Faculty Bibliography

OBJECTIVE:Patients with non-small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS:A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS:The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.81, p = 2.5 × 10-3; HR 2.51, 95% CI 1.45-4.34, p = 9.8 × 10-4, respectively). CONCLUSIONS:The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

PURPOSE/OBJECTIVE(S): Multiple brain metastases (BM) from non-small cell lung cancer (NSCLC) historically has a dismal prognosis. Advances in systemic therapy for NSCLC have significantly improved survival, but the effect on prognosis in patients with NSCLC and BM is poorly understood. Stereotactic radiosurgery (SRS) may result in local control even with higher numbers of BM. We report survival outcomes of upfront SRS for >=5 BM from metastatic NSCLC. MATERIALS/METHODS: Review of our registry identified 177 patients treated for >=5 BM from NSCLC between 2012 and 2020, and did not undergo prior intracranial radiation or resection.
RESULT(S): Adenocarcinoma was found in 129 patients (73%). EGFR/ALK mutations were identified in 54 patients (31%). The median number of tumors at initial SRS were 8 (range 5-35). 121 patients (68%) were treated for 5-10 BM, 31 patients (18%) for 11-15 BM, and 25 patients (14%) for > 15 BM. The median overall survival (OS) from initial SRS for all patients was 15.1 months (95% CI 11.5-18.7). Survival at 1, 2, and 3 years was 57%, 39%, and 28% respectively. Adenocarcinoma was associated with improved survival compared to non-adenocarcinoma (P < 0.001), median OS 17.1 months (95% CI 11.4-22.9) and median OS 5.7 months (95% CI 2.8-8.6), respectively. Patients with EGFR/ALK mutations had a significantly greater survival time compared to those without (P=0.008), and median OS of 26.3 months (95% CI 19.1-33.6) versus 10.4 months (95% 6.2-14.6). Treatment of 5-10, 11-15, or > 15 tumors at initial GK were not associated with differences in survival (P=0.48). On multivariate analysis, survival benefit remained significant in patients with adenocarcinoma (HR 0.42, 95% CI 0.24-0.72, P=0.002), and patients with EGFR/ALK mutations (HR 0.58, 95% CI 0.37-0.91, P=0.02).
CONCLUSION(S): Patients treated with initial SRS for multiple BM from NSCLC in the modern era demonstrate longer survival as compared with historical reports. Adenocarcinoma subtype, particularly in the setting of EGFR/ALK mutation is associated with improved prognosis, even in patients with higher number of metastases. AUTHOR DISCLOSURE: J. Gurewitz: None. D. Patel: None. C. Benjamin: None. B.R. Donahue: None. J. Silverman: None. M. Mureb: None. K. Bernstein: None. D. Kondziolka: None.
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PURPOSE/OBJECTIVES/OBJECTIVE:To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions. Materials/Methods Analysis of our prospective registry identified 89 patients treated with SRS for ≥ 25 brain metastases. HC avoidance regions (HA-region) were created on treatment planning MRIs by 5mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed. RESULTS:Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC Dmin (D100), D40, D50, Dmax, and Dmean (Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D40, D50, and Dmin were significantly correlated with the tumor number and tumor volume (p <0.001). Of the total3059 treated tumors,83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself. CONCLUSIONS:Hippocampal dose, is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.

Purpose/UNASSIGNED:COVID-19 profoundly affected the United States, with New York City rapidly becoming the epicenter of the disease. Patients with cancer represent a vulnerable population in this pandemic, with data suggesting a higher risk for severe events and unfavorable outcomes. Timely identification of COVID-19 in patients with cancer has been thwarted by the limited availability of outpatient testing for SARS-CoV-2. Chest computed tomography (CT) plays a major role in the identification of COVID-19 pneumonia, with radiologic hallmarks including bilateral, peripheral ground-glass opacities (GGOs) and consolidation. Patients with cancer undergoing radiation therapy (RT) commonly have daily cone beam computed tomography (CBCT) obtained for image-guided RT, and such imaging frequently includes the chest. Methods and Materials/UNASSIGNED:We retrospectively reviewed the CBCT scans of an initially asymptomatic patient undergoing image-guided RT for breast cancer who developed COVID-19 symptoms during the second week of RT. Lung windows of daily CBCT scans were reviewed with diagnostic radiology to survey for changes consistent with COVID-19. Diagnostic CT scans at the time of recovery were obtained and compared with the CBCTs. Results/UNASSIGNED:Five consecutive CBCT scans were retrospectively reviewed. Bilateral, peripheral GGOs were noted on the fourth and fifth CBCT scans in the 2 days before symptom onset. CBCT on the day of RT resumption demonstrated substantial worsening of the GGO compared with scans obtained during the asymptomatic phase. Diagnostic CTs demonstrated bilateral, peripheral GGOs and mediastinal lymphadenopathy, findings suggesting COVID-19 pneumonitis. Repeat diagnostic CT 3 days later showed improved pulmonary findings, and the patient resumed RT without incident. Conclusions/UNASSIGNED:Familiarity with typical CT changes of COVID-19 pneumonitis may allow for early detection in cancer patients undergoing CBCT for RT treatment. Prompt review of the lung windows is recommended to identify such changes, with the hope that presymptomatic diagnosis leads to expedited patient management, improved outcomes, and a reduction of inadvertent COVID-19 dissemination.

OBJECTIVE The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging. METHODS From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies. RESULTS Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm3 in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm3 in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm3 had improved overall survival. CONCLUSIONS SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases. CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort; evidence: Class II.