Int Surg 2014;99:640–644 DOI: 10.9738/INTSURG-D-13-00123.1
Case Report
Definitive Chemoradiotherapy and Salvage Esophagectomy for Esophageal Cancer Associated With Multiple Lung Metastases: A Case Report Yoshihiko Fujinaka, Masaru Morita, Takefumi Ohga, Yoshihiro Kakeji, Tokujiro Yano, Yoshihiko Maehara Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
The prognosis of esophageal cancer with distant metastasis is dismal. We report a 70year-old man with esophageal cancer and multiple lung and lymph node metastases. Complete response was achieved following definitive chemoradiotherapy. Twenty-four months after the initial chemoradiotherapy, local recurrence was detected but there was no evidence of distant metastasis. Therefore, the patient underwent salvage esophagectomy. The surgery was well tolerated without any postoperative complications. The patient is still alive 48 months after the salvage surgery. Our experience suggests that salvage esophagectomy is an important component of multimodal therapy for the recurrence of esophageal cancer. Key words: Esophageal cancer – Chemoradiotherapy – Salvage surgery
T
he prognosis of esophageal cancer has improved in recent years, but remains poor despite curative resection.1 The prognosis is extremely dismal in patients with distant metastasis. The Radiation Therapy Oncology Group (RTOG) trial 85-01 showed that chemoradiotherapy (CRT) improved outcomes, with a 5-year overall survival
rate of 26% compared with 0% following radiotherapy alone. Moreover, residual cancer was less common following CRT (26%) than following radiotherapy alone (37%).2 However, local recurrence occurs in 37% of patients after definitive CRT.3 Salvage esophagectomy is one strategy for residual cancer or local recurrence after definitive CRT. Of
Reprint requests: Yoshihiko Fujinaka, MD, PhD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812- 8582, Japan. Tel.: 81-92-642-5466; Fax: 81-92-642-5482; E-mail: [email protected]
640
Int Surg 2014;99
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
Fig. 1
FUJINAKA
(A, B) Barium-enhanced esophagography and endoscopic examination revealed an infiltrative ulcerating tumor in the upper-
middle thoracic esophagus.
note, when R0 resection is achieved, long-term survival can be expected.4 6 On the other hand, this is an invasive procedure associated with high morbidity and mortality6 and the patient’s prognosis is extremely poor after R1/R2 resection.4 6 Therefore, salvage esophagectomy should only be performed if complete removal of the tumor is expected. Here, we report a rare case with esophageal cancer and multiple lung metastases, in which complete response (CR) was achieved after definitive CRT and salvage esophagectomy was effective for the local recurrence.
Case Presentation A 70-year-old male was admitted to our hospital because of dysphagia. On physical examination, the patient was well and had a performance status (PS) of 1. Barium-enhanced esophagography and endoscopy revealed an infiltrative ulcerating tumor in the upper-middle thoracic esophagus (Fig. 1A, B), which was subsequently diagnosed as squamous cell carcinoma. Computed tomography (CT) revealed circumferential wall thickening of the upper thoracic esophagus (Fig. 2A). We also noted uppermediastinal lymphadenopathy and multiple lung nodules (Fig. 2B, D). At the time, positron emission tomography/CT was not used in clinical practice, based on these findings, the TMN classification was T2N1M1 (UICC), the patient was treated with definitive CRT consisting of continuous 5-FU infusion (5 days/week, 500 mg/d; total 10,000 mg) and cisplatin (5 days/week, 7 mg/d; total 140 mg) for 4 Int Surg 2014;99
weeks in combination with radiotherapy (65 Gy). After CRT, CT revealed improvements in wall thickening, and the resolution of the lymph node and lung metastases (Fig. 3A–D). After achieving CR, the patient was given a two-course adjuvant chemotherapy with nedaplatin plus 5-FU regimen. The patient’s CR was maintained for 24 months after CRT, but then complained of dysphagia. Endoscopy revealed an elevated lesion covered by normal esophageal mucosa (Fig. 4A). Endoscopic ultrasonography indicated a hypoechoic intraluminal tumor (Fig. 4B) and fine needle aspiration cytology revealed squamous carcinoma cells. On positron emission tomography/CT FDG accumulation was limited to the primary lesion (Fig. 5). Since the recurrence was considered to be localized in the esophagus, we performed salvage esophagectomy (esophagectomy and reconstruction using gastric tube via a retro-sternal route). Pathological examination of the resected specimen confirmed squamous cell carcinoma, but no malignant cells were found in the resected lymph nodes. The surgery was well tolerated and the patient did not develop any postoperative complications. The patient has regularly attended our clinic for followup examinations and is still alive, without evidence of local recurrence or metastatic disease, 48 months after salvage surgery (72 months after the initial diagnosis).
Discussion The RTOG trial 85-01 demonstrated that CRT increased overall survival compared with radiother641
FUJINAKA
Fig. 2
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
(A–D) Computed tomography showed thickening of the upper thoracic esophageal wall, along with upper-mediastinal
lymphadenopathy and multiple lung metastases.
apy alone in patients with advanced esophageal cancer patients.2 Accordingly, CRT has become the standard therapy for inoperable advanced esophageal cancer. In fact, one study showed that the CR rate was 33% and the 3-year survival rate was 23% following definitive CRT for clinical T4 and/or M1 lymph node esophageal cancer.7 Esophagectomy is an effective treatment for submucosal esophageal cancer, but CRT archived CR in 87.5% of such patients and the cause-specific 4-year overall survival rate was 80.5% suggesting that definitive CRT is a reasonable alternative to surgery for patients with severe complications or refusing surgical resection.8 Therefore, definitive CRT is now accepted as a primary treatment for esophageal cancer. The prognosis of patients with distant metastases is poor often living for less than 6 months after diagnosis. Therefore, these patients are often considered as candidates for multimodal therapy or for palliative therapy.9 In a recent study, the 1-year overall survival rate of patients treated with multimodal therapy (31.0%) was significantly better than that of patients given single modal or best supportive care alone (23.7%).10 Salvage esophagectomy may be the only effective therapy for residual cancer and local recurrence after CRT. However, it is associated with a high 642
frequency of postoperative complications, particularly anastomotic leakage (38% versus 7%) and mortality (15% versus 6%), as compared with esophagectomy performed as a planned procedure after CRT.5 Multivariate analysis revealed that the most significant factor associated with long-term survival is resection without residual tumors (R0).1,11 Moreover, the prognosis after salvage surgery tended to be better in patients developing recurrence more than 1 year after definitive CRT than in patients with earlier recurrence.5 Kozu et al reviewed surgical treatment for pulmonary metastases from esophageal carcinoma could provide a long survival for those whose primary treatment was definitive CRT and who achieved a CR, surgical treatment should be taken into consideration for patients archived long CR.12 This case was diagnosed as esophageal cancer with lung and lymph node metastases, and the long duration of CR was achieved by definitive CRT. Indeed, local recurrence was detected 24 months after CRT. Most patients with recurrence after definitive CRT are inoperable due to deterioration of PS, distant metastasis. However, the present case was indicated for salvage esophagectomy because of (1) his good general health, (2) the probability of R0 resection with no evidence of distant metastasis, and Int Surg 2014;99
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
Fig. 3
FUJINAKA
(A–D) Thickening of the esophageal wall improved and the lymph node and lung metastases completely disappeared
following chemoradiotherapy.
(3) maintenance of CR for 24 months after CRT. Our
Acknowledgments
experience suggests that salvage esophagectomy following definitive CRT offers a possible therapeutic strategy for esophageal cancer patients with distance metastasis if the CR is maintained for a long period of time.
Fig. 4
This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan. The authors report no conflicts of interest.
(A,B) Upper gastrointestinal endoscopy revealed a submucosal tumor, which was identified as a hypoechoic intraluminal
tumor on endoscopic ultrasonography. Int Surg 2014;99
643
FUJINAKA
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
2. Cooper J, Guo M, Herskovic A, Macdonald J, Martenson JJ, AlSarraf M et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 1999;281(17):1623–1627 3. Toita T, Ogawa K, Adachi G, Kakinohana Y, Nishikuramori Y, Iraha S et al. Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation. Jpn J Clin Oncol 2001;31(8):375–381 4. Oki E, Morita M, Kakeji Y, Ikebe M, Sadanaga N, Egasira A et al. Salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer. Dis Esophagus 2007;20(4):301–304 5. Swisher S, Wynn P, Putnam J, Mosheim M, Correa A, Komaki R et al. Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy. J Thorac Cardiovasc Surg 2002;123(1):175–183 6. Tachimori Y. Role of salvage esophagectomy after definitive chemoradiotherapy. Gen Thorac Cardiovasc Surg 2009;57(2):71– 78 7. Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 1999; 17(9):2915–2921 8. Kato H, Sato A, Fukuda H, Kagami Y, Udagawa H, Togo A et al. A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708). Jpn J Clin Oncol 2009;39(10):638–643 9. Mariette C, Guillaume P, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007;8(6):545–553 10. Tanaka T, Fujita H, Matono S, Nagano T, Nishimura K, Murata K et al. Outcomes of multimodality therapy for stage IVB esophageal cancer with distant organ metastasis (M1-Org). Dis Esophagus 2010;23(8):646–651 Fig. 5 Positron emission tomography/CT s
11. Takeuchi H, Saikawa Y, Oyama T, Ozawa S, Suda K, Wada N et al. Factors influencing the long-term survival in patients with
References
esophageal cancer who underwent esophagectomy after chemoradiotherapy. World J Surg 2010;34(2):277–284
1. Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N
12. Kozu Y, Sato H, Tsubosa Y, Ogawa H, Yasui H, Kondo H.
et al. Advances in esophageal cancer surgery in Japan: an
Surgical treatment for pulmonary metastases from esophageal
analysis of 1000 consecutive patients treated at a single
carcinoma after definitive chemoradiotherapy: experience
institute. Surgery 2008;143(4):499–508
from a single institution. J Cardiothorac Surg 2011;6:135
644
Int Surg 2014;99
Case Report
Definitive Chemoradiotherapy and Salvage Esophagectomy for Esophageal Cancer Associated With Multiple Lung Metastases: A Case Report Yoshihiko Fujinaka, Masaru Morita, Takefumi Ohga, Yoshihiro Kakeji, Tokujiro Yano, Yoshihiko Maehara Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
The prognosis of esophageal cancer with distant metastasis is dismal. We report a 70year-old man with esophageal cancer and multiple lung and lymph node metastases. Complete response was achieved following definitive chemoradiotherapy. Twenty-four months after the initial chemoradiotherapy, local recurrence was detected but there was no evidence of distant metastasis. Therefore, the patient underwent salvage esophagectomy. The surgery was well tolerated without any postoperative complications. The patient is still alive 48 months after the salvage surgery. Our experience suggests that salvage esophagectomy is an important component of multimodal therapy for the recurrence of esophageal cancer. Key words: Esophageal cancer – Chemoradiotherapy – Salvage surgery
T
he prognosis of esophageal cancer has improved in recent years, but remains poor despite curative resection.1 The prognosis is extremely dismal in patients with distant metastasis. The Radiation Therapy Oncology Group (RTOG) trial 85-01 showed that chemoradiotherapy (CRT) improved outcomes, with a 5-year overall survival
rate of 26% compared with 0% following radiotherapy alone. Moreover, residual cancer was less common following CRT (26%) than following radiotherapy alone (37%).2 However, local recurrence occurs in 37% of patients after definitive CRT.3 Salvage esophagectomy is one strategy for residual cancer or local recurrence after definitive CRT. Of
Reprint requests: Yoshihiko Fujinaka, MD, PhD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812- 8582, Japan. Tel.: 81-92-642-5466; Fax: 81-92-642-5482; E-mail: [email protected]
640
Int Surg 2014;99
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
Fig. 1
FUJINAKA
(A, B) Barium-enhanced esophagography and endoscopic examination revealed an infiltrative ulcerating tumor in the upper-
middle thoracic esophagus.
note, when R0 resection is achieved, long-term survival can be expected.4 6 On the other hand, this is an invasive procedure associated with high morbidity and mortality6 and the patient’s prognosis is extremely poor after R1/R2 resection.4 6 Therefore, salvage esophagectomy should only be performed if complete removal of the tumor is expected. Here, we report a rare case with esophageal cancer and multiple lung metastases, in which complete response (CR) was achieved after definitive CRT and salvage esophagectomy was effective for the local recurrence.
Case Presentation A 70-year-old male was admitted to our hospital because of dysphagia. On physical examination, the patient was well and had a performance status (PS) of 1. Barium-enhanced esophagography and endoscopy revealed an infiltrative ulcerating tumor in the upper-middle thoracic esophagus (Fig. 1A, B), which was subsequently diagnosed as squamous cell carcinoma. Computed tomography (CT) revealed circumferential wall thickening of the upper thoracic esophagus (Fig. 2A). We also noted uppermediastinal lymphadenopathy and multiple lung nodules (Fig. 2B, D). At the time, positron emission tomography/CT was not used in clinical practice, based on these findings, the TMN classification was T2N1M1 (UICC), the patient was treated with definitive CRT consisting of continuous 5-FU infusion (5 days/week, 500 mg/d; total 10,000 mg) and cisplatin (5 days/week, 7 mg/d; total 140 mg) for 4 Int Surg 2014;99
weeks in combination with radiotherapy (65 Gy). After CRT, CT revealed improvements in wall thickening, and the resolution of the lymph node and lung metastases (Fig. 3A–D). After achieving CR, the patient was given a two-course adjuvant chemotherapy with nedaplatin plus 5-FU regimen. The patient’s CR was maintained for 24 months after CRT, but then complained of dysphagia. Endoscopy revealed an elevated lesion covered by normal esophageal mucosa (Fig. 4A). Endoscopic ultrasonography indicated a hypoechoic intraluminal tumor (Fig. 4B) and fine needle aspiration cytology revealed squamous carcinoma cells. On positron emission tomography/CT FDG accumulation was limited to the primary lesion (Fig. 5). Since the recurrence was considered to be localized in the esophagus, we performed salvage esophagectomy (esophagectomy and reconstruction using gastric tube via a retro-sternal route). Pathological examination of the resected specimen confirmed squamous cell carcinoma, but no malignant cells were found in the resected lymph nodes. The surgery was well tolerated and the patient did not develop any postoperative complications. The patient has regularly attended our clinic for followup examinations and is still alive, without evidence of local recurrence or metastatic disease, 48 months after salvage surgery (72 months after the initial diagnosis).
Discussion The RTOG trial 85-01 demonstrated that CRT increased overall survival compared with radiother641
FUJINAKA
Fig. 2
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
(A–D) Computed tomography showed thickening of the upper thoracic esophageal wall, along with upper-mediastinal
lymphadenopathy and multiple lung metastases.
apy alone in patients with advanced esophageal cancer patients.2 Accordingly, CRT has become the standard therapy for inoperable advanced esophageal cancer. In fact, one study showed that the CR rate was 33% and the 3-year survival rate was 23% following definitive CRT for clinical T4 and/or M1 lymph node esophageal cancer.7 Esophagectomy is an effective treatment for submucosal esophageal cancer, but CRT archived CR in 87.5% of such patients and the cause-specific 4-year overall survival rate was 80.5% suggesting that definitive CRT is a reasonable alternative to surgery for patients with severe complications or refusing surgical resection.8 Therefore, definitive CRT is now accepted as a primary treatment for esophageal cancer. The prognosis of patients with distant metastases is poor often living for less than 6 months after diagnosis. Therefore, these patients are often considered as candidates for multimodal therapy or for palliative therapy.9 In a recent study, the 1-year overall survival rate of patients treated with multimodal therapy (31.0%) was significantly better than that of patients given single modal or best supportive care alone (23.7%).10 Salvage esophagectomy may be the only effective therapy for residual cancer and local recurrence after CRT. However, it is associated with a high 642
frequency of postoperative complications, particularly anastomotic leakage (38% versus 7%) and mortality (15% versus 6%), as compared with esophagectomy performed as a planned procedure after CRT.5 Multivariate analysis revealed that the most significant factor associated with long-term survival is resection without residual tumors (R0).1,11 Moreover, the prognosis after salvage surgery tended to be better in patients developing recurrence more than 1 year after definitive CRT than in patients with earlier recurrence.5 Kozu et al reviewed surgical treatment for pulmonary metastases from esophageal carcinoma could provide a long survival for those whose primary treatment was definitive CRT and who achieved a CR, surgical treatment should be taken into consideration for patients archived long CR.12 This case was diagnosed as esophageal cancer with lung and lymph node metastases, and the long duration of CR was achieved by definitive CRT. Indeed, local recurrence was detected 24 months after CRT. Most patients with recurrence after definitive CRT are inoperable due to deterioration of PS, distant metastasis. However, the present case was indicated for salvage esophagectomy because of (1) his good general health, (2) the probability of R0 resection with no evidence of distant metastasis, and Int Surg 2014;99
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
Fig. 3
FUJINAKA
(A–D) Thickening of the esophageal wall improved and the lymph node and lung metastases completely disappeared
following chemoradiotherapy.
(3) maintenance of CR for 24 months after CRT. Our
Acknowledgments
experience suggests that salvage esophagectomy following definitive CRT offers a possible therapeutic strategy for esophageal cancer patients with distance metastasis if the CR is maintained for a long period of time.
Fig. 4
This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan. The authors report no conflicts of interest.
(A,B) Upper gastrointestinal endoscopy revealed a submucosal tumor, which was identified as a hypoechoic intraluminal
tumor on endoscopic ultrasonography. Int Surg 2014;99
643
FUJINAKA
CHEMORADIOTHERAPY AND SALVAGE ESOPHAGECTOMY FOR CANCER
2. Cooper J, Guo M, Herskovic A, Macdonald J, Martenson JJ, AlSarraf M et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 1999;281(17):1623–1627 3. Toita T, Ogawa K, Adachi G, Kakinohana Y, Nishikuramori Y, Iraha S et al. Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation. Jpn J Clin Oncol 2001;31(8):375–381 4. Oki E, Morita M, Kakeji Y, Ikebe M, Sadanaga N, Egasira A et al. Salvage esophagectomy after definitive chemoradiotherapy for esophageal cancer. Dis Esophagus 2007;20(4):301–304 5. Swisher S, Wynn P, Putnam J, Mosheim M, Correa A, Komaki R et al. Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy. J Thorac Cardiovasc Surg 2002;123(1):175–183 6. Tachimori Y. Role of salvage esophagectomy after definitive chemoradiotherapy. Gen Thorac Cardiovasc Surg 2009;57(2):71– 78 7. Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 1999; 17(9):2915–2921 8. Kato H, Sato A, Fukuda H, Kagami Y, Udagawa H, Togo A et al. A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708). Jpn J Clin Oncol 2009;39(10):638–643 9. Mariette C, Guillaume P, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007;8(6):545–553 10. Tanaka T, Fujita H, Matono S, Nagano T, Nishimura K, Murata K et al. Outcomes of multimodality therapy for stage IVB esophageal cancer with distant organ metastasis (M1-Org). Dis Esophagus 2010;23(8):646–651 Fig. 5 Positron emission tomography/CT s
11. Takeuchi H, Saikawa Y, Oyama T, Ozawa S, Suda K, Wada N et al. Factors influencing the long-term survival in patients with
References
esophageal cancer who underwent esophagectomy after chemoradiotherapy. World J Surg 2010;34(2):277–284
1. Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N
12. Kozu Y, Sato H, Tsubosa Y, Ogawa H, Yasui H, Kondo H.
et al. Advances in esophageal cancer surgery in Japan: an
Surgical treatment for pulmonary metastases from esophageal
analysis of 1000 consecutive patients treated at a single
carcinoma after definitive chemoradiotherapy: experience
institute. Surgery 2008;143(4):499–508
from a single institution. J Cardiothorac Surg 2011;6:135
644
Int Surg 2014;99
