Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: An international multicenter study.

BACKGROUND: Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited. METHODS: RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN. RESULTS: Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06-42.38 cm3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27-111.22 cm3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant. CONCLUSIONS: Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Early mortality of stage IV non-small cell lung cancer in the United States.

Background: Early mortality is a major deterrent to oncologic management, often preventing delivery of therapy or leading to administration of treatment that offers limited benefit from aggressive interventions. Due to more recent progress in therapeutic options for stage IV non-small cell lung cancer (NSCLC) patients, identifying those at high risk of early mortality (within 30 days) could have implications for treatment selection. Because early mortality following diagnosis of metastatic non-small cell lung cancer (NSCLC) is not well-characterized, this investigation evaluated national trends and predictors thereof. Material and methods: The National Cancer Database was queried for cases of pathologically confirmed metastatic NSCLC with complete vital status and clinical information, diagnosed between 2006 and 2014. Multivariable logistic regression ascertained factors associated with 30-day mortality. Results: Of 346,681 patients, 45,861 (13%) experienced early mortality over the past decade, which remained relatively constant over time. Predictors of early mortality included advancing age (>65 years), male gender, Caucasian race, non-private insurance, lower income, greater comorbidities, residence in metropolitan and/or lesser-educated areas, treatment at community centers, patients with no prior history of cancer and regional differences (p < .01 for all). Early mortality was highest in patients older than 80 years with multiple comorbidities (29%). The majority of patients (71%) who died within 30 days did not receive any therapy. Conclusions: A fair proportion of NSCLC patients experience early mortality, which has not decreased over time. The majority of patients with early mortality do not receive treatment. Prognostic factors for early mortality should be considered during initial evaluation and subsequent follow-up of these patients. Doing so may impact systemic treatment selection by medical oncologists, management of (oligo)metastatic disease by radiation and surgical oncologists and cost-effective administration of these therapies in the stage IV NSCLC population.

Malignant Peritoneal Mesothelioma: National Practice Patterns, Outcomes, and Predictors of Survival.

PURPOSE: This study of a large, contemporary national database evaluated management patterns, outcomes, and prognostic factors of malignant peritoneal mesothelioma (MPM) in the USA. METHODS: The National Cancer Data Base was queried for newly diagnosed nonmetastatic MPM. Patients were divided into five cohorts: observation, chemotherapy alone, cytoreductive surgery (CRS) alone, CRS/chemo [referring to any non-hyperthermic intraperitoneal chemotherapy (HIPEC) chemotherapy], and CRS/HIPEC. Statistics included multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling. RESULTS: Of 1514 patients, 379 (25%) underwent observation, 370 (24%) received chemotherapy only, 197 (13%) CRS alone, 352 (23%) CRS/chemo, and 216 (14%) CRS/HIPEC. No major temporal trends in management were noted. Factors predictive of CRS administration included younger age, female gender, insurance status, residence in educated areas, living farther from treating institutions, and treatment at academic centers (p < 0.05 for all). Compared with epithelioid histology, those with sarcomatoid and biphasic histology were less and more likely to undergo CRS, respectively (p < 0.05 for both). In all CRS patients, 30- and 90-day mortality rates were 0.8 and 1.2%, respectively. At median follow-up of 50 months, median OS in the respective groups was 6, 17, 21, 52, and 61 months (p < 0.001). Poor prognostic factors included advanced age, male gender, uninsured/Medicaid insurance, and sarcomatoid/biphasic histology (p < 0.05 for all). CONCLUSIONS: In the USA, MPM is treated using a wide variety of strategies. Many factors impact the type of treatment delivered, including age, sociodemographics, geography, histology, and facility type. Although these data do not imply causation, combined-modality management seems associated with the longest OS.

Repeat reirradiation of the spinal cord: multi-national expert treatment recommendations.

BACKGROUND: Improved survival of patients with spinal bone metastases has resulted in an increased number of referrals for retreatment and repeat reirradiation. METHODS: A consortium of expert radiation oncologists (RO) has been established with the aim of providing treatment recommendations for challenging clinical scenarios for which there are no established guidelines. In this case, a patient developed local progression of a T5 vertebral lesion after two prior courses of palliative radiotherapy (time interval >12 months, assumed cumulative biologically equivalent dose in 2­Gy fractions [EQD2] for spinal cord [alpha/beta 2 Gy] 75 Gy). Expert recommendations were tabulated with the aim of providing guidance. RESULTS: Five of seven RO would offer a third course of radiotherapy, preferably with advanced techniques such as stereotactic radiotherapy. However, the dose-fractionation concepts were heterogeneous (3-20 fractions) and sometimes adjusted to different options for systemic treatment. All five RO would compromise target volume coverage to reduce the dose to the spinal cord. Definition of the spinal cord planning-organ-at-risk volume was heterogeneous. All five RO limited the EQD2 for spinal cord. Two were willing to accept more than 12.5 Gy and the highest EQD2 was 19 Gy. CONCLUSIONS: The increasing body of literature about bone metastases and spinal cord reirradiation has encouraged some expert RO to offer palliative reirradiation with cumulative cord doses above 75 Gy EQD2; however, no consensus was achieved. Strategies for harmonization of clinical practice and development of evidence-based dose constraints are discussed.

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. RESULTS: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). CONCLUSIONS: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

National patterns of care and predictors of neoadjuvant and concurrent chemotherapy use with definitive radiotherapy in the treatment of patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: To the authors' knowledge, the patterns of care for the radiotherapy-based treatment of patients with stage III to IVB oropharyngeal squamous cell carcinoma (OPSCC) are poorly defined. The objective of the current study was to characterize the use and predictors of chemotherapy with radiotherapy for this population using the National Cancer Database. METHODS: Patients in the National Cancer Database with AJCC (American Joint Committee on Cancer) stage III to IV OPSCC who were treated with radiotherapy between 2003 and 2012 were eligible for analysis. Treatment was defined as radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy (IC). Multivariable regression with multilevel modeling was used to determine predictors of any chemotherapy use and, among patients receiving chemotherapy, the predictors of IC. RESULTS: The majority (90%) of the 30,875 eligible patients received chemotherapy, the majority of whom (71% of the total) were treated with definitive chemoradiotherapy; a sizeable percentage of patients received IC (19% of total). On multivariable regression, younger age, favorable comorbidity status, and more advanced tumor and lymph node disease were found to be independent predictors of any chemotherapy and IC use. Nonwhite patients (odds ratio [OR], 0.71; P<.0001), women (OR, 0.74; P<.0001), and individuals without private insurance were found to be significantly less likely to receive chemotherapy. Patients treated at higher-volume institutions were significantly less likely to receive IC (OR, 0.69; P = .0006). Human papillomavirus status did not appear to independently influence treatment choice. CONCLUSIONS: The vast majority of patients with stage III to IVB OPSCC who were treated with definitive radiotherapy received chemotherapy, which is consistent with high-level data and national recommendations. However, disparities with regard to race, sex, and insurance status emerged thereby requiring additional investigation. The frequent use of IC despite limited supportive evidence warrants research on physician and patient decision making and presents an opportunity to improve evidence-based treatment delivery. Cancer 2017;123:273-282. © 2016 American Cancer Society.

Adjuvant radiotherapy improves overall survival in patients with resected gastric adenocarcinoma: A National Cancer Data Base analysis.

BACKGROUND: For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens. METHODS: Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed. RESULTS: A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001). CONCLUSIONS: In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society.

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

AIM/BACKGROUND: Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. MATERIALS AND METHODS: The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. RESULTS: In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p = 0.032) and for patients >18 years (n = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p = 0.049), respectively. CONCLUSIONS: In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared.

Association of health insurance with outcomes in adults ages 18 to 64 years with melanoma in the United States.

BACKGROUND: Studies evaluating insurance status and melanoma outcomes are limited. OBJECTIVE: We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma. METHODS: This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database. RESULTS: Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001). LIMITATIONS: This was a retrospective study. CONCLUSION: Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes.

Should we customize PTV expansions for BMI? Daily cone beam computerized tomography to assess organ motion in postoperative endometrial and cervical cancer patients.

AIM: A single-institution review assessing patient characteristics contributing to daily organ motion in postoperative endometrial and cervical cancer patients treated with intensity-modulated radiotherapy (IMRT). BACKGROUND: The Radiation Therapy Oncology Group has established consensus guidelines for postoperative pelvic IMRT, recommending a 7 mm margin on all three axes of the target volume. MATERIALS AND METHODS: Daily shifts on 457 radiation setups for 18 patients were recorded in the x axis (lateral), y axis (superior-inferior) and z axis (anterior-posterior); daily positions of the planning tumor volume were referenced with the initial planning scan to quantify variations. RESULTS: Of the 457 sessions, 85 (18.6%) had plan shifts of at least 7 mm in one of the three dimensions. For obese patients (body mass index [BMI] ≥ 30), 75/306 (24.5%) sessions had plan shifts ≥7 mm. Odds of having a shift ≥7 mm in any direction was greater for obese patients under both univariate (OR 4.227, 95% CI 1.235-14.466, p = 0.021) and multivariate (OR 5.000, 95% CI 1.341-18.646, p = 0.016) analyses (MVA). Under MVA, having a BMI ≥ 30 was associated with increased odds of shifts in the anterior-posterior (1.173 mm, 95% CI 0.281-2.065, p = 0.001) and lateral (2.074 mm, 95% CI 1.284-2.864, p < 0.000) directions but not in the superior-inferior axis (0.298 mm, 95% CI -0.880 to 1.475, p = 0.619) exceeding 7 mm. CONCLUSIONS: Based on these findings, the standard planned tumor volume expansion of 7 mm is less likely to account for daily treatment changes in obese patients.

Sarcomas of the aorta: a systematic review and pooled analysis of published reports.

BACKGROUND: Aortic sarcomas are rare and aggressive tumors with a propensity for arterial embolization, disseminated metastases, and rapid clinical deterioration. Overall, little is known about the evaluation and management of this disease. METHODS: A systematic review and pooled analysis were performed from a comprehensive search of the MEDLINE database for reports of primary aortic sarcomas published in the English language. RESULTS: One hundred sixty-five cases were analyzed. The median age was 60 years, and the male:female ratio was 1.5:1. High tumor grade (87.3%), arterial embolization (46.7%), and metastatic disease at diagnosis (44.8%) were common. Typical histologies were undifferentiated (39.4%), angiosarcomatous (37%), leiomyosarcomatous (13.3%), and fibroblastic (7.3%). Management was diverse and included combinations of surgical resection (46.7%), palliative vascular surgeries (37.7%), chemotherapy (28.7%), and radiotherapy (14.7%). The median survival was 11 months, and the 1-, 3-, and 5-year survival rates were 46.7%, 17.1%, and 8.8%, respectively. On univariate analyses, metastatic disease at diagnoses, surgical resection, and chemotherapy were associated with survival. On multivariate analysis, only metastatic disease remained significant (P < 0.001). CONCLUSIONS: Aortic tumors are devastating malignancies with distinct clinical features from sarcomas at other sites. Although prognosis is poor overall, long-term survivors have been reported, and aggressive management with surgical resection and adjuvant therapy should be considered in medically suitable patients. High embolic rates suggest a potential role for prophylactic anticoagulation.

The Role of Local Therapy for Oligo-Progressive Disease in Oncogene-Addicted Non-Small-Cell Lung Cancer.

Purpose: We first described the role of local radiation therapy (LT) for oligoprogressive disease (OPD) on targeted therapy in 2012. Here, we present an updated and larger data set and extend the analysis beyond EGFR and ALK. Methods: A retrospective review of patients with metastatic NSCLC harboring EGFR/BRAF V600E mutations, or ALK/ROS1/RET rearrangements, who had OPD on respective tyrosine-kinase inhibitor (TKI) and treated with LT was performed. OPD was defined as disease progression on therapy in ≤5 sites. PFS1 (progression-free survival 1) was defined as time from initiation of TKI-containing regimen to the first course of LT for OPD. Subsequent PFS times (eg, PFS2, PFS3) were defined as time from prior LT to subsequent LT, switch of systemic therapy, death, or loss to follow-up, whichever occurred first. Extended-PFS was defined as time from the first day of the first LT course to the day of change in systemic therapy, death, or loss to follow-up, whichever came first. Results: Eighty-nine patients were identified. In 75.4% of the LT courses, a single lesion was treated. Median PFS1 was 10.2 months (95% CI, 8.7-13.1) and median Extended-PFS was 6.7 months (95% CI, 4.9-8.3). Extended-PFS was similar across different oncogenic drivers; 51.4% of patients who underwent LT to a single site had only 1 site on next disease progression. Conclusions: LT is effective in prolonging treatment duration on TKI in oncogene-addicted NSCLC across multiple oncogenes.

Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report.

PURPOSE: A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. MATERIALS AND METHODS: Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. RESULTS: Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P > .053). CONCLUSIONS: The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas: A Multicenter Study (STORM).

PURPOSE: The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM (Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas), a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. METHODS AND MATERIALS: Data on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from 8 academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than 2 lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes, including progression-free survival (PFS) and overall survival, as well as toxicity outcomes, were reported at the patient level. RESULTS: From 2000 to 2022, 108 patients were identified (94% grade 2, 6.0% grade 3). A total of 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiation therapy (RT). Median time to first progression was 2.5 years (IQR, 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of 2 lesions (87% received single-fraction SRS). The median follow-up time after SRS was 2.6 years. The 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively, after treatment with SRS. The 1-, 2-, and 3-year overall survival was 97%, 94%, and 92%, respectively. In the multivariable analysis, grade 3 disease (HR, 6.80; 95% CI, 1.61-28.6), male gender (HR, 3.48; 95% CI, 1.47-8.26), and receipt of prior RT (HR, 2.69; 95% CI, 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. CONCLUSIONS: This is the largest multicenter study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with a potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation.