To present the primary endpoint results, toxicities and quality of life (QoL) after two-year follow-up (FU) of the HypoFocal Phase II trial.

Intermediate- and high-risk prostate cancer (PCa) patients were treated with moderately hypofractionated radiotherapy (MHRT) of 60 Gy in 20 fractions and a focal-boost of up to 75 Gy in Arm A, or high-dose-rate-brachytherapy (HDR-BT) of 15 Gy to the whole-gland with a boost of up to 19 Gy, followed by external beam RT (EBRT) of 44 Gy in 20 fractions in Arm B. Boost was based on combined information by multiparametric-magentic-resonance-tomography (mpMRI) and positron-emission-tomography targeting prostate-specific-membrane-antigen (PSMA-PET). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed according to CTCAEv5.0. QoL was assessed with validated questionnaires (IPSS, QLQ-PR25 and QLQ-PR30).

Twenty-five patients were treated with MHRT and 30 patients with HDR-BT + EBRT. At two-year-FU, the rate of grade 2 + GU and GI toxicity was 24 % and 8 % in Arm A and 10 % and 0 % in Arm B, respectively. Two grade 3 GI toxicities were reported in Arm A, which can be attributed to multifactorial genesis and interventions. QoL was good with significant and minimally-important-differences only in bowel symptoms in Arm A and sexual functioning in Arm B. One patient in each arm relapsed. Limitations are the relatively small sample size.

This is the first trial do demonstrate safety and feasibility of focal dose-escalation based on mpMRI and PSMA-PET in MHRT and HDR-BT + EBRT in intermediate- and high-risk PCa. Particularly, HDR-BT offers good toxicity and QoL profiles. Radiation proctitis demands careful management.

We previously reported outcomes after hypofractionated postprostatectomy radiotherapy (HYPORT) with a median follow-up of 32 months. This was a primary citation supporting the fractionation selection for NRG-GU003, which showed noninferiority of HYPORT versus conventional radiotherapy.

One hundred sixty-one consecutive patients with biochemically recurrent prostate cancer after prostatectomy underwent HYPORT from 2003 to 2013 at a single academic institution using image guided intensity modulated radiation therapy, with the majority (154 of 161) receiving 65 Gy in 26 fractions.

Median follow-up was 13.5 years. Forty-four patients (27.3%) experienced 58 late grade 3 to 5 toxicities (LTOX3) a median of 106 months after HYPORT. Fifty-five of 58 LTOX3 were genitourinary related. Higher-grade toxicities included 6 cystectomies and 3 deaths. At 2 years, only 2 patients had experienced an LTOX3. At 15 years, overall survival was 70%, freedom from biochemical recurrence was 52%, and the risk of LTOX3 was 34%.

Long follow-up is needed to fully capture severe toxicities after dose-escalated HYPORT. This should be considered prior to the broad adoption of similar regimens for this patient population with long survival potential.

The field of radiation oncology has achieved significant technological and scientific advancements in the 21st century. Yet uptake of new evidence-based practices has been heterogeneous, even in the presence of national and international guidelines. Addressing barriers to practice change requires a deliberate focus on developing and testing strategies tailored to improving care delivery and quality, especially for vulnerable patient populations. Implementation science provides a systematic approach to developing and testing strategies, though applications in radiation oncology remain limited. In this critical review, we aim to (1) assess the time from first evidence to widespread adoption, or "time to translation," across multiple evidence-based practices involving radiation therapy, and (2) provide a primer on the application of implementation science to radiation oncology. Specifically, we discuss potential targets for implementation research in radiation oncology, including both evidence-based practices and quality metrics, and highlight examples of studies evaluating implementation strategies. We also define key concepts and frameworks in the field of implementation science, review common study designs, including hybrid trials and cluster randomization, and discuss the interaction with related disciplines such as quality improvement and behavioral economics. Ultimately, this review aims to illustrate how a comprehensive understanding of implementation science could be used to promote equity and quality in cancer care through the development of effective, scalable, and sustainable care delivery solutions.

Prostate cancer (PCa) remains the most prevalent cancer among men and the second leading cause of cancer-related deaths worldwide. Early diagnosis is crucial as it opens up various treatment options with curative intent. Recent advancements confirm that radiotherapy (RT), particularly through modern techniques like stereotactic body RT (SBRT) and single-dose RT (SDRT), is a safe and effective treatment for both localized and advanced PCa. This manuscript reviews the evolution and current state of primary prostate SDRT, focusing on its benefits and limitations. SDRT offers advantages such as reduced treatment time and enhanced patient convenience, showing promising efficacy and safety, especially for low- and intermediate-risk PCa. Challenges include controlling intrafraction variability and organ motion, as well as minimizing urethral toxicity. Next-generation imaging and MR-guided RT are improving treatment accuracy. While SDRT shows potential for cost-effective PCa treatment, further research is needed to address its limitations and refine its clinical application.

To aid personalized treatment selection, we developed a predictive model for acute rectal toxicity in patients with prostate cancer undergoing radiotherapy with photons and protons.

We analyzed a prospective multi-institutional cohort of 278 patients treated from 2012 to 2023 across 10 centers. Dosimetric and nondosimetric variables were collected, and key predictors were identified using purposeful feature selection. The cohort was split into discovery (n = 227) and validation (n = 51) data sets. The dose along the rectum surface was transformed into a two-dimensional surface, and dose-area histograms (DAHs) were quantified. A convolutional neural network (CNN) was developed to extract dosimetric features from the DAH and integrate them with nondosimetric predictors. Model performance was benchmarked against logistic regression (LR) using the AUC.

Key predictors included rectum length, race, age, and hydrogel spacer use. The CNN model demonstrated stability in the discovery data set (AUC = 0.81 ± 0.11) and outperformed LR in the validation data set (AUC = 0.81 v 0.54). Separate analysis of photon and proton subsets yielded consistent AUCs of 0.7 and 0.92, respectively. In the photon high-risk group, the model achieved 83% sensitivity, and in proton subsets, it achieved 100% sensitivity and specificity, indicating the potential to be used for treatment selection in these patients.

Our novel approach effectively predicts rectal toxicity across photon and proton subsets, demonstrating the utility of integrating dosimetric and nondosimetric features. The model's strong performance across modalities suggests potential for guiding treatment decisions, warranting prospective validation.

Prostate Cancer Study 5 (PCS5) compared conventional fractionated radiotherapy (CFRT) with hypofractionated radiotherapy (HFRT) in high-risk prostate cancer (PCa) patients, hypothesizing similar toxicity and survival outcomes. This report presents the efficacy analysis.

PCS5 is a Canadian multicenter, open-label, phase 3 randomized control trial. Men with histologically proven, clinically localized PCa with one or more high-risk features (T3/T4, Gleason score ≥8, and prostate-specific antigen >20) were eligible. Patients were randomized 1:1 to CFRT (76 Gy/38 fractions [Fx] to the prostate and 46 Gy/23 Fx to the pelvic lymph nodes [PLNs]) or HFRT (68 Gy/25 Fx to the prostate and 45 Gy/25 Fx to the PLNs) and 28 mo of androgen suppression. The primary endpoint was toxicity; secondary endpoints included survival outcomes.

Of 329 patients, 164 were randomized to HFRT and 165 to CFRT, with 159 in the HFRT arm and 160 in the CFRT arm included in survival analyses. At the 5-yr median follow-up, there were no significant differences in overall survival (OS; 90.3% vs 89.7%; risk ratio [RR]: 1.01; 95% confidence interval [CI]: 0.93-1.09), PCa-specific survival (PCSS; 97.4% vs 97.5%; RR: 1.00; 95% CI: 0.93-1.07), biochemical recurrence-free survival (BCRFS; 85.2% vs 85.2%; RR: 1.00; 95% CI: 0.91-1.10), or distant metastasis-free survival (DMFS; 87.1% vs 87.1%; RR: 1.00; 95% CI: 0.92-1.09). Hazard ratios were 0.92 (95% CI: 0.56-1.53) for OS, 1.31 (95% CI: 0.46-3.78) for PCSS, 0.85 (95% CI: 0.56-1.30) for BCRFS, and 0.90 (95% CI: 0.56-1.43) for DMFS. Sample size was a limiting factor.

There were no differences in survival outcomes between HFRT (68 Gy/25 Fx) and CFRT (76 Gy/38 Fx). HFRT, including PLN radiotherapy and long-term androgen deprivation therapy, should be considered a new standard of care for high-risk PCa patients undergoing external beam radiotherapy.

The association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy.

This was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023. Trials without individual patient data were excluded. Data were provided to MARCAP by study investigators. The associations between acute (≤3 months after radiotherapy) and late (>3 months after radiotherapy) grade 2 or greater genitourinary and gastrointestinal toxicities were assessed using adjusted generalised linear mixed models (adjusted for age, androgen deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule). In the subset of trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were also evaluated.

Six of 26 available trials met all the eligibility criteria. 6593 patients were included (conventionally fractionated: n=4248; moderately hypofractionated: n=2345). Median follow-up was 72 months (IQR 61-94). Acute grade 2 or greater genitourinary toxicity was associated with both late grade 2 or greater genitourinary toxicity (odds ratio 2·20 [95% CI 1·88-2·57], p<0·0001) and decrement at least twice the MCID in urinary QOL (1·41 [1·17-1·68], p=0·0002). Acute grade 2 or greater gastrointestinal toxicity was associated with both late grade 2 or greater gastrointestinal toxicity (2·53 [2·07-3·08], p<0·0001) and decrement at least twice the MCID in bowel QOL (1·52 [1·26-1·83], p<0·0001).

Acute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity.

National Institutes of Health and US Department of Defense.

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.

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.

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.

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.

Not applicable.

IntroductionThis study evaluates the clinical outcomes, survival benefits, and toxicities of two moderate-hypofractionated radiotherapy (MHRT) patterns, 60 Gy in 20 fractions (60 Gy/20f) and 70 Gy in 28 fractions (70 Gy/28f), in early-stage prostate cancer patients.MethodsThis retrospective study analyzed data from 187 patients diagnosed between 2014 and 2023, using propensity score matching to ensure efficacy assessment accuracy. The primary endpoints reported were overall survival (OS) and disease-free survival (DFS), calculated using Kaplan-Meier analysis. Toxicity and side effects were evaluated using Criteria for Adverse Events v5.0, focusing on the urinary and gastrointestinal (GI) systems.ResultsAfter matching, each of the 60 Gy and 70 Gy groups included 73 patients. The median follow-up duration for all patients was 36.0 months. The OS rates for the 60 Gy and 70 Gy groups were 86.3% and 89.0%, respectively, with 3-year OS rates of 92.4% and 89.0% (P = 0.375). The 3-year DFS rates were 91.0% in the 60 Gy group and 81.0% in the 70 Gy group (P = 0.096), indicating no significant differences between the groups. The incidence of acute Grade 2 or higher urinary toxicities was comparable between the two groups (60 Gy group vs 70 Gy group: 9.6% vs 9.6%, P = 1.0), while the 70 Gy group demonstrated an advantage for late Grade 2 or higher toxicities (60 Gy group vs 70 Gy group: 12.3% vs 2.8%, P = .028). For the GI system, the incidence of acute toxicities was higher in the 60 Gy group, albeit not statistically significant (60 Gy group vs 70 Gy group: 11.0% vs 6.8%, P = .383), while late toxicities were equivalent between the groups (60 Gy group vs 70 Gy group: 1.4% vs 1.4%, P = 1.0).ConclusionBoth MHRT fractionation patterns demonstrate comparable survival outcomes and toxicities in early-stage prostate cancer, suggesting MHRT's viability as a primary treatment. The 60 Gy/20f pattern marginally favored survival, albeit not with statistical significance.

Radical prostatectomy (RP) is one possible curative treatment for localized prostate cancer. Despite that, up to 40% of patients will later relapse. Currently, post-operative radiotherapy (PORT) courses deliver 1.8-2 Gy daily to reach a total dose ranging between 64 and 74 Gy, completed in 7-8 weeks. Several articles reported encouraging data in terms of the effectiveness and the related toxicities using hypofractionation schedules. The objective of the present systematic review was to evaluate the clinical outcomes and toxicity of the use of hypofractionation in adjuvant/salvage prostate cancer treatments.

Medline was searched via PubMed and Scopus from inception to July 2024 to retrieve studies on hypofractionation in adjuvant/salvage prostate cancer treatments. This study was conducted under PRISMA guidelines.

A total of 139 articles were identified from the initial search. Subsequently, the 139 studies were reviewed by title and abstract. Ninety-five studies were excluded due to being either abstracts or articles not available in English. In the second step, the full texts of 44 studies were reviewed. Eleven studies were excluded for being reviews, study protocols, or focused on SBRT treatments. Finally, 33 studies were included in our analysis, with a total number of 4269 patients. Of the 33 selected studies, 20 were retrospective trials and 11 were phase I/II prospective trials, while 2 studies were prospective phase III trials. The follow-up ranged from 18 to 217 months. Failure-free survival, for those with the longer follow-up, ranged between 85% and 91% at 3 years, 47 and 78.6% at 5 years and 51.5% at 10 years. Genitourinary (GU) and gastrointestinal acute toxicity was mild to moderate with similar rates across the normofractionated and hypofractionated groups. Acute grade-3 GU toxicity events were unusual, occurring in less than 4% of the cases overall.

The present study is the first systematic review of the literature that includes the first two randomized phase III studies published in the literature. Hypofractionated treatment has been shown to be safe, effective, with moderate toxicity and not inferior to conventional RT, with good biochemical control rates.

In this article, we comment on the article by Ono et al. We focus specifically on the carbon ion radiotherapy studies and the method to calculate the dosing schedule. While photon hypofractionated radiotherapy in prostate cancer has demonstrated improvement in tumor control with reduced gastrointestinal toxicity compared to conventional radiotherapy, carbon ion radiotherapy (CIRT) offers additional physical and biological advantages. Recent findings, including those from Ono et al, have established new dose constraints of CIRT for prostate cancer treatment and risk factors for rectal bleeding. Due to limited data on CIRT dosing, this study underscores the need for more research to refine dose calculation methods and better understand their effects on clinical outcomes.

Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate.

Between 2011-2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35-40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0).

Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6-94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5-19.8 %) for CFRT, 6.5 % (0.8-12.2 %) MHRT, and 1.8 % (0-5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities.

ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

The aim of the Oncology Committee of the French Urology Association is to propose updated recommendations for the diagnosis and management of localized prostate cancer (PCa).

A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the elements of diagnosis and therapeutic management of localized PCa, evaluating references with their level of evidence.

The recommendations set out the genetics, epidemiology and diagnostic methods of PCa, as well as the concepts of screening and early detection. MRI, the reference imaging test for localized cancer, is recommended before prostate biopsies are performed. Molecular imaging is an option for disease staging. Performing biopsies via the transperineal route reduces the risk of infection. Active surveillance is the standard treatment for tumours with a low risk of progression. Therapeutic methods are described in detail, and recommended according to the clinical situation.

This update of French recommendations should help to improve the management of localized PCa.

Radical prostatectomy is appropriate for any patient whose cancer appears clinically localised to prostate. However because of potential perioperative morbidity, radical prostatectomy is generally reserved for patients whose life expectancy is more than ten years. Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience, but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low α/β ratio, then do late responding organs at risk such as the rectum or bladder.

From January 2017 to December 2020 we treated 112 patients of localised Prostate Cancer with Image Guided Radiotherapy (IGRT). They were in range of 75-85 years. They were of stage T1-T3, N0 or N1. There were significant comborbidities. ECOG performance status was 0-1. They were given 3 months of Androgen Deprivation Therapy (ADT) before starting IGRT. Patients were immobilised with casts and subject to CT simulation. CBCT was taken daily. Dose was 70 Gy @ 250 cGy per fraction at a frequency of 5 fractions per week. Complete blood counts were done weekly for assessment of haematological toxicity. Androgen Deprivation Therapy was continued post IGRT.

All the patients were able to complete the treatment. Evaluation was done at one month, three month and six months post treatment. 104 out of 112 patients achieved complete response. Other 8 had near complete response. There were no acute grade 3-4 toxicities. Grade 1-2 toxicities like skin desquamation, diarrhoea, burning micturition were managed conservatively. Late toxicity was rectal bleeding seen after one year of completion of treatment and was managed with steroid enemas. 23 patients required argon plasma laser therapy.

Image guided radiotherapy is well tolerated, easy to implement and an effective alternative to radical prostatectomy in elderly patients with comorbidities and low life expectancy.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

This retrospective study was conducted to ensure that irradiation of the pelvic lymph node areas associated with simultaneous hypofractionated boost to the prostate according to the protocol implemented at the university hospital of Tours (France) does not result in excess urinary and digestive toxicity in the short and medium term.

The study population included patients with localized unfavourable intermediate or high-risk prostate cancer. The dose delivered was 65Gy in 25 fractions of 2.6Gy to the prostate and seminal vesicles, and 50Gy in 25 fractions of 2Gy to the pelvic lymph nodes. Acute toxicity events (between the start of radiotherapy and the first follow-up consultation) and medium-term toxicity events (after the first follow-up consultation) were assessed using the CTCAE version 5.0 classification.

Sixty-three patients were treated according to the protocol between January 1st, 2020, and October 31st, 2022. The majority of them had high-risk prostate cancer (79%). The median follow-up was 15 months. Very few patients reported grade 3-4 toxicity acutely (6% urinary and 0% digestive toxicity) or in the medium term (7% urinary and 0% and digestive toxicity).

Radiotherapy of pelvic lymph node areas with simultaneous hypofractionated boost to the prostate is feasible, with low rates of severe acute and medium-term toxicity.

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 75Gy in 30 fractions of 2.5Gy 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 46Gy 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 71.4years and 3.96years. 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 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years 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.

The goal is to describe the evolution of radiation therapy (RT) utilization in the management of localized and metastatic prostate cancer.

Long term data for a variety of hypofractionated definitive RT dose-fractionation schemes has matured, allowing patients and providers many standard-of-care options to choose from. Post-prostatectomy, adjuvant RT has largely been replaced by an early salvage approach. Multiparametric MRI and PSMA PET have enabled increasingly targeted RT delivery to the prostate and oligometastatic tumors. Areas of active investigation include determining the value of proton beam therapy and perirectal spacers, and optimally incorporate genomic tumor profiling and next generation hormonal therapies with RT in the curative setting. The use of radiation therapy to treat prostate cancer is rapidly evolving. In the coming years, there will be continued improvements in a variety of areas to enhance the value of RT in multidisciplinary prostate cancer management.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).

Treatment outcomes of definitive photon radiation therapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) are reportedly unsatisfactory. Carbon ion radiation therapy (CIRT) has shown favorable tumor control in various malignancies, including radioresistant tumors. Therefore, we retrospectively evaluated the clinical outcomes of CIRT for nmCRPC.

Patients with nmCRPC (N0M0) treated with CIRT at a total dose of 57.6 Gy (relative biologic effectiveness) in 16 fractions or 51.6 Gy (relative biologic effectiveness) in 12 fractions were included. The castration-resistant status received a diagnosis based on prostate-specific antigen kinetics showing a monotonic increase during primary androgen deprivation therapy or the need to change androgen deprivation therapy. Clinical factors associated with patient prognosis were explored. Twenty-three consecutive patients were identified from our database. The median follow-up period was 63.6 months (range, 14.1-120).

Seven patients developed biochemical relapse, 6 had clinical relapse, and 4 died of the disease. The 5-year overall survival, local control rate, biochemical relapse-free survival, and clinical relapse-free survival were 87.5%, 95.7%, 70.3%, and 75.7%, respectively. One patient with diabetes mellitus requiring insulin injections and taking antiplatelet and anticoagulant drugs developed grade 3 hematuria and bladder tamponade after CIRT. None of the patients developed grade 4 or worse toxicity.

The present findings indicate the acceptable safety and favorable efficacy of CIRT, encouraging further research on CIRT for nmCRPC.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/β ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

While moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC) is commonly delivered by intensity modulated radiation therapy, IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in this context. We conducted a secondary analysis of the phase III RTOG 0415 trial comparing survival and toxicity outcomes for low-risk PC following MHRT with IMRT versus 3D-CRT.

RTOG 0415 was a phase III, non-inferiority trial randomizing low-risk PC patients to either MHRT or conventionally fractionated radiation with stratification by RT technique. A secondary analysis for differences in overall survival (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed.

1079 patients received the allocated intervention with a median follow up of 5.8 years. 79.1% of patients were treated with IMRT and radiation technique was balanced between arms. Across all patients, RT technique was not associated with significant differences in BRFS, OS, or rates of acute and late toxicities. For patients completing MHRT, there was a difference in the late GU toxicity distribution between 3D-CRT and IMRT but no difference in late grade 2 or greater GU or GI toxicity. Stratifying patients by RT technique and fractionation, no significant differences were observed in the minimal clinically important difference (MCID) in EPIC urinary and bowel scores following RT.

RT technique did not impact clinical outcomes following MHRT for low-risk PC. Despite different late GU toxicity distributions in patients treated with MHRT by IMRT or 3D-CRT, there was no difference in late Grade 2 or greater GU or GI toxicity or patient reported toxicity. Increases in late GU and GI toxicity following MHRT compared to CFRT, as demonstrated in the initial publication of RTOG 0415, do not appear related to a 3D-CRT treatment technique.

Prostate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics.

To compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC).

We retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23.

114 patients were selected according to the inclusion criteria. Mean age was 68 years (61-75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant).

Hypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

This study compares the dosimetric performance of the field-in-field (FIF) technique with intensity modulated radiation therapy (IMRT) for delivering hypofractionated radiation therapy to prostate patients with cancer. The FIF technique uses 6 beams, whereas IMRT uses 9 beams.

This study was conducted on 15 patients with prostate cancer treated with step-and-shoot IMRT. The prescribed dose was 60 Gy in 20 fractions. The FIF plans contained 6 photon beams, and IMRT plans were designed using a 9-field step-and-shoot technique. Dose-volume histograms and dose distributions were evaluated to compare FIF and IMRT.

The results of the planning target volume indices analysis showed a significant difference in the maximum dose, dose to 2% of volume, and homogeneity index in favor of FIF and in the mean dose, dose to 98% of volume, and D95 in favor of IMRT. The results of the organs-at-risk analysis showed significant differences in the volume of the rectum and bladder receiving 60 Gy in favor of FIF and the volume of the rectum and femoral heads receiving 30 Gy, as well as the mean dose to the rectum, in favor of IMRT. IMRT had a higher median number of monitor units (MUs) and segments (886 MU, 64 segments) compared to FIF (434 MUs, 6 segments).

The FIF technique and IMRT had comparable results in delivering hypofractionated radiation therapy for prostate cancer. The findings of this study may aid in decision-making for patients undergoing treatment.

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.

The low α\β ratio of 1.2 to 2 for prostate cancer (PCa) suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of hypofractionated (HF) radiation therapy (RT). To date, no phase 3 randomized clinical trial has compared moderately HF RT with standard fractionation (SF) exclusively in high-risk PCa patients. We are reporting the safety of moderate HF RT in high-risk PCa in an initially noninferiority-designed phase 3 clinical trial.

From February 2012 to March 2015, 329 high-risk PCa patients were randomized to receive either SF or HF RT. All patients received neoadjuvant, concurrent, and long-term adjuvant androgen deprivation therapy. Standard fractionation RT consisted of 76 Gy in 2 Gy per fraction to the prostate, where 46 Gy was delivered to the pelvic lymph nodes. Hypofractionated RT included concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate and 45 Gy in 1.8 Gy per fraction to the pelvic lymph nodes. The coprimary endpoints were acute and delayed toxicity at 6 and 24 months, respectively. The trial was originally designed as a noninferiority with a 5% absolute margin. Given the lower-than-expected toxicities in both arms, the noninferiority analysis was completely dropped.

Of the 329 patients, 164 were randomized to the HF and 165 to the SF arms. In total, there were more grade 1 or worse acute gastrointestinal (GI) events in the HF arm, 102 versus 83 events in the HF and SF arm, respectively (P = .016). This did not remain significant at 8 weeks of follow-up. There were no differences in grade 1 or worse acute GU events in the 2 arms, 105 versus 99 events in the HF and SF arm, respectively (P = .3). At 24 months, 12 patients in the SF arm and 15 patients in the HF arm had grade 2 or worse delayed GI-related adverse events (hazard ratio, 1.32; 95% CI, 0.62-2.83; P = .482). There were 11 patients in the SF arm and 3 patients in the HF arm with grade 2 or higher delayed genitourinary (GU) toxicities (hazard ratio, 0.26; 95% CI, 0.07-0.94; P = .037). There were 3 grade 3 GI and one grade 3 GU delayed toxicities in the HF arm and 3 grade 3 GU and no grade 3 GI toxicities in the SF arm. No grade 4-toxicities were reported.

This is the first study of moderate HF dose-escalated RT in exclusively high-risk patients with prostate cancer treated with long-term androgen deprivation therapy and pelvic RT. Although our data were not analyzed as a noninferiority, our results demonstrate that moderately HF RT is well-tolerated, similar to SF RT at 2 years, and could be considered an alternative to SF RT.

In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk.

Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14).

From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment.

SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

This pilot study aimed to explore the preliminary effects and safety of stereotactic body radiotherapy (SBRT) combined with preventive pelvic radiotherapy and primary gross tumor volumes (GTVp) boost in patients with high-risk prostate cancer based on multiparameter magnetic resonance image (mpMRI). Tumors were contoured as GTVp based on mpMRI. The prostate and proximal seminal vesicles were considered as the clinical target volume1. The pelvic lymphatic drainage area constituted clinical target volume 2. Radiation doses were 40Gy or 45Gy/5fractions to planning target volume of primary tumor, 37.5Gy/5f to prostate, seminal vesicle, and positive pelvic lymph nodes, and 25Gy/5f to pelvic synchronously. The treatment was delivered 3 times per week. Volumetric modulated arc radiotherapy and intensity-modulated radiotherapy were used to complete SBRT. The genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated. Quality of life data was also captured. A total of 15 patients were enrolled in this study with a median age of 78 (56-87) from 2017 to 2020. All patients received SBRT. At 3 months after radiotherapy, the proportion of PSA < 0.006 ng/mL was 66.7% (10/15). The 2-year biochemical relapse-free survival was 93.3%. The incidence of grade 1 acute GU side effects was 80% (12/15); the incidence of acute grade 1 GI toxicity was 66.7% (10/15); and no grade 2 or higher acute GU and GI side effects was observed. Two patients presented with temporary late grade 2 GI toxicity. International Prostatic System Score increased rapidly after a transient increase at 1 week (P = .001). There were no significant differences in EORTC quality of life scores in all domains except global health status. In this pilot study, it was revealed that SBRT combined with preventive pelvic radiotherapy and GTVp boost based on mpMRI image was effective and well tolerated for patients with high-risk prostate cancer.

This study aimed to evaluate the treatment outcomes and define the prostate-specific antigen (PSA) kinetics as potential prognostic factors in patients with intermediate- or high-risk localized prostate cancer (PCa) who underwent moderately hypofractionated radiation therapy.

The study retrospectively reviewed the medical records of 149 patients with intermediate- or high-risk localized PCa who underwent definitive radiation therapy (70 Gy in 28 fractions) without androgen deprivation therapy. Clinical outcomes were analyzed based on risk stratification (favorable-intermediate, unfavorable-intermediate, and high-risk). The biochemical failure rate (BFR) and clinical failure rate (CFR) were stratified based on the PSA nadir and the time to the PSA nadir to identify the prognostic effect of PSA kinetics. Acute and late genitourinary and gastrointestinal adverse events were analyzed.

Significant differences were observed in the BFR and CFR according to risk stratification. No recurrence was observed in the favorable intermediate-risk group. The 7-year BFR and CFR for the unfavorable intermediate-risk and high-risk groups were 19.2% and 9.8%, and 31.1% and 25.3%, respectively. Patients with a PSA nadir >0.33 ng/mL or a time to the PSA nadir <36 months had a significantly greater BFR and CFR. The crude rate of grade 3 late adverse events was 3.4% (genitourinary: 0.7%; gastrointestinal: 2.7%). No grade 4-5 adverse event was reported.

A significant difference in clinical outcomes was observed according to risk stratification. The PSA nadir and time to the PSA nadir were strongly associated with the BFR and CFR. Therefore, PSA kinetics during follow-up are important for predicting prognosis.

The genomic era has significantly changed the practice of clinical oncology. The use of genomic-based molecular diagnostics including prognostic genomic signatures and new-generation sequencing has become routine for clinical decisions regarding cytotoxic chemotherapy, targeted agents and immunotherapy. In contrast, clinical decisions regarding radiation therapy (RT) remain uninformed about the genomic heterogeneity of tumors. In this review, we discuss the clinical opportunity to utilize genomics to optimize RT dose. Although from the technical perspective, RT has been moving towards a data-driven approach, RT prescription dose is still based on a one-size-fits all approach, with most RT dose based on cancer diagnosis and stage. This approach is in direct conflict with the realization that tumors are biologically heterogeneous, and that cancer is not a single disease. Here, we discuss how genomics can be integrated into RT prescription dose, the clinical potential for this approach and how genomic-optimization of RT dose could lead to new understanding of the clinical benefit of RT.

To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes.

A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: NCT02874014) of moderately hypofractionated IMPT. IMPT with pencil beam scanning was used to deliver 6750 and 4500 cGy relative biological effectiveness in 25 daily fractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using Common Terminology Criteria for Adverse Events version 4.0, at baseline, weekly during radiation therapy, 3-month postradiation therapy, and then every 6 months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method.

Median age was 75.5 years. Fifty-four patients were available for late toxicity evaluation. Median follow-up was 43.9 months (range, 16-66). The actuarial rate of late grade ≥2 GI toxicity at both 2 and 3 years was 7.4% (95% confidence interval [CI], 0.2%-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI, 0%-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥2 GU toxicity was 20.5% (95% CI, 8.9%-30.6%) at 2 years, and 29.2 % (95% CI, 15.5%-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity.

A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase 3 study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiation therapy.

Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.

To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.

This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.

For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.

Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01).

The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.

ClinicalTrials.gov Identifier: NCT04189913.

After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases.

The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed.

Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection.

The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.

Recent studies have shown that radiation-induced pelvic toxicity often requires urological consultation. However, the 10-year incidence of genitourinary toxicity following intensity-modulated radiotherapy (IMRT) amongst patients with localised prostate cancer remains unclear. Hence, we conducted a systematic review and meta-analysis to determine the incidence of late genitourinary toxicity relying on Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) grade as well as the incidence of specific genitourinary toxicity. Secondary objectives involved quantifing the number of studies reporting 120-month follow-up endpoints, time to event analysis, predictive factors or economic evaluation.

Articles published from January 2008 to December 2021 describing prospective studies were systematically searched in MEDLINE, EMBASE and Cochrane (PROSPERO protocol CRD42019133320). Quality assessment was performed by use of the Cochrane Risk of Bias 2 Tool for RCTs and the Newcastle Ottowa Scale for non-RCTs. Meta-analysis was performed on the 60-month incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity, haematuria, urinary retention and urinary incontinence.

We screened 4721 studies and six studies met our inclusion criteria. All included studies involved normofractionation, three included a hypofractionation comparator arm and none involved nodal irradiation. The pooled 60-month cumulative incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity were 17% (95% CI: 5-20%, n = 678) and 33% (95% CI: 27-38%, n = 153), respectively. The pooled 60-month cumulative incidence of Haematuria was 5% (95% CI: -4-14%, n = 48), Urinary incontinence 12% (95% CI: 6-18%, n = 194), Urinary retention 24% (95% CI: 9-40%, n = 10). One study reported time to event analyses, one reported predictive factors, no studies reported economic analysis or 120-month toxicity. There was considerable heterogeneity amongst the studies.

There are few high-quality studies reporting 60-month toxicity rates after IMRT. Conservative estimates of 60-month toxicity rates are high and there is need for longer follow-up and consistent toxicity reporting standards.

Radiotherapy represents an important therapeutic option in the management of prostate cancer (PCa). As helical tomotherapy may improve toxicity outcomes, we aimed to evaluate and report the toxicity and clinical outcomes of localized PCa patients treated with moderately hypofractionated helical tomotherapy.

We retrospectively analyzed 415 patients affected by localized PCa and treated with moderately hypofractionated helical tomotherapy in our department from January 2008 to December 2020. All patients were stratified according to the D'Amico risk classification: low-risk 21%, favorable intermediate-risk 16%, unfavorable intermediate-risk 30.4%, and high-risk 32.6%. The dose prescription for high-risk patients was 72.8 Gy to the prostate (planning tumor volume-PTV1), 61.6 Gy to the seminal vesicles (PTV2), and 50.4 Gy to the pelvic lymph nodes (PTV3) in 28 fractions; for low- and intermediate-risk patients 70 Gy for PTV1, 56 Gy for PTV2, and 50.4 Gy for PTV3 in 28 fractions. Image-guided radiation therapy was performed daily in all patients by mega-voltage computed tomography. Forty-one percent of patients received androgen deprivation therapy (ADT). Acute and late toxicity was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v.5.0 (CTCAE).

Median follow-up was 82.7 months (range=12-157 months) and the median age of patients at diagnosis was 72.5 years (range=49-84 years). The 3, 5, and 7 yr overall survival (OS) rates were 95%, 90%, and 84%, respectively, while 3, 5, and 7 yr disease-free survival (DFS) were 96%, 90%, and 87%, respectively. Acute toxicity was as follows: genitourinary (GU) G1 and G2 in 35.9% and 24%; gastrointestinal (GI) in 13.7% and 8%, with G3 or more acute toxicities less than 1%. The late GI toxicity G2 and G3 were 5.3% and 1%, respectively, and the late GU toxicity G2 and G3 were 4.8% and 2.1%, respectively, and only three patients had a G4 toxicity.

Hypofractionated helical tomotherapy for PCa treatment appeared to be safe and reliable, with favorable acute and late toxicity rates and encouraging results in terms of disease control.