Randomised controlled trials on radiation dose fractionation in breast cancer: systematic review and meta-analysis with emphasis on side effects and cosmesis.

OBJECTIVE: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). STUDY SELECTION: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions). DATA EXTRACTION: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively. DATA SYNTHESIS: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence. MAIN OUTCOME MEASURES: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics. RESULTS: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. CONCLUSIONS: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460249.

Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

Tumor volume changes after stereotactic, hypofractionated and conventional radiotherapy in paragangliomas of head and neck.

BACKGROUND: The aim of this study is comparison the effectiveness of stereotactic, hypofractionated and conventional radiotherapy assessed by the tumor volume changes of paraganglioma located in the head and neck region concerning fractional and total doses. METHODS: We analyzed 76 patients after radiotherapy due to paraganglioma who were assigned to 3 groups considering fractional (≤2 Gy, 3-5.5 Gy, ≥6 Gy) and total (≤20 Gy, 21-40 Gy, >40 Gy) doses. The volumes of irradiated tumors were measured and compared based on diagnostic images performed before and after the treatment. RESULTS: The mean tumor volume after the treatment with the lowest fractional dose (≤2 Gy) was decreased by 14.4 cm3. In patients treated with higher fractional doses (>2 Gy), the mean tumor volumes decreased by less than 1 cm3 for hypofractionated and stereotactic radiotherapy. 15.9 cm3 reduction of the mean tumor volume after the treatment with the highest RT total dose (>40 Gy) was stated. In patients treated with total doses ≤20 Gy and 21-40 Gy, the mean tumor volume was stable and reduced by 1.15 cm3, respectively. The analysis demonstrates a statistically significant (p < 0.05) treatment advantage in patients after the lowest fractional and highest total doses. CONCLUSION: The reduction of the tumor's volume was reported after conventional and unconventional radiotherapy. The most significant depletion of the paraganglioma volume was noted after a factional dose ≤2 Gy and a total dose >40 Gy.

Spatially fractionated GRID radiation potentiates immune-mediated tumor control.

BACKGROUND: Tumor-immune interactions shape a developing tumor and its tumor immune microenvironment (TIME) resulting in either well-infiltrated, immunologically inflamed tumor beds, or immune deserts with low levels of infiltration. The pre-treatment immune make-up of the TIME is associated with treatment outcome; immunologically inflamed tumors generally exhibit better responses to radio- and immunotherapy than non-inflamed tumors. However, radiotherapy is known to induce opposing immunological consequences, resulting in both immunostimulatory and inhibitory responses. In fact, it is thought that the radiation-induced tumoricidal immune response is curtailed by subsequent applications of radiation. It is thus conceivable that spatially fractionated radiotherapy (SFRT), administered through GRID blocks (SFRT-GRID) or lattice radiotherapy to create areas of low or high dose exposure, may create protective reservoirs of the tumor immune microenvironment, thereby preserving anti-tumor immune responses that are pivotal for radiation success. METHODS: We have developed an agent-based model (ABM) of tumor-immune interactions to investigate the immunological consequences and clinical outcomes after 2 Gy × 35 whole tumor radiation therapy (WTRT) and SFRT-GRID. The ABM is conceptually calibrated such that untreated tumors escape immune surveillance and grow to clinical detection. Individual ABM simulations are initialized from four distinct multiplex immunohistochemistry (mIHC) slides, and immune related parameter rates are generated using Latin Hypercube Sampling. RESULTS: In silico simulations suggest that radiation-induced cancer cell death alone is insufficient to clear a tumor with WTRT. However, explicit consideration of radiation-induced anti-tumor immunity synergizes with radiation cytotoxicity to eradicate tumors. Similarly, SFRT-GRID is successful with radiation-induced anti-tumor immunity, and, for some pre-treatment TIME compositions and modeling parameters, SFRT-GRID might be superior to WTRT in providing tumor control. CONCLUSION: This study demonstrates the pivotal role of the radiation-induced anti-tumor immunity. Prolonged fractionated treatment schedules may counteract early immune recruitment, which may be protected by SFRT-facilitated immune reservoirs. Different biological responses and treatment outcomes are observed based on pre-treatment TIME composition and model parameters. A rigorous analysis and model calibration for different tumor types and immune infiltration states is required before any conclusions can be drawn for clinical translation.

Two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with prostate cancer (SMART PRO trial): protocol for a confirmatory clinical trial.

INTRODUCTION: In an MRI-guided linear accelerator (MR-LINAC) system, the planned doses for organs at risk and for tumours are assessed by MR imaging and re-contouring at every treatment. This allows treatment to be safer and more precise by ensuring that it is suitable for the state of the patient's organs on that day, as well as by allowing images to be acquired during radiation therapy to prevent radiation while organs are in motion.Here, we will conduct a confirmatory study of two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with localised prostate cancer. METHODS AND ANALYSIS: This will be a single-arm study to demonstrate the safety and efficacy of ultra-hypofractionated radiation (26 Gy/2 Fr) using an MR-LINAC system in patients with very low-intermediate risk prostate cancer.The primary endpoint will be the incidence of grade ≥2 acute urinary tract adverse events occurring within 90 days of the start of radiation therapy.The sample size has been determined to be 58. ETHICS AND DISSEMINATION: This study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects, published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare and the modified act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee of the National Cancer Center on 20 November 2021.The findings of this trial will be submitted to an international peer-reviewed journal and the key findings will be presented at an international scientific conference.Authorship will be ascribed in accordance with the International Committee of Medical Journal Editors guidance. TRIAL REGISTRATION NUMBER: UMIN000049746.

Sequential Moderate Hypofractionated Boost in Breast Cancer Patients: A Monoinstitutional Analysis of Late Side Effects.

BACKGROUND/AIM: In breast cancer (BC) patients who have received breast-conserving surgery, moderate hypofractionation is standard of care for whole-breast irradiation (HF-WBI). On the other hand, the fractionation schedule for the boost is less well defined. A previous prospective study of our group aimed at evaluating acute and late cutaneous and subcutaneous side effects related to a sequential hypofractionated boost (HB) in patients who had received HF-WBI. The present study aimed at evaluating late side effects at a longer follow-up. PATIENTS AND METHODS: From 2014 to 2015, 219 BC patients received moderate HF-WBI (42.4 Gy in 16 fractions) at the Radiation Oncology Section of the University of Perugia. Patients with negative prognostic factors received a HB (2.65 Gy for 4 or 5 fractions). Late side effects were assessed using the Common Terminology Criteria for Adverse Events v5.0. Univariate and multivariate analyses estimated predictive factors for late toxicity. RESULTS: Median follow-up was 8.6 years (range=6.7-9.6). One hundred and sixty-five patients were evaluable in the present analysis; HB was administered to 47.3% of them. Late cutaneous and subcutaneous side effects occurred in 26/165 patients (15.8%); and all were G1. In univariate analysis ≥10 excised lymph nodes and HB administration emerged as risk factors for late side effects (p=0.003 and p=0.041, respectively). In multivariate analysis only ≥10 excised lymph nodes were confirmed as a risk factor for side effects (OR=3.431; 95%CI=1.209-9.737). CONCLUSION: HB after HF-WBI was safe and well-tolerated, even at a long-term follow-up; consequently, it can be used in routine practice.

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.

Multifraction stereotactic radiotherapy utilizing inhomogeneous dose distribution for brainstem metastases: a single-center retrospective analysis.

Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30 Gy in five fractions, 35 Gy in five fractions or 42 Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6 months (interquartile range, 10.0-24.3 months; range, 1.8-39.0 months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1 cc, whereas no toxicity was observed in treatments with a GTV less than 1 cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation.

Postoperative complications of hypofractionated and conventional fractionated radiation therapy in patients with implant-based breast reconstruction: A systematic review and meta-analysis.

INTRODUCTION: Post-mastectomy radiation therapy is an important component of adjuvant therapy for high-risk patients. However, radiation to reconstructed breasts can cause various complications. Recently, hypofractionated (HF) protocols have been adopted in several countries. Here, we aimed to assess the impact of HF protocols on implant-reconstructed breasts through a meta-analysis and systematic review of the currently available literature. METHODS: Records published until August 2023 were systematically searched in PubMed, Cochrane Library, and EMBASE databases. Keywords included hypofractionation radiotherapy, mastectomy, and breast reconstruction. Studies that utilized HF and conventional fractionation (CF) after prosthetic reconstruction were selected. Due to the rarity of events in outcomes, Mantel-Haenszel's odds ratios were calculated using a fixed-effect model to compare the complication rates between HF and CF groups. For analysis with high heterogeneity, a random effect model was used. RESULTS: Seven articles with 924 implant reconstructions, in which 506 (54.8 %) underwent HF were included. HF patients received 43.8 Gy on average, while CF patients received 51.2 Gy. Mean follow-up ranged from 10.6 to 35 months. Seven studies were included in the meta-analysis. HF groups had a significantly lower risk of capsular contracture (OR 0.25, 95 % CI 0.11-0.55), major revision surgery (OR 0.19, 95 % CI 0.05-0.80), and wound dehiscence (OR 0.24, 95 % CI 0.07-0.78) compared to CF groups. The risks of other complications were not statistically significant. CONCLUSION: This study indicates that HF protocols are associated with fewer complications than CF protocols in implant-reconstructed patients. These findings suggest that the application of HF PMRT in implant-reconstructed patients with breast cancer is plausible.

Fractionation dose optimization facilities the implementation of transmission proton FLASH-RT.

Objective.The beam switching time and fractional dose influence the FLASH effect. A single-beam-per-fraction (SBPF) scheme using uniform fractional dose (UFD) has been proposed for FLASH- radiotherapy (FLASH-RT) to eliminate the beam switching time. Based on SBPF schemes, a fractionation dose optimization algorithm is proposed to optimize non-UFD plans to maximize the fractionation effect and dose-dependent FLASH effect.Approach.The UFD plan, containing five 236 MeV transmission proton beams, was optimized for 11 patients with peripheral lung cancer, with each beam delivering a uniform dose of 11 Gy to the target. Meanwhile, the non-UFD plan was optimized using fractionation dose optimization. To compare the two plans, the equivalent dose to 2 Gy (EQD2) for the target and normal tissues was calculated with anα/ßratio of 10 and 3, respectively. Both UFD and non-UFD plans ensured that the target received an EQD2 of 96.3 Gy. To investigate the overall improvement in normal tissue sparing with the non-UFD plan, the FLASH-enhanced EQD2 was calculated.Main results.The fractional doses in non-UFD plans ranged between 5.0 Gy and 24.2 Gy. No significant differences were found in EQD22%and EQD298%of targets between UFD and non-UFD plans. However, theD95%of the target in non-UFD plans was significantly reduced by 15.1%. The sparing effect in non-UFD plans was significantly improved. The FLASH-enhanced EQD2meanin normal tissue and ipsilateral lung was significantly reduced by 3.5% and 10.4%, respectively, in non-UFD plans. The overall improvement is attributed to both the FLASH and fractionation effects.Significance.The fractionation dose optimization can address the limitation of multiple-beam FLASH-RT and utilize the relationship between fractional dose and FLASH effect. Consequently, the non-UFD scheme results in further improvements in normal tissue sparing compared to the UFD scheme, attributed to enhanced fractionation and FLASH effects.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments.

PURPOSE: This study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. METHODS: 1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. RESULTS: Group systematic error (M) was approximately -0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left-right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. CONCLUSIONS: The corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

A competing risks machine learning study of neutron dose, fractionation, age, and sex effects on mortality in 21,000 mice.

This study explores the impact of densely-ionizing radiation on non-cancer and cancer diseases, focusing on dose, fractionation, age, and sex effects. Using historical mortality data from approximately 21,000 mice exposed to fission neutrons, we employed random survival forest (RSF), a powerful machine learning algorithm accommodating nonlinear dependencies and interactions, treating cancer and non-cancer outcomes as competing risks. Unlike traditional parametric models, RSF avoids strict assumptions and captures complex data relationships through decision tree ensembles. SHAP (SHapley Additive exPlanations) values and variable importance scores were employed for interpretation. The findings revealed clear dose-response trends, with cancer being the predominant cause of mortality. SHAP value dose-response shapes differed, showing saturation for cancer hazard at high doses (> 2 Gy) and a more linear pattern at lower doses. Non-cancer responses remained more linear throughout the entire dose range. There was a potential inverse dose rate effect for cancer, while the evidence for non-cancer was less conclusive. Sex and age effects were less pronounced. This investigation, utilizing machine learning, enhances our understanding of the patterns of non-cancer and cancer mortality induced by densely-ionizing radiations, emphasizing the importance of such approaches in radiation research, including space travel and radioprotection.

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules.

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5-100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Extended Long-Term Outcome After Conservative Decompressive Microsurgery and Routine Adjuvant Fractionated Stereotactic Radiotherapy for Symptomatic Cavernous Sinus Meningiomas.

BACKGROUND AND OBJECTIVES: Cavernous sinus meningiomas (CSM) pose one of the most difficult to treat subgroup of skull base meningiomas. The purpose of this study was to evaluate the efficacy of an interdisciplinary treatment approach for symptomatic CSM which incorporated conservative function preserving microsurgery and routine adjuvant fractionated stereotactic radiotherapy (FSRT). METHODS: A homogenous group of patients with symptomatic primary CSM with extracavernous extension was treated between 2005 and 2012. All patients were available for a minimum follow-up of 5 years. Clinical follow-up included detailed examination of oculomotor deficits, visual status, and endocrinologic function. Radiologic follow-up was conducted by tumor volumetry. RESULTS: Overall, 23 patients were included in this study (78.3% women; median age 58 years). Diplopia was the most common presenting symptom, followed by headache and visual disturbances. Surgical morbidity was low (3/23; 13%). FSRT was applied after a median of 2 months after surgery. At a median clinical follow-up of 113 months, 70.45% of the presenting symptoms had improved, 25% remained unchanged, and in 2 cases (4.54%), worsening occurred. Overall tumor regression was evident in 19/21 World Health Organization 1 and in 1/2 of World Health Organization 2 CSM, respectively, at a median radiological follow-up of 103 months. CONCLUSION: Our findings demonstrate the efficacy of an interdisciplinary treatment approach for symptomatic primary CSM with extracavernous extension with decompression of neurovascular elements followed by FSRT. Precise preoperative planning and intraoperative decision making in combination with routine postoperative radiotherapy can achieve excellent tumor control, improve neurologic function, and minimize long-term morbidity.

Stereotactic ablative radiotherapy versus conventional fractionated radiotherapy for clinical early-stage non-small-cell lung cancer: a population-based study.

INTRODUCTION: The use of stereotactic ablative radiotherapy (SABR) over conventional fractionated radiotherapy (CFRT) for early-stage non-small-cell lung cancer (NSCLC) has been advocated, but is also debated in the literature. METHODS: In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients diagnosed between 2011 and 2021 using the Taiwan Cancer Registry. In the primary analysis, the overall survival (OS) was the primary endpoint, whereas incidences of lung cancer mortality and radiation pulmonary toxicity were the secondary endpoints. Extensive supplementary analyses were also conducted. RESULTS: We included 351 patients in the primary analysis and found that the OS was not significantly different between the SABR (n = 290) and CFRT (n = 61) groups. The propensity score weighting adjusted hazard ratio of death was 0.75 (95% confidence interval 0.53-1.07, p = 0.118). The secondary endpoints and supplementary analyses showed no significant differences. CONCLUSIONS: The OS of patients with early-stage NSCLC treated with SABR was not significantly different from that of patients treated with CFRT alone. The results of the relevant ongoing clinical trials are eagerly awaited.

Feasibility and Safety of the "One-Week Breast Radiation Therapy" Program.

AIMS: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results. MATERIAL AND METHODS: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale. RESULTS: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%). CONCLUSION: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing.