Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol.

INTRODUCTION: Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. METHODS: This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. DISCUSSION: This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

Stage-matched survival differences by ethnicity among gastric cancer patients of Asian ancestry treated in the United States.

BACKGROUND: Differences have been noted in overall survival (OS) in gastric cancer (GC) between trials conducted in Western vs Asian countries. The National Cancer Database (NCDB) reports outcomes and patient/disease variables relevant to OS. METHODS: Using NCDB, we identified 89 558 adult patients with GC diagnosed (2004-2012), where self-reported race/ethnicity was available. Cox proportional hazard model was used to calculate multivariable hazard ratio (HR) of death, adjusting for race/ethnicity, age, gender, insurance, histology, grade, location, stage, and treatment type. RESULTS: After adjustment, Asian patients had improved OS (HR = 0.74, 95% confidence intervals [CI] = 0.71-0.77). There were differences in OS between Asian ethnicities compared with white patients (n = 69 945), notably with Korean (n = 1249, HR = 0.70, 95% CI = 0.64-0.75), Chinese (n = 1271, HR = 0.69, 95% CI = 0.64-0.75), and Indian/Pakistani patients (n = 492, HR = 0.68, 95% CI = 0.61-0.76). Japanese (n = 829, HR = 0.84, 95% CI = 0.77-0.91) and Vietnamese (n = 560, HR = 0.79, 95% CI = 0.71-0.88) OS was also improved (P < 0.0001), while Filipino patients showed no difference (n = 415, HR = 1.00). Black patients had slightly improved OS (n = 13 500, HR = 0.98, 95% CI = 0.95-1.00, P = 0.035). CONCLUSIONS: This analysis supports improved OS in Asian patients independent of stage, treatment, and known patient or disease characteristics in this large US cohort, and is the largest to define OS differences between Asian ethnicities.

Analysis of Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department.

Purpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and Materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.

Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation.

Introduction: Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. Methods: A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Results: Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. Discussion: These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.

Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes.

Purpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.

Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department.

PURPOSE: In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. METHODS AND MATERIALS: Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. RESULTS: In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. CONCLUSIONS: Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy.

BACKGROUND: Whole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate. PATIENTS AND METHODS: The National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors. RESULTS: A total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001). CONCLUSIONS: SFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.

Predictors of Positive Margins After Definitive Resection for Gastric Adenocarcinoma and Impact of Adjuvant Therapies.

PURPOSE: Positive margins after definitive resection in gastric adenocarcinoma are associated with inferior outcomes. There are few randomized data to guide optimal adjuvant therapy after positive margins. METHODS: Using the National Cancer Database, we identified 24,619 nonmetastatic gastric adenocarcinoma patients who received diagnoses from 2004 to 2013 and underwent definitive resection to analyze for predictors of positive surgical margins. Of these patients, 2754 had positive margins (11.2%). Multivariate prevalence ratios were used to determine predictors. Survival analyses were performed with a Cox proportional hazards model by use of several methods of propensity score analysis. RESULTS: Increasing T and/or N category, high grade, and lymphovascular invasion predicted higher rates of positive margins. Asian race, treatment at an academic center, and robotic surgery predicted lower rates of positive margins. Among positive-margin patients with adjuvant treatment (n=1021), with a median follow-up period of 55 months, age, comorbidity score, nodal disease, and T4 disease predicted for worse overall survival (OS). Treatment at an academic center was associated with improved OS. Use of adjuvant concurrent chemoradiation therapy (CCRT) was associated with higher OS compared with chemotherapy alone after positive margins (hazard ratio, 0.72; 95% confidence interval, 0.58-0.91; P=.005) after propensity matching adjusting for predictors of OS. The 2-year and 3-year OS for positive-margin patients with chemotherapy alone was 43% and 29%, respectively, compared with 53% and 38%, respectively, with adjuvant CCRT. The log-rank P value for survival was .0015. CONCLUSIONS: Stage, race, treatment center, and surgery approach predict for margin status after resection. Adjuvant CCRT after positive margins is associated with improved OS after accounting for available clinical variables.