Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 2. Lung (non-small cell lung cancer).

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

Lattice radiotherapy in inflammatory breast cancer: report of a first case treated with curative aim.

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

Radiation-induced dermatitis among breast cancer patients undergoing adjuvant radiotherapy in Ghana.

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.

Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study.

Introduction: We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating. Methods: Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.25 Gray (Gy) in 5 fractions on the MRL were analysed. Using the data from 20 patients, the percentage of radiotherapy (RT) delivery time where the prostate position moved beyond 1, 2, 3, 4 and 5 mm in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) and any direction was calculated. Results: The prostate moved less than 3 mm in any direction for 90% of the monitoring period in 95% of patients. On a per-fraction basis, 93% of fractions displayed motion in all directions within 3 mm for 90% of the fraction delivery time. Recurring motion patterns were observed showing that the prostate moved with shallow drift (most common), transient excursions and persistent excursions during treatment. Conclusion: A 3 mm CTV-PTV margin is safe to use for the treatment of 5 fraction prostate SBRT on the MRL, without gating. In the context of gating this work suggests that treatment time will not be extensively lengthened when an appropriate gating window is applied.

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer.

Background: Moderately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. Methods: The current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. Results: A total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. Conclusion: Our data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option.

Late urinary toxicity after extreme or moderate hypofractionated prostate radiotherapy in patients with prior transurethral resection of prostate (TURP).

PURPOSE: To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiotherapy. METHODS: Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity modulated radiotherapy (MHRT or SBRT), were included in this study. Severity and duration of urinary symptoms observed during serial follow up after at least three months from radiotherapy were graded per CTCAE v5.0 using information from prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analysed with univariable and multivariable binary logistic regression. RESULTS: Total 203 eligible patients were included (MHRT=114, 64-68Gy/25#; SBRT=89, 35-37.5Gy/5#). Median time from TURP to radiotherapy was 10 months (IQR 7-16), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17cc (IQR 0.5-1.35), while in MHRT and SBRT groups was 1.03 cc (IQR 0.4-1.15) and 1.27 cc (IQR 0.5-1.4), respectively. At a median follow up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n=17) and 23.2% (n=47) respectively. Grade 3 symptoms were observed at median 29 months (IQR 19-62) after radiotherapy completion, lasting for a median duration of 8 months (IQR 2-14). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiotherapy, fraction size, prostate volume, TURP to radiotherapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. CONCLUSION: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiotherapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiotherapy.

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.

10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity.

INTRODUCTION: To retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. MATERIAL AND METHODS: Patients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: One hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. CONCLUSION: Our study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients' convenience and significantly reduce RT department workloads.

Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

PURPOSE: Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. METHODS: The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. RESULTS: Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. CONCLUSION: To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.

Hemostatic radiotherapy for bleeding gastrointestinal tumors.

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal (GI) tumors, promoting tumor shrinkage, blood supply reduction, and fibrotic tissue formation. It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories. Hypofractionation schedules are also effective for tumor control and patient compliance.

Gemcitabine-Induced Myonecrosis Following Hypofractionated Radiation.

Palliative radiation is often used to abate pain and prevent bone fractures in patients with metastatic cancer. Hypofractionation, meaning delivery of larger doses of radiation in each treatment session (fraction), has become the standard of care in most cases. It not only reduces the burden on the medical system and facilitates the relief of symptoms but also enables the maintenance of the continuity of systemic therapy. Radiation recall phenomenon (RRP) is an acute inflammatory reaction in previously irradiated tissues that is provoked by chemotherapeutic drug administration. The incidence, severity, and prognosis of RRP following hypofractionated radiation therapy have not been studied. The symptoms of RRP depend on the radiation field, with the greatest concern associated with mucosal and dermal damage, though other symptoms have also been reported. Here, we describe a case of a 41-year-old woman with metastatic breast cancer (hormone receptor-positive, HER2/neu negative), who received palliative radiation to four other fields along the course of her disease, before her presentation with isolated myonecrosis of the thigh muscles. This RRP occurred four months following the last of two fractions of 8 Gy radiation to this region, given three months apart, and after six courses of cisplatin + gemcitabine. The symptoms improved with cessation of gemcitabine and prolonged administration of non-steroidal anti-inflammatory medications.

Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy.

Purpose: In stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. Methods: A retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. Results: All treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (-46.1 %) and 1.3 min (-56.2 %) for 6 and 10 MV FFF respectively. Conclusions: The high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

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

A Strategic Approach to Addressing Aggressive Vertebral Hemangiomas With Hypofractionated Stereotactic Body Radiotherapy.

This case report describes the treatment of a recurrent T2 vertebral hemangioma in a 46-year-old man who had prior decompression and fusion surgery. Despite initial stability, the patient developed worsening symptoms, leading to a comprehensive approach involving embolization, microscopic excision, and posterior fixation. Recurrence prompted the choice of Stereotactic Body Radiotherapy (SBRT) over redo surgery. Administered with 30 Gy in five fractions, SBRT significantly reduced hemangioma size and resolved neurological symptoms. The case highlights the effectiveness of hypofractionated SBRT as a promising intervention for aggressive vertebral hemangiomas.

The impact of advancing the standard of care in radiotherapy on operational treatment resources.

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

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.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

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.

Hypofractionation for Regional Nodal Irradiation in Breast Cancer: Best of Both the Worlds.

Locoregional radiotherapy play an important role in controlling the disease after surgery in patients with breast cancer. Radiotherapy schedules vary from conventional fraction to hypofractionation. The purpose of this review is to get an insight into the data on regional nodal irradiation (RNI) with hypofractionation in patients with breast cancer. This systematic review was constructed in accordance with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework. Electronic databases such as PubMed, Cochrane and EMBASE were searched from January 1, 2023 to March 31, 2023 to identify studies published in English language on hypofractionated RNI in post mastectomy patients. The search was carried out with the National Library of Medicine's Medical Subject Heading (MeSH) terms like "regional nodal irradiation," "hypofractionated" and "hypofractionation in breast cancer" with different Boolean operators (and/or). A manual search of reference lists of included articles was also performed to make sure there were no additional cases unidentified from the primary search. Studies deemed potentially eligible were identified and assessed by same independent reviewers to confirm eligibility. RNI data are mainly from a randomized study from Beijing and pooled data from START trials. There are also data from retrospective and single institutional studies and a few phase II studies with limited number of patients using different dose fractionations and techniques of radiotherapy. Doses used in these trials ranged from 26-47.7 Gy in 5-19 fractions over 1-4 weeks. Grade ≥ 2 pulmonary fibrosis and lymphedema rate ranged from 2%-7.9% and 3%-19.8% respectively. Grade ≥ 2 shoulder dysfunction and brachial plexopathy ranged from 0.2%-28% and 0%-< 1%, respectively. Late effects with a dose range of 26-40 Gy delivered in 5 to 15 fractions over 1-3 weeks were less/similar to conventional fraction. Current data showed lower/similar rates of toxicity with hypofractionated RNI compared with conventional fractionation RNI. Doses of 26 Gy to 40 Gy delivered in 5 to 15 fractions over 1-3 weeks are safe for RNI. With limited data, ultra-hypofractionation 26 Gy/5 fractions/1 week also seems to be safe. However, long-term outcome is awaited and many trials are going on to address its efficacy and safety.