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Pavan P. Shah, Jennifer L. Franke, Ravi Medikonda, Christopher M. Jackson, Siddhartha Srivastava, John Choi, Patrick M. Forde, Julie R. Brahmer, David S. Ettinger, Josephine L. Feliciano, Benjamin P. Levy, Kristen A. Marrone, Jarushka Naidoo, Kristin J. Redmond, Lawrence R. Kleinberg, and Michael Lim

OBJECTIVE

Non–small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis.

METHODS

The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression.

RESULTS

Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival.

CONCLUSIONS

Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

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Stephen B. Tatter, Edward G. Shaw, Mark L. Rosenblum, Kastytis C. Karvelis, Lawrence Kleinberg, Jon Weingart, Jeffrey J. Olson, Ian R. Crocker, Steven Brem, James L. Pearlman, Joy D. Fisher, Kathryn A. Carson, Stuart A. Grossman, and other members of The New Approaches to Brain Tumor Therapy Central Nervous System Consortium

Object. In this study the authors evaluated the safety and performance of the GliaSite Radiation Therapy System (RTS) in patients with recurrent malignant brain tumors who were undergoing tumor resection.

Methods. The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of tumor debulking. Low-dose-rate radiation is delivered with an aqueous solution of organically bound iodine-125 (Iotrex [sodium 3-(125I)-iodo-4-hydroxybenzenesulfonate]), which are temporarily introduced into the balloon portion of the device via a subcutaneous port. Adults with recurrent malignant glioma underwent resection and GliaSite implantation. One to 2 weeks later, the device was filled with Iotrex for 3 to 6 days, following which the device was explanted. Twenty-one patients with recurrent high-grade astrocytomas were enrolled in the study and received radiation therapy. There were two end points: 1) successful implantation and delivery of brachytherapy; and 2) safety of the device.

Implantation of the device, delivery of radiation, and the explantation procedure were well tolerated. At least 40 to 60 Gy was delivered to all tissues within the target volume. There were no serious adverse device-related events during brachytherapy. One patient had a pseudomeningocele, one patient had a wound infection, and three patients had meningitis (one bacterial, one chemical, and one aseptic). No symptomatic radiation necrosis was identified during 21.8 patient-years of follow up. The median survival of previously treated patients was 12.7 months (95% confidence interval 6.9–15.3 months).

Conclusions. The GliaSite RTS performs safely and efficiently. It delivers a readily quantifiable dose of radiation to tissue at the highest risk for tumor recurrence.

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Matthew J. McGirt, Khoi D. Than, Jon D. Weingart, Kaisorn L. Chaichana, Frank J. Attenello, Alessandro Olivi, John Laterra, Lawrence R. Kleinberg, Stuart A. Grossman, Henry Brem, and Alfredo Quiñones-Hinojosa

Object

Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). It remains unstudied whether combining Gliadel and TMZ therapy is safe or further improves survival in patients with newly diagnosed GBM. The authors reviewed their initial experience utilizing combined Gliadel, TMZ, and radiation therapy for the treatment of GBM.

Methods

All cases involving patients undergoing primary resection of GBM with or without Gliadel wafer (3.85% BCNU) implantation and adjuvant XRT over a 10-year period (1997–2006) were retrospectively reviewed. Beginning in 2004, concomitant TMZ became the standard of care at the authors' institution and all patients with Gliadel implantation also received concomitant TMZ (Stupp protocol). Overall survival and treatment-related morbidity were assessed for all patients treated with Gliadel plus concomitant TMZ (XRT + Gliadel + TMZ). Age-matched (≤ 70 years) comparison of survival and morbidity was performed between the XRT + Gliadel + TMZ (post-2003) and XRT + Gliadel (pre-2004) cohorts.

Results

Thirty-three patients were treated with XRT + Gliadel + TMZ. The median survival in this group was 20.7 months, with a 2-year survival rate of 36%. Six-month morbidity included surgical site infection in 1 case (3%), perioperative seizures in 2 cases (6%), deep-vein thrombus in 1 (3%), pulmonary embolism in 3 (9%), and cerebral edema requiring admission for intravenous dexamethasone in 1 case (3%). Myelosuppression required premature termination of TMZ in 7 patients (21%) (thrombocytopenia in 5, neutropenia in 2 cases). In patients ≤ 70 years of age, XRT + Gliadel + TMZ (30 patients, post-2003) was independently associated with improved median survival (21.3 vs 12.4 months, p = 0.005) versus XRT + Gliadel (78 patients, pre-2004), with 2-year survival of 39 versus 18%, respectively. In these patients, XRT + Gliadel + TMZ was not associated with an increase in perioperative morbidity in comparison with XRT + Gliadel.

Conclusions

In this experience, concomitant TMZ therapy in addition to Gliadel wafer implantation was associated with a median survival of nearly 21 months without increased perioperative morbidity. Temozolomide can be safely administered to patients receiving Gliadel wafers after resection of GBM.

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Varun Puvanesarajah, Sheng-fu Larry Lo, Nafi Aygun, Jason A. Liauw, Ignacio Jusué-Torres, Ioan A. Lina, Uri Hadelsberg, Benjamin D. Elder, Ali Bydon, Chetan Bettegowda, Daniel M. Sciubba, Jean-Paul Wolinsky, Daniele Rigamonti, Lawrence R. Kleinberg, Ziya L. Gokaslan, Timothy F. Witham, Kristin J. Redmond, and Michael Lim

OBJECT

The number of patients with spinal tumors is rapidly increasing; spinal metastases develop in more than 30% of cancer patients during the course of their illness. Such lesions can significantly decrease quality of life, often necessitating treatment. Stereotactic radiosurgery has effectively achieved local control and symptomatic relief for these patients. The authors determined prognostic factors that predicted pain palliation and report overall institutional outcomes after spine stereotactic body radiation therapy (SBRT).

METHODS

Records of patients who had undergone treatment with SBRT for either primary spinal tumors or spinal metastases from June 2008 through June 2013 were retrospectively reviewed. Data were collected at the initial visit just before treatment and at 1-, 3-, 6-, and 12-month follow-up visits. Collected clinical data included Karnofsky Performance Scale scores, pain status, presence of neurological deficits, and prior radiation exposure at the level of interest. Radiation treatment plan parameters (dose, fractionation, and target coverage) were recorded. To determine the initial extent of epidural spinal cord compression (ESCC), the authors retrospectively reviewed MR images, assessed spinal instability according to the Bilsky scale, and evaluated lesion progression after treatment.

RESULTS

The study included 99 patients (mean age 60.4 years). The median survival time was 9.1 months (95% CI 6.9–17.2 months). Significant decreases in the proportion of patients reporting pain were observed at 3 months (p < 0.0001), 6 months (p = 0.0002), and 12 months (p = 0.0019) after treatment. Significant decreases in the number of patients reporting pain were also observed at the last follow-up visit (p = 0.00020) (median follow-up time 6.1 months, range 1.0–56.6 months). Univariate analyses revealed that significant predictors of persistent pain after intervention were initial ESCC grade, stratified by a Bilsky grade of 1c (p = 0.0058); initial American Spinal Injury Association grade of D (p = 0.011); initial Karnofsky Performance Scale score, stratified by a score of 80 (p = 0.002); the presence of multiple treated lesions (p = 0.044); and prior radiation at the site of interest (p < 0.0001). However, when multivariate analyses were performed on all variables with p values less than 0.05, the only predictor of pain at last follow-up visit was a prior history of radiation at the site of interest (p = 0.0038), although initial ESCC grade trended toward significance (p = 0.073). Using pain outcomes at 3 months, at this follow-up time point, pain could be predicted by receipt of radiation above a threshold biologically effective dose of 66.7 Gy.

CONCLUSIONS

Pain palliation occurs as early as 3 months after treatment; significant differences in pain reporting are also observed at 6 and 12 months. Pain palliation is limited for patients with spinal tumors with epidural extension that deforms the cord and for patients who have previously received radiation to the same site. Further investigation into the optimal dose and fractionation schedule are needed, but improved outcomes were observed in patients who received radiation at a biologically effective dose (with an a/b of 3.0) of 66.7 Gy or higher.