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BACKGROUND: Node-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy. METHODS: A retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses. RESULTS: After a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test). CONCLUSION: Pretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

BACKGROUND: Modern radiotherapy is associated with dermatitis (RD) in approximately one-third of patients treated for breast cancer. There is currently no standard for treating RD. OBJECTIVE: The objective of this study was to determine whether LUT014, a topical BRAF inhibitor which paradoxically activates mitogen-activated protein kinase, can safely improve RD. METHODS: A phase I/II study was designed to first follow a small cohort of women with grade 2 RD regarding toxicity and response. Then, 20 patients were randomized to compare LUT014 to vehicle relative to safety and response (measured with common terminology criteria for adverse events, Dermatology Life Quality Index). RESULTS: No substantial toxicity (eg, 0 serious adverse event) was associated with LUT014. All 8 women receiving LUT014 achieved treatment success (5-point Dermatology Life Quality Index reduction at day 14) compared to 73% (8/11) on the placebo arm (P = .591). The time to complete recovery was shorter in the treatment arm. LIMITATIONS: The sample size was limited. Only 2 hospitals were included. CONCLUSIONS: Topical LU014 is tolerable and may be efficacious for grade 2 RD.

Purpose of Review: This review summarizes the clinical and radiobiologic data regarding hypofractionation in breast cancer, applying it to the postmastectomy setting in a comprehensive review of recent and ongoing trial data. Recent Findings: Experience with hypofractionated postmastectomy radiation in the 1960s demonstrated high rates of brachial plexopathy, prompting a trend towards conventionally fractionated schemas. Subsequent radiobiologic data identified that breast cancer has a relatively low α/β ratio (approximately 4 Gy). Following breast conservation, hypofractionation has maximized the therapeutic window by eradicating tumor while minimizing normal tissue effects. Postmastectomy patients, however, usually require comprehensive regional nodal irradiation and often opt for reconstruction. Five trials have shown excellent disease control and toxicity profiles with hypofractionation, with those in the modern era also supporting hypofractionation after reconstruction. Summary: Hypofractionated postmastectomy radiation is at minimum noninferior in complication rates and quality of life metrics and should be widely accepted as a standard option for appropriate patients in the post-mastectomy setting. [ABSTRACT FROM AUTHOR]

Background: The incidence of prostate cancer is increasing in Asian countries. Although moderately hypofractionated radiotherapy is not inferior to conventional fractionated radiation according to the updated guidelines, data regarding its efficacy and safety in Taiwan are currently lacking. The aim of this study was to investigate the outcomes of prostate cancer patients treated with hypofractionated image-guided radiotherapy at a single institution in Taiwan. Methods: We retrospectively included patients with prostate cancer across all risk groups who were treated with hypofractionated image-guided radiotherapy 70 Gy (Gy) in 28 fractions (at 2.5 Gy/fraction) between 2007 and 2022. We analyzed treatment efficacy by assessing overall survival, prostate cancer-specific survival, event-free survival, biochemical failure, locoregional recurrence, and distant metastasis. The safety of the treatment was evaluated through acute and late gastrointestinal (GI) and genitourinary (GU) toxicity grading based on the Radiation Therapy Oncology Group criteria. Event-free survival, overall survival, prostate cancer-specific survival, biochemical failure, locoregional recurrence, and distant metastasis were evaluated using the Kaplan–Meier method. Results: We identified 150 consecutive men with prostate cancer: 12.7% were at low risk, 32.7% were at intermediate risk, 44.6% were at high risk, and 10% had N1 disease. The median follow-up time was 68.9 months (range: 2.3–172 months). The 5-year overall survival rate was 91.7% for the entire cohort, with rates of 100%, 94.3%, 93.3% and 71.1% for the low-risk, intermediate-risk, high-risk, and N1-disease groups, respectively (p < 0.001). The 5-year event-free survival rate for all patients was 75.8%. Among the risk groups, the 5-year event-free survival rates were 100%, 86.3%, 68.3% and 52.5% for the low-risk, intermediate-risk, high-risk, and N1 disease groups, respectively (p < 0.001). Grade ≥ 2 late GI toxicity was rare (0.7%), and grade ≥ 2 late GU toxicity was observed in 9.3% of the patients. Conclusions: Hypofractionated image-guided radiotherapy, delivering 70 Gy at 2.5 Gy per fraction, is both effective and safe for Taiwanese patients with prostate cancer across all risk groups, consistent with findings from existing large randomized trials. Therefore, as a solution to enhance patient convenience, hypofractionated radiotherapy is a reasonable option for the definitive treatment of prostate cancer. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Objectives: Few studies have analyzed surgical site infections associated with hypofractionated RT. The purpose of this study was to identify risk factors for surgical site infections with a particular focus on volumetric parameters that reflect the size of the volumes treated, including tumors, surgical cavities, and breasts. Methods: A total of 145 early breast cancer patients who were surgically staged 0—II undergoing hypofractionated RT on the whole breast were retrospectively reviewed. Tumor size (cm) was measured from surgical pathology. Surgical cavity volume (cc) and breast volume (cc) were calculated by segmenting each axial slice of simulation CT. The cavity-to-breast ratio (%) was calculated as surgical cavity volume/breast volume × 100. Results: The incidence of surgical site infection was 4.8% at a median of 6.3 months after the completion of RT. In univariate analysis, tumor size (OR 2.01, p = 0.025), surgical cavity volume (OR 1.03, p = 0.013), cavity-to-breast ratio (OR 1.29, p = 0.005), and BMI (OR 1.23, p = 0.014) were significantly associated with surgical site infection. In multivariate analysis, the cavity-to-breast ratio (OR 1.24, p = 0.039) remained significantly associated with surgical site infection. Conclusions: This study highlights the importance of volumetric parameters, specifically the cavity-to-breast ratio, as significant predictors of surgical site infection in a pure cohort of early breast cancer patients undergoing breast-conserving surgery and hypofractionated RT. Tailored approaches, including the use of prophylactic antibiotics, prophylactic aspiration, and close follow-up, may reduce the morbidity associated with surgical site infection and prevent the potential compromise of tumor outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study provides valuable insights into the safety and outcomes of HF radiation therapy after mastectomy and breast reconstruction. The absence of significant differences in major implant complications between HF and CF radiotherapy groups supports the feasibility of adopting HF in this patient population. However, careful consideration of patient age and meticulous follow-up protocols remain imperative in optimizing outcomes for breast cancer patients undergoing PMRT. Of note, the limitations in the retrospective nature of our data and small number of patients may impact the generalizability of our findings. Further multi-institutional studies with extended follow-up periods could enhance our understanding of the long-term implications and benefits of HF radiotherapy in this specific clinical setting. Introduction: Radiation therapy plays an important role in the treatment of localized breast cancer. Hypofractionated (HF) radiation therapy has emerged as a promising alternative to conventional fractionation (CF) schedules, offering comparable efficacy with reduced treatment duration and costs. However, concerns remain regarding its safety and rate of toxicity, particularly in patients undergoing mastectomy with breast reconstruction. This study aimed to assess the implant-related complications in breast cancer patients receiving HF post-mastectomy radiation therapy (PMRT) and reconstruction compared to CF PMRT. Methods: A retrospective study was conducted on 59 breast cancer patients who underwent mastectomy and breast reconstruction between 2013 and 2021 and received adjuvant PMRT. Patient demographics, treatment characteristics, and implant-related complications were analyzed. Statistical tests including chi-square, Fischer's exact test, and multivariable Cox regression were employed for analysis. Results: Of the 59 patients, 29 received HF PMRT and 30 received CF PMRT. At a median follow-up of 23.4 months, there was no significant difference in major implant-related complications between the two groups (24.1% in HF vs. 33.3% in CF, p = 0.436). Most complications in the HF group occurred within the first two years post-radiation. Age over 40 was identified as a significant predictor for higher implant-related complications (p = 0.029). Conclusions: Our findings indicate that HF PMRT and reconstruction does not increase the risk of major implant-related complications compared to CF PMRT. These results align with the existing literature, supporting the safety of HF radiation in breast cancer patients who underwent mastectomy with reconstruction. [ABSTRACT FROM AUTHOR]

Background: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT‐STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow‐up to update local control and report late toxicities, as well as functional and patient‐reported outcomes. Methods: HYPORT‐STS was a single‐center, open‐label, single‐arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3‐week course of preoperative RT followed by surgery 4–8 weeks later. End points and follow‐up were analyzed from the date of surgery. Results: The median follow‐up was 43 months (interquartile range, 37–52 months), and the 4‐year local recurrence‐free survival rate was 93%. Overall RT‐related late toxicities improved with time from local therapy (p <.001), and few patients had grade ≥2 toxicities (9%; n = 8 of 88) at 2 years. These included: 2% grade ≥2 skin toxicity, 2% fibrosis, 3% lymphedema, and 1% joint stiffness. Four patients (3%) had bone fractures. Both functional outcomes, as measured by the Musculoskeletal Tumor Society Rating Scale (p <.001), and quality of life, as measured by the Functional Assessment of Cancer Therapy‐General (p <.001), improved with time from treatment, and both measures were better in follow‐up at 2 years compared with baseline. Conclusions: Long‐term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective. Higher grade late toxicities affect a minority of patients. Late toxicities decrease over time, whereas functional outcomes and health‐related quality of life seem to improve with more time from combined modality treatment. Favorable local control is maintained with long‐term follow‐up, late toxicities are lower than historical controls, and functional outcomes and quality of life improve with time. These findings suggest that preoperative, moderately hypofractionated radiotherapy delivered over 3 weeks for patients with soft tissue sarcoma is safe and effective, but a multicenter phase 3 trial comparing hypofractionated and conventionally fractionated radiotherapy is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To report a single‐institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)‐positive oropharyngeal cancer. Methods and materials: A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16‐positive squamous cell carcinoma of the oropharynx. Sixty‐seven patients (67%) were never smokers. Results: The 3‐year actuarial rates of overall survival, local‐regional control, and progression‐free survival were 94%, 93%, and 89%, respectively. Among never‐smokers, the 3‐year rates of overall survival and local–regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Conclusion: Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV‐positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de‐escalation is currently underway. [ABSTRACT FROM AUTHOR]

Breast cancer is the one of the most common cancers and causes a significant disease burden. Currently, postmastectomy radiotherapy (PMRT) is indicated for breast cancer patients with higher risk of recurrence, such as those with positive surgical margins or high-risk breast cancer (T3 with positive lymph nodes, ≥4 positive lymph nodes or T4 disease). Whether PMRT should be used in intermediate-risk breast cancer (T3 with no positive lymph nodes or T1-2 with 1-3 positive lymph nodes) is contentious. Rates of breast reconstruction postmastectomy are increasing in countries like Australia, and PMRT usage in such settings is another area of active research. Ongoing trials are also assessing the safety and efficacy of hypofractionated PMRT, a clinical scenario now widely accepted for early-stage breast cancer. This brief review is unique in that it aims to examine three current and controversial aspects of the PMRT field (PMRT in intermediate-risk breast cancer, PMRT in conjunction with breast reconstruction and its hypofractionation). To achieve this aim, we discuss available and emerging literature and guidelines to offer insights important to the PMRT field. Current literature suggests that PMRT could play a role in improving the overall survival rate and in reducing locoregional recurrence in intermediate-risk breast cancer. In terms of recommending a timing or type of breast reconstruction best suited to the setting of PMRT, we found that individual patient preferences and circumstances need to be considered alongside a multidisciplinary approach. Research into PMRT hypofractionation safety and efficacy is ongoing and its place remains to be elucidated. [ABSTRACT FROM AUTHOR]

Introduction: This study develops two new multi-institutional hippocampal-sparing whole-brain RapidPlan™ models (HLS-EC-WB and HMS-EC-WB) inspired by CCTG-CE.7 featuring enhanced target coverage with varying hippocampal sparing (limited and moderate). Methods: New dosimetric scorecards were created to quantify the models' clinical intent. The models were trained using a multi-institution dataset, and a recursive method was employed to generate consistent, high-quality plans. The models were validated using a five-case set and compared at 20- and 30-Gy prescriptions. Results: Each model scored highest on its associated dosimetric scorecard. The new models achieved higher brain PTV prescription coverage (98%–99%) compared to the previous HSWBv2 model (95.12%), with some trade-off in hippocampal sparing. Conclusions: Three high-quality automated RapidPlan™ models for hippocampal-sparing whole brain are now available, each with a distinct dosimetric scorecard. The new models prioritize increased PTV coverage at some expense to hippocampal sparing. All models, example plans, scorecards, and scoring tools are freely available online. [ABSTRACT FROM AUTHOR]

In this paper, we review the use of hypofractionated radiotherapy for gastrointestinal malignancies, focusing on primary and metastatic liver cancer, and recurrent rectal cancer. Technological advancements in radiotherapy have facilitated the direct delivery of high-dose radiation to tumors, while limiting normal tissue exposure, supporting the use of hypofractionation. Hypofractionated radiotherapy is particularly effective for primary and metastatic liver cancer where high-dose irradiation is crucial to achieve effective local control. For recurrent rectal cancer, the use of stereotactic body radiotherapy offers a promising approach for re-irradiation, balancing efficacy and safety in patients who have been administered previous pelvic radiotherapy and in whom salvage surgery is not applicable. Nevertheless, the potential for radiation-induced liver disease and gastrointestinal complications presents challenges when applying hypofractionation to gastrointestinal organs. Given the lack of universal consensus on hypofractionation regimens and the dose constraints for primary and metastatic liver cancer, as well as for recurrent rectal cancer, this review aims to facilitate clinical decision-making by pointing to potential regimens and dose constraints, underpinned by a comprehensive review of existing clinical studies and guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Head and Neck Cancer (HNC) accounts for 14.3% of all cancers in India and 4.8% of all cancers worldwide. In India, the most common sites are the lip and oral cavity (>80%), which are more prevalent in men than in women. Histologically, most cases are Squamous Cell Carcinomas (SCC). The majority of patients present with locally advanced stages, where surgery and definitive chemoradiation therapy are not possible and palliative Radiotherapy (RT) is considered a treatment option for better symptomatic relief and improved Quality of Life (QoL). The Quad Shot (QS) palliative regimen has shortened treatment time, reduced toxicity and increased compliance. Aim: To compare the QS regimen administered over two consecutive days versus the Conventional Palliative Regimen in the treatment of locally advanced HNC, in terms of treatment response, acute toxicities and QoL. Materials and Methods: In this prospective randomised clinical trial conducted from May 2023 to July 2024 in the Department of Radiation Oncology at King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India, patients with biopsy-proven locally advanced carcinoma of the head and neck were recruited, with a sample size of 50 in each of the study Group B and control Group A arms. Patients in the control arm received 30 Gray (Gy) in 10 fractions, 5 fractions per week over two weeks (Conventional palliative arm). In the study arm, patients received 14 Gy in 4 fractions delivered in two daily sessions, six to eight hours apart, for two consecutive days over three cycles (QS arm). The Response Evaluation Criteria in Solid Tumours (RECIST) Criteria 1.1 was used to assess the tumour response objectively three months post-RT. Health-related QoL was assessed using questionnaires developed by the European Organisation for Research and Treatment of Cancer (EORTC), specifically the EORTC Quality of Life Questionnaire (QLQ). Continuous data were compared using the t-test for nominal data and the Mann-Whitney U test was used otherwise. Results: The mean age was 39.66±12.05 years in Group A and 42.76±11.65 years in Group B. The QS and conventional palliative arms each had 47 and 49 patients recruited, respectively. The QS arm exhibited fewer instances of skin toxicity, with 25 (53.2%) experiencing Grade I and 7 (14.9%) experiencing Grade II toxicity, compared to the conventional palliative arm, where 30 (61.2%) had Grade I and 12 (24.5%) had Grade II toxicity. Mucositis in the QS arm included 22 (46.9%) cases, with 14 (29.7%) classified as Grade I and Grade II, whereas the conventional arm had 12 (24.5%) Grade I cases, 29 (59.5%) Grade II cases and 3 (6.1%) Grade III cases. The treatment response, in terms of partial and stable disease combined, was observed in 61.2% of the conventional arm compared to 78.7% in the QS arm. QoL was reported to be better in the QS regimen post-treatment. Conclusion: Given the total number of patients recruited, the QS arm, with its shorter treatment time, demonstrated better benefits in terms of reduced toxicities and improved treatment response, as well as enhanced QoL compared to the conventional palliative arm. [ABSTRACT FROM AUTHOR]

In the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. BIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). 61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. Focal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. NCT02125175. • Focal boosting is a safe prostate radiotherapy technique with a low toxicity profile. • It can be used with moderately fractionated radiotherapy schedules (20 fractions). • High-risk localised prostate cancer patients achieve excellent long-term outcomes. • Patients with PET-avid pelvic lymph nodes were treated with prostate focal boost, pelvic node and nodal boost radiotherapy. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) without androgen deprivation therapy (ADT) has lower rates of incontinence and sexual dysfunction, with a small trade-off in bowel bother, compared with prostatectomy. At 2 yr, 50% of men who underwent prostatectomy reported using urinary pads, compared with 6.5% who underwent SBRT, whilst only a modest reduction in the Expanded Prostate Index Composite (EPIC) bowel domain score was seen for SBRT compared with that for prostatectomy. Prostatectomy participants reported worse sexual function at 2 yr. Randomised data on patient-reported outcomes (PROs) for stereotactic body radiotherapy (SBRT) and prostatectomy in localised prostate cancer are lacking. PACE-A compared patient-reported health-related quality of life after SBRT with that after prostatectomy. PACE is a phase 3 open-label, randomised controlled trial. PACE-A randomised men with low- to intermediate-risk localised prostate cancer to SBRT or prostatectomy (1:1). Androgen deprivation therapy (ADT) was not permitted. The coprimary outcomes were the Expanded Prostate Index Composite (EPIC-26) number of absorbent urinary pads required daily and bowel domain score at 2 yr. The secondary endpoints were clinician-reported toxicity, sexual functioning, and other PROs. In total, 123 men were randomised (60 undergoing prostatectomy and 63 SBRT) from August 2012 to February 2022. The median follow-up time was 60.7 mo. The median age was 65.5 yr and the median prostate-specific antigen (PSA) value 7.9 ng/ml; 92% had National Comprehensive Cancer Network (NCCN) intermediate-risk disease. Fifty participants received prostatectomy and 60 received SBRT. At 2 yr, 16/32 (50%) prostatectomy and three of 46 (6.5%) SBRT participants used one or more urinary pads daily (p < 0.001; 15 and two, respectively, used one pad daily); the estimated difference was 43% (95% confidence interval [CI]: 25%, 62%). At 2 yr, bowel scores were better for prostatectomy (median [interquartile range] 100 [100–100]) than for SBRT (87.5 [79.2–100]; p < 0.001), with an estimated mean difference of 8.9 between these (95% CI: 4.2, 13.7); sexual scores were worse for prostatectomy (18 [13.8–40.3]) than for SBRT (62.5 [32.0–87.5]). The limitations were slow recruitment and incomplete 2-yr PRO response rates. SBRT was associated with less patient-reported urinary incontinence and sexual dysfunction, and slightly more bowel bother than prostatectomy. These randomised data should inform treatment decision-making for patients with localised, intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Extremity soft-tissue sarcomas are treated by wide surgical resection with normofractionated radiotherapy. Over the past 3 years, several phase II trials emerged on perioperative hypofractionated radiotherapy. We aimed to review the current practice in France and Luxembourg of hypofractionated radiotherapy as curative treatment for extremity soft-tissue sarcomas. We sent an electronic adaptive survey to sarcoma radiation oncologists at 28 centres in France and the Grand Duchy of Luxembourg belonging to the NETSARC network. The questionnaire was distributed via the NETSARC mailing list in December 2021 and January 2022. It consisted of four to nine questions with closed multiple choice, or open-ended (short or long) answers. Some questions assessed agreement with proposals for pre- or postoperative hypofractionated radiotherapy for extremity soft-tissue sarcomas. Of the 28 radiation oncologists surveyed, 11 (39.2 %) from nine centres responded. Of these, 55 % used hypofractionated radiotherapy, mainly for elderly and frail patients. The main reason why hypofractionated radiotherapy was not used was the lack of scientific evidence and therapeutic habits. Hypofractionated radiotherapy for extremity soft-tissue sarcomas remains to be investigated in high-powered studies but could be offered in the future for well-selected patients by a multidisciplinary board in a sarcoma referral centre. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence of prostate cancer is increasing in Asian countries. Although moderately hypofractionated radiotherapy is not inferior to conventional fractionated radiation according to the updated guidelines, data regarding its efficacy and safety in Taiwan are currently lacking. The aim of this study was to investigate the outcomes of prostate cancer patients treated with hypofractionated image-guided radiotherapy at a single institution in Taiwan. Methods We retrospectively included patients with prostate cancer across all risk groups who were treated with hypofractionated image-guided radiotherapy 70 Gy (Gy) in 28 fractions (at 2.5 Gy/fraction) between 2007 and 2022. We analyzed treatment efficacy by assessing overall survival, prostate cancer-specific survival, event-free survival, biochemical failure, locoregional recurrence, and distant metastasis. The safety of the treatment was evaluated through acute and late gastrointestinal (GI) and genitourinary (GU) toxicity grading based on the Radiation Therapy Oncology Group criteria. Event-free survival, overall survival, prostate cancer-specific survival, biochemical failure, locoregional recurrence, and distant metastasis were evaluated using the Kaplan–Meier method. Results We identified 150 consecutive men with prostate cancer: 12.7% were at low risk, 32.7% were at intermediate risk, 44.6% were at high risk, and 10% had N1 disease. The median follow-up time was 68.9 months (range: 2.3–172 months). The 5-year overall survival rate was 91.7% for the entire cohort, with rates of 100%, 94.3%, 93.3% and 71.1% for the low-risk, intermediate-risk, high-risk, and N1-disease groups, respectively (p

Purpose of review: Globally, breast cancer is the most commonly diagnosed cancer in women. Locally advanced breast cancers (LABCs) may necessitate palliative radiation therapy (RT) due to the severity of the patients' symptoms, inoperability, or other reasons precluding curative-intent treatment such as poor performance status and patient comorbidities. This review aims to discuss current evidence on palliative RT in LABC. Recent findings: Advanced targeted RT techniques have led to improvements in local control with reduced treatment-related toxicities. Emerging short-course palliative RT prescriptions offer feasible options that avoid delay in systemic therapy. Additionally, recent studies also highlight approaches for integrating palliative RT with systemic therapies. Summary: Palliative RT plays a vital role in managing symptoms and enhancing quality of life for LABC patients. However, there is currently no consensus on the optimal prescriptions for palliative RT in these patients. Standardized reporting of palliative RT studies is needed for robust comparison of efficacy and toxicity between various treatment regimens. Furthermore, future research on the optimal integration of RT with novel systemic agents is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Node-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy. Methods A retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses. Results After a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test). Conclusion Pretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

Abstract Purpose/Objective(s) Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution. Materials/Methods The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk. Results A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups. Conclusion Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

Abstract Background This retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated. Methods Different baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed. Results The study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor. Conclusion The risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Background: The other side of radiotherapy (RT), in addition to the cytotoxic effect, is the ability to modulate the immune system in terms of activation or suppression, also depending on the dose and fractionation delivered. This immune RT effect can be detected both locally in the irradiated tumor site and in the peripheral blood. The aim of this study was to assess the consequence of pelvic irradiation on peripheral immune cells and cytokine secretions in localized prostate cancer (PC) patients undergoing pelvic irradiation with a simultaneous moderately hypofractionated prostate/prostate bed boost by Volumetric Modulated Arc Therapy (VMAT). Furthermore, we analyzed whether there was a correlation between these peripheral immune parameters and acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Methods: Thirty-eight PC patients were treated with pelvis irradiation (dose per fraction 1.8 Gy) and simultaneous hypofractionated (median dose per fraction: 2.7 Gy) prostate/prostate bed boost. A longitudinal analysis was performed for 12 months on peripheral blood to assess changes in 9 different lymphocyte subpopulations by flow cytometry and 10 circulating cytokines by Multiplex Luminex assay and ELISA. Results: Our analysis revealed that basal IFN-γ serum values were significantly lower in the definitive (curative intent for patients with prostate) patient group respect to the post-operative one. All the lymphocyte subsets and IFN-α, IFN-β and Il-2 peripheral concentrations displayed significant variations between the different time points considered. The immune cell population that suffers the greatest RT toxicity in the blood was B lymphocyte. We found an interesting correlation between basal TGF-β1 and late GU toxicity. In particular, TGF-β1 concentrations before RT were significantly higher in patients that experienced grade 2-3 of late GU toxicity, respect to grade 0-1. Exploring possible correlations between some clinical/biological findings and radiation planning parameters, we found no statistical significance. Conclusions: Our study analyzed, in the context of hypofractionated radiotherapy in prostate cancer, different parameters of the peripheral immune system. We have highlighted longitudinally the peripheral behavior of the different lymphocyte subpopulations and of a group of 10 cytokines during the first year after RT. One of the analyzed cytokines, such as TGF-β1, has proven to be promising predictive factor of severe late GU toxicity. [ABSTRACT FROM AUTHOR]

Trimodal therapy consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy, has emerged as a valuable therapeutic alternative to radical cystectomy in patients with muscle invasive bladder cancer. Concomitant radiosensitising chemotherapy is a component of trimodality increasing locoregional control compared to radiotherapy alone. The combinations 5-fluorouracil with mitomycin or cisplatin are the best supported in the literature. Gemcitabine appears to be a feasible and promising alternative. There is considerable international heterogeneity in terms of dose, volumes and fractionation. The most commonly used regimens are moderately hypofractionated (55 Gy in 20 fractions over 4 weeks) and normofractionated (64 Gy in 32 fractions) regimens. Radiotherapy for bladder cancer is an effective and evolving treatment, with current technical developments, and studies of new combinations with systemic treatments underway. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8–2 Gy fractions treated daily over 4–6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution. Materials/Methods: The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk. Results: A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups. Conclusion: Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592–3864 AUD (£1350–2012 GBP) per patient was estimated had these patients been treated with the protocol. The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol. • Cost per 5-year local control outcome was similar for Stage I-III breast cancer ranging from $29,675 AUD to $32,478 AUD. • Cost per 5-year overall survival outcome was cheaper for stage III breast cancer compared with Stage I-II breast cancer. • Use of the FAST-Forward ultrahypofractionation protocol significantly reduces RT costs. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials. [ABSTRACT FROM AUTHOR]

Background: This retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated. Methods: Different baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed. Results: The study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor. Conclusion: The risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development. [ABSTRACT FROM AUTHOR]

Background: Recurrent high-grade gliomas present a therapeutic challenge. Repeat surgery, re-irradiation, and systemic therapy have been explored, with re-irradiation requiring precise tumor relapse delineation and advanced dosimetric techniques. This study aims to evaluate the effectiveness and tolerability of re-irradiation using Hypofractionated Stereotactic Radiation (HFSRT) schedules. Materials and methods: In a retrospective analysis from 2011 to 2021, 52 adult patients with recurrent high-grade gliomas were examined, including 42.3% with glioblastoma, 32.5% with grade 3 gliomas, and 25% with grade 2 gliomas as initial diagnosis. All received prior radiotherapy at doses ranging from 54-60 Gy, with a median time to tumor relapse of 19.8 months. Salvage surgery was performed in 42.3% of cases, with a median interval of 22.45 months between radiation courses. Re-irradiation doses were 30 Gy in 5 fractions for 54% and 40 Gy in 10 fractions for 46%. Concurrent systemic treatments included temozolomide (30.8%), nevacizumab (27%), or none (35%). Results: In-field and out-field tumor progression occurred in 65.4% and 25% of patients, with median times to local and distant progression of 5.17 and 4.57 months. Median overall survival (OS) from re-irradiation was 12 months. Univariate analysis showed a trend favoring 30 Gy in 5 fractions for disease progression-free survival (DPFS). Treatment was generally well-tolerated, with only 5.7% experiencing acute Grade-3 toxicity, and symptomatic radionecrosis occurred in 2 patients. Conclusion: Re-irradiation using HFSRT for recurrent high-grade gliomas is viable and well-tolerated, demonstrating survival rates comparable to existing literature. These findings underscore the potential of HFSRT in managing recurrent high-grade gliomas. [ABSTRACT FROM AUTHOR]

Purpose: To develop a single NTCP model for grade ≥ 2 late rectal bleeding (G2 LRB) after conventional or hypofractionated radiotherapy for prostate cancer. Methods and Materials: The development dataset consisted of prostate cancer patients (n = 656) previously randomized to conventional (39 x 2 Gy) or hypofractionated (19 x 3.4 Gy) external beam radiotherapy with N = 89 G2 LRB cases. Candidate predictors were obtained from literature. We fitted five separate logistic regression models to the data, each with one of the following dose parameters as candidate predictors in biological effective dose (BED), assuming α/β = 3 Gy: Equivalent uniform dose (EUD) with n = 0.1, EUD with n = 0.2, the relative volume receiving ≥ 111.9 Gy in BED (V111.9, the equivalent of physical V70 for a conventional schedule), minimum BED to the hottest 0.1 cm3 (D0.1cm3) or 2 cm3 (D2cm3). Previous abdominal surgery was included in every model and fractionation schedule was tested as predictor in each model. A sensitivity analysis was performed by varying the α/β-ratio, n and dose-volume cutoff. Results: The pre-selected candidate dosimetric predictor and previous abdominal surgery were significantly associated with the outcome in all five models. Fractionation schedule was eliminated by the backward scheme in only the EUD (n = 0.1), D0.1cm3 and D2cm3-based models. In internal validation these models showed AUC’s of 0.64, 0.60 & 0.62, respectively. The sensitivity analyses showed that EUD models with n ≥ 0.15 and / or α/β ≥ 4 Gy failed, and EUD models based on α/β = 2 Gy with n = 0.05–0.2 showed good fits as well. Conclusions: Our trial data set with different fractionation schedules offered the unique possibility to generate unbiased BED-based models. EUD (n = 0.1), D0.1cm3 and D2cm3 performed overall best in predicting G2 LRB; with α/β = 2 Gy equally good models were obtained. External validation is required to confirm our results.

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region.

Introduction: Oesophageal cancer is the seventh most common cancer worldwide and the sixth highest cause of cancer-related mortality. Radiation plays an important role in the multimodality treatment of carcinoma of the oesophagus. Aim: To compare locoregional control and toxicity of two External Beam Radiation Therapy (EBRT) fractionation schedules of concurrent chemoradiotherapy and high-dose intraluminal brachytherapy in patients with oesophageal carcinoma at a single institute. Materials and Methods: The present study was a pilot study including a total of 33 participants with histologically confirmed oesophageal cancer. Patients were prospectively randomised into two groups. Arm I: EBRT with a total dose of 46 Gy delivered in 23 fractions at a rate of 2 Gy per fraction over 4.3 weeks, along with Concurrent Injection of Cisplatin (CDDP) 100 mg/m2 on days 1 and 22, followed by Intraluminal Radiation Therapy (ILRT) with 6 Gy per session weekly. Arm II: EBRT with a total dose of 30 Gy delivered in 10 fractions at a rate of 3 Gy per fraction over two weeks and CDDP 100 mg/m2 on day 1 only. The primary endpoint of this study was to compare the locoregional response and toxicities (both acute and late) in the two arms at the end of radiotherapy and six months. Results: At the end of the two-month follow-up, no statistically significant difference was found in the response between the two arms (p-value=0.2697). Dysphagia relief was comparable in both arms; however, this difference was not statistically significant (p-value=0.9235). Conclusion: The responses in both arms were comparable, and further randomised trials with larger sample sizes should be encouraged.

Background: Modern radiotherapy is associated with dermatitis (RD) in approximately one-third of patients treated for breast cancer. There is currently no standard for treating RD. Objective: The objective of this study was to determine whether LUT014, a topical BRAF inhibitor which paradoxically activates mitogen-activated protein kinase, can safely improve RD. Methods: A phase I/II study was designed to first follow a small cohort of women with grade 2 RD regarding toxicity and response. Then, 20 patients were randomized to compare LUT014 to “vehicle” relative to safety and response (measured with common terminology criteria for adverse events, Dermatology Life Quality Index). Results: No substantial toxicity (eg, 0 serious adverse event) was associated with LUT014. All 8 women receiving LUT014 achieved treatment success (5-point Dermatology Life Quality Index reduction at day 14) compared to 73% (8/11) on the placebo arm (P = .591). The time to complete recovery was shorter in the treatment arm. Limitations: The sample size was limited. Only 2 hospitals were included. Conclusions: Topical LU014 is tolerable and may be efficacious for grade 2 RD.

Le cancer de la prostate est le plus fréquent chez l'homme et, au stade localisé, les schémas d'hypofractionnement de la radiothérapie sont devenus des standards, mais l'absence de risque aggravé de toxicité aiguë et tardive génito-urinaire et gastro-intestinale de l'escalade de dose reste à prouver. La population étudiée comprenait tous les patients pris en charge à l'institut Curie de février 2016 à mars 2018 pour un adénocarcinome prostatique localisé traité par irradiation externe délivrée par un accélérateur linéaire en technique conformationnelle avec modulation d'intensité guidée par l'image à la dose totale de 75 Gy en 30 fractions de 2,5 Gy dans le volume cible prévisionnel comprenant la prostate et les vésicules séminales proximales, et pouvait associer une radiothérapie prophylactique ganglionnaire de 46 Gy en 23 fractions avec la technique de boost intégré. En tout, 166 patients ont été inclus, dont 114 étaient atteints de cancer de risque au moins intermédiaire défavorable (soit 68,7 %). L'âge et le suivi médians étaient de 71,4 ans et 3,96 ans. Cent quarante-neuf patients ont reçu une radiothérapie ganglionnaire (soit 89,8 %). Cent trente et un patients ont reçu une hormonothérapie (soit 78,9 %). Une toxicité génito-urinaire de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans respectivement dans 36,7 %, 8,8 %, 3,1 % et 4,7 % des cas. Deux patients ont souffert à 5 ans d'une toxicité de grade 4 (soit 1,6 %). Une toxicité gastro-intestinale de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans dans respectivement 15,1 %, 1,9 %, 14,6 % et 9,3 % des cas. Parmi ces derniers, huit patients ont souffert d'une toxicité de grade 3 (soit 6,2 %). Il n'y a eu aucune toxicité de grade 4. Les analyses n'ont pas mis en évidence de facteur prédictif de toxicité. Les taux de survie globale, sans progression et spécifique à 5 ans étaient respectivement de 82,4 %, 85,7 % et 93,3 %. La concentration sérique d'antigène spécifique de la prostate et les facteurs de risque cardiovasculaires ont été retrouvés comme facteurs prédictifs d'une dégradation de la survie globale (p = 0,0028 pour les deux). La radiothérapie externe pour un cancer prostatique localisé avec notre schéma modérément hypofractionné avec escalade de dose est bien tolérée. En l'absence de toxicité tardive majorée, l'analyse des modes de rechutes à long terme sera intéressante pour déterminer l'intérêt de cette escalade de dose sur les rechutes locales et à distance. Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75 Gy in 30 fractions of 2.5 Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46 Gy in 23 fractions with simultaneous integrated boost. A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4 years and 3.96 years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6 months, 1 year and 5 years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5 years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6 months, 1 year and 5 years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P = 0.0028 for both). External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses. [ABSTRACT FROM AUTHOR]

There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5–3.125Gy per fraction (total dose 50–60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6–88.0%. These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. PROSPERO; CRD42023457791. • Hypofractionated radiotherapy has promising efficacy in oesophageal cancer. • Moderately hypofractionated regimens appear well tolerated with reasonable toxicity. • The histological subtype response to hypofractionation is uncertain. [ABSTRACT FROM AUTHOR]

Introduction: Oesophageal cancer is the seventh most common cancer worldwide and the sixth highest cause of cancer-related mortality. Radiation plays an important role in the multimodality treatment of carcinoma of the oesophagus. Aim: To compare locoregional control and toxicity of two External Beam Radiation Therapy (EBRT) fractionation schedules of concurrent chemoradiotherapy and high-dose intraluminal brachytherapy in patients with oesophageal carcinoma at a single institute. Materials and Methods: The present study was a pilot study including a total of 33 participants with histologically confirmed oesophageal cancer. Patients were prospectively randomised into two groups. Arm I: EBRT with a total dose of 46 Gy delivered in 23 fractions at a rate of 2 Gy per fraction over 4.3 weeks, along with Concurrent Injection of Cisplatin (CDDP) 100 mg/m2 on days 1 and 22, followed by Intraluminal Radiation Therapy (ILRT) with 6 Gy per session weekly. Arm II: EBRT with a total dose of 30 Gy delivered in 10 fractions at a rate of 3 Gy per fraction over two weeks and CDDP 100 mg/m² on day 1 only. The primary endpoint of this study was to compare the locoregional response and toxicities (both acute and late) in the two arms at the end of radiotherapy and six months. Results: At the end of the two-month follow-up, no statistically significant difference was found in the response between the two arms (p-value=0.2697). Dysphagia relief was comparable in both arms; however, this difference was not statistically significant (p-value=0.9235). Conclusion: The responses in both arms were comparable, and further randomised trials with larger sample sizes should be encouraged. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the impact of implementing hypofractionated prescription regimens and advanced treatment techniques on institutional operational hours and radiotherapy personnel resources in a multi‐institutional setting. The study may be used to describe the impact of advancing the standard of care with modern radiotherapy techniques on patient and staff resources. Methods: This study uses radiation therapy data extracted from the radiotherapy information system from two tertiary care, university‐affiliated cancer centers from 2012 to 2021. Across all patients in the analysis, the average fraction number for curative and palliative patients was reported each year in the decade. Also, the institutional operational treatment hours are reported for both centers. A sub‐analysis for curative intent breast and lung radiotherapy patients was performed to contextualize the impact of changes to imaging, motion management, and treatment technique. Results: From 2012 to 2021, Center 1 had 42 214 patient plans and Center 2 had 43 252 patient plans included in the analysis. Averaged over both centers across the decade, the average fraction number per patient decreased from 6.9 to 5.2 (25%) and 21.8 to 17.2 (21%) for palliative and curative patients, respectively. The operational treatment hours for both institutions increased from 8 h 15 min to 9 h 45 min (18%), despite a patient population increase of 45%. Conclusion: The clinical implementation of hypofractionated treatment regimens has successfully reduced the radiotherapy workload and operational treatment hours required to treat patients. This analysis describes the impact of changes to the standard of care on institutional resources. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer characterized by poor prognosis. The treatment requires a multidisciplinary approach, with neoadjuvant chemotherapy, surgery, and radiation therapy (RT). Particularly, high doses of conventional RT have been historically delivered in the adjuvant setting after chemotherapy and mastectomy or as radical treatment in patients ineligible for surgery. Here, we report the case of a 49-year-old woman patient with IBC unsuitable for surgery and treated with a combination of lattice RT and fractionated external beam RT concurrent with trastuzumab, with a curative aim. One year after RT, the patient showed a complete response and tolerable toxicities. This is the first reported case of a not-operable IBC patient treated with this particular kind of RT. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. Methods: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. Results and conclusion: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy. [ABSTRACT FROM AUTHOR]