Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401)

Takuya Kawabe, Masaaki Yamamoto, Yasunori Sato, Shoji Yomo, Takeshi Kondoh, Osamu Nagano, Toru Serizawa, Takahiko Tsugawa, Hisayo Okamoto, Atsuya Akabane, Kazuyasu Aita, Manabu Sato, Hidefumi Jokura, Jun Kawagishi, Takashi Shuto, Hideya Kawai, Akihito Moriki, Hiroyuki Kenai, Yoshiyasu Iwai, Masazumi GondoToshinori Hasegawa, Soichiro Yasuda, Yasuhiro Kikuchi, Yasushi Nagatomo, Shinya Watanabe, Naoya Hashimoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11-17
Number of pages7
JournalJournal of neurosurgery
Volume125
Publication statusPublished - 2016 Dec 1
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Large Cell Carcinoma
Radiosurgery
Neoplasm Metastasis
Lung
Brain
Lung Neoplasms
Neoplasms
Survival
Small Cell Lung Carcinoma
Kaplan-Meier Estimate
Tumor Burden

Keywords

  • brain metastases
  • Gamma Knife
  • GKRS = Gamma Knife radiosurgery
  • KPS = Karnofsky Performance Scale
  • large cell neuroendocrine carcinoma
  • LCNEC
  • LCNEC = large cell neuroendocrine carcinoma
  • lung cancer
  • MET = metastasis
  • MST = median survival time
  • NSCLC = non–small cell lung carcinoma
  • oncology
  • PCI = prophylactic cranial irradiation
  • RPA = recursive partitioning analysis
  • RTOG = Radiation Therapy Oncology Group
  • SCLC = small cell lung carcinoma
  • SRS = stereotactic radiosurgery
  • stereotactic radiosurgery
  • WBRT = whole-brain radiation therapy

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma : a Japanese multi-institutional cooperative study (JLGK1401). / Kawabe, Takuya; Yamamoto, Masaaki; Sato, Yasunori; Yomo, Shoji; Kondoh, Takeshi; Nagano, Osamu; Serizawa, Toru; Tsugawa, Takahiko; Okamoto, Hisayo; Akabane, Atsuya; Aita, Kazuyasu; Sato, Manabu; Jokura, Hidefumi; Kawagishi, Jun; Shuto, Takashi; Kawai, Hideya; Moriki, Akihito; Kenai, Hiroyuki; Iwai, Yoshiyasu; Gondo, Masazumi; Hasegawa, Toshinori; Yasuda, Soichiro; Kikuchi, Yasuhiro; Nagatomo, Yasushi; Watanabe, Shinya; Hashimoto, Naoya.

In: Journal of neurosurgery, Vol. 125, 01.12.2016, p. 11-17.

Research output: Contribution to journalArticle

Kawabe, T, Yamamoto, M, Sato, Y, Yomo, S, Kondoh, T, Nagano, O, Serizawa, T, Tsugawa, T, Okamoto, H, Akabane, A, Aita, K, Sato, M, Jokura, H, Kawagishi, J, Shuto, T, Kawai, H, Moriki, A, Kenai, H, Iwai, Y, Gondo, M, Hasegawa, T, Yasuda, S, Kikuchi, Y, Nagatomo, Y, Watanabe, S & Hashimoto, N 2016, 'Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401)', Journal of neurosurgery, vol. 125, pp. 11-17.
Kawabe, Takuya ; Yamamoto, Masaaki ; Sato, Yasunori ; Yomo, Shoji ; Kondoh, Takeshi ; Nagano, Osamu ; Serizawa, Toru ; Tsugawa, Takahiko ; Okamoto, Hisayo ; Akabane, Atsuya ; Aita, Kazuyasu ; Sato, Manabu ; Jokura, Hidefumi ; Kawagishi, Jun ; Shuto, Takashi ; Kawai, Hideya ; Moriki, Akihito ; Kenai, Hiroyuki ; Iwai, Yoshiyasu ; Gondo, Masazumi ; Hasegawa, Toshinori ; Yasuda, Soichiro ; Kikuchi, Yasuhiro ; Nagatomo, Yasushi ; Watanabe, Shinya ; Hashimoto, Naoya. / Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma : a Japanese multi-institutional cooperative study (JLGK1401). In: Journal of neurosurgery. 2016 ; Vol. 125. pp. 11-17.
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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.",
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author = "Takuya Kawabe and Masaaki Yamamoto and Yasunori Sato and Shoji Yomo and Takeshi Kondoh and Osamu Nagano and Toru Serizawa and Takahiko Tsugawa and Hisayo Okamoto and Atsuya Akabane and Kazuyasu Aita and Manabu Sato and Hidefumi Jokura and Jun Kawagishi and Takashi Shuto and Hideya Kawai and Akihito Moriki and Hiroyuki Kenai and Yoshiyasu Iwai and Masazumi Gondo and Toshinori Hasegawa and Soichiro Yasuda and Yasuhiro Kikuchi and Yasushi Nagatomo and Shinya Watanabe and Naoya Hashimoto",
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TY - JOUR

T1 - Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma

T2 - a Japanese multi-institutional cooperative study (JLGK1401)

AU - Kawabe, Takuya

AU - Yamamoto, Masaaki

AU - Sato, Yasunori

AU - Yomo, Shoji

AU - Kondoh, Takeshi

AU - Nagano, Osamu

AU - Serizawa, Toru

AU - Tsugawa, Takahiko

AU - Okamoto, Hisayo

AU - Akabane, Atsuya

AU - Aita, Kazuyasu

AU - Sato, Manabu

AU - Jokura, Hidefumi

AU - Kawagishi, Jun

AU - Shuto, Takashi

AU - Kawai, Hideya

AU - Moriki, Akihito

AU - Kenai, Hiroyuki

AU - Iwai, Yoshiyasu

AU - Gondo, Masazumi

AU - Hasegawa, Toshinori

AU - Yasuda, Soichiro

AU - Kikuchi, Yasuhiro

AU - Nagatomo, Yasushi

AU - Watanabe, Shinya

AU - Hashimoto, Naoya

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

KW - brain metastases

KW - Gamma Knife

KW - GKRS = Gamma Knife radiosurgery

KW - KPS = Karnofsky Performance Scale

KW - large cell neuroendocrine carcinoma

KW - LCNEC

KW - LCNEC = large cell neuroendocrine carcinoma

KW - lung cancer

KW - MET = metastasis

KW - MST = median survival time

KW - NSCLC = non–small cell lung carcinoma

KW - oncology

KW - PCI = prophylactic cranial irradiation

KW - RPA = recursive partitioning analysis

KW - RTOG = Radiation Therapy Oncology Group

KW - SCLC = small cell lung carcinoma

KW - SRS = stereotactic radiosurgery

KW - stereotactic radiosurgery

KW - WBRT = whole-brain radiation therapy

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