title: Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401).
abstract: OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm3, and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.
authors.affiliation: Department of Neurosurgery, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto.|Katsuta Hospital Mito Gamma House, Hitachi-naka.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawabe
authors.affiliation: Katsuta Hospital Mito Gamma House, Hitachi-naka.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Clinical Research Center, Chiba University Graduate School of Medicine, Chiba.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Saitama Gamma Knife Center, Sanai Hospital, Saitama.|Department of Neurosurgery, Aizawa Hospital, Matsumoto.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yomo
authors.affiliation: Department of Neurosurgery, Shinsuma Hospital, Kobe.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Gamma Knife House, Chiba Cardiovascular Center, Ichihara.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagano
authors.affiliation: Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo.
authors.forename: Toru
authors.initials: T
authors.lastname: Serizawa
authors.affiliation: Nagoya Radiosurgery Center, Nagoya Kyoritsu Hospital, Nagoya.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tsugawa
authors.affiliation: Department of Neurosurgery, Takashima Hospital, Yonago.
authors.forename: Hisayo
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Gamma Knife Center, NTT Medical Center Tokyo, Tokyo.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Akabane
authors.affiliation: Department of Neurosurgery, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto.|Kyoto Gamma Knife Center, Rakusai Shimizu Hospital, Kyoto.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Aita
authors.affiliation: Kyoto Gamma Knife Center, Rakusai Shimizu Hospital, Kyoto.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Jiro Suzuki Memorial Gamma House, Furukawa Seiryo Hospital, Osaki.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Jokura
authors.affiliation: Jiro Suzuki Memorial Gamma House, Furukawa Seiryo Hospital, Osaki.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawagishi
authors.affiliation: Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shuto
authors.affiliation: Department of Neurosurgery, Research Institute for Brain and Blood Vessels-Akita, Akita.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Department of Neurosurgery, Mominoki Hospital, Kochi.
authors.forename: Akihito
authors.initials: A
authors.lastname: Moriki
authors.affiliation: Department of Neurosurgery, Nagatomi Neurosurgical Hospital, Oita.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kenai
authors.affiliation: Department of Neurosurgery, Osaka City General Hospital, Osaka.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Iwai
authors.affiliation: Gamma Center Kagoshima, Atsuchi Neurosurgical Hospital, Kagoshima.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Gondo
authors.affiliation: Department of Neurosurgery, Komaki City Hospital, Komaki.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Neurosurgery, Shiroyama Hospital, Habikino.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Neurosurgery, Southern Tohoku Research Institute for Neuroscience, Southern Tohoku General Hospital, Koriyama; and.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Neurosurgery, Kouseikai Takai Hospital, Tenri, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nagatomo
authors.affiliation: Katsuta Hospital Mito Gamma House, Hitachi-naka.
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Neurosurgery, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D018278:Carcinoma, Neuroendocrine / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery; D012189:Retrospective Studies
keywords: GKRS = Gamma Knife radiosurgery; Gamma Knife; KPS = Karnofsky Performance Scale; LCNEC; LCNEC = large cell neuroendocrine carcinoma; MET = metastasis; MST = median survival time; NSCLC = non–small cell lung carcinoma; PCI = prophylactic cranial irradiation; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group; SCLC = small cell lung carcinoma; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; brain metastases; large cell neuroendocrine carcinoma; lung cancer; oncology; stereotactic radiosurgery