Comparative evaluation of outcomes amongst different radiosurgery management paradigms for patients with large brain metastasis.

INTRODUCTION: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. CONCLUSION: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

An Update on H3K27M-altered Diffuse Midline Glioma: Diagnostic and Therapeutic Challenges in Clinical Practice.

H3K27-altered diffuse midline glioma (DMG H3K27-altered) is a relatively newly-designated WHO entity which primarily affects the midline structures of the central nervous system (CNS), including the brainstem (predominantly pontine region), thalamus, midbrain, or spinal cord, and primarily affects children and young adults. Despite the proximity of these tumors to eloquent areas in the CNS, novel stereotactic approaches have facilitated the ability to obtain tissue diagnoses without significant morbidity, providing molecular diagnostic information in more than half of patients. Conventionally fractionated radiation therapy to a total dose of 54-60 Gy in 27-30 fractions and 24 Gy in 12 fractions play a crucial role in the definitive treatment of these tumors in the primary and salvage settings, respectively. Hypofractionated regimens may allow for accelerated treatment courses in selected patients without jeopardizing disease control or survival. The decision to add concurrent or adjuvant systemic therapy mainly relies on the physicians' experience without solid evidence in the literature in favor of any particular regimen. Recently, novel agents, such as ONC201 have demonstrated promising oncologic outcomes in progressive/recurrent tumors and are currently under investigation in ongoing randomized trials. Given the scarcity of data and well-established guidelines due to the rare nature of the disease, we provide a contemporary overview on the molecular underpinnings of this disease entity, describe the role of radiotherapy and systemic therapy, and present practice management principles based on the published literature.

Double isocenter optimization with HD-MLC linear accelerator to treat extended fields in patients with head and neck cancers.

PURPOSE: For departments with a congested patient burden or with a limited number of eligible LINACs, we investigated whether LINACS dedicated for SRS-SBRT with limited field high-definition (HD) multi-leaf collimator (MLC) could help to carry this load, and utilized a double-isocenter (DI) optimization with a limited field size of HD-MLC to defeat the craniocaudal field size restriction to match treated plans in a wide-field MLC LINAC for head and neck cancer patients. METHODS: Fourteen patients with locally advanced head and neck cancers were included, previously treated with simultaneous integrated boost volumetric modulated arc treatment (VMAT) in 33 fractions of clinical target volumes (CTV) of 70Gy, 63Gy, and 57Gy, via single isocenter (SI) plans in Millennium MLC-120 of Varian Trilogy. The DI plans were generated on Pinnacle TPS to be delivered in HD 120 leaves MLC on Varian Truebeam. The organs at risk (OAR) doses and the prescription volume parameters were compared. RESULTS: The DI plans in HD-MLC LINACs were successfully matching the previously treated plans for OAR and CTV constraints. The CI (1.18 versus 1.26; p=0.004) and HI (0.23 versus 0.29; p<0.001) were significantly improved with DI, while the MUs (1321.5 versus 800.3; p<0.001) and the treatment delivery times (6.1 versus 3.7 min; p<0.001) per fraction increased modestly with DI compared to SI, respectively. CONCLUSIONS: We revealed that DI optimization plans prepared for HD-MLC could effectively accomplish our goal dosimetrically in locoregionally advanced head and neck cases, despite a modest increase in the MU and treatment delivery times per fraction. This technique may provide an alternative in case of downtimes of standard MLC systems or a standalone treatment machine in case of high volumes requiring extended-field IMRT procedures, or possibly shorten the lengthy waiting times in facilities with limited SRS or SBRT patients.

Vaginal cuff brachytherapy practice in endometrial cancer patients: a report from the Turkish Oncology Group.

PURPOSE: The American Brachytherapy Association is attempting to develop standards for delivering brachytherapy, although differences in practice have been reported in the literature. This study evaluated vaginal cuff brachytherapy (VBT) practice and quality of life-related recommendations among Turkish radiation oncologists. MATERIAL AND METHODS: A nationwide web-based 17-item survey was distributed to the members of the Turkish Society for Radiation Oncology. These members received e-mail notifications, and a link was posted on the Turkish Society for Radiation Oncology internet site to solicit voluntary responses The survey addressed the simulation processes, target volume, prescribed dose, delivery schedules, and recommendations related to vaginal side effects. RESULTS: Fifty-seven radiation oncologists responded to the survey. The most used dose fraction schemes for adjuvant VBT were 7 Gy × 3 fractions (30%), 5.5 Gy × 5 fractions (26%), and 6 Gy × 5 fractions (28%). The preferred VBT scheme was 5 Gy × 3 fractions (50%) when the external beam radiotherapy (EBRT) dose was 45 Gy external radiotherapy, while the preferred schemes were 6 Gy × 3 fractions (30%) or 5 Gy × 3 fractions (32%) when the external radiotherapy dose was increased to 50.4 Gy. One-half of the respondents delivered VBT twice a week, and the dose was prescribed to 0.5 cm from vaginal mucosa by 86% of the respondents. There was no common definition for the dose prescription length, which was defined as 3 cm from the vaginal cuff in 33% of responses and as 4 cm in 35% of responses. For serous and clear cell histological types, 38% of the respondents targeted "full cylinder length". To prevent vaginal side effects, 78% of the respondents recommended using a vaginal dilator and/or sexual intercourse after VBT. CONCLUSIONS: This survey revealed variations in the clinical practice of VBT among Turkish radiation oncologists, which suggests that standardization is necessary.

Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study.

BACKGROUND: We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). METHODS: Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups. RESULTS: The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%; P=0.52) and median overall survival (25.2 versus 24.6 months; P=0.69), locoregional progression-free survival (15.3 versus 15.1 months; P=0.52), and progression-free survival (11.7 versus 11.2 months; P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P < 0.001) were all significantly higher in the ENI than in the IFRT group, respectively. CONCLUSION: Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.