 1.1] mm and 1.9 mm [1.5 − 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in Δ NTCP. The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the Δ NTCP calculations could be discerned. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) patients' anatomy may undergo significant changes during radiotherapy (RT). This potentially affects dose distribution and compromises conformity between planned and delivered dose. Adaptive radiotherapy (ART) is a promising technique to overcome this problem but requires a significant workload. This systematic review aims to estimate the clinical and dosimetric benefits of ART using prospective data. A search on PubMed and Web of Science according to the PRISMA guidelines was made on Feb 6, 2023. Search string used was: 'adaptive radiotherapy head neck cancer'. English language filter was applied. All studies were screened for inclusion on title and abstract, and the full text was read and discussed in the research group in case of uncertainty. Inclusion criteria were a prospective ART strategy for HNC investigating clinical or dosimetric outcomes. A total of 1251 articles were identified of which 15 met inclusion criteria. All included studies were published between 2010 and 2023 with a substantial diversity in design, endpoints, and nomenclature. The number of patients treated with ART was small with a median of 20 patients per study (range 4 to 86), undergoing 1-2 replannings. Mean dose to the parotid glands was reduced by 0.4-7.1 Gy. Maximum dose to the spinal cord was reduced by 0.5-4.6 Gy. Only five studies reported clinical outcome and disease control was excellent. Data on toxicity were ambiguous with some studies indicating reduced acute toxicity and xerostomia, while others found reduced quality of life in patients treated with ART. The literature on clinical ART in HNC is limited. ART is associated with small reductions in doses to organs at risk, but the influence on toxicity and disease control is uncertain. There is a clear need for larger, prospective trials with a well-defined control group. [ABSTRACT FROM AUTHOR]

Background: Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patientreported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. Material and methods: A total of 302 patients with PCa with prospective registration of patientreported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. Results: At a median follow-up of 15 (3-51) months, the overall crude incidence of patients reporting 'quite a bit' or 'a lot' of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of 'quite a bit' and 'a lot' of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for 'quite a bit' or 'a lot' of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported 'quite a bit' and 2.9% (±0.5%) reported 'very much' LLE (p<0.001), respectively. Results: Significant risk factors (p<0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI = 30 compared to normal weight patients. Conclusion: Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report 'quite a bit' or 'very much' LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE. [ABSTRACT FROM AUTHOR]

Background and purpose: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. Materials and methods: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). Results: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. Conclusion: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate different methods for calibrating EBT-XD films to develop a precise pre-treatment verification method for stereotactic radiotherapy (SRT) patients using the HyperArc (HA, Varian Medical System) technique. Methods: Gafchromic EBT-XD films were calibrated using three different approaches: manual calibration, EDW calibration, and PDD calibration. Films were digitalized with an Epson V850 Pro scanner applying the local scanning protocol. Three clinical treatment plans were selected for evaluation. Patient-specific QA films were irradiated in the Mobius MVP phantom and the STEEV phantom. Scanned film images were converted into dose images using the calibration curves. Gamma analysis was performed to compare film dose and TPS calculated dose with various criteria. Results: The scan-to-scan variation was evaluated to be ≤ 0.2%. The accuracy of the calibration curves was verified and the deviation from the converted dose deviates ≤ 3% from the known delivered dose. The gamma passing rate for all calibration methods was found to be over 94% with clinically relevant criteria. EDW calibration demonstrated higher average gamma passing rates compared to the manual method for single target plans, which is 99% ± 1.2% and 98.8% ± 1.5%, respectively. PDD method demonstrated improved agreement for multiple targets with the result of 99.3% ± 0.8%. Conclusions: The three calibration methods were validated, and they produced accurate calibration curves for EBT-XD films to enable pre-treatment patient-specific QA for stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for D50 and γ50 were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship for a patient without pulmonary co-morbidities, caudally located tumor, no history of smoking, < 63 years old, and receiving no sequential chemotherapy was estimated as D500 = 34.4 Gy (95% CI 30.7, 38.9), γ500 = 1.19 (95% CI 1.00, 1.43). Individual patient risk estimates were calculated. The cumulative incidences of RP in the validation dataset were not significantly different in high/low-risk patients when doing risk allocation with the QUANTEC model (p = 0.11), but were significantly different using the individualized model (p = 0.006). C-indices were significantly different between the dose-only and the individualized model. Conclusion. This study presents a method to combine a published dose-response function with known clinical risk factors and demonstrates the increased predictive power of the combined model. The method allows for individualization of dose constraints and individual patient risk estimates. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) always requires a compromise between tumor control and normal tissue side-effects. Technical innova- tion in radiation therapy (RT), such as three dimensional RT, is now established. Concerning prostate cancer (PC), it is reasonable to assume that RT of PC will increase in the future. The combination of small margins, a movable target (prostate), few fractions and high doses will probably demand dynamically positioning systems and in real time. This is called four dimensional radiotherapy (4DRT). Moreover, biological factors must be included in new treatments such as hypofractionation schedules. This new era is called five dimensional radiotherapy, 5DRT. In this paper we discuss new concepts in RT in respect to PC. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) always requires a compromise between tumor control and normal tissue side-effects. Technical innovation in radiation therapy (RT), such as three dimensional RT, is now established. Concerning prostate cancer (PC), it is reasonable to assume that RT of PC will increase in the future. The combination of small margins, a movable target (prostate), few fractions and high doses will probably demand dynamically positioning systems and in real time. This is called four dimensional radiotherapy (4DRT). Moreover, biological factors must be included in new treatments such as hypofractionation schedules. This new era is called five dimensional radiotherapy, 5DRT. In this paper we discuss new concepts in RT in respect to PC. [ABSTRACT FROM AUTHOR]

Little has been reported on the errors of setup and daily organ motion that occur during radiation therapy (RT) for esophageal cancer. The purpose of this paper was to determine the margins of esophageal motion during RT. Methods and materials. The shift of the esophagus was analyzed in 20 consecutive patients treated with RT for esophageal cancer from November 2007. CT images for RT planning were used as the primary image series. Computed tomography (CT) images were acquired using an Elekta Synergy System, equipped with a kilovoltage-based cone-beam CT (CBCT) unit. The subsequent CBCT image series used for daily RT setup were compared with the primary image series to analyze esophageal motion. CBCT was performed before treatment sessions a total of 10 times in each patient twice a week. The outer esophageal wall was contoured on the CBCT images of all 200 sets. Results. In the 200 sets of CBCT images, the mean (absolute) ± standard deviation (SD) of setup errors were 2 +/− 2 mm (max, 8 mm) in the lateral direction, 4 +/− 3 mm (max, 11 mm) in the longitudinal direction, and 4 +/− 3 mm (max, 13 mm) in the vertical direction. Additionally, the mean ± SD values of daily esophageal motion comparing the CBCT with RT planning CT were 5 +/− 3 mm (max, 15 mm) in the lateral direction and 5 +/− 3 mm (max, 15 mm) in the vertical direction. Conclusions. Our data support the use of target margins (between the clinical target volume and planning target volume) of 9 mm for day-to-day esophageal motion and 8 mm for patient setup in all directions, respectively. [ABSTRACT FROM AUTHOR]

Introduction. The breath-hold is one of the techniques to obtain the dose escalation for lung tumors. However, the change of the patient's breath pattern can influence the stability of the inhaled air volume, IAV, used in this work as a surrogate parameter to assure the tumor position reproducibility during dose delivery.Materials. and methodIn this paper, an Elekta active breathing coordinator has been used for lung tumor irradiation. This device is not an absolute spirometer and the feasibility study here presented developed (i) the possibility to select a specific range ε of IAV values comfortable for the patient and (ii) the ability of a transit signal rate [image omitted] , obtained by a small ion-chamber positioned on the portal image device, to supply in real time the in vivo isocenter dose reproducibility. Indeed, while the selection of the IAV range depends on the patient's ability to follow instructions for breath-hold, the [image omitted] monitoring can supply to the radiation therapist a surrogate of the tumor irradiation reproducibility.Results. The detection of the [image omitted] in real time during breath-hold was used to determine the interfraction isocenter dose variations due to the reproducibility of the patient's breathing pattern. The agreement between the reconstructed and planned isocenter dose in breath-hold at the interfraction level was well within 1.5%, while in free breathing a disagreement up to 8% was observed. The standard deviation of the [image omitted] in breath-hold observed at the intrafraction level is a bit higher than the one obtained without the patient and this can be justified by the presence of a small residual tumor motion as heartbeat.Conclusion. The technique is simple and can be implemented for routine use in a busy clinic. [ABSTRACT FROM AUTHOR]

Ionizing radiation is a well established carcinogen for human cells. At low doses, radiation exposure mainly results in generation of double strand breaks (DSBs). Radiation-related DSBs could be directly linked to the formation of chromosomal rearrangements as has been proven for radiation-induced thyroid tumors. Repair of DSBs presumably involves two main pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). A number of known inherited syndromes, such as ataxia telangiectasia, ataxia-telangiectasia like-disorder, radiosensitive severe combined immunodeficiency, Nijmegen breakage syndrome, and LIG4 deficiency are associated with increased radiosensitivity and/or cancer risk. Many of them are caused by mutations in DNA repair genes. Recent studies also suggest that variations in the DNA repair capacity in the general population may influence cancer susceptibility. In this paper, we summarize the current status of DNA repair proteins as potential targets for radiation-induced cancer risk. We will focus on genetic alterations in genes involved in HR- and NHEJ-mediated repair of DSBs, which could influence predisposition to radiation-related cancer and thereby explain interindividual differences in radiosensitivity or radioresistance in a general population. [ABSTRACT FROM AUTHOR]

DBCG (Danish Breast Cancer Cooperative Group) constitutes a multidisciplinary organization established in 1975 by the Danish Surgical Society. The purpose involves first and foremost a nation-wide standardization of breast cancer treatment based on novel therapeutic principles, collaboration between experts handling diagnostic work-up, surgery, radiotherapy, medical oncology, and basic research, and, further, complete registration of relevant clinical data in a national data base attached to DBCG. Data are processed by the Secretariat personnel composed of statisticians, data managers, and data secretaries making current analyses of outcome results feasible. DBCG is run by the Executive Committee consisting of expert members appointed by their respective society. From 1978 the DBCG project gained widely accession from participating units, and since then nearly all newly diagnosed breast cancer incident cases are reported and registered in the national data base. Today, the data base includes approximately 80 000 incidents of primary breast cancer. Annually, the Secretariat receives roughly 1.5 million parameters to be entered into the data base. Over time DBCG has generated seven treatment programmes including in situ lesions and primary invasive breast cancer. Probands are subdivided into risk groups based on a given risk pattern and allocated to various treatment programmes accordingly. The scientific initiatives are conducted in the form of register- and cohort analysis or randomized trials in national or international protocolized settings. Yearly, about 4 000 new incident cases of primary invasive breast cancer and about 200 in situ lesions enter the national programmes. Further, about 600 women with hereditary disposition of breast cancer are registered and evaluated on a risk scale. The main achievements resulted in a reduction of relative risk of death amounting up to 20% and increased 5-year overall survival ascending from 60% to roughly 80%. This article is partly based on a Danish paper to be published in the Centenary Jubilee book of the Danish Surgical Society, 2008. [ABSTRACT FROM AUTHOR]

This paper describes the procedure of changing from 2D to 3D treatment planning guidelines for post-mastectomy radiotherapy in Denmark. The aim of introducing 3D planning for post-mastectomy radiotherapy was to optimize the target coverage and minimize the dose to the normal tissues. Initially, it was investigated whether it was possible to find a treatment technique alternative to the one recommended by the Danish Breast Cancer Cooperative Group (DBCG). A dosimetric comparison of a combined photon/electron 3-field technique (3F) and a partial wide tangent technique (PWT) was carried out on individual planning CT-scans from seven patients selected to represent a wide range of sizes and shapes of chest walls. The heart dose was lower for PWT than for 3F, however, for both techniques the dose was within the accepted constraints. The lung dose was higher but acceptable for six of the seven patients with PWT. The dose to the internal mammary nodes (IMN) was not satisfactory for five of the seven patients for 3F, whereas only two of the seven patients had a minimum dose lower than 95% of the prescribed dose with PWT. Finally, the dose to the contralateral breast was increased when using PWT compared to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy centres participated. This work also included a definition of the tissue structures needed to be outlined on the planning CT-scan. The work was initiated in 2003 and the guidelines were approved by the DBCG Radiotherapy Committee in 2006. The first of January 2007 the 3D guidelines had been fully implemented in five of the seven radiotherapy centres. [ABSTRACT FROM AUTHOR]

During the time period 1977-2007 postoperative radiotherapy in DBCG has varied considerably with regard to techniques and indications together with changes in the extent of surgery and adjuvant systemic therapy. The radiation treatment has been developed on the basis of clinical, radiophysical and radiobiological principles, encompassing also practical problems such as available equipment in the different centres and at times lack of sufficient machine capacity. The paper focus especially on the comprehensive work done prior to the DBCG 82 b&c studies, in order to optimize radiotherapy in all aspects prior to the evaluation of the efficacy of this treatment modality. The results from these trials did succeed in clear evidence that radiotherapy has an important role in the multidisciplinary treatment of early breast cancer. In parallel to these studies a new and challenging use of radiotherapy after breast conserving surgery was evaluated in the DBCG TM 82 protocol. The experience obtained with different techniques in this study formed the basis for the current principles of radiotherapy after lumpectomy. Reduction of radiation related morbidity has been a major issue for the DBCG radiotherapy group, and in this aspect several studies, including quality control visits, have been carried out to make the relevant modifications and to evaluate deviations from the guidelines between the centres. The background for the changes in radiotherapy is described for each of the programme periods as well as future perspectives which will include further refinements of the target and adjustments of dose and fractionation in selected patients. [ABSTRACT FROM AUTHOR]

Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications. [ABSTRACT FROM AUTHOR]

The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFα. The therapeutic gene (TNFα) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments. [ABSTRACT FROM AUTHOR]

In 1963-1965 a group of 71 patients operated on for breast cancer with total mastectomy and axillary clearance were given aggressive postoperative telecobalt therapy to the axillary, supraclavicular and parasternal lymph node regions. The prescribed dose to these lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day. Retrospective dose calculations showed that the total dose in the brachial plexus from the axillary and supraclavicular fields was c. 57 Gy in 16-17 fractions over 3-4 weeks. After a few years, symptoms and signs of brachial plexus injury appeared in many patients, which was reported in some early papers. The cohort has now been followed-up to 34 years. As expected, there was progression of both prevalence and severity of the late effects between 5 and 34 years and 11 of 12 patients who are still alive have paralysis of their arms. The neuropathy seems to be closely linked to fibrosis around the nerve trunks. The use of large daily fractions, in some cases combined with hot spots from overlapping fields, was certainly the cause of the complication. [ABSTRACT FROM AUTHOR]

The article focuses on late complications and survival in soft tissue sarcoma (STS) patients who received adjuvant chemotherapy, particularly doxorubicin-based chemotherapy. Topics discussed include the incidence of doxorubicin-induced cardiotoxicity, other treatment-related late-onset adverse events, and survival outcomes in two different treatment groups.

To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann–Whitney U-tests. 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p =.662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p =.493). Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen. [ABSTRACT FROM AUTHOR]

Life expectancy for patients diagnosed with metastatic breast cancer (BC) has improved in recent years, especially due to better systemic treatment. This has led to an increased incidence of brain metastases (BM), and BC is now the leading cause of BM in women. Treatment of BM primarily consists of surgery and/or radiotherapy. We aimed to investigate survival time and prognostic factors for BC patients treated with radiotherapy for BM. During the period 1st of January 2015 to 1st of June 2020, 144 consecutive BC patients treated for BM from one centre were retrospectively analyzed. The patients were either diagnosed with BM as the first metastatic lesion, or developed BM during palliative therapy for distant non-brain metastasis. The study was approved by the Central Denmark Region. Median age at BM diagnosis was 66 years, and 90% of the patients already had extracranial metastatic disease at BM diagnosis. Median overall survival after diagnosis of BM was 6.1 months. Short survival was observed for patients with poor performance status, leptomeningeal metastasis or more than three solid BM. Several of these factors were overrepresented in patients with estrogen receptor-positive (ER+) tumours who had poorer survival than patients with different receptor status. The number of metastatic BC patients developing BM is high, and survival following local treatment remains poor. Several prognostic factors appear to influence survival after radiotherapy. Treatment of BC patients with BM should be individualized according to performance status, leptomeningeal disease, number of BM, and receptor status of the disease. [ABSTRACT FROM AUTHOR]

Given the scarcity of evidence concerning the long-term sexual health of breast cancer (BC) survivors (BC-Pop), we aimed to assess how BC treatments affect short- and long-term sexual functioning, sexual enjoyment, and body image, and compare with aged-matched women in the Norwegian general population (F-GenPop). The 349 patients in BC-Pop treated at Trondheim University Hospital in 2007–2014, were assessed in clinical controls at the hospital; before starting radiotherapy (T1, baseline), immediately after ending radiotherapy (T2), and after 3, 6, and 12 months (T3–T5), and at a long-term follow-up 7–12 years after baseline (T6). Meanwhile, F-GenPop included 2254 age-matched women in the Norwegian general population. The impact of BC treatment on sexual functioning was examined using a Linear Mixed Model. Sexual functioning, sexual enjoyment, and body image were assessed with the EORTC′s QLQ-BR23 scales and compared between the populations in the four age groups (30–49, 50–59, 60–69, and 70+ years) using means with 95% confidence intervals and Student t-test. Linear regression, adjusted for age and comorbidity was applied to estimate individual scores. BC survivors treated with mastectomy had overall lower sexual functioning than patients who had received breast-conserving surgery (p = 0.017). Although BC survivors treated with chemotherapy had lower sexual functioning than those treated without chemotherapy at T1–T5 (p = 0.044), both groups showed the same level of functioning at T6. BC-Pop exhibited significantly poorer sexual functioning (p < 0.001), lower sexual enjoyment (p < 0.05), and better body image (p < 0.001) than F-GenPop in all age groups. The impact of specific BC treatments on sexual functioning was modest; only mastectomy had a persistent negative influence. Nevertheless, all age groups in BC-Pop displayed significantly poorer sexual functioning than F-GenPop at both 12 months and up to 12 years after treatment. [ABSTRACT FROM AUTHOR]

Adjuvant therapy in the treatment of breast cancer commonly refers to therapies that supplement primary treatment, traditionally mastectomy and, more recently, breast-conserving surgery. The present paper examines the evolution of systemic therapies and radiotherapy in their role as adjuvants to mastectomy, and offers a brief description of current treatment regimens for early and locally advanced disease. [ABSTRACT FROM AUTHOR]

Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT. [ABSTRACT FROM AUTHOR]

The irradiation of sub-regions of the parotid has been linked to xerostomia development in patients with head and neck cancer (HNC). In this study, we compared the xerostomia classification performance of radiomics features calculated on clinically relevant and de novo sub-regions of the parotid glands of HNC patients. All patients (N = 117) were treated with TomoTherapy in 30–35 fractions of 2–2.167 Gy per fraction with daily mega-voltage-CT (MVCT) acquisition for image-guidance purposes. Radiomics features (N = 123) were extracted from daily MVCTs for the whole parotid gland and nine sub-regions. The changes in feature values after each complete week of treatment were considered as predictors of xerostomia (CTCAEv4.03, grade ≥ 2) at 6 and 12 months. Combinations of predictors were generated following the removal of statistically redundant information and stepwise selection. The classification performance of the logistic regression models was evaluated on train and test sets of patients using the Area Under the Curve (AUC) associated with the different sub-regions at each week of treatment and benchmarked with the performance of models solely using dose and toxicity at baseline. In this study, radiomics-based models predicted xerostomia better than standard clinical predictors. Models combining dose to the parotid and xerostomia scores at baseline yielded an AUCtest of 0.63 and 0.61 for xerostomia prediction at 6 and 12 months after radiotherapy while models based on radiomics features extracted from the whole parotid yielded a maximum AUCtest of 0.67 and 0.75, respectively. Overall, across sub-regions, maximum AUCtest was 0.76 and 0.80 for xerostomia prediction at 6 and 12 months. Within the first two weeks of treatment, the cranial part of the parotid systematically yielded the highest AUCtest. Our results indicate that variations of radiomics features calculated on sub-regions of the parotid glands can lead to earlier and improved prediction of xerostomia in HNC patients. [ABSTRACT FROM AUTHOR]

Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p <.001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p <.001), 20.1% (p <.001) and 29.9% (p <.001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT. [ABSTRACT FROM AUTHOR]

Post radiation mucosal ulcers (PRMU) after treatment for oropharyngeal squamous cell carcinoma (OPSCC) can have a huge negative impact on patients' quality of life, but little is known concerning risk factors and the impact of fraction size. Therefore, the goal of this study was to determine the pattern of PRMU development and to identify risk factors after a hypofractionated stereotactic body radiotherapy boost (SBRT) compared to conventionally fractionated radiotherapy for OPSCC. We performed a retrospective cohort study (N = 332) of OPSCC patients with ≥ 1-year disease-free survival, treated with 46 Gy Intensity Modulated Radiotherapy (IMRT) (2 Gy fractions) followed by either an SBRT boost of 16.5 Gy (5.5 Gy fractions) (N = 180), or 24 Gy IMRT (2 Gy fractions) (N = 152). PRMU (grade ≥ 2) was scored when observed > three months after the last radiotherapy (RT) fraction (CTCAE v5.0). Potential risk factors were analyzed with Cox regression models using death as competing risk. Dose at the PRMU site was calculated by projecting delineated PRMU on the planning CT. All cases of PRMU (N = 64) occurred within 24 months; all were grade 2. The cumulative incidence at 2 years in the SBRT boost group was 26% (N = 46) vs. 12% (N = 18) for conventional fractionation (p = 0.003). Most PRMU developed within nine months (N = 48). PRMU occurring > nine months (N = 16) were mainly observed in the SBRT boost group (N = 15). Sex (p = 0.048), acute tube feeding (p = < 0.001), tumor subsite tonsil (p = 0.001), and N stage (p = 0.017) were associated with PRMU risk at multivariable regression in the hypofractionated SBRT boost group. All 25 delineated PRMU were located within the high dose regions. The risk of PRMU should be included in the cost benefit analysis when considering future research using a hypofractionated SBRT boost for OPSCC patients. [ABSTRACT FROM AUTHOR]

The article reports that the spot-scanning proton arc therapy was introduced in 2016 offering superior target conformity and simplify the proton therapy treatment workflow. Topics include examines it is considered an advanced intensity modulated proton therapy (IMPT) technique through arc trajectory optimization.

Chronic fatigue (CF), substantial fatigue for ≥ six months, can manifest as a late effect (LE) after cancer treatment, and may affect several aspects of life. In a Norwegian cohort of Hodgkin's lymphoma survivors (HLS), more than a decade after contemporary risk-adapted treatment regimens with limited use of radiotherapy (RT), we assessed: (1) Prevalence of, (2) factors associated with (3) and implications of CF on socioeconomic status (SES) and work ability (WA). HLS treated between 1997–2006, aged 8–49 years at diagnosis, were invited to participate in a population-based cross-sectional study on late effects in 2018–2019. In a mailed questionnaire, HLS responded to a fatigue questionnaire (FQ), work ability score (WAS) and short-form health survey (SF-36). Disease- and treatment data were extracted from hospital records. Factors associated with CF were identified by uni- and multivariate analysis. To study the implications of CF on SES and WA, a multinomial regression analysis was performed. Invitations were extended to 518 HLS and 298 (58%) responded to FQ, of whom 42% had CF with mean (standard deviation [SD]) physical- and mental fatigue scores of 10.2 (4.3) and 5.5 (2.1) respectively. Median age at survey was 45 years, 47% were females. In multivariate analysis female sex (p = 0.03), lower education (p = 0.03), body mass index ≥30 kg/m2 (p = 0.04), and an increasing number of comorbidities (p = 0.01) were associated with CF. No association with disease stage, chemotherapy or RT was found. CF was associated with poorer WAS scores at survey (p < 0.001), unemployment (p = 0.03), and receiving disability pension (p = 0.003). After risk-adapted treatment, CF is still a frequent LE among long-term HLS, without apparent association with disease or treatment-related parameters. CF is associated with reduced WA and SES. As no apparent risk reduction is seen with contemporary treatment, further studies should emphasize etiological factors of CF and treatment to alleviate this common LE. [ABSTRACT FROM AUTHOR]

Heterogeneity in tumor sensitivity to therapy within patient populations is a major factor affecting tumor control probability (TCP) models, typically flattening dose-response curves. Knowledge of the major clinical factors affecting TCP would allow incorporation of these factors into TCP models, or stratification of patients and tumors, yielding steeper and more specific and predictive TCP curves. Methods. Literature review of the results of therapy for oropharyngeal cancer. Results. In recent years an improvement in control rates of cancers such as oropharyngeal cancer has been reported as potentially gained due to the dosimetric superiority of intensity modulated radiotherapy (IMRT). However, the emergence of Human Papilloma Virus (HPV)-related oropharyngeal cancer in recent years is an example of a major clinical factor which likely supersedes the dosimetric gains of IMRT. Conclusions. Clinical factors such as the example discussed in this paper: HPV-related oropharyngeal cancer, must be taken into account in TCP models in order for such models to be relevant. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including benefits of proton therapy for prostate cancer, stereotactic body radiation therapy (SBRT) in radiotherapy (RT) and volumetric arc therapy (VMAT) of the prostate metastases.

To assess if cancer-specific survival (CSS) following curative intent treatment (CIT) for muscle-invasive bladder cancer (MIBC) differs between patients presenting with MIBC (primary) and patients presenting with non-muscle-invasive bladder cancer who progress to MIBC (secondary). This study uses data from the Cancer Registry of Norway on patients initially diagnosed with bladder cancer in 2008–2012 and treated with radical cystectomy (RC) or radiotherapy (RT). To ensure a clinically relevant population, we selected patients with a pre-treatment histology confirming muscle-invasion. Survival models were applied to evaluate differences in observed and adjusted CSS by type of MIBC and stratified by type of CIT. Adjustment was made for age group, sex, previous cancer, diagnostic hospital's academic status and geographical region, and type of CIT. We identified 650 eligible patients: 589 (91%) primary MIBC and 61 (9%) secondary MIBC. A total of 556 (86%) patients underwent RC and 94 (14%) RT. The 5-year CSS for primary MIBC was 56% and 59% for secondary MIBC (p = 0.68). The type of MIBC did not impact the risk of bladder cancer death (HR = 0.85, CI = 0.55–1.33, p = 0.48), nor when stratified for CIT (RC: HR = 0.93, CI = 0.57–1.53, p = 0.78); RT: HR = 0.71, CI = 0.24–2.16, p = 0.55). This first nation-wide population-based study comparing CSS between primary and secondary MIBC showed no significant difference in survival regardless of type of CIT. Continued surveillance of patients with non-muscle-invasive bladder cancer is necessary to detect early progression to MIBC. Future studies should include molecular and genetic characteristics in addition to detailed clinicopathologic information. [ABSTRACT FROM AUTHOR]

Reduced planning target volume (PTV) margins are commonly used in stereotactic body radiotherapy (SBRT) of the prostate. In addition, MR-only treatment planning is becoming more common in prostate radiotherapy and compared to CT-MRI-based contouring results in notable smaller clinical target volume (CTV). Tight PTV margins coupled with MR-only planning raise a concern whether the margins are adequate enough to cover possible volumetric changes of the prostate. The aim of this study was to evaluate the volumetric change of the prostate and its effect on PTV margin during 5x7.25 Gy SBRT of the prostate. Twenty patients were included in the study. Three MRI scans, first prior to treatment (baseline), second after third fraction (mid-treatment) and third after fifth fraction (end-treatment) were acquired for each patient. Prostate contours were delineated on each MRI scan and used to assess the prostate volume and maximum prostate diameter on left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions at baseline, mid- and end-treatment. Median (IQR) change in the prostate volume relative to the baseline was 12.0% (3.1, 17.7) and 9.2% (2.0, 18.9) at the mid- and end-treatment, respectively, and the change was statistically significant (p = 0.004 and p = 0.020, respectively). Compared to the baseline, median increase in the maximum LR, SI and AP prostate diameters were 0.8, 2.3 and 1.5 mm at mid-treatment, and 0.5, 2.5 and 2.3 mm at end-treatment, respectively. If prostate contouring is based solely on MRI (e.g., in MR-only protocol), additional margin of 1–2 mm should be considered to account for prostate swelling. The study is part of clinical trial NCT02319239. [ABSTRACT FROM AUTHOR]

Chemo- and radiotherapy (RT) is standard treatment for patients with high-grade glioma, but may cause side-effects on the patient's cognitive function. Use of diffusion tensor imaging (DTI) to investigate the longitudinal changes in normal-appearing brain tissue in glioblastoma patients undergoing modern arc-based RT with volumetric modulated arc therapy (VMAT) or helical tomotherapy. The study included 27 patients newly diagnosed with glioblastoma and planned for VMAT or tomotherapy. All subjects underwent magnetic resonance imaging at the start of RT and at week 3, 6, 15, and 26. Fourteen subjects were additionally imaged at week 52. The DTI data were co-registered to the dose distribution maps. Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were assessed in the corpus callosum, the centrum semiovale, the hippocampus, and the amygdala. Significant longitudinal changes in FA, MD, and RD were mainly found in the corpus callosum. In the other examined brain structures, only sparse and transient changes were seen. No consistent correlations were found between biodose, age, or gender and changes in DTI parameters. Longitudinal changes in MD, FA, and RD were observed but only in a limited number of brain structures and the changes were smaller than expected from literature. The results suggest that modern, arc-based RT may have less negative effect on normal-appearing parts of the brain tissue up to 12 months after radiotherapy. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses several articles published within issue on topics including proton therapy indications and strategies for identification of patients for proton therapy, property of proton therapy, and patient's perspective in proton therapy.