Assessment of Radiation Induced Pneumonitis and Pericarditis in Patients Undergoing Breast Conservative Treatment Using Hypofractionated Simultaneous Integrated Boost Technique.

INTRODUCTION: To determine the proportion of radiationinduced pneumonitis and pericarditis in patients who have received Hypo-fractionated Radiation along with simultaneous integrated boost technique after breast conservative surgery using a prospective observational study from a tertiary hospital. MATERIALS & METHODS: The incidence of radiationinduced pneumonitis and pericarditis was evaluated in all adult patients with biopsy-proven early-stage unilateral breast cancer who underwent breast-conserving surgery followed by hypo-fractionated radiation with a simultaneous integrated boost technique. Baseline assessments including a six-minute walk test, highresolution computed tomography (HRCT), pulmonary function tests (PFTs), electrocardiography (ECG) and echocardiography (ECHO) were performed. At three months post-radiation treatment, patients underwent follow-up assessments with a six-minute walk test, ECG and ECHO. At six months post-radiation treatment, patients underwent further assessments with a six-minute walk test, ECG, ECHO, PFTs, and HRCT of the thorax. Data analysis was performed using SPSS version 19. RESULTS: Our study investigated the incidence of acute radiation-induced pneumonitis and pericarditis in patients treated with hypofractionated VMAT-SIB technique in 20 eligible early breast cancer patients. The study found that the technique is feasible and achieves encouraging dosimetric parameters, including well achieved ipsilateral lung and heart doses. The reduced treatment time of 3-4 weeks compared to the previous 6-7 weeks with sequential boost was also found to be desirable in resource-constrained settings. The incidence of acute radiation pneumonitis and pericarditis was acceptable and comparable to existing data, with 90% of patients experiencing grade 1 radiation pneumonitis according to CTCAE v5.0. Post-treatment pulmonary function tests showed significant changes, particularly in patients who had received neoadjuvant chemotherapy and nodal irradiation. The six-minute walk test and Borg scale also showed a significant positive correlation with pulmonary function tests. There was no significant pericarditis during the follow-up. The study proposes that the hypofractionated radiotherapy using VMAT-SIB is a suitable alternative to conventional fractionation, with acceptable acute toxicities, but longer follow-up is required to assess the impact on late toxicities. CONCLUSION: Our research has shown that hypofractionated adjuvant radiotherapy with SIB is a safe and feasible treatment for patients with early breast cancer. This treatment method doesn't pose any significant short-term risks to the lungs or heart, and the SIB technique provides better coverage, conformity and sparing of organs at risk. Additionally, patients have reported positive cosmetic outcomes with this treatment. However, to make more accurate conclusions, we need to conduct further studies with larger sample sizes and longer follow-up periods to evaluate the potential longterm side effects of this treatment using VMAT in whole breast radiation.

In Response to "Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity".

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Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

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.

Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design.

BACKGROUND: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma. METHODS: Our study titled "PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)" is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2-12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response. DISCUSSION: PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting. TRIAL REGISTRATION: NCT05917301 (registered 23/6/2023).

Online Adaptive MR-Guided Ultrahypofractionated Radiotherapy of Prostate Cancer on a 1.5 T MR-Linac: Clinical Experience and Prospective Evaluation.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Dosimetric evaluation of different planning strategies for hypofractionated whole-breast irradiation technique.

Purpose.The dose hotspot areas in hypofractionated whole-breast irradiation (WBI) greatly increase the risk of acute skin toxicity because of the anatomical peculiarities of the breast. In this study, we presented several novel planning strategies that integrate multiple sub-planning target volumes (sub-PTVs), field secondary placement, and RapidPlan models for right-sided hypofractionated WBI.Methods.A total of 35 cases of WBI with a dose of 42.5 Gy for PTVs using tangential intensity-modulated radiotherapy (IMRT) were selected. Both PTVs were planned for simultaneous treatment using the original manual multiple sub-PTV plan (OMMP) and the original manual single-PTV plan (OMSP). The manual field secondary placement multiple sub-PTV plan (m-FSMP) with multiple objects on the original PTV and the manual field secondary placement single-objective plan (m-FSSP) were initially planned, which were distribution-based of V105 (volume receiving 105% of the prescription dose). In addition, two RapidPlan-based plans were developed, including the RapidPlan-based multiple sub-PTVs plan (r-FSMP) and the RapidPlan-based single-PTV plan (r-FSSP). Dosimetric parameters of the plans were compared, and V105 was evaluated using multivariate analysis to determine how it was related to the volume of PTV and the interval of lateral beam angles (ILBA).Results.The lowest mean V105 (5.64 ± 6.5%) of PTV was observed in m-FSMP compared to other manual plans. Upon validation, r-FSSP demonstrated superior dosimetric quality for OAR compared to the two other manual planning methods, except for V5(the volume of ipsilateral lung receiving 5 Gy) of the ipsilateral lung. While r-FSMP showed no significant difference (p = 0.06) compared to r-FSSP, it achieved the lowest V105 value (4.3 ± 4.5%), albeit with a slight increase in the dose to some OARs. Multivariate GEE linear regression showed that V105 is significantly correlated with target volume and ILBA.Conclusions.m-FSMP and r-FSMP can substantially enhance the homogeneity index (HI) and reduce V105, thereby minimizing the risk of acute skin toxicities, even though there may be a slight dose compromise for certain OARs.

IFN-Type-I Response and Systemic Immunity in Rectal Adenocarcinoma Patients Treated with Conventional or Hypofractionated Neoadjuvant Radiotherapy.

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 IFNß 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 IFNß plasma levels was noted in patients undergoing scRT (p = 0.004). Improved pathological tumor regression was associated with elevated post-RT IFNß 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.

Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Hypofractionated radiotherapy combined with lenalidomide improves systemic antitumor activity in mouse solid tumor models.

Background: Hypofractionated radiotherapy (hRT) can induce a T cell-mediated abscopal effect on non-irradiated tumor lesions, especially in combination with immune checkpoint blockade (ICB). However, clinically, this effect is still rare, and ICB-mediated adverse events are common. Lenalidomide (lena) is an anti-angiogenic and immunomodulatory drug used in the treatment of hematologic malignancies. We here investigated in solid tumor models whether lena can enhance the abscopal effect in double combination with hRT. Methods: In two syngeneic bilateral tumor models (B16-CD133 melanoma and MC38 colon carcinoma), the primary tumor was treated with hRT. Lena was given daily for 3 weeks. Besides tumor size and survival, the dependence of the antitumor effects on CD8+ cells, type-I IFN signaling, and T cell costimulation was determined with depleting or blocking antibodies. Tumor-specific CD8+ T cells were quantified, and their differentiation and effector status were characterized by multicolor flow cytometry using MHC-I tetramers and various antibodies. In addition, dendritic cell (DC)-mediated tumor antigen cross-presentation in vitro and directly ex vivo and the composition of tumor-associated vascular endothelial cells were investigated. Results: In both tumor models, the hRT/lena double combination induced a significant abscopal effect. Control of the non-irradiated secondary tumor and survival were considerably better than with the respective monotherapies. The abscopal effect was strongly dependent on CD8+ cells and associated with an increase in tumor-specific CD8+ T cells in the non-irradiated tumor and its draining lymph nodes. Additionally, we found more tumor-specific T cells with a stem-like (TCF1+ TIM3- PD1+) and a transitory (TCF1- TIM3+ CD101- PD1+) exhausted phenotype and more expressing effector molecules such as GzmB, IFNγ, and TNFα. Moreover, in the non-irradiated tumor, hRT/lena treatment also increased DCs cross-presenting a tumor model antigen. Blocking type-I IFN signaling, which is essential for cross-presentation, completely abrogated the abscopal effect. A gene expression analysis of bone marrow-derived DCs revealed that lena augmented the expression of IFN response genes and genes associated with differentiation, maturation (including CD70, CD83, and CD86), migration to lymph nodes, and T cell activation. Flow cytometry confirmed an increase in CD70+ CD83+ CD86+ DCs in both irradiated and abscopal tumors. Moreover, the hRT/lena-induced abscopal effect was diminished when these costimulatory molecules were blocked simultaneously using antibodies. In line with the enhanced infiltration by DCs and tumor-specific CD8+ T cells, including more stem-like cells, hRT/lena also increased tumor-associated high endothelial cells (TA-HECs) in the non-irradiated tumor. Conclusions: We demonstrate that lena can augment the hRT-induced abscopal effect in mouse solid tumor models in a CD8 T cell- and IFN-I-dependent manner, correlating with enhanced anti-tumor CD8 T cell immunity, DC cross-presentation, and TA-HEC numbers. Our findings may be helpful for the planning of clinical trials in (oligo)metastatic patients.

Neutrophil-to-lymphocyte ratio for the prediction of soft tissue sarcomas response to pre-operative radiation therapy.

PURPOSE/OBJECTIVE: This study aims to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in soft tissue sarcomas (STS) treated with pre-operative hypofractionated radiotherapy (HFRT). MATERIALS/METHODS: This retrospective analysis included patients treated with pre-operative HFRT of 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, and complete blood count (CBC) data were collected. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Only patients with CBCs conducted within 6 months after radiotherapy were included. Cox proportional-hazard regression models were used to assess the impact of NLR and different variables on outcomes. Kaplan Meier were used to illustrate survival curves. A p-value < 0.05 was considered significant, and 95 % confidence intervals (CI) were employed. RESULTS: A total of 40 patients received HFRT and had CBCs within 6 months after radiotherapy. There were 17 (42.5 %) females and 23 (57.5 %) males with a mean age of 66 years. The mean largest tumor size dimension was 7.1 cm, and the mean NLR post-RT was 5.3. The most frequent histological subtypes were myxofibrosarcoma (17.5 %), pleomorphic spindle cell sarcoma (10 %), leiomyosarcoma (7.5 %), and myxoid liposarcoma (5 %). The median follow-up period was 15.4 months. From all patients, 14 patients had disease progression, 12 metastatic disease and 3 died of disease. Multivariable Cox proportional-hazards regression analysis displayed that a higher post-RT NLR was associated with worse disease-free survival (DFS) (HR: 1.303 [1.098-1.548], p = 0.003), and distant metastasis-free survival (DMFS) (HR: 1.38 [1.115-1.710], p = 0.003). Moreover, post-NLR ≥ 4 as a single variable was associated with worse DFS, DMFS, but not worse local recurrence or overall survival. CONCLUSION: This study is the first to evaluate NLR as a prognostic biomarker in STS patients treated with pre-operative radiotherapy. A higher NLR after pre-operative radiotherapy was associated with increased disease progression.

Hypofractionated whole breast IMRT with HDR brachytherapy boost in early-stage breast cancer: Long-term results from a single-center.

INTRODUCTION/OBJECTIVES: The addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme. MATERIALS AND METHODS: We included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis. RESULTS: Between 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4-11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%. CONCLUSION: Adjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects.

Optimal hypofractionated radiation therapy schemes for early-stage hepatocellular carcinoma.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been emerging as an efficacious and safe treatment modality for early-stage hepatocellular carcinoma (HCC), but optimal fractionation regimens are unknown. This study aims to analyze published clinical tumor control probability (TCP) data as a function of biologically effective dose (BED) and to determine radiobiological parameters and optimal fractionation schemes for SBRT and hypofractionated radiation therapy of early-stage HCC. MATERIAL AND METHODS: Clinical 1- to 5-year TCP data of 4313 patients from 41 published papers were collected for hypofractionated radiation therapy at 2.5-4.5 Gy/fraction and SBRT of early-stage HCC. BED was calculated at isocenter using three representative radiobiological models developed per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. Radiobiological parameters were determined from a fit to the TCP data using the least χ2 method with one set of model parameters regardless of tumor stages or Child-Pugh scores A and B. RESULTS: The fits to the clinical TCP data for SBRT of early-stage HCC found consistent α/ß ratios of about 14 Gy for all three radiobiological models. TCP increases sharply with BED and reaches an asymptotic maximal plateau, which results in optimal fractionation schemes of least doses to achieve asymptotic maximal tumor control for SBRT and hypofractionated radiation therapy of early-stage HCC that are found to be model-independent. CONCLUSION: From the fits to the clinical TCP data, we presented the first determination of radiobiological parameters and model-independent optimal fractionation regimens in 1-20 fractions to achieve maximal tumor control whenever safe for SBRT and hypofractionated radiation therapy of early-stage HCC. The determined optimal fractionation schemes agree well with clinical practice for SBRT of early-stage HCC. However, most existing hypofractionated radiation therapy schemes of 3-5 Gy/fraction are not optimal, higher doses are required to maximize tumor control, further validation of these findings is essential with clinical TCP data.

Thirty-day mortality after palliative radiotherapy in advanced cancer patients: Optimizing end-of-life care in Asia.

INTRODUCTION: Evidence-based guidelines recommend hypofractionated palliative radiotherapy (PRT); nonetheless, many patients receive prolonged course of PRT. To identify patients with limited benefits from PRT in end-of-life care, we evaluated the pattern of PRT at an Asian institution and factors associated with 30-day mortality after PRT (30dM). METHODS: We retrospectively reviewed 228 patients who died after PRT in Yonsei Wonju Severance Christian hospital between October 2014 and March 2022. The associations between clinical factors and survival were assessed using the Cox proportional hazards method. Survival was analysed using the existing models to evaluate their performance in our cohort. RESULTS: The median PRT duration was 13 (IQR, 7-15) days. Only 11.4% of the patients were treated with hypofractionated radiotherapy. One-third of the patients (32.9%) could not complete PRT and 39 (17.1%) died during PRT. The 30dM was 31.6%. The median time from PRT to death was 17 (IQR, 11-23) days for the patients who died within 30 days. The number of involved organs (≤2 vs. >2; P < 0.001), albumin level (<3.3 vs. ≥3.3; P = 0.016), admission during PRT (P < 0.001), admission 3 months before PRT (P = 0.036) and ICU care during PRT (P < 0.001) were prognostic factors. A comparison of survival based on the existing models yielded unsatisfactory results in our cohort. CONCLUSION: Almost one-third of the patients received PRT in the last 30 days of life. The use of hypofractionation for PRT was low in this Asian population. Further research is necessary to develop a predictive model of early mortality, allowing tailored end-of-life care for Asian patients.

Hypofractionated radiation therapy combined with androgen deprivation therapy for high-risk localized prostate cancer.

INTRODUCTION: This study aimed to analyse the treatment outcomes of moderately hypofractionated radiation therapy (RT) combined with androgen deprivation therapy (ADT) and the prognostic implications of prostate-specific antigen (PSA) kinetics in high-risk localized prostate cancer. METHODS: The medical records of 140 patients who underwent definitive RT (70 Gy in 28 fractions) combined with ADT were retrospectively reviewed. ADT consists of a gonadotropin-releasing hormone agonist and an anti-androgen. Clinical outcomes included the biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS) and prostate cancer-specific survival (PCSS). The BFR and CFR were stratified by the PSA nadir and the time to the PSA nadir, respectively. Acute and late genitourinary and gastrointestinal adverse events were also recorded. RESULTS: The 5-year BFR, CFR, OS and PCSS rates were 9.8%, 4.5%, 90.2% and 98.7%, respectively. Ninety-five (67.9%) patients achieved a PSA nadir of 0.01 ng/mL. Patients with a PSA nadir >0.01 ng/mL had a significantly higher BFR and CFR (BFR, P = 0.001; CFR, P = 0.027), even after adjusting for other prognostic factors [per 0.1 ng/mL; BFR, hazard ratio (HR) 4.440, P < 0.001; CFR, HR 4.338, P = 0.001]. However, the time to the PSA nadir and pre-RT PSA were not significantly associated with the BFR and CFR. Six patients (4.3%) reported grade 3 late adverse events, mostly haematuria and haematochezia. CONCLUSION: Definitive RT with moderate hypofractionation combined with long-term ADT showed good efficacy for high-risk localized prostate cancer. The lowest PSA nadir was significantly associated with a low recurrence rate, indicating the importance of PSA follow-up.

Genitourinary toxicity in patients receiving TURP prior to hypofractionated radiotherapy for clinically localized prostate cancer: A scoping review.

BACKGROUND: When compared with conventional external beam radiotherapy, hypofractionated radiotherapy has led to less treatment sessions and improved quality of life without compromising oncological outcomes for men with prostate cancer. Evidence has shown transurethral prostatic resection prior to brachytherapy and external beam radiotherapy is associated with worsening genitourinary toxicity. However, there is no review of genitourinary toxicity when TURP occurs prior to definitive hypofractionated radiotherapy. In this review, we seek to illustrate the genitourinary outcomes for men with localized prostate cancer who underwent transurethral resection of the prostate prior to receiving definitive hypofractionated radiotherapy. Genitourinary outcomes are explored, and any predictive risk factors for increased genitourinary toxicity are described. METHODS: PubMed, Medline (Ovid), EMBASE and Cochrane Library were all searched for relevant articles published in English within the last 25 years. This scoping review identified a total of 579 articles. Following screening by authors, 11 articles were included for analysis. RESULTS: Five studies reported on acute and late toxicity. One article reported only acute toxicity while 5 documented late toxicity only. While most articles found no increased risk of acute toxicity, the risk of late toxicity, particularly hematuria was noted to be significant. Risk factors including poor baseline urinary function, prostate volume, number of prior transurethral prostatic resections, timing of radiotherapy following transurethral prostatic resection, volume of the intraprostatic resection cavity and mean dose delivered to the cavity were all found to influence genitourinary outcomes. CONCLUSION: For those who have undergone prior TURP hypofractionated radiotherapy may increase the risk of late urinary toxicity, particularly hematuria. Those with persisting bladder dysfunction following TURP are at greatest risk and careful management of these men is required. Close collaboration between urologists and radiation oncologists is recommended to discuss the management of patients with residual baseline bladder dysfunction prior to commencing hypofractionated radiotherapy.

Hypofractionated re-irradiation for diffuse intrinsic pontine glioma.

BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis. CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.