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Purpose: We provide for the first time a comprehensive situational diagnosis and propose an artificial intelligence (AI)-assisted nationwide plan of implementation, attending the most urgent needs., Methods: Baseline information was collected from open-source databases of the Peruvian Government. Data on cancer incidence from the Health Authorities and GLOBOCAN were collected and compared. The existing external-beam radiotherapy (EBRT) devices and brachytherapy (BT) units were identified and information on their obsolescence was additionally collected. The ten most common cancer entities with RT indication were considered for the analysis. Utilizing open-source softwares, population clusters based on density, cancer incidence, geographic distribution, existing facilities able to be implemented with radiotherapy and travel times for patients were defined. A coding for identifying the best possible locations with AI was developed, keeping the allocation of resources to the minimum possible. A projection until 2030 on required resources was additionally elaborated., Results: As of 2023 eight additional EBRT and seven BT devices were needed to cover the existing demand. The artificial-intelligence algorithm yielded the regions where these resources should be primarily allocated. An increase in demand of approximately 22% is expected until 2030, which translates into additional 23 EBRT and 16 BT devices, considering the replacement of obsolete units until then., Conclusion: Increased investment pace is required to cover the existing RT demand in Peru. This AI-assisted analysis might help prioritize allocation of resources. The code employed in this work will be made publicly available, so this method could be replicated in other developing economies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to assess the effect of gadopiclenol versus gadobenate dimeglumine contrast-enhanced magnetic resonance imaging (MRI) on decision-making between whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for treatment of brain metastases (BMs)., Methods: Patients with BMs underwent 2 separate MRI examinations in a double-blind crossover phase IIb comparative study between the MRI contrast agents gadopiclenol and gadobenate dimeglumine, both administered at 0.1 mmol/kg. The imaging data of a single site using identical MRI scanners and protocols were included in this post hoc analysis. Patients with 1 or more BMs in any of both MRIs were subjected to target volume delineation for treatment planning. Two radiation oncologists contoured all visible lesions and decided upon SRS or WBRT, according to the number of metastases. For each patient, SRS or WBRT treatment plans were calculated for both MRIs, considering the gross target volume (GTV) as the contrast-enhancing aspects of the tumor. Mean GTVs and volume of healthy brain exposed to 12 Gy (V 12 ), as well as Dice similarity coefficient scores, were obtained. The Spearman rank (ρ) correlation was additionally calculated for assessing linear differences. Three different expert radiation oncologists blindly rated the contrast enhancement for contouring purposes., Results: Thirteen adult patients were included. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Of a total of 63 identified metastatic lesions in both MRI sets, 3 subgroups could be defined: A, 48 (24 pairs) detected equal GTVs visible in both modalities; B, 13 GTVs only visible in the gadopiclenol set (mean ± SD, 0.16 ± 0.37 cm 3 ); and C, 2 GTVs only visible in the gadobenate dimeglumine set (mean ± SD, 0.01 ± 0.01). Treatment indication was changed for 2 (15%) patients, 1 from no treatment to SRS and for 1 from SRS to WBRT. The mean GTVs and brain V 12 were comparable between both agents ( P = 0.694, P = 0.974). The mean Dice similarity coefficient was 0.70 ± 0.14 (ρ = 0.82). According to the readers, target volume definition was improved in 63.9% of cases (23 of 36 evaluations) with gadopiclenol and 22.2% with gadobenate dimeglumine (8 of 36), whereas equivalence was obtained in 13.9% (5 of 36)., Conclusions: Gadopiclenol-enhanced MRI improved BM detection and characterization, with a direct impact on radiotherapy treatment decision between WBRT and SRS. Additionally, a more exact target delineation and planning could be performed with gadopiclenol. A prospective evaluation in a larger cohort of patients is required to confirm these findings., Competing Interests: Conflicts of interest and sources of funding: Funded by Guerbet SA, Villepinte, France. G.R.S. received personal fees and grants from Carl Zeiss Meditec AG, not related to this work. F.A.G. reports financial support from Guerbet SA (travel expenses), nonfinancial support from Implacit GmbH (consulting, partnership) and Oncare GmbH, grants and personal fees from NOXXON Pharma AG, grants and personal fees from CARL ZEISS MEDITEC AG, personal fees from Bristol-Myers Squibb, personal fees from Roche Pharma AG, personal fees from MSD Sharp and Dohme GmbH, and personal fees from AstraZeneca GmbH, outside of the submitted work; in addition, F.A.G. has a patent pending (US 62/435405). M.B. received personal fees from Guerbet (consultation, related to this work), Seagen, Novartis, Boehringer-Ingelheim (paid lectures, not related), DFG, European Union, and Novartis (grants to the institution, not related). J.F., M. Eckl, F.S., A.R., L.C.S., A.F., D.K., M. Essig, and F.W. have nothing to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Stereotactic body radiotherapy (SBRT) is emerging as a valuable treatment modality for localized prostate cancer, with promising biochemical progression-free survival rates. Longitudinal assessment of prostate-specific antigen (PSA) is the mainstay of follow-up after treatment. PSA kinetics and dynamics are well-established in the context of brachytherapy and conventionally fractionated radiotherapy, yet little is known in the context of prostate SBRT., Methods: A review of available literature in MEDLINE, Scopus, and Embase was performed, focusing on studies reporting PSA slope, nadir, bounce, and biochemical failure after prostate SBRT., Results: Thirty-three records (45 % prospective) encompassing 9949 patients were included. SBRT dose ranged from 32-50 Gy in 4-5 fractions and overall median follow-up time (range) was 41 (15-74) months. Use of androgen deprivation therapy ranged from 0-38 %. SBRT was characterized by a steep initial decline of PSA, slowing down over time and ultimately yielding a lower nadir in comparison with conventional radiotherapy, with a median value (range) of 0.24 (0.1-0.6) ng/mL after a median time (range) of 33.1 (6-54) months. There was an inverse correlation between the highest SBRT dose in a trial and PSA nadir (r = - 0.59; p < 0.001). Benign PSA bounce occurred in 30 % of patients across all studies, after a median time (range) of 14.8 (9-36) months and with a median size (range) of 0.5 (0.3-1.1) ng/mL. There was no significant correlation between bounce and dose, nadir nor biochemical failure. There was, however, a significant inverse correlation between ADT use and PSA bounce frequency (r = -0.49; p = 0.046)., Conclusion: PSA kinetics and dynamics after SBRT for localized prostate cancer are different from those in other established radiotherapy modalities. Benign PSA bounce is very common. Clinicians should be aware of these factors and patients should be counseled accordingly, preventing unnecessary distress or salvage treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Radiotherapy plays a critical role in the management of non-metastatic lung cancer, offering curative potential and symptom relief. It serves as a primary treatment modality or adjuvant therapy post-surgery, enhancing local control and survival rates. Modern techniques like Stereotactic Body Radiotherapy (SBRT) enable precise tumor targeting, minimizing damage to healthy tissue and reducing treatment duration. The synergy between radiotherapy and systemic treatments, including immunotherapy, holds promise in improving outcomes. Immunotherapy augments the immune response against cancer cells, potentially enhancing radiotherapy's efficacy. Furthermore, radiotherapy's ability to modulate the tumor microenvironment complements the immunotherapy's mechanism of action. As a result, the combination of radiotherapy and immunotherapy may offer superior tumor control and survival benefits. Moreover, the integration of radiotherapy with surgery and chemotherapy in multidisciplinary approaches maximizes treatment efficacy while minimizing toxicity. Herein we present an overview on modern radiotherapy and potential developments in the close future., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background and Purpose: In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy., Materials and Methods: MEDLINE, Embase, and Scopus were searched with the terms "Hippocampus", "Brain Neoplasms", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included., Results: Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 - 27 %) and 9.2 % (3 - 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 - 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17)., Conclusion: The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the value of radiation therapy (RT) with helical tomotherapy (HT) in the management of locally advanced malignant pleural mesothelioma (MPM) receiving no or lung-sparing surgery., Methods: Consecutive MPM cases not undergoing extrapleural pneumonectomy and receiving intensity-modulated (IM) HT were retrospectively evaluated for local control, distant control, progression-free survival (PFS), and overall survival (OS). Impact of age, systemic treatment, RT dose, and recurrence patterns was analyzed by univariate and multivariate analysis. As a secondary endpoint, reported toxicity was assessed., Results: A total of 34 localized MPM cases undergoing IMHT were identified, of which follow-up data were available for 31 patients. Grade 3 side effects were experienced by 26.7% of patients and there were no grade 4 or 5 events observed. Median PFS was 19 months. Median OS was 20 months and the rates for 1‑ and 2‑year OS were 86.2 and 41.4%, respectively. OS was significantly superior for patients receiving adjuvant chemotherapy (p = 0.008)., Conclusion: IMHT of locally advanced MPM after lung-sparing surgery is safe and feasible, resulting in satisfactory local control and survival. Adjuvant chemotherapy significantly improves OS. Randomized clinical trials incorporating modern RT techniques as a component of trimodal treatment are warranted to establish an evidence-based standard of care pattern for locally advanced MPM., (© 2023. The Author(s).)

Purpose: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs)., Methods and Materials: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival., Results: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival., Conclusions: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: A correct placement of the applicator during intraoperative radiation therapy for brain metastasis is of paramount importance, to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation because the applicator itself limits the visual range. No image guided verification is currently performed intracranially. We hypothesize that image guided intraoperative radiation therapy would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience., Methods and Materials: Phantom-based measurements were performed to reach the best cone beam computed tomography imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room cone beam computed tomography device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required., Results: An optimal image quality was achieved with 120-kV voltage, 20-mA current, and a tube current time product of 150 mAs. An additional 0.51 mSv patient exposure was calculated for the entire procedure. The wide dynamic range (-600 HU to +600 HU) of cone beam computed tomography and a 27 HU mean computed tomography values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact., Conclusions: This first in-human procedure confirmed the feasibility of kilovoltage image guided intraoperative radiation therapy in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details., Competing Interests: Gustavo R. Sarria reports no personal fees and travel expenses from Carl Zeiss Meditec AG, not related to this work; speakers funding from Buro Carl Zeiss Meditec AG. Molina Grimmer reports travel expenses from Carl Zeiss Meditec AG, not related to this work. Hartmut Vatter reports travel expenses from Carl Zeiss Meditec AG, not related to this work., (© 2024 The Author(s).)

Background: Radiation dermatitis (RD) remains the most common side effect in radiation therapy (RT) with various pharmaceutical options available for prevention and treatment. We sought to determine pharmaceutical management patterns of radiation dermatitis among radiation oncology professionals., Methods: We conducted a survey on RD among the German-speaking community of radiation oncologists inquiring for their opinion on preventive and therapeutic pharmaceutical approaches for acute RD., Results: 244 health professionals participated. Dexpanthenol lotion is the agent most widely used both for prevention (53.0%) and treatment (76.9%) of RD, followed by urea (29.8%) for prevention and corticosteroids (46.9%) for treatment. A wide range of substances is used by participants, though the overall experience with them is rather limited. 32.5% of participants do generally not recommend any preventative treatment. 53.4% of participants recommend alternative medicine for RD management. While seldomly used, corticosteroids were considered most effective in RD therapy, followed by dexpanthenol and low-level laser therapy. A majority of participants prefers moist over dry treatment of moist desquamation and 43.8% prescribe antiseptics., Conclusions: Pharmaceutical management of RD in the German-speaking radiation oncology community remains controversial, inconsistent, and partially not supported by evidence-based medicine. Stronger evidence level and interdisciplinary consensus is required amongst practitioners to improve these care patterns., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37-73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI ( p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness ( p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use.

Background and Purpose: To investigate the effect of topical non-invasive physical plasma (NIPP), a volatile mix generated out of ambient air, on prevention of acute radiation dermatitis (RD) during and after whole-breast irradiation (WBI)., Materials and Methods: Lateral and medial breast halves were randomised within each patient to receive either 120 s of NIPP or sham treatment daily during WBI. Standard skin care with urea lotion was applied to the whole breast. Blinded acute skin toxicity was assessed weekly for each breast half separately and included clinician- (CTCAE) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. As an additional external control, a comparable standard of care (SoC) patient collective from a previous prospective trial was used., Results: Sixty-four patients were included. There were no significant differences between breast halves. Post-hoc comparison with a similar SoC control collective revealed OR = 0.28 (95% CI 0.11-0.76; p  = 0.014) for grade ≥ 2 RD upon WBI completion, along with less hyperpigmentation ( p  < 0.001), oedema ( p  = 0.020), dry ( p  < 0.001) and moist desquamation ( p  = 0.017), pain, itching, and burning ( p  < 0.001 for each). Tolerability of NIPP was excellent and side effects were not observed., Conclusion: Even though there were no differences between intrapatient-randomised breast halves, the overall incidence and severity of acute radiation-induced skin toxicity were considerably lower when compared to a prospectively collected SoC cohort. Our data suggest the potential benefit of NIPP in RD prevention. A randomised trial with a physical control group is warranted to confirm these promising results (DRKS00026225)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: The study's purpose was to compare the performance of artificial intelligence (AI) in auto-contouring compared with a human practitioner in terms of precision, differences in dose distribution, and time consumption., Methods and Materials: Datasets of previously irradiated patients in 3 different segments (head and neck, breast, and prostate cancer) were retrospectively collected. An experienced radiation oncologist (MD) performed organs-at-risk (OARs) and standard clinical target volume delineations as baseline structures for comparison. AI-based autocontours were generated in 2 additional CT copies; therefore, 3 groups were assessed: MD alone, AI alone, and AI plus MD corrections (AI+C). Differences in Dice similarity coefficient (DSC) and person-hour burden were assessed. Furthermore, changes in clinically relevant dose-volume parameters were evaluated and compared., Results: Seventy-five previously treated cases were collected (25 per segment) for the analysis. Compared with MD contours, the mean DSC scores were higher than 0.7 for 74% and 80% of AI and AI+C, respectively. After corrections, 17.1% structures presented DSC score deviations higher than 0.1 and 10.4% dose-volume parameters significantly changed in AI-contoured structures. The time consumption assessment yielded mean person-hour reductions of 68%, 51%, and 71% for breast, prostate, and head and neck cancer, respectively., Conclusions: In great extent, AI yielded clinically acceptable OARs and certain clinical target volumes in the explored anatomic segments. Sparse correction and assessment requirements place AI+C as a standard workflow. Minimal clinically relevant differences in OAR exposure were identified. A substantial amount of person-hours could be repurposed with this technology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Purpose: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers., Methods: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD., Results: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices., Conclusion: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns., (© 2023. The Author(s).)

Purpose: Radiation dermatitis (RD) is the most common side effect of adjuvant whole-breast or chest wall irradiation, majorly impacting quality of life in numerous patients. The use of barrier films (polyurethane dressings such as Hydrofilm® and Mepitel® film remaining on the skin for the duration of the radiation treatment) has been investigated as a prophylactic measure in several prospective trials. Here, we critically appraise the available evidence behind preventive barrier film application in the context of breast cancer treatment., Methods: International literature was reviewed and high-quality randomised controlled trials (RCTs) were included in this meta-analysis., Results: The results of 5 RCTs (663 patients; >90% Caucasian) were analysed. Overall, barrier films lead to improved clinician- and patient-reported outcomes: fewer grade ≥2 RD (11% vs. 42%; OR = 0.16; p < 0.001) and moist desquamation (2% vs. 16%; OR = 0.12; p = 0.006), as well as less patient-reported pain (standardised mean difference [SMD] -0.51; p < 0.001), itching (SMD -0.52; p = 0.001), burning (SMD -0.41; p = 0.011), and limitations in daily activities (SMD -0.20; p = 0.007). Furthermore, barrier films have a high acceptance rate among patients, as well as a favourable cost-benefit ratio. Possible side effects due to its application are mild and mostly self-limiting. Overall, there was a lack of information on the radiation treatment techniques used., Conclusion: The evidence presented in this meta-analysis suggests that barrier films are an excellent tool in the prevention of RD among Caucasian patients receiving whole-breast or chest wall irradiation. Its use should therefore be considered routinely in these patients., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time., Methods: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups., Results: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001)., Conclusion: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT., (© 2023. The Author(s).)

Modern irradiation techniques for optimized conformal TBI can be realized by Helical Tomotherapy (HT) or Volumetric Modulated Arc Therapy (VMAT), depending on the availability of suitable specialized equipment. In this dosimetric planning study, we compared both modalities and addressed the question of whether VMAT with small field sizes is also suitable as a backup in case of HT equipment malfunctions. For this purpose, we retrospectively used planning computed tomography (CT) data from 10 patients treated with HT with a total dose of 8 Gy (n = 5) or 12 Gy (n = 5) for treatment planning for VMAT with a small field size (36 × 22 cm). The target volume coverage, dose homogeneity at target volume, and dose reduction in organs at risk (OAR) (lungs, kidneys, lenses) were analyzed and compared. One patient was irradiated with both modalities due to a device failure of the HT equipment during the study, which facilitated a comparison in a real clinical setting. The findings indicate that in addition to a higher mean dose to the lenses in the 12 Gy group for VMAT and a better dose homogeneity in the target volume for HT, comparably good and adequate target dose coverage and dose reduction in the other OAR could be achieved for both modalities, with significantly longer treatment times for VMAT. In conclusion, after appropriate optimization of the treatment times, VMAT using linear accelerator radiosurgery technology can be used both as a backup in addition to HT and in clinical routines to perform optimized conformal TBI.

Purpose: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT., Methods: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection., Results: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively)., Conclusion: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT., (© 2023. The Author(s).)

Background: Intensity-modulated helical tomotherapy (HT) is a promising technique in preparation for bone marrow transplantation. Nevertheless, radiation-sensitive organs can be substantially compromised due to suboptimal delivery techniques of total body irradiation (TBI). To reduce the potential burden of radiation toxicity to organs at risk (OAR), high-quality coverage and homogeneity are essential. We investigated dosimetric data from kidney, lung and thorax, liver, and spleen in relation to peripheral blood kinetics. To further advance intensity-modulated total body irradiation (TBI), the potential for dose reduction to lung and kidney was considered in the analysis., Patients and Methods: 46 patients undergoing TBI were included in this analysis, partially divided into dose groups (2, 4, 8, and 12 Gy). HT was performed using a rotating gantry to ensuring optimal reduction of radiation to the lungs and kidneys and to provide optimal coverage of other OAR. Common dosimetric parameters, such as D05, D95, and D50, were calculated and analysed. Leukocytes, neutrophils, platelets, creatinine, GFR, haemoglobin, overall survival, and graft-versus-host disease were related to the dosimetric evaluation using statistical tests., Results: The mean D95 of the lung is 48.23%, less than half the prescribed and unreduced dose. The D95 of the chest is almost twice as high at 84.95%. Overall liver coverage values ranged from 96.79% for D95 to 107% for D05. The average dose sparing of all patients analysed resulted in an average D95 of 68.64% in the right kidney and 69.31% in the left kidney. Average D95 in the spleen was 94.28% and D05 was 107.05%. Homogeneity indexes ranged from 1.12 for liver to 2.28 for lung. The additional significance analyses conducted on these blood kinetics showed a significant difference between the 2 Gray group and the other three groups for leukocyte counts. Further statistical comparisons of the dose groups showed no significant differences. However, there were significant changes in the dose of OAR prescribed with dose sparing (e.g., lung vs. rib and kidney)., Conclusion: Using intensity-modulated helical tomotherapy to deliver TBI is a feasible method in preparation for haematopoietic stem cell transplantation. Significant dose sparing in radiosensitive organs such as the lungs and kidneys is achievable with good overall quality of coverage. Peripheral blood kinetics support the positive impact of HT and its advantages strongly encourage its implementation within clinical routine., (© 2023. The Author(s).)

Background: Total body irradiation (TBI) is often a component of the conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematological malignancies. However, total marrow irradiation (TMI) could be an alternative method for reducing radiation therapy-associated toxicity, as it specifically targets the skeleton and thus could better protect organs at risk. Here, we compared dosimetric changes in irradiation received by the target volume and organs at risk between TBI and TMI plans., Materials and Methods: Theoretical TMI plans were calculated for 35 patients with various hematological malignancies who had already received TBI in our clinic. We then statistically compared irradiation doses between the new TMI plans and existing TBI plans. We examined whether TMI provides greater protection of organs at risk while maintaining the prescribed dose in the targeted skeletal area. We also compared beam-on times between TBI and TMI., Results: TMI planning achieved significant reductions in the mean, minimum, and maximum irradiation doses in the lungs, kidneys, liver, spleen, and body (i.e., remaining tissue except organs and skeleton). In particular, the mean dose was reduced by 49% in the liver and spleen and by 55-59% in the kidneys. Moreover, TMI planning reduced the corpus beam-on time by an average of 217 s., Conclusion: TMI planning achieved significant dose reduction in organs at risk while still achieving the prescribed dose in the target volume. Additionally, TMI planning reduced the beam-on time for corpus plans despite a high modulation factor., (© 2023. The Author(s).)

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making.

Background and Purpose: This study aimed to differentially assess the frequency and severity of late radiation-induced toxicity following adjuvant whole-breast irradiation for early breast cancer with conventional fractionation (CF) and moderate hypofractionation (mHF). Materials and Methods: Patients recruited in a previous randomised controlled trial comparing acute toxicity between CF and mHF without disease recurrence were included in a post hoc analysis. Spectrophotometric and ultrasonographic examinations were performed for an objective evaluation and subsequent comparison of long-term skin toxicity. Furthermore, patient- and clinician-reported outcomes were recorded. Results: Sixty-four patients with a median age of 58 (37-81) years were included. The median follow-up was 57 (37-73) months. A total of 55% underwent CF and 45% mHF. A total of 52% received a sequential boost to the tumour bed. A significant decrease in mean L* ( p = 0.011) and an increase in a* ( p = 0.040) and b* values ( p < 0.001) were observed, indicating hyperpigmentation. In comparison with the non-irradiated breast, there was a significant increase in both cutis (+14%; p < 0.001) and subcutis (+17%; p = 0.011) thickness, significantly more pronounced in CF patients ( p = 0.049). In CF patients only, a sequential boost significantly increased the local cutis thickness and oedema compared to non-boost regions in the same breast ( p = 0.001 and p < 0.001, respectively). Conclusions: mHF objectively resulted in reduced long-term skin toxicity compared to CF. A sequential boost increased the local fibrosis rate in CF, but not in mHF. This might explain the subjectively reported better cosmetic outcomes in patients receiving mHF and reinforces the rationale for favouring mHF as the standard of care.

Purpose: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts., Methods and Materials: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030., Results: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) $349,650,480 in 2020 would have covered the existing demand. An investment of US $872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only., Conclusions: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen has shown strong efficacy as perioperative therapy for patients with locally advanced gastric (GC) and gastroesophageal (AEG) carcinoma. In the palliative situation, FLOT is recommended only for young fit patients. Data of efficacy and tolerability of FLOT in elderly patients are scarce and controversial. Thus, this study aimed to provide real-life experience of elderly patients with GC and AEG treated with FLOT as first-line palliative chemotherapy., Methods: Patients with advanced or metastatic GC or AEG and treated with FLOT as first-line palliative therapy between 2010 and 2021 were analyzed. Patients were grouped into < 65 years old (n = 35) and ≥ 65 years old (n = 22) groups. Overall survival (OS), progression-free survival (PFS), feasibility and toxicity were analyzed., Results: The median OS was 10.4 months with no significant difference between both groups (HR 0.86; 95% CI 0.48, 1.57; p = 0.632). The ECOG performance status showed powerful influence on OS in the subgroup analysis with median OS of 12.3 months for ECOG = 0 compared to 5.0 months for ECOG ≥ 1 (p = 0.015) as well as in multivariate analysis (HR 2.62; 95% CI 1.36, 5.04; p = 0.004)., Conclusion: In the present study the ECOG performance status showed a stronger prognostic value than patient age in FLOT as first- line therapy in a real-life cohort with advanced and metastatic GC and AEG. The performance status should therefore be considered in the therapeutic decision making of elderly patients with GC and AEG., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Breast cancer patients often engage in shared decision-making to select an individualized treatment regimen from multiple options. However, dissatisfaction with treatment outcomes can lead to decision regret. We evaluated decision regret and physical and psychological well-being among breast cancer patients who underwent adjuvant radiotherapy and explored their associations with patient, tumor, treatment, and symptom characteristics., Methods: This cross-sectional study involved retrospectively obtaining clinical data and data collected through interviews carried out as part of regular long-term medical aftercare. Decision regret regarding the radiotherapy was assessed using the Ottawa Decision Regret Scale, physical and psychological well-being were assessed using the PROMIS Global Health-10 questionnaire, and patients were asked about their treatment outcomes and symptoms. The questionnaire was administered 14 months to 4 years after completion of radiotherapy., Results: Of the 172 included breast cancer patients, only 13.9% expressed high decision regret, with most patients expressing little or no decision regret. More decision regret was associated with volumetric modulated arc therapy, chest wall irradiation, use of docetaxel as a chemotherapy agent, lymphangiosis carcinomatosa, new heart disease after radiotherapy, and lower psychological well-being., Conclusion: Although most patients reported little or no decision regret, we identified several patient, treatment, and symptom characteristics associated with more decision regret. Our findings suggest that psychological well-being influences patients' satisfaction with therapy decisions, implying that practitioners should pay special attention to maintaining psychological well-being during shared decision-making and ensuring that psychological assessment and treatment is provided after cancer therapy to deal with long-term effects of radiotherapy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally., Material and Methods: 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver., Results: The median FU time was 1 year [6-48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2 α/β=3 Gy ( p  = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT ( p  < 0.0001). The volume reduction decelerated longitudinally for both MMA ( p  < 0.0001) and liver size ( p  = 0.0033). Radiation doses (PTV-BED α/β=3 Gy and 10 Gy ) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2 α/β=3 Gy > 18 Gy were characterized by greater MMA volumes ( p  = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2 α/β=3 Gy ≤ 18 Gy ( p  < 0.0001)., Conclusion: Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU.

Background: Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics., Methods: Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT 1 ) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT 2-n ) (IGRT scenario). Two additional TPs were generated on sCT 2-n : one minimizing the lung-dose while preserving the D 95% (PTV) (isoeffective scenario), the other escalating the D 95% (PTV) with a constant V 20Gy (lung ipsilateral ) (isotoxic scenario)., Results: Compared to the original TPs predicted dose, the median D 95% (PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V 20Gy (lung ipsilateral ) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V 20Gy (lung ipsilateral ) by 3.1% ± 3.6%. Furthermore, the median V 5% (heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V 20Gy (lung ipsilateral ) and V 5% (heart) was feasible., Conclusions: We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials., (© 2023. The Author(s).)

Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment., Methods: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS)., Results: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1-56.2) months. The median age was 64.5 (34-92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8-23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1-56.2) months and significantly superior in those patients presenting with RN., Conclusions: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings.

Purpose: Helical tomotherapy (HT) is a viable method for delivering total body irradiation (TBI) when preparing patients for allogenic stem cell or bone-marrow transplantation. TBI can be planned to reduce the amount of radiation delivered to organs at risk, such as the lungs, with the aim of decreasing toxicity. However, it is important for the ribcage to receive the prescribed radiation dose in preparation for bone-marrow transplantation. In this retrospective study, we analyzed radiation dose coverage of the lungs and ribcage in patients who underwent TBI delivered by HT to achieve lung dose sparing., Methods: Thirty-five patients were included in the analysis and divided into three groups based on their prescribed radiation dose (4, 8, or 12 Gy). HT was performed using a rotating gantry to reduce radiation to the lungs. Dosimetric parameters for the lungs and ribcage as well as dose-volume histograms were calculated., Results: The mean lung D 95 was 60.97%, 54.77%, and 37.44% of the prescribed dose for patients receiving 4 Gy, 8 Gy, and 12 Gy, respectively. Ribcage coverage was most optimal for patients receiving 4 Gy, with a D 95 of 91.27% and mean homogeneity index of 1.17, whereas patients receiving 12 Gy had a mean D 95 of 78.65% and homogeneity index of 1.37, which is still within the range recommended by treatment guidelines., Conclusions: Using HT to achieve lung tissue sparing is a viable approach to minimizing pulmonic complications in patients undergoing TBI. As this planning adjustment does not compromise the dose and quality of coverage received by the ribcage, it is a feasible tool within conditioning regimens for allogeneic bone-marrow transplantation., (© 2022. The Author(s).)

Background: Helical TomoTherapy ® is widely used for total body irradiation as a component of conditioning regimens before allogeneic bone-marrow transplantation. However, this technique limits the maximum length of a planning target volume to 135 cm. Therefore, patients taller than 135 cm require two planning computed tomography scans and treatment plans. The junctional target between these two treatment plans is thus a critical region for treatment planning and delivery. Here, we compare radiation coverage of the junctional target between helical and static approaches to treatment planning and delivery to determine which approach allows high quality irradiation planning and provides more robustness against patient movement., Methods: We retrospectively analyzed 10 patients who underwent total body irradiation using a static four-field box planning approach and nine patients who underwent total body irradiation using a helical planning approach. All patients were taller than 135 cm. The junctional target volume was divided into 10 slices of 1 cm thickness (JT 1 -JT 10 ) for analysis. Dosimetric parameters and dose-volume histograms were compared to assess the quality of coverage of the junctional target between the helical and static planning approaches., Results: The D 50 for the total junctional target was slightly higher than the prescribed dose for both helical and static approaches, with a mean of 108.12% for the helical group and 107.81% for the static group. The mean D 95 was 98.44% ± 4.19% for the helical group and 96.20% ± 4.59% for the static group. The mean homogeneity index covering the entire junctional target volume was 1.20 ± 0.04 for the helical group and 1.21 ± 0.05 for the static group. The mean homogeneity index ranged from 1.08 ± 0.01 in JT 1 to 1.22 ± 0.06 in JT 6 for the helical group and from 1.06 ± 0.02 in JT 1 to 1.19 ± 0.05 in JT 6 for the static group. There were no significant differences in parameters between helical and static groups. However, the static approach provided robustness against up to 30 mm of lateral movement of the patient., Conclusions: As long as TBI using helical TomoTherapy ® is limited to a maximum length of 135 cm, the junctional target must be addressed during treatment planning. Our analysis shows that the static four-field box approach is viable and offers higher robustness against lateral movement of the patient than the helical approach., (© 2022. The Author(s).)

Objective. The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs. Approach. A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses. Main results. Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R 2  = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%. Significance. An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs., (© 2022 IOP Publishing Ltd.)

Radiation dermatitis (RD) is the most common acute side effect of breast irradiation. More than a century following the therapeutic utilisation of X-rays, potent preventative and therapeutic options are still lacking. Non-invasive physical plasma (NIPP) is an emerging approach towards treatment of various dermatological disorders. In this study, we sought to determine the safety and feasibility of a NIPP device on RD. Thirty patients undergoing hypofractionated whole-breast irradiation were included. Parallel to radiation treatment, the irradiated breast was treated with NIPP with different application regimens. RD was assessed during and after NIPP/radiation, using clinician- and patient-reported outcomes. Additionally, safety and feasibility features were recorded. None of the patients was prescribed topical corticosteroids and none considered the treatment to be unpleasant. RD was less frequent and milder in comparison with standard skin care. Neither NIPP-related adverse events nor side effects were reported. This proven safety and feasibility profile of a topical NIPP device in the prevention and treatment of RD will be used as the framework for a larger intrapatient-randomised double-blind placebo-controlled trial, using objective and patient-reported outcome measures as an endpoint., Competing Interests: None of the authors declared any conflict of interest or personal, financial, professional, political, or legal interes that could have a significant chance of interfering with the data presented here. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Purpose: To compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery., Methods: Sixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%., Results: The Median follow-up was 4.93 (0.57-8.65) years for R-HF and 5.02 (0.65-8.72) years for L-NF (p=0.236). The median age was 68 (60-83 and 60-80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273-2805) cm 3 (R-HF) and 1058.28 (315-2709) cm 3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found., Conclusion: In this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT., Competing Interests: GS: Personal fees and travel expenses from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Trials, travel costs from Guerbet SA, not related to this work. FW: Personal fees from Roche Pharma AG and Eli Lilly and Company, grants and others from Carl Zeiss Meditec AG and Elekta AB, a patent by Carl Zeiss Meditec AG, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a declared a past co-authorship with one of the authors FW., (Copyright © 2022 Sarria, Welzel, Polednik, Wenz and Abo-Madyan.)

Background: Continuing medical education in stereotactic technology are scarcely accessible in developing countries. We report the results of upscaling a longitudinal telehealth training course on stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS), after successfully developing a pilot course in Latin America., Methods: Longitudinal training on SBRT and SRS was provided to radiation oncology practitioners in Peru and Colombia at no cost. The program included sixteen weekly 1-hour live conferencing sessions with interactive didactics and a cloud-based platform for case-based learning. Participant-reported confidence was measured in 16 SBRT/SRS practical domains, based on a 1-to-5 Likert scale. Pre- and post-curriculum exams were required for participation credit. Knowledge-baseline, pre- and post-curriculum surveys, overall and single professional-group confidence changes, and exam results were assessed., Results: One hundred and seventy-three radiotherapy professionals participated. An average of 56 (SD ±18) attendees per session were registered. Fifty (29.7%) participants completed the pre- and post-curriculum surveys, of which 30% were radiation oncologists (RO), 26% radiation therapists (RTT), 20% residents, 18% medical physicists and 6% neurosurgeons. Significant improvements were found across all 16 domains with overall mean +0.55 (SD ±0.17, p<0.001) Likert-scale points. Significant improvements in individual competences were most common among medical physicists, RTT and residents. Pre- and post-curriculum exams yielded a mean 16.15/30 (53.8 ± 20.3%) and 23.6/30 (78.7 ± 19.3%) correct answers (p<0.001)., Conclusion: Longitudinal telehealth training is an effective method for improving confidence and knowledge on SBRT/SRS amongst professionals. Remote continuing medical education should be widely adopted in lower-middle income countries., Competing Interests: GRS, grants and personal fees from Carl Zeiss Meditec AG and personal fees from Roche Pharma AG, not related to this work. GJS, personal fees from Carl Zeiss Meditec AG, not related to this work. FG reports research grants and travel expenses from ELEKTA AB, grants, stocks, travel expenses and honoraria from NOXXON Pharma AG, research grants, travel expenses and honoraria from Carl Zeiss Meditec AG, travel expenses and honoraria from Bristol-Myers Squibb, Roche Pharma AG, MSD Sharp and Dohme GmbH and AstraZeneca GmbH, non-financial support from Oncare GmbH and Opasca GmbH. IC, research grants and travel expenses from Varian Medical Systems, Inc., research grants from Phillips Healthcare. GRS, RT, MH, SM, BC, RC, DM, IC, DR, and BL are volunteer non-paid members of Rayos Contra Cancer, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sarria, Timmerman, Hermansen, Malhotra, Chang, Carter, Martinez, Sarria, Giordano, Chetty, Roa and Li.)

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort., Materials/methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors., Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%., Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings., Competing Interests: GS: personal fees and travel costs from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Trials, travel costs from Guerbet SA, not related to this work. FW: reports personal fees from Celgene GmbH, fees Roche Pharma AG, fees Eli Lilly and Company, fees from Ipsen Pharma GmbH and grants and other from Carl Zeiss Meditec AG and Elekta AB, patent by Carl Zeiss Meditec AG, not related to this work, outside the submitted work. FG: grants and personal fees from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, grants and personal fees from Elekta AB, grants and personal fees from NOXXON Pharma AG, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from MSD Sharp and Dome GmbH, grants and personal fees from AstraZeneca GmbH, non-financial support from ONCARE GmbH, non-financial support from OPASCA GmbH, outside the submitted work. GS: personal fees and travel costs from Carl Zeiss Meditec AG, not related to this work. ES: grants from the Ministry for Science and Arts and others from Carl Zeiss Meditec, outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sarria, Ramos, Palacios, Del Castillo, Castro, Calvo, Cotrina, Heredia, Galarreta, Fuentes-Rivera, Avalos, Martinez, Colqui, Ziegler, Schmeel, Pinillos, Wenz, Giordano, Sarria and Sperk.)

Intraoperative radiotherapy (IORT) of the operative cavity for surgically treated brain metastasis (BM) has gained increasing prominence with respect to improved local tumor control. However, IORT immediately performed at the time of surgery might be associated with increased levels of perioperative adverse events (PAEs). In the present study, we performed safety metric profiling in patients who had undergone surgery for BM with and without IORT in order to comparatively analyze feasibility of IORT as an adjuvant radiation approach. Between November 2020 and October 2021, 35 patients were surgically treated for BM with IORT at our neuro-oncological center. Perioperative complication profiles were collected in a prospective observational cohort study by means of patient safety indicators (PSIs), hospital-acquired conditions (HACs), and specific cranial-surgery-related complications (CSCs) as high-standard quality metric tools and compared to those of an institutional cohort of 388 patients with BM resection without IORT in a balanced comparative matched-pair analysis. Overall, 4 out of 35 patients (11%) with IORT in the course BM resection suffered from PAEs, accounting for 3 PSIs (9%) and 1 HAC (3%). Balanced matched-pair analysis did not reveal significant differences in the perioperative complication profiles between the cohorts of patients with and without IORT ( p = 0.44). Thirty-day mortality rates were 6% for patients with IORT versus 8% for patients without IORT ( p = 0.73). The present study demonstrates that IORT constitutes a safe and clinically feasible adjuvant treatment modality in patients undergoing surgical resection of BM.

Aims: To carry out a dosimetric comparison and constraints feasibility proof of adjuvant radiotherapy through helical tomotherapy or volumetric modulated arc therapy (VMAT) for malignant pleural mesothelioma patients after pleurectomy/decortication., Materials and Methods: Retrospective calculations were carried out on previously acquired simulations. A whole-pleura volume with 50.4 Gy in 28 fractions was prescribed, simulating a no residual tumour situation. Calculations were carried out using an anisotropic analytical algorithm with a 2.0 mm grid. Beam-on time, planning target volume (PTV) coverage, homogeneity index and organ at risk exposure were compared., Results: Sixteen patient plans were calculated per device. Constraints were met overall by both modalities. For helical tomotherapy and VMAT plans, median beam-on times were 13.8 (11.6-16.1) min and 6.4 (6.1-7.0) min; P = 0.006. The median left-sided radiotherapy PTV D 98 were 48.1 (48.0-48.8) Gy and 47.6 (46.5-48.3) Gy; P = 0.023. No significant difference for right-sided radiotherapy was found. PTV D 2 for left-sided radiotherapy was higher with VMAT (P = 0.014). For right-sided radiotherapy, helical tomotherapy showed higher doses (P = 0.039). No homogeneity index differences for left-sided radiotherapy (P = 1.00) and right-sided radiotherapy (P = 0.598) were seen. Significant organ at risk exposure differences were found on left-sided radiotherapy whole-lung V 20, as well as D 50 (both P = 0.008). Higher contralateral lung and ipsilateral kidney exposures were found with VMAT plans for both treatment sides., Conclusion: Adjuvant radiotherapy after pleurectomy/decortication in malignant pleural mesothelioma patients, with a VMAT- or helical tomotherapy-based platform, is dosimetrically feasible. Lung sparing was mostly improved with helical tomotherapy. Technique selection must be carried out according to availability and clinical criteria., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic has forever affected healthcare and posed an incredible challenge to our society to care for our sick. Patients with cancer were found early on to have higher rates of complications with COVID-19. Radiation therapy is an integral part of treatment for many types of gynecologic cancer and adaptation on its utilization during the pandemic varied across the globe. In this review, we detail certain guidelines for the use of radiation in gynecologic cancers during the pandemic as well as real world accounts of how different countries adapted to these guidelines or created their own based on individualized resources, staffing, government restrictions, and societal norms. Critically, this review demonstrates the breadth of fractionation schemes and technologies used when resources were limited but highlights the importance of long term follow-up for many of our patients during this time., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

A disproportionate burden of gynecologic malignancies occurs in low- and middle-income countries. Radiation therapy is an integral component of treatment for gynecologic malignancies both from a curative (locally advanced cervical cancer) and palliative (bleeding cervical or pelvic mass) standpoint. Critical to understanding how better to serve patients in this regard is understanding both the extent of disease epidemiology and the radiotherapy infrastructure to treat these diseases. In this review, we explore various geographic regions and how they address a unique set of challenges specific to the peoples and culture of the region. We identify common threads across regions, including sparse distribution of radiation equipment, geographic access, and specialized training. We also highlight examples of success in the use of telemedicine and cross-cultural partnerships to help bolster access to training to ensure increased access to adequate and appropriate treatment of gynecologic malignancies., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To use MC simulations and phantom measurements to investigate the dosimetry of a kilovoltage x-ray beam from an IR fluoroscope to deliver low-dose (0.3-1.0 Gy) radiotherapy to the lungs., Materials and Methods: PENELOPE was used to model a 125 kV, 5.94 mm Al HVL x-ray beam produced by a fluoroscope. The model was validated through depth-dose, in-plane/cross-plane profiles and absorbed dose at 2.5-, 5.1-, 10.2- and 15.2-cm depths against the measured beam in an acrylic phantom. CT images of an anthropomorphic phantom thorax/lungs were used to simulate 0.5 Gy dose distributions for PA, AP/PA, 3-field and 4-field treatments. DVHs were generated to assess the dose to the lungs and nearby organs. Gafchromic film was used to measure doses in the phantom exposed to PA and 4-field treatments, and compared to the MC simulations., Results: Depth-dose and profile results were within 3.2% and 7.8% of the MC data uncertainty, respectively, while dose gamma analysis ranged from 0.7 to 1.0. Mean dose to the lungs were 1.1-, 0.8-, 0.9-, and 0.8- Gy for the PA, AP/PA, 3-field, and 4-field after isodose normalization to cover ∼ 95% of each lung volume. Skin dose toxicity was highest for the PA and lowest for the 4-field, and both arrangements successfully delivered the treatment on the phantom. However, the dose distribution for the PA was highly non-uniform and produced skin doses up to 4 Gy. The dose distribution for the 4-field produced a uniform 0.6 Gy dose throughout the lungs, with a maximum dose of 0.73 Gy. The average percent difference between experimental and Monte Carlo values were -0.1% (range -3% to +4%) for the PA treatment and 0.3% (range -10.3% to +15.2%) for the 4-field treatment., Conclusion: A 125 kV x-ray beam from an IR fluoroscope delivered through two or more fields can deliver an effective low-dose radiotherapy treatment to the lungs. The 4-field arrangement not only provides an effective treatment, but also significant dose sparing to healthy organs, including skin, compared to the PA treatment. Use of fluoroscopy appears to be a viable alternative to megavoltage radiation therapy equipment for delivering low-dose radiotherapy to the lungs., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS)., Methods: We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1)., Results: IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation (p = 0.013 and p = 0.022) and GFAP expression (p < 0.001 and p = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group (p = 0.002 and p = 0.006); negativity for both factors combined did not occur in the LTS group., Conclusion: In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials., (© 2022. The Author(s).)

Access to high-quality continuing medical education, particularly in Radiation Oncology, can be challenging in some developing countries due to economic barriers. Despite the current offer of free-access self-educational material, end user training faces a backlog still difficult to overcome. The purpose of this investigation is to report the willingness-to-pay profile of practitioners in Latin America, as a surrogate of quality perception of remote educational resources. Related factors include professional experience and baseline practice confidence levels. Most of practitioners would cover their own expenses, while an increased tendency in less-experienced professionals was observed. However, baseline knowledge confidence levels were not influential in decision making. This report contributes to better know the profile of Latin American professionals, in order to design future educational interventions in the region and bridging the current accessibility gap., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose/objectives: To perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases., Methods/materials: Diagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities., Results: Eight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm 3 (SD, 650.82), and the mean GTV volume was 12.23 cm 3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm 3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm 3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm 3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5-4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V 9.1 showed significantly smaller volumes with IORT [63.39 cm 3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm 3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm 3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D 90 was 85.3% (SD, 6.05), whereas D 95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively., Conclusion: Kilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis., Competing Interests: DS has stocks from AstraZeneca GmbH. MG-C received travel expenses and honoraria from Bristol-Myers Squibb, Roche, MSD, IPSEN, Eisai, Amgen, and Servier not related to this work. FG received research grants and travel expenses from ELEKTA AB; grants, stocks, travel expenses, and honoraria from NOXXON Pharma AG; research grants, travel expenses and honoraria from Carl Zeiss Meditec AG; travel expenses and honoraria from Bristol-Myers Squibb, Roche Pharma AG, MSD Sharp and Dohme GmbH and AstraZeneca GmbH; non-financial support from Oncare GmbH and Opasca GmbH, not related to this work. LS GS received personal fees from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Research BV, and travels expenses from Guerbet GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scafa, Muedder, Holz, Koch, Nour, Garbe, Gonzalez-Carmona, Feldmann, Vilz, Köksal, Giordano, Schmeel and Sarria.)

Purpose: To simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB)., Methods: Imaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors > 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V 12 ), and doses to various organs-at-risk (OARs)., Results: Seventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm 3 (SD ± 19.36) and mGTV 29.64 cm 3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm 3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D 95 was 97.13% (SD ± 3.48) the SRS D 99 99.91% (SD ± 0.35) and IORT D 90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V 12 was 49.68 cm 3 (SD ± 26.70) and 16.94 cm 3 (SD ± 13.33) (p<0.001) for SRS and IORT, respectively. After adding EBRT results respectively to SRS and IORT doses, significant lower doses were found in the latter for mean D max of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (p<0.001). No significant differences were obtained for brainstem and cochleae., Conclusion: Dose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS., Competing Interests: GS: personal fees from Carl Zeiss Meditec AG and personal fees from Roche Pharma AG, not related to this work. FG: research grants and travel expenses from ELEKTA AB; grants, stocks, travel expenses and honoraria from NOXXON Pharma AG; research grants, travel expenses and honoraria from Carl Zeiss Meditec AG; travel expenses and honoraria from Bristol-Myers Squibb, Roche Pharma AG, MSD Sharp and Dohme GmbH and AstraZeneca GmbH; non-financial support from Oncare GmbH and Opasca GmbH, not related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sarria, Smalec, Muedder, Holz, Scafa, Koch, Garbe, Schneider, Hamed, Vatter, Herrlinger, Giordano and Schmeel.)

Background: Hypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits., Methods: Treatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score., Results: Compared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V 37Gy (bladder) and V 36Gy (rectum) from a mean of 7.4cm 3 and 2.0cm 3 to (5.9cm 3 , 6.1cm 3 , 5.2cm 3 ) as well as to (1.4cm 3 , 1.4cm 3 , 1.0cm 3 ), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation., Conclusion: Treatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy., (© 2021. The Author(s).)

Purpose: To assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC)., Patients and Methods: A total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS)., Results: A total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, <0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5)., Conclusion: In well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Henkenberens, Derlin, Bengel, Ross, Kuczyk, Giordano, Sarria, Schmeel, Christiansen and von Klot.)

The aim of the study was to report on the association of trial sponsors with intervention type, treatment intent, recruitment success and reasons to terminate cancer trials. The ClinicalTrials database was searched for interventional Phase 3 cancer trials (01/2006-05/2017). Noncancer studies and ongoing studies were excluded, permanently suspended studies were counted as terminated. Trials were stratified according to sponsors (industry/nonindustry), intervention type, setting (curative/palliative) and intent of intervention (curative/symptom-control/life-extending). We identified 345 terminated trials and 1137 completed studies as a control group. The frequency of premature termination did not differ significantly between sponsors. Time to termination was shorter but recruitment per month prior to termination was higher in industry-sponsored studies (7.0 vs 2.2 patients/month; P < .001). Drug interventions were more common in industry-sponsored, all other interventions in nonindustry-sponsored settings (P < .001). Life-extending palliative interventions occurred more frequently, symptom-control interventions in a curative setting less frequently in industry-sponsored trials (both P < .001). Intervention, setting and intent were not associated with termination in industry-sponsored trials. In nonindustry-sponsored trials, the frequency of drug interventions and life-extending (noncurative) interventions were increased in terminated trials (both P < .05); symptom-control interventions in curative settings occurred more frequently in completed studies. Industry-sponsored trials were more often terminated due to toxicity/inefficacy while lack of accrual occurred more frequently in nonindustry-sponsored trials (P < .01). Interventions, treatment setting/intent and reasons for termination differed between sponsor types. In nonindustry-sponsored trials, drug interventions and life-extending (noncurative) interventions were associated with premature termination and symptom-control interventions (curative setting) were associated with trial completion., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)