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Introduction: Patients with brain metastases (BrMs) arising from EGFR and ALK driven non-small cell lung cancer (NSCLC) have favorable prognoses and evolving treatment options. We evaluated multicenter outcomes for stereotactic radiosurgery (SRS) to multiple (≥4) BrMs, where randomized data remain limited., Methods: Data were collected retrospectively from 5 academic centers on EGFR and ALK NSCLC who received SRS to ≥4 BrMs with their first SRS treatment between 2008 and 2018. Analyzed endpoints included overall survival (OS), freedom from CNS progression (FFCNSP), and freedom from whole-brain radiotherapy (FFWBRT)., Results: Eighty-nine patients (50 EGFR, 39 ALK) received a total of 159 SRS treatments to 1,080 BrMs, with a median follow up of 51.3 months. The median number of BrMs treated with SRS treatment-1 was 6 (range 4-26) and median for all treatments was 9 (range 4-47). Sixteen patients (18 %) had received WBRT prior to SRS treatment-1. The median OS was 24.2, 21.2, and 33.2 months for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, only receipt of a next-generation tyrosine kinase inhibitor was associated with OS (HR 0.40, p = 0.005). No differences in OS were observed based on number of BrMs treated. The median FFCNSP was 9.4, 11.6, and 7.5 months, for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, the number of BrMs (continuous) treated during treatment-1 was the only negative prognostic factor associated with FFCNSP (HR 1.071, p = 0.045). The 5-year FFWBRT was 73.6 %., Conclusions: This multicenter analysis over a >10-year period demonstrated favorable OS, FFCNSP, and FFWBRT, in patients with EGFR and ALK driven NSCLC receiving SRS to ≥4 BrMs. These data support SRS as an option in the upfront and salvage setting for higher burden CNS disease in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: The clinical outcomes of multicourse lung stereotactic body radiotherapy (SBRT) have yet to be validated in a prospective study, and there are a lack of data on allowable composite dosimetry., Patients and Methods: Forty-four patients underwent multicourse lung SBRT for recurrent or metachronous NSCLC. The median biologically effective dose (BED 10 ) for the first course and subsequent courses were 132 and 100 Gy, respectively. Patient and treatment characteristics were evaluated to determine the correlation with the development of radiation pneumonitis (RP)., Results: The local control rate was 91%. A total of 13.6% developed a grade 2+ RP, and 4.5% developed a grade 3+ RP, including one grade 5. On univariable analysis, multiple composite dosimetric factors (V 5 [proportion of lung structure receiving at least 5 Gy], V 10 , V 20 , V 40 , and mean lung dose) were correlated with the development of RP. When comprised of the first and second course of SBRT, a composite lung V 5 of < 30% and > 50% was associated with a 0 and 75% incidence of grade 2+ RP, respectively. We identified no significant correlation on multivariable analysis but observed a strong trend between composite lung V 5 and the development of grade 2+ RP (hazard ratio, 1.157; P = .058). Evaluation of multiple clinical factors also identified a significant correlation between the timing of repeat lung SBRT and the development of grade 2+ RP after the second course (P = .0028)., Conclusion: Subsequent courses of lung SBRT, prescribed to a median BED 10 of 100 Gy, can provide a high rate of local control with a 4.5% incidence of grade 3+ toxicity. Composite lung V 5 and the timing of the second course of lung SBRT may be correlated to the development of RP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy is a well-established treatment for symptomatic bone metastases. Despite continued advances in both planning techniques and treatment delivery, the standard workflow has remained relatively unchanged, often requiring 1 to 3 weeks and resulting in patient inconvenience and delayed palliation. We developed an expedited method wherein computed tomography simulation, treatment planning, quality assurance, and treatment delivery are performed in 1 day. This prospective pilot clinical trial evaluates the safety, efficacy, and patient satisfaction of this rapid workflow., Methods and Materials: Patients with 1 to 3 painful bone metastases were prospectively enrolled and treated with 1 fraction of stereotactic body radiation therapy, using a same-day Scan-Plan-QA-Treat workflow, termed STAT RAD, in a phase 1/2 dose escalation trial from 8 Gy to 15 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated before and at 1, 4, 8, 12, 26, and 52 weeks after treatment. Outcomes and treatment-related toxicity were analyzed., Results: A total of 49 patients were enrolled, and 46 patients with 60 bone metastases were treated per the protocol. Partial or greater pain response occurred in 50% of patients at 1 week, 75% of patients at 8 weeks, 68.7% of patients at 6 months, and 33.3% of patients at 12 months. There were 2 grade-3 toxicities, including 1 spinal fracture associated with disease progression and hyperbilirubinemia. Reirradiation was required in 16.7% of treated lesions at a median time to retreatment of 4.9 months. Most patient responses (78.6%) indicated that patients would choose this workflow again., Conclusions: The results demonstrate that treating bone metastases with palliative stereotactic body radiation therapy via a single-fraction, patient-centric workflow is feasible and safe with doses up to 15 Gy. However, pain response decreased at 12 months and was associated with a 16.7% retreatment rate, which suggests that further dose escalation is warranted., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Pituitary adenomas represent a common intracranial pathology, usually resulting in the systemic secretion of hormones and compression of local endocrine and optic structures, causing a wide variety of clinical sequelae. While they are typically treated with upfront endocrine and/or surgical decompressive therapy, in patients with residual, recurrent, or refractory disease, decades of data support management with stereotactic radiosurgery. This modality offers favorable local tumor control, endocrine remission rates, and infrequent toxicity. In the future, this alternative to resection will continue to gain popularity among patients and health care providers., (© 2019 S. Karger AG, Basel.)

Purpose: To determine the magnitude and reason for discrepancies between frame- and cone beam computed tomography (CBCT)-determined stereotactic coordinates, we reviewed frame-based Gamma Knife radiosurgery procedures in which CBCT was performed before treatment., Methods and Materials: Clinical and treatment documentation was reviewed for 150 frame placements for which stereotactic coordinates were defined via both frame and fiducials on computed tomography imaging and CBCT. Treatment planning system-reported rotational and translational differences and standard deviations (SDs) between frame-based and CBCT-based stereotactic coordinates were recorded. Potential clinical predictors for increased differences were collected. Multiple linear regressions were performed to evaluate for associations with increased translations and rotations., Results: The absolute mean of the measured pitch, yaw, and roll shifts was 0.14 degrees (range -0.71-0.63 degrees, SD 0.19 degrees), 0.16 degrees (range -0.50 to 0.83 degrees, SD 0.21 degrees), and 0.12 degrees (range 0.37-0.51 degrees, SD 0.15 degrees), respectively. The absolute mean of the measured shifts in the left-right, anteroposterior, and superior-inferior direction was 0.29 mm (range -1.29 to 0.82 mm, SD 0.35 mm), 0.24 mm (range -0.59 to 0.33 mm, SD 0.19 mm), and 0.24 mm (range -0.69 to 0.91 mm, SD 0.27 mm), respectively. Three cases (2.0%) exceeded 1 mm in translational difference, all in the left-right direction (1.05, 1.13, and 1.29 mm). Lower Karnofsky Performance Scale status was associated with greater translational differences (vector magnitude, P = .023) and rotation (pitch, P = .044; yaw, P = .002). Usage of longer total pin length (sum of all 4 fixation pin lengths) was associated with increased rotation but not with translation (P < .001 and P = .56, respectively)., Conclusions: CBCT imaging in this cohort of frame-based cases suggests that the discrepancy in stereotactic coordinates is less than 1 mm or degree in most cases. Low Karnofsky Performance Scale status and longer total pin length correlate with larger differences between frame-defined and CBCT-defined stereotactic coordinates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Currently no firm consensus exists regarding utilization of stereotactic radiosurgery (SRS) alone versus whole brain radiation (WBRT) ± SRS in patients with multiple brain metastases. The International Gamma Knife Research Foundation conducted a survey to review international practice patterns., Methods: Through 2 international radiosurgery societies, clinicians who are involved in the radiosurgical management of patients with brain metastases were invited to complete a questionnaire. Respondents selected therapeutic options based on brief case vignettes and could select (1) SRS alone, (2) SRS with adjuvant WBRT, (3) WBRT alone, or (4) omission of upfront local radiation., Results: A total of 71 respondents replied to the survey, including 41 radiation oncologists (57%), 24 neurosurgeons (34%), and 6 (8%) other clinicians. For a patient with 7 brain metastases (NSCLC), all under 1 cm, and stable extracranial disease, 77% would perform SRS alone and 17% would recommend WBRT alone. For a patient with 7 or more brain metastases, the majority selected SRS alone, irrespective of tumor histology (p > 0.5). However, neurosurgeons would more often utilize SRS alone or SRS combined with WBRT compared to radiation oncologists (p = 0.002). Key clinical factors in selection were KPS (82% of respondents), total tumor volume (81%), number (80%), and less-so histology (42%)., Conclusion: Regardless of number of metastases, patients with small total volume of brain disease, high KPS, or who are receiving novel therapies are often recommended to undergo SRS. Neurosurgeons more often recommend SRS, emphasizing the importance of additional studies to clarify the role of SRS in these patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas after radiosurgery, controlling for several known prognostic factors., Methods and Materials: An institutional review board-approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching for patient sex, age at radiosurgery, interval between the last resection and radiosurgery, use of previous radiation therapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined as a normal serum insulin-like growth factor-1 (GH secreting) or a normal 24-hour urine-free cortisol (ACTH secreting) level without suppressive medications. Endocrine remission and the incidence of new hypopituitarism after single-fraction radiosurgery were recorded and compared between the 2 groups., Results: The data from 242 patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. Of the 242 patients, 75% had cavernous sinus invasion and 10% had suprasellar extension at radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, the factors associated with an increased time to endocrine remission included patient age (hazard ratio [HR] 1.016; P = .023), cavernous sinus invasion (HR 1.793; P = .004), and the presence of acromegaly (HR 2.912; P < .001). The incidence of new hypopituitarism developing after stereotactic radiosurgery was 29% and did not appreciably differ by adenoma subtype (P = .180)., Conclusions: After radiosurgery, patients with ACTH-secreting tumors achieved endocrine remission sooner than did those with GH-secreting tumors. These results provide insight into the relative tumor biology and disease course after radiosurgery that will serve to further improve clinical outcomes and patient treatment in the future., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To analyze the national trends of patients treated radiotherapy for brain metastases from non-small cell lung cancer (NSCLC) that were found at diagnosis., Methods: The National Cancer Database was queried for patients with NSCLC diagnosed from 2004 to 2013 that received brain irradiation for metastases and patients grouped into having had received fractionated brain radiotherapy (5-15 fractions with or without radiosurgery) or intracranial radiosurgery alone (1-5 fractions). Univariable and multivariable (MVA) analyses were performed to investigate factors associated with the receipt of SRS alone, and temporal/regional trends., Results: 47,746 patients met inclusion criteria, of which 42,148 received fractionated brain irradiation (88%) and 5,598 received radiosurgery (12%). 345 patients received fractioned brain irradiation with a radiosurgical boost (0.8%). The utilization of radiosurgery-alone increased over time owing to increases in each radiosurgery modality. On MVA, several factors were associated with increased odds of receiving intracranial radiosurgery-alone over fractionated brain radiotherapy including more recent year of diagnosis, increased median income, eastern U.S. regions, further distance to the hospital, and the receipt of chemotherapy (each p<0.001). Patients of Asian descent were less likely to receive radiosurgery alone (p=0.044)., Conclusions: In the management of brain metastases from NSCLC, overall utilization of an intracranial radiosurgery alone treatment strategy has increased over the past decade. Despite this, there appear to be significant geographic variations and disparities remain based on patient income level and race. Further study is needed to define the reasons for these disparities and appropriate actions to mitigate them., (Copyright © 2017 Elsevier Ltd. All rights reserved.)