onc brain

PURPOSE The 2022 AUA/ASTRO guidelines recommend 18-36 months of androgen deprivation therapy (ADT) with definitive radiotherapy for localized, high-risk prostate cancer. The STAMPEDE M0 trial supports intensification with androgen receptor pathway inhibitors (ARPIs) for patients with ≥2 cT3/T4, Grade Group [GG] 4-5, prostate-specific antigen (PSA) ≥40 ng/mL, or cN1. Given advances in imaging, risk stratification, and treatment delivery, we characterized contemporary practice patterns using prospective data from the Michigan Radiation Oncology Quality Consortium (MROQC). METHODS Patients enrolled in MROQC with intact, high-risk M0/N0-1 prostate cancer were included. Clinical information, including intended ADT duration and ARPI use, was prospectively collected. The primary outcome was intended guideline-concordant ADT (GC-ADT, ≥18 months). Multivariable analyses (MVA) assessed associations between clinical factors and GC-ADT recommendations. We compared the adoption of ARPI with standard therapies before and after the publication of STAMPEDE M0. Facility-level variability was evaluated using a mixed-effects model, with the treatment site as a random intercept. RESULTS Between June 2020 and November 2024, 553 patients across 26 centers were included: cT3/4 (13.3%), cN1 (19.9%), GG 4-5 (75.0%), and PSA ≥20 ng/mL (40.0%). Overall, 91.3% were recommended ADT, with 67.0% being guideline-concordant. On MVA, GC-ADT was significantly associated with cN1 (odds ratio [OR], 2.94 [95% CI, 1.44 to 5.99]), GG (GG4 OR, 6.23 [95% CI, 2.85 to 13.62]; GG5 OR, 9.45 [95% CI, 4.46 to 20.06]), and PSA ≥40 (OR, 3.64 [95% CI, 1.22–10.87]). Facility-level variability persisted in the MVA ( P < .0001). Among the 27.9% who met meeting STAMPEDE criteria, ARPI recommendations increased from 0% prepublication to 23.2% afterward. CONCLUSION Within a statewide quality consortium, guideline-concordant ADT recommendations occurred in two thirds of patients, with ARPI intensification in under 25% among STAMPEDE-eligible patients. These findings highlight the need for individualized ADT strategies and collaborative efforts to standardize high-quality care.

6000 Background: The role of adjuvant radiotherapy (RT) in early-stage, node-negative oral squamous cell carcinoma (OSCC) with one or more intermediate risk factors - such as depth of invasion (DOI) ≥5 to ≤10mm, perineural invasion (PNI), lymphovascular emboli (LVE), or poor differentiation - remains debatable and is largely based on retrospective data. This multicenter, open-label, phase III randomized controlled trial was designed to assess the impact of post-operative adjuvant RT in this setting. Methods: Patients with early-stage (pT1-T2), node-negative (pN0) OSCC undergoing adequate surgery (defined as clear margins ≥5mm and at least ipsilateral level I-III neck dissection with ≥16 nodes) with presence of one or more intermediate risk factors were screened. Eligible patients underwent stratified randomization (oral cavity subsite, PNI/LVE, and differentiation) in 1:1 ratio to either observation or adjuvant RT (60Gy in 30 fractions over 6-weeks) to the resected tumor-bed and at-risk neck nodal region after written informed consent. Primary endpoint was loco-regional recurrence-free survival (LRFS) measured from randomization to first documented event of local and/or regional recurrence from index cancer. All time-to-event outcomes were computed using Kaplan-Meier (KM) method with log-rank test for comparison and expressed as 3-year point estimates with 95% confidence intervals (CI). The planned sample size (N=392) provided 80% power at an α of 0.05 to detect a Hazard Ratio (HR) of 0.6256, assuming 3-year LRFS of 70% in the observation arm. Results: Following curative surgery, a total of 392 patients were randomized (191 to adjuvant RT; 201 to observation). Baseline characteristics were balanced between the two arms. At a median follow-up of 47.2 months (inter-quartile range=30-59.4 months), 3-year KM estimate of LRFS was 89.2% in adjuvant RT arm vs 80.9% in observation arm (HR=0.52, 95%CI=0.30-0.91; p=0.02) in the intention-to-treat (ITT) population and 91.1% vs 80.9% (HR=0.43, 95%CI=0.23-0.80; p=0.01) on per-protocol (PP) analyses. Cumulative incidence of loco-regional failure with death as competing event was 10.6% (95%CI=6.1%-15.1%) with adjuvant RT and 18.9% (95%CI=13.3%-24.6%) with observation (HR=0.52, 95%CI=0.30-0.91; p=0.021) in the ITT population and 8.7% (95%CI=4.3%-13.1%) vs 18.9% (95%CI=13.3%-24.6%) (HR=0.43, 95%CI=0.23-0.79; p=0.007) on PP analyses. Disease-free and overall survival were not significantly different between the two arms. Subgroup analysis identified oral tongue deriving higher benefit of adjuvant RT compared to buccal mucosa. Conclusions: Adjuvant RT significantly reduces risk of loco-regional recurrence for early-stage, node-negative adequately resected OSCC, particularly oral tongue. However, such reduction in loco-regional failure does not translate into significant survival benefit. Clinical trial information: CTRI/2017/07/009114.

PURPOSE: For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance.<br/><br/>METHODS: NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes.<br/><br/>RESULTS: Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms.<br/><br/>CONCLUSION: Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.