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IntroductionThis 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).MethodsNew 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.ResultsEach 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.ConclusionsThree 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.

BackgroundThe 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.MethodsThirty-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.ResultsOur 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.ConclusionsOur 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.

Purpose/objectives: The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methods: The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher’s exact tests. Results: Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15–20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25–30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. Conclusion: Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Background: The major drivers of carbon dioxide (CO2eq) emissions of external beam radiation therapy (EBRT) are not well known and limit our ability to initiate mitigation strategies. Material and methods: We describe the carbon footprint of four typical centers. We explore direct EBRT associated factors such as the impact of fractionation and use of MRI-LINAC, as well as indirect factors (e.g. patient rides). Treatment strategy related CO2eq emissions are included in a health technology assessment analysis that takes into account CO2eq emissions. Results: A typical EBRT treatment emits from 185 kgCO2eq to 2066 kgCO2eq. CO2eq emissions are mostly driven by (i) accelerator acquisition and maintenance (37.8 %), (ii) patients and workers rides (32.7 %), (iii) drugs and medical devices (7.3 %), (iv) direct energy consumption (6.1 %), and (v) building and bunker construction (5.6 %) with a substantial heterogeneity among centers. Hypofractionation has a strong impact to mitigate emissions. MRI-LINAC is associated with a substantial increase in CO2eq emissions per fraction and requires ultra hypofractionation in 5 fractions to achieve a similar carbon footprint compared to 20 fractions treatment schemes. The expected limited small increase in toxicities due to hypofractionation (when existing) are in the same range as avoided detrimental effects to future people’s health thanks to CO2eq mitigation. Conclusion: Carbon footprint of EBRT is not neglectable and could be mitigated. When safely feasible, hypofractionation is one of the main factors to decrease this impact. Taking into account CO2eq emissions has a substantial impact on the health technology assessment of EBRT, favoring hypofractionated regimens.

Modern advances in diagnostics, surgery, systemic therapies, and radiotherapy (RT) have drastically revolutionized treatment strategies for breast cancer. This review outlines current and evolving treatment paradigms for RT in the breast-conserving therapy and post-mastectomy setting. In early-stage breast cancer, there is active investigation in expanding eligibility for omission of RT in women with more biologically favorable tumors and growing options to effectively irradiate less breast tissue and shorten RT treatment courses. For locally advanced breast cancer, we discuss several patient cohorts in which the necessity of post-mastectomy RT (PMRT) is commonly debated. Ongoing efforts to better refine indications for PMRT and evaluate the feasibility of hypofractionated PMRT are being studied. Metastasis-directed therapy with ablative RT is an emerging topic of interest in many cancers, including its role and impact in oligometastatic breast cancer. In this review, we will discuss the rationale for current standard of care and address in greater detail the aforementioned concepts.

BackgroundTo evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost.MethodsPatients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0.ResultsBetween 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months.ConclusionsAccelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease.

Abstract Background Magnetic resonance (MR)‐guided ultra‐hypofractionated radiotherapy with whole‐pelvic irradiation (UHF‐WPRT) is a novel approach to radiotherapy for patients with high‐risk (HR) and very high‐risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF‐WPRT might inevitably result in longer on‐couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF‐WPRT on a 1.5‐Tesla MR‐Linac. Methods Ten patients with clinical stage T3a‐4N0‐1M0‐1c PCa, who consecutively received UHF‐WPRT, were enrolled prospectively. The contours of the target and organ‐at‐risks on the position verification‐MR (PV‐MR), beam‐on 3D‐MR(Bn‐MR), and post‐MR (after radiotherapy delivery) were derived from the pre‐MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. Results In total, we collected 188 MR scans (50 pre‐MR, 50 PV‐MR, 44 Bn‐MR, and 44 post‐MR scans). With median 59 min, the mean prostate clinical target volume (CTV)‐V100% was 98.59% ± 2.74%, and the mean pelvic CTVp‐V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was −2% (−18% to 20%). With a median follow‐up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion UHF‐RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt‐To‐Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam‐on phase was clinically acceptable based on the 3D‐MR–based dosimetry analysis. Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

Abstract Background Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. Methods All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

There is new data in the fractionation modalities and these are the really the practice-changing trials of last years: can we use hypo fractionated whole breast radiotherapy in patients presented with ductal carcinoma in situ? Can we realize hypofractionated whole breast radiotherapy with simultaneous integrated boost? What about hypofractionated irradiation after mastectomy with reconstruction? Can we do hypofractionation to lymph nodes without risk of increased toxicity? The purpose of this work is to respond with the last evidence-based recently presented or published data. [ABSTRACT FROM AUTHOR]

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The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60–119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1–6.9) and 4% (95% CI: 1.5–10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule. [ABSTRACT FROM AUTHOR]

The IFN-type-I pathway is involved in radiotherapy (RT)-mediated immune responses. Large RT fractions have been suggested to potently induce this pathway. Neoadjuvant hypofractionated short-course (scRT) and conventional long-course (lcRT) RT applied for the treatment of locally advanced rectal adenocarcinoma patients provides a unique model to address the immuno-stimulatory properties of RT on a systemic level. We prospectively analyzed the IFNβ plasma levels and lymphocyte counts (LCs) of rectal adenocarcinoma patients before and after treatment with scRT (n = 22) and lcRT (n = 40). Flow cytometry was conducted to assess the effects on lymphocytic subpopulations in a subset of 20 patients. A statistically significant increase in the post-RT IFNβ plasma levels was noted in patients undergoing scRT (p = 0.004). Improved pathological tumor regression was associated with elevated post-RT IFNβ levels (p = 0.003). Although all patients experienced substantial lymphopenia after treatment, the post-RT LC of patients treated with scRT were significantly higher compared to lcRT (p = 0.001). Patients undergoing scRT displayed significantly lower percentages of regulatory CD4+/CD25+ T-cells after therapy (p = 0.02). scRT enables effective stimulation of the IFN-type-I pathway on a systemic level and confers decreased lymphocytic cytotoxicity and limited regulatory T-cell activation compared to lcRT, supporting its increasing role in immuno-RT trials. [ABSTRACT FROM AUTHOR]

Opinion statement: Neoadjuvant radiotherapy (RT) over 5–6 weeks with daily doses of 1.8–2.0 Gy to a total dose of 50–50.4 Gy is standard of care for localized high-grade soft tissue sarcomas (STS) of the extremities and trunk wall. One exception is myxoid liposarcomas where the phase II DOREMY trial applying a preoperative dose of 36 Gy in 2 Gy fractions (3–4 weeks treatment) has achieved excellent local control rates of 100% after a median follow-up of 25 months. Hypofractionated preoperative RT has been investigated in a number of phase II single-arm studies suggesting that daily doses of 2.75–8 Gy over 1–3 weeks can achieve similar oncological outcomes to conventional neoadjuvant RT. Prospective data with direct head-to-head comparison to conventional neoadjuvant RT investigating oncological outcomes and toxicity profiles is eagerly awaited. For the entire group of retroperitoneal sarcomas, RT is not the standard of care. The randomized multi-center STRASS trial did not find a benefit in abdominal recurrence-free survival by the addition of preoperative RT. However, for the largest histological subgroup of well-differentiated and grades I and II dedifferentiated liposarcomas, the STRASS trial and the post-hoc propensity-matched STREXIT analysis have identified a possible benefit in survival by preoperative RT. These patients deserve to be informed about the pros and cons of preoperative RT while the longer follow-up data from the STRASS trial is awaited. [ABSTRACT FROM AUTHOR]

Background: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. Methods: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks. [ABSTRACT FROM AUTHOR]

For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0–III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51–68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5–128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869–1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer. • Relative risk of second cancers for hypofractionated vs conventionally fractionated breast EBRT (hEBRT vs cEBRT) is unclear. • We performed a retrospective NCDB analysis of women with non-metastatic breast cancer. • Multivariable logistic regression allowed relative (but not absolute) comparison of second malignancy risk. • Among 125 228 patients, hEBRT showed no difference in relative second malignancy risk versus cEBRT. • Subgroup analyses found no difference in second malignancy risk between hEBRT and cEBRT. [ABSTRACT FROM AUTHOR]

In the UK, hypofractionated radiotherapy (50 Gy in 16 fractions) to the larynx is an accepted standard for early cancer of the glottic larynx, but is only supported by Grade C evidence1-2. Alternative schedules (e.g., 63 Gy in 28 fractions) are supported by Grade B evidence, and may be advantageous from a late-toxicity perspective on account of a lower dose-per-fraction, but involve more visits to the department and may be less desirable from a patient experience perspective3. In this study, we assessed oncologic and toxicity outcomes for a contemporary cohort of patients treated over 16 fractions at a large UK tertiary cancer centre. A retrospective review of prospectively-collected data. Eligibility criteria: all patients who completed hypofractionated radiotherapy to the larynx for Tis /T1 N0 M0 squamous cell carcinoma of the glottis at The Christie NHS Foundation Trust between 01/01/2016 and 31/08/2022. Relevant patient-, cancer-and treatment factors were collected. A multivariable Cox proportional hazards (PH) model was fitted, with overall survival (OS) as the endpoint of interest. Multivariable logistic regression was used to explore variables associated with binary late toxicity outcomes. Competing risk regression, using the method of Fine and Gray, was used to assess local control (LC) as an alternative endpoint, with death as a competing event. 236 patients met the eligibility criteria; patient characteristics are shown in the Table. [Display omitted] There were 36 OS events at a median of 1.9 years from radiotherapy start (IQR 2.6 years). For surviving patients (n = 200), the median follow-up was 3.7 years (IQR 3.2 years). 10 patients developed locally recurrent disease at a median of 0.8 years from radiotherapy start. Of these, 9 had salvage surgery (laryngectomy); 1 of 9 developed a further (para-stomal) local recurrence and 8 remain cancer-free. Curves demonstrating the cumulative incidence of local recurrence, with death from non-cancer causes as a competing event, are shown in the Figure. [Display omitted] On multivariable Cox PH regression, the only covariates associated with OS were an ECOG PS of 3 (vs 0, HR 9.12; 95% CI 2.05 - 40.5; p=0.004) and moderate co-morbidity (ACE-27 2 vs 0, HR 2.86; 95% CI 1.02 -8.04; p=0.046). On competing risk regression, increasing patient age was associated with a significantly reduced risk of local recurrence vs competing events (HR 0.96; 95% CI 0.93-0.99, p<0.01), as were both ECOG PS = 3 and ACE-27 = 2 (HR 0.02; 95% CI 0.01-0.04, p<0.01 and HR 0.01; 95% CI 0.00-0.02, p<0.01 respectively). 4 patients (1.7%) required NG feeding, at a median time of 19 days from radiotherapy start (IQR 5.75 days). On logistic regression, patients with an ECOG PS of 3 were more likely to require NG insertion (OR 1.26; 95% CI 1.14 - 1.39; p<0.001). 17 patients (7.2%) required emergency inpatient admission during or within six weeks of finishing radiotherapy. Patients with an ECOG PS of 3 were more likely to require admission (OR 1.36; 95% CI 1.10 - 1.68; p=0.004). 142 patients (60.2%) were prescribed strong opiate analgesia (i.e., oral morphine solution). Never / light former smokers were less likely to be prescribed opiates (OR 0.81; 95% CI 0.66 - 0.99; p=0.042). One patient (<1%) developed laryngeal cartilage necrosis and required a functional laryngectomy. Hypofractionated radiotherapy to the larynx is effective (local tumour control of 96%) and well-tolerated for patients with Tis / T1 N0 M0 squamous cell carcinoma of the glottic larynx, and should remain a standard of care approach. [ABSTRACT FROM AUTHOR]

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 a/ß 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. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate radiation-induced epidermal desquamation among breast cancer patients undergoing radiotherapy with 6MV linac and Co-60 teletherapy units. Method: Quantitative data was collected using self-administered closed ended questionnaires addressing the desquamation in relation to some patient-and treatment-related factors. The Radiation Therapy Oncology Group (RTOG) criteria for acute skin toxicity was used to grade the toxicity. Chi square and logistic regression analyses were respectively used to test statistical significance and evaluate the effects of the various factors on radiation induced epidermal desquamation Results: Majority of the participants had high BMIs (overweight: 39.5 %; obese: 50 %). Patients with BMI ≥ 25 kg/m2 presented with wet desquamation (RTOG grade 2). A chi-square analysis showed a significant difference (p = 0.02) between BMI and severity of desquamation. There was no significant difference between type of treatment machine and cumulative incidence dose of desquamation (p = 0.251). The logistic regression analysis showed that patients who had undergone mastectomy (OR = 0.562) were less likely to develop wet desquamation (RTOG grade 2) on the Co-60 machine within the 20–30 Gy threshold (OR=0.981) compared to those on the linear accelerator. Patients with lower BMI (OR = 0.412,[ < 25 vs ≥30]; OR = 0.286, [25–29.9 vs ≥30]) were also less likely to develop wet desquamation compared to those with higher BMI. Conclusion: Radiation-induced epidermal desquamation is a common side effect of breast cancer patients undergoing radiotherapy. BMI has an effect on the severity of desquamation experienced during breast irradiation.

Background and purpose: Introducing moderately hypofractionated salvage radiotherapy (SRT) following prostatectomy obligates investigation of its effects on clinical target volume (CTV) coverage and organ-at-risk (OAR) doses. This study assessed interfractional volume and dose changes in OARs and CTV in moderately hypofractionated SRT and evaluated the 8-mm planning target volume (PTV) margin. Materials and methods: Twenty patients from the PERYTON-trial were included; 10 received conventional SRT (35 × 2 Gy) and 10 hypofractionated SRT (20 × 3 Gy). OARs were delineated on 539 pre-treatment Cone Beam CT (CBCT) scans to compare interfractional OAR volume changes. CTVs for the hypofractionated group were delineated on 199 CBCTs. Dose distributions with 4 and 6 mm PTV margins were generated using voxel-wise minimum robustness evaluation of the original 8-mm PTV plan, and dose changes were assessed. Results: Median volume changes for bladder and rectum were −26 % and −10 %, respectively. OAR volume changes were not significantly different between the two treatment schedules. The 8-mm PTV margin ensured optimal coverage for prostate bed and vesicle bed CTV (V95 = 100 % in >97 % fractions). However, bladder V60

Purpose: Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10–25 fractions over 2–5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods: Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results: The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6–17 fractions/2.67–5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34–93%) for the entire cohort and 100, 87 (95% CI: 56.4–96.5%), and 42% (95% CI: 1.1–84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9–90.5%) and 100, 66.1 (95% CI: 36.4–84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusions: HFRT in HM provides excellent local control to be validated in a larger prospective study.

Abstract Background This study analyzed the impact of the coronavirus disease 2019 (COVID‐19) pandemic on radiotherapy delivery in Japan using a high‐quality Japanese national database based on universal health coverage. Methods We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID‐19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID‐19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture. Results The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (−5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (−4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single‐fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID‐19 cases. Conclusions Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID‐19 cases.

Summary: Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8–10Gy/2–4#/2–4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6–84 months). Mean age was 48 years (24–75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Summary: Background: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. Methods: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). Primary endpoint: invasive loco-regional control (ILRC); secondary overall survival. Findings: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99–1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82–2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99–2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28–1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7–119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07–15.5, p = 0.978) radiotherapy. Interpretation: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Funding: Cancer Research UK, NIHR, MRC.

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Simple Summary: Historically, frail patients who were older and showed poor performance status have been treated with a total dose of 40–45 Gy in 15 fractions, 34 Gy in 10 fractions, or 25 Gy in 5 fractions. We analyzed the oncologic outcomes after dose-escalated fractionated radiotherapy with a total dose of 56 Gy in 20 fractions for high-grade glioma in frail patients who were older than 70 years or showed poor performance status. This dose-escalated regimen with a total dose of 56 Gy in 20 fractions were comparable equivalent dose to conventional radiotherapy with a total dose 60 Gy in 30 fractions for non-frail patients. We observed survival outcomes outperforming historical data. The median overall survival was 12 months. Also, none of these patients experienced severe treatment-related toxicities. Furthermore, salvage treatment (either systemic therapy or local therapy) after progressive disease significantly improved survival outcomes after recurrence compared to supportive care even in frail patients. For high-grade glioma (HGG) patients with old age or poor performance status, hypofractionated radiotherapy (hypoRT) in 10–15 fractions is recommended. Also, limited data exist on the impact of salvage treatment after progression in frail patients. We retrospectively analyzed the outcomes of dose-escalated hypoRT in 40 frail HGG patients who were treated with hypoRT between 2013 and 2021. With a median biologically effective dose of 71.7 Gy, a total dose of 56 Gy in 20 fractions was the most frequently used regimen (53.7%). The median age and Karnofsky Performance Status of patients were 74 years and 70, respectively. Most patients (n = 31, 77.5%) were diagnosed with glioblastoma, IDH-wildtype, CNS WHO grade 4. Only 10 (25.0%) patients underwent surgical resection, and 28 (70.0%) patients received concurrent temozolomide during hypoRT. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.2 months. Of the 30 (75.0%) patients with disease progression, only 12 patients received salvage treatment. The OS after progression differed significantly depending on salvage treatment (median OS, 9.6 vs. 4.6 months, p = 0.032). Dose-escalated hypoRT in 20 fractions produced survival outcomes outperforming historical data for frail patients. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate the long-term treatment outcome of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients. Material and Methods: A total of 140 postmastectomy breast cancer patients were included in this retrospective study, who were treated from 2012 to 2014 with chemotherapy and various fractionation radiotherapy schedules. Radiotherapy treatment records for study group-I received radiotherapy 4256 cGy in 16 fractions over 31/2 weeks, group-II patients received 4005 cGy in 15 fractions over 3 weeks, and conventional radiotherapy group-III received 5000 cGy in 25 fractions over 5 weeks. Results: The median follow-up of patients from all groups was 60 months (range 9 to 111 months). There were 39 cases with disease failure, 13 (26%) in group I (42.56 Gy), 16 (40%) in group II (40.05 Gy), and 10 (20%) in group III (50 Gy). There were 4 locoregional recurrences (LRRs), two isolated, and 11 distant failures in group I, 3 LRRs (1 isolated LRR) and 15 distant failures in group II, and only one LRR and 9 distant failures in group III. The disease-free survival (DFS) were 74%, 60%, and 80%, respectively, in groups I, II, and III (P =0.044). Conclusion: The long-term results of this study show that hypofractionation radiotherapy in postmastectomy cases is well tolerated and acute and late side effects are also comparable to conventional fractionation. In our study, locoregional and distant failure seems slightly higher with hypofractionation schedules than in other studies, highlighting the need for more studies with long-term follow-up in postmastectomy patients. [ABSTRACT FROM AUTHOR]

Hypoxia in solid tumors is an important predictor of poor clinical outcome to radiotherapy. Both physicochemical and biological processes contribute to a reduced sensitivity of hypoxic tumor cells to ionizing radiation and hypoxia-related treatment resistances. A conventional low-dose fractionated radiotherapy regimen exploits iterative reoxygenation in between the individual fractions, nevertheless tumor hypoxia still remains a major hurdle for successful treatment outcome. The technological advances achieved in image guidance and highly conformal dose delivery make it nowadays possible to prescribe larger doses to the tumor as part of single high-dose or hypofractionated radiotherapy, while keeping an acceptable level of normal tissue complication in the co-irradiated organs at risk. However, we insufficiently understand the impact of tumor hypoxia to single high-doses of RT and hypofractionated RT. So-called FLASH radiotherapy, which delivers ionizing radiation at ultrahigh dose rates (> 40 Gy/sec), has recently emerged as an important breakthrough in the radiotherapy field to reduce normal tissue toxicity compared to irradiation at conventional dose rates (few Gy/min). Not surprisingly, oxygen consumption and tumor hypoxia also seem to play an intriguing role for FLASH radiotherapy. Here we will discuss the role of tumor hypoxia for radiotherapy in general and in the context of novel radiotherapy treatment approaches. [ABSTRACT FROM AUTHOR]

Purpose: Concurrent chemoradiation has been the mainstay of treatment for cervix cancer. We aimed to evaluate the non-inferiority of hypofractionated chemoradiation. Methods: This study was designed as a phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial and we report the interim results after 50% accrual. Cervical cancer patients with FIGO stages IIA–IIIC were recruited from April 2021 to September 2022. The intervention consisted of 40 Gy of 3D-conformal radiation therapy (RT) in 15 fractions over 3 weeks. In the control group, patients received standard chemoradiation of 45 Gy in 25 fractions over 5 weeks. Both groups received concurrent weekly cisplatin (40 mg/m2). Intravaginal brachytherapy of 28 Gy in 4 weekly fractions was delivered starting 1 week after the end of chemoradiation. The primary outcome was complete clinical response(CCR) at 3 months. Secondary outcomes included acute gastrointestinal (GI), genitourinary(GU), skin, and hematologic toxicities. A p value less than 0.05 was considered significant for analyses. Results: 59 patients were randomized; 30 in the control group and 29 in the intervention group. 20/30 (66.7%) of the patients in the control group and 19/29 (65.5%) in the intervention group achieved a CCR (absolute difference of 0.011, 95% CI − 0.23 to 0.25, p value: 0.13). There was a significantly higher rate of acute grade ≥ 3 GI toxicity in the intervention group (27.6%) compared with the control group (6.7%) (p value 0.032). Conclusions: Despite an absolute difference of 1.1% in the 3-month CCR, our interim analysis failed to show the non-inferiority of the hypofractionated chemoradiation. Due to the higher GI toxicities, we will continue this trial using intensity-modulated radiation therapy. Registration number and date: ClinicalTrials.gov: NCT04831437, 2021.4.1. [ABSTRACT FROM AUTHOR]

Background: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. Material and methods: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5–60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. Results: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1–2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1–40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). Conclusions: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10–25 fractions over 2–5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods: Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results: The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6–17 fractions/2.67–5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34–93%) for the entire cohort and 100, 87 (95% CI: 56.4–96.5%), and 42% (95% CI: 1.1–84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9–90.5%) and 100, 66.1 (95% CI: 36.4–84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusions: HFRT in HM provides excellent local control to be validated in a larger prospective study. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite ongoing medical advancements, glioblastoma remains a nearly uniformly fatal disease with a median survival of less than two years. This is largely attributable to its aggressive infiltration of surrounding brain parenchyma, which leads to a high risk of locoregional recurrence after the first line of therapy. Many strategies have been explored in an attempt to improve locoregional control, including hypofractionation. Here, we review a range of preclinical and clinical research on hypofractionation in the neoadjuvant, adjuvant, and recurrent or palliative setting. Additionally, we discuss novel hypofractionation strategies currently under investigation, such as FLASH radiotherapy. Glioblastoma (GBM) is the most common primary brain malignancy in adults, and its incidence is increasing worldwide. Its prognosis remains limited despite recent imaging and therapeutic advances. The current standard of care is maximal safe resection followed by conventionally fractionated radiotherapy with concurrent and adjuvant temozolomide (TMZ), with or without tumor-treating fields (TTF). However, hypofractionated radiotherapy (HFRT) has also been utilized for a variety of reasons. It is an established treatment option in the palliative setting, where shortened treatment duration can positively impact the overall quality of life for older patients or those with additional health or socioeconomic considerations. HFRT, and in particular stereotactic radiosurgery (SRS), has also been explored in both the pre- and post-operative setting for newly diagnosed and recurrent diseases. In this review, we summarize the ways in which HFRT has been utilized in the GBM patient population and its evolving role in the experimental space. We also provide commentary on scenarios in which HFRT may be indicated, as well as guidance on dose and fractionation regimens informed by our institutional experience. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT. Methods: We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes. Results: There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78 Gy in 39 fractions vs 42.7 Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78 Gy in 39-fraction or 62 Gy in 20-fraction vs 36.25 Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2 years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1–4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT. Conclusion: Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged. [ABSTRACT FROM AUTHOR]

Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%–100%), and 5-year OS was 96.0% (95%CI: 92.6–99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04–1.42, p =.01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p <.01; p =.02; respectively) and late fibrosis (p <.01; p =.049; respectively). ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our 'real-life' cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities. [ABSTRACT FROM AUTHOR]

Abstract Background This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems. Methods Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values. Results In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses. Conclusions Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.

This overview provides the historical perspective of external beam breast hypofractionation over the last 50 years. It highlights the serious harm suffered by patients with breast cancer in the 1970's and 1980's because of new hypofractionation regimens based on a theoretical radiobiology model being adopted into clinical practice to solve a resource issue without testing within clinical trials and without the essential radiotherapy quality assurance.It then describes the high-quality clinical trials comparing 3-week with 5-week standard of care regimens that were initiated based on a strong scientific rationale for hypofractionation in breast cancer. Today, there are still challenges with universal implementation of the results of these moderate hypofractionation studies, but there is now a substantial body of evidence to support 3-week breast radiotherapy with several large randomised trials still to report.The limit of breast hypofractionation is then explored and randomised trials investigating 1-week radiotherapy are described. This approach is now standard of care in many countries for whole or partial breast radiotherapy and chest wall radiotherapy without immediate reconstruction. It also has the advantage of reducing burden of treatment for patients and providing cost-effective care.Further research is needed to establish the safety and efficacy of 1-week breast locoregional radiotherapy and following immediate breast reconstruction. In addition, clinical studies are required to determine how a tumour bed boost for patients with breast cancer at higher risk of relapse can be incorporated simultaneously into a 1-week radiotherapy schedule. As such, the breast hypofractionation story is still unfolding.