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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 8  |  Page : 256-258

Metastatic brain tumors from small-cell esophageal cancer: Clinical characteristics and outcome


1 Department of Radiation Oncology, Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P. R. China; Division of Radiation Oncology, Shizuoka Cancer Center, Shizuoka, Japan
2 Division of Radiation Oncology, Shizuoka Cancer Center, Shizuoka, Japan
3 Department of Radiation Oncology, Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P. R. China
4 Division of Neurosurgery, Shizuoka Cancer Center, Shizuoka, Japan
5 Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan

Date of Web Publication17-Feb-2015

Correspondence Address:
Hideyuki Harada
1007, Shimonagakubo, Nagaizumi-Cho., Shizuoka, Japan

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Source of Support: This work was supported by grants from the Zhejiang Province Science and Technology Project of Traditional Chinese Medicine (2011ZB017) and the Talent Project of Medical and Health Sciences Fund of Zhejiang Province (2012RCB005), Conflict of Interest: None


DOI: 10.4103/0973-1482.151469

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 > Abstract 

Aims: Few studies have examined the clinical characteristics of patients with brain metastases from small-cell esophageal cancer. In this study, we review the clinical characteristics and outcomes in patients with brain metastases from small-cell esophageal cancer.
Patients and Methods: From August 2002 to August 2012, consecutive patients diagnosed with brain metastases from small-cell esophageal cancer and treated with radiotherapy were enrolled. Clinical features, diagnostic findings, and survival were analyzed.
Results: Six patients treated with brain radiotherapy were identified. The median age was 64 (range 61-74) years. All patients had neurological impairments. Three patients had supra- and infra-tentorial metastases, and three patients had cerebrum metastases. Brain metastases were detected when esophageal cancer was initially diagnosed in two patients. In three patients, magnetic resonance imaging findings after radiotherapy confirmed a significant response to treatment. The median overall survival was 6.0 months. During the same period, 43 patients with squamous cell carcinoma and seven patients with adenocarcinoma who had brain metastases were identified. Survival periods for squamous cell carcinoma and adenocarcinoma patients who had brain metastases were 5.5 months and 4.2 months, respectively. There was no significant difference in overall survival according to the histological type.
Conclusions: Brain metastases from small-cell esophageal cancer tend to spread to the cerebellum and impair patients' quality-of-life. Brain radiotherapy had a positive effect in this case series; however, overall survival remains short.

Keywords: Brain metastases, esophageal cancer, small cell carcinoma


How to cite this article:
Feng W, Harada H, Zhang P, Mitsuya K, Zheng X, Yasui H, Nakasu Y, Chen M, Nishimura T. Metastatic brain tumors from small-cell esophageal cancer: Clinical characteristics and outcome. J Can Res Ther 2014;10, Suppl S4:256-8

How to cite this URL:
Feng W, Harada H, Zhang P, Mitsuya K, Zheng X, Yasui H, Nakasu Y, Chen M, Nishimura T. Metastatic brain tumors from small-cell esophageal cancer: Clinical characteristics and outcome. J Can Res Ther [serial online] 2014 [cited 2020 Jun 4];10:256-8. Available from: http://www.cancerjournal.net/text.asp?2014/10/8/256/151469


 > Introduction Top


Small-cell esophageal cancer is a common type of extra pulmonary small-cell carcinoma. In China, more than 1000 patients of small-cell esophageal cancer have been reported. [1] During the course of diagnosis and treatment, 50-80% of patients with small-cell lung cancer develop brain metastases. Unlike small-cell lung cancer cases, no previous reports have examined the clinical characteristics of patients with brain metastases from small-cell esophageal cancer with regards to the diagnosis and prognosis. Here, we reviewed patients with brain metastases from small-cell esophageal cancer treated in our institutions and attempted to clarify common clinical characteristics.


 > Patients and methods Top


This is a retrospective, multi-institutional study. From August 2002 to August 2012, consecutive patients diagnosed with brain metastases from small-cell esophageal cancer and treated with radiotherapy in two institutions were included. Their symptoms, diagnostic images, and treatment outcomes were reviewed. Overall survival for these patients was calculated. Furthermore, survival for squamous cell carcinoma and adenocarcinoma patients with brain metastases from esophageal cancer during the same period was calculated and reported for comparison.


 > Results Top


Six patients with brain metastases from small-cell esophageal cancer who underwent radiation therapy at the Shizuoka Cancer Center in Japan and the Zhejiang Cancer Hospital in China were identified. At the end of the follow-up period, all patients had died. The cohort comprised of five men and one woman. The median age at diagnosis of brain metastases was 64 (range 61-74) years. [Table 1] summarizes the clinical characteristics of all patients. During the same period, 50 additional patients were diagnosed with brain metastasis from esophageal cancer (43 and seven patients with squamous cell carcinoma and adenocarcinoma, respectively) and treated. Patients with esophageal small-cell carcinoma metastasis in the brain represent only one-tenth of all patients with esophageal cancer with brain metastases.
Table 1: Patient characteristics

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Among the six patients with small-cell carcinoma, five underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain, and one underwent brain contrast-enhanced computed-tomography. The initial symptoms were headache in four patients, hemiplegia in one patient, and loss of consciousness in one patient. Two patients were diagnosed with the primary esophageal cancer lesion and brain metastases simultaneously. In the remaining four patients, the median duration from the primary tumor diagnosis to the development of brain metastases was 9.7 months (range: 4.83-19.6 months).

Three patients had lesions in the cerebellum and brain stem [Figure 1], and the other three patients had lesions in the supra-tentorial region. Four of the six patients presented with multiple brain lesions. Among them, three patients had adjacent meninges enhanced on MRI [Figure 2]. One of these three patients developed leptomeningeal carcinomatosis confirmed by pathological examination of the cerebrospinal fluid 9 months later.
Figure 1: Supra-and infratentorial metastases

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Figure 2: Occipital lobe lesion with meningeal enhancement

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Of the two patients who were simultaneously diagnosed with brain metastases and the primary lesion, one patient underwent concurrent chemoradiotherapy (whole-brain radiotherapy and camptothecin-11 + cisplatin). Another patient received four cycles of etoposide and cisplatin chemotherapy followed by whole-brain radiotherapy. The remaining four patients were diagnosed with brain metastases 4.8-19.6 months after primary diagnosis. The primary treatments were concurrent chemoradiotherapy in three patients and consecutive surgery and radiotherapy in one patient. Treatments for brain metastases included brain radiotherapy and chemotherapy in two patients and only brain radiotherapy in two patients.

Follow-up MRI findings were available in three patients, and all confirmed a significant response to treatment. Two of remaining three patients showed improved symptoms. Another patient died of pneumonia soon after whole-brain radiotherapy, and we were not able to evaluate the therapeutic effect.

During the same period, 43 cancer patients with squamous cell carcinoma and seven patients with adenocarcinoma underwent treatment for brain metastases from esophageal cancers. There was no significant difference in overall survival according to the histological types (6.0 months, 5.5 months, and 4.2 months for a small cell carcinoma, squamous cell carcinoma, and adenocarcinoma types, respectively).


 > Discussion Top


Approximately 50% of extra-pulmonary small-cell carcinomas are reported to originate from esophageal cancer. [2],[3] In 1952, McKeown published the first study on esophageal small-cell carcinoma. [4] Since then, reports have increased in number, and incidence rates of 0.05-2.4% and 7.6% [5],[6],[7],[8] have been reported in Western countries and Eastern Asia. Since the first study on esophageal cancer brain metastasis by Raven, [9] there has been a gradual increase in the number of reports. This increase is attributed mainly to the development of advanced imaging technologies; hence, the reported rates vary from 0.6% to 13%. [10],[11],[12],[13],[14],[15],[16] However, the clinical characteristics and prognosis of patients with brain metastasis from small-cell esophageal cancer remain unclear.

Here, we reported the cases of two patients who were diagnosed with simultaneous brain and primary esophageal lesions. The fact that brain metastases were discovered at the time of initial diagnosis as a small-cell lung cancer [16] may be a characteristic of this disease, and it is worth investigating further to confirm this relationship.

Among three patients with adjacent meninges enhanced on MRI, one patient developed leptomeningeal carcinomatosis. Based on these findings, we recommend whole-brain radiotherapy as the primary treatment modality for brain metastasis from small-cell esophageal cancer. Moreover, chemotherapy is also an important treatment modality. The treatment recommendations for patients with small-cell esophageal cancer are either concomitant chemotherapy with radiotherapy or adjuvant chemotherapy after radiotherapy as the primary treatment. The effect of chemotherapy plus radiotherapy on overall survival is greater than that of surgery plus chemotherapy. [1],[17],[18] The median survival time was only 5 months for patients who received only local treatment, while it increased to 20 months [8] with the addition of chemotherapy. We found that three patients who received chemotherapy and whole-brain radiotherapy achieved more than 6 months overall survival, whereas patients who underwent only whole-brain radiotherapy survived only 1 month. If patients' systemic disease was not controlled, whole-brain radiotherapy could not effectively extend the overall survival time. However, this difference in survival could be a result of selection bias. This means that patients who potentially had a better performance status most likely received both chemotherapy and radiotherapy, whereas patients with poor performance status and/or extensive disease only underwent radiotherapy.

Although whole-brain radiotherapy improved neurological impairments in this case series, crude overall survival is still short for patients with brain metastasis from small-cell esophageal cancer. There are no significant differences in overall survival between small-cell carcinoma and other histological types of esophageal cancer; however, in cases of small-cell esophageal carcinoma, simultaneous brain metastases can exist at the time of primary diagnosis, and meningeal spread might require special attention.


 > Acknowledgment Top


We thank Dr. Tsuyoshi Onoe, Dr. Hirofumi Asakura, and Dr. Hirofumi Ogawa for their help with data collection.

 
 > References Top

1.
Lu XJ, Luo JD, Ling Y, Kong YZ, Feng LL, Zhou J, et al. Management of small cell carcinoma of esophagus in China. J Gastrointest Surg 2013;17:1181-7.  Back to cited text no. 1
    
2.
Li AF, Hsu HS, Hsu CY, Li AC, Li WY, Liang WY, et al. A 20-year retrospective study of small-cell carcinomas in Taiwan. J Surg Oncol 2010;102:497-502.  Back to cited text no. 2
    
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Brenner B, Shah MA, Gonen M, Klimstra DS, Shia J, Kelsen DP. Small-cell carcinoma of the gastrointestinal tract: A retrospective study of 64 cases. Br J Cancer 2004;90:1720-6.  Back to cited text no. 3
    
4.
Mckeown F. Oat-cell carcinoma of the oesophagus. J Pathol Bacteriol 1952;64:889-91.  Back to cited text no. 4
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Caldwell CB, Bains MS, Burt M. Unusual malignant neoplasms of the esophagus. Oat cell carcinoma, melanoma, and sarcoma. J Thorac Cardiovasc Surg 1991;101:100-7.  Back to cited text no. 5
    
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Casas F, Ferrer F, Farrús B, Casals J, Biete A. Primary small cell carcinoma of the esophagus: A review of the literature with emphasis on therapy and prognosis. Cancer 1997;80:1366-72.  Back to cited text no. 8
    
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Raven RW. Carcinoma of the oesophagus; a clinico-pathological study. Br J Surg 1948;36:70-3.  Back to cited text no. 9
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Weinberg JS, Suki D, Hanbali F, Cohen ZR, Lenzi R, Sawaya R. Metastasis of esophageal carcinoma to the brain. Cancer 2003;98:1925-33.  Back to cited text no. 10
    
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Kanemoto A, Hashimoto T, Harada H, Asakura H, Ogawa H, Furutani K, et al. Occurrence and clinical features of brain metastasis after chemoradiotherapy for esophageal carcinoma. J Radiat Res 2011;52:509-15.  Back to cited text no. 11
    
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Go PH, Klaassen Z, Meadows MC, Chamberlain RS. Gastrointestinal cancer and brain metastasis: A rare and ominous sign. Cancer 2011;117:3630-40.  Back to cited text no. 12
    
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Ogawa K, Toita T, Sueyama H, Fuwa N, Kakinohana Y, Kamata M, et al. Brain metastases from esophageal carcinoma: Natural history, prognostic factors, and outcome. Cancer 2002;94:759-64.  Back to cited text no. 13
    
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Smith RS, Miller RC. Incidence of brain metastasis in patients with esophageal carcinoma. World J Gastroenterol 2011;17:2407-10.  Back to cited text no. 14
    
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Spallone A, Izzo C. Esophageal cancer presenting as a brain metastasis: A case report. Oncol Lett 2013;6:722-24.  Back to cited text no. 15
    
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van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 2011;378:1741-55.  Back to cited text no. 16
    
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Meng MB, Zaorsky NG, Jiang C, Tian LJ, Wang HH, Liu CL, et al. Radiotherapy and chemotherapy are associated with improved outcomes over surgery and chemotherapy in the management of limited-stage small cell esophageal carcinoma. Radiother Oncol 2013;106:317-22.  Back to cited text no. 17
    
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Hussein AM, Feun LG, Sridhar KS, Benedetto P, Waldman S, Otrakji CL. Combination chemotherapy and radiotherapy for small-cell carcinoma of the esophagus. A case report of long-term survival and review of the literature. Am J Clin Oncol 1990;13:369-73.  Back to cited text no. 18
    


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