Neoadjuvant Chemotherapy for Clinical Stage II and III Thoracic Esophageal Squamous Cell Carcinoma with Curative Esophagectomy
Author(s)
Masahide Ikeguchi1*,
Yusuke Kohno1,
Kyoichi Kihara1,
Kazunori Suzuki1,
Kanenori Endo1,
Seiichi Nakamura1,
Takashi Sawada1,
Tetsu Shimizu1,
Tomoyuki Matsunaga2,
Yoji Fukumoto2,
Hiroaki Saito2
Affiliation(s)
1 Tottori Prefectural Central Hospital, Tottori, Japan. 2 Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Tottori, Japan.
1 Tottori Prefectural Central Hospital, Tottori, Japan. 2 Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Tottori, Japan.
ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal carcinoma with a poor prognosis. To improve the survival of patients with this disease, neoadjuvant chemotherapy (NAC) has been introduced. However, the survival benefits of NAC or the correlation between NAC and postoperative complications have not been well considered. In the present study, we retrospectively investigated the clinicopathological effectiveness of NAC in patients with clinical stage II and III thoracic ESCC. This retrospective study enrolled 63 patients with clinical stage II and III thoracic ESCC, who underwent resection of the thoracic esophagus and three-field lymph node dissection between January 2007 and December 2013. NAC with cisplatin plus 5-fluorouracil (5-FU) was introduced in 38 patients. NAC did not correlate with the occurrence of postoperative complications. The 5-year disease-free survival (DFS) rate of the 38 patients with NAC (41.6%) was similar to that for the 25 patients who did not receive NAC (38.1%; P = 0.784). However, we found that the DFS of 17 patients with histopathological Grade 2 and 3 tumors who received NAC (5-year DFS rate: 58.1%) was significantly higher than that of 21 patients with low histopathological grade tumors who received NAC (5-year DFS rate: 28.6%), or than that of the 25 patients who did not receive NAC (38.1%). Moreover, we found that the effectiveness of NAC assessed macroscopically did not correlate with the effectiveness of NAC assessed microscopically. These findings may indicate that preoperative estimation of NAC effectiveness is important in avoiding unnecessary adverse drug effects caused by NAC, and in prolonging the survival of patients with thoracic ESCC.
Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal carcinoma with a poor prognosis. To improve the survival of patients with this disease, neoadjuvant chemotherapy (NAC) has been introduced. However, the survival benefits of NAC or the correlation between NAC and postoperative complications have not been well considered. In the present study, we retrospectively investigated the clinicopathological effectiveness of NAC in patients with clinical stage II and III thoracic ESCC. This retrospective study enrolled 63 patients with clinical stage II and III thoracic ESCC, who underwent resection of the thoracic esophagus and three-field lymph node dissection between January 2007 and December 2013. NAC with cisplatin plus 5-fluorouracil (5-FU) was introduced in 38 patients. NAC did not correlate with the occurrence of postoperative complications. The 5-year disease-free survival (DFS) rate of the 38 patients with NAC (41.6%) was similar to that for the 25 patients who did not receive NAC (38.1%; P = 0.784). However, we found that the DFS of 17 patients with histopathological Grade 2 and 3 tumors who received NAC (5-year DFS rate: 58.1%) was significantly higher than that of 21 patients with low histopathological grade tumors who received NAC (5-year DFS rate: 28.6%), or than that of the 25 patients who did not receive NAC (38.1%). Moreover, we found that the effectiveness of NAC assessed macroscopically did not correlate with the effectiveness of NAC assessed microscopically. These findings may indicate that preoperative estimation of NAC effectiveness is important in avoiding unnecessary adverse drug effects caused by NAC, and in prolonging the survival of patients with thoracic ESCC.
KEYWORDS
Esophageal Squamous Cell Carcinoma, Histopathological Grade, Neoadjuvant Chemotherapy, Prognosis
Esophageal Squamous Cell Carcinoma, Histopathological Grade, Neoadjuvant Chemotherapy, Prognosis
Cite this paper
Ikeguchi, M. , Kohno, Y. , Kihara, K. , Suzuki, K. , Endo, K. , Nakamura, S. , Sawada, T. , Shimizu, T. , Matsunaga, T. , Fukumoto, Y. and Saito, H. (2015) Neoadjuvant Chemotherapy for Clinical Stage II and III Thoracic Esophageal Squamous Cell Carcinoma with Curative Esophagectomy. Journal of Cancer Therapy, 6, 1207-1213. doi: 10.4236/jct.2015.615131.
Ikeguchi, M. , Kohno, Y. , Kihara, K. , Suzuki, K. , Endo, K. , Nakamura, S. , Sawada, T. , Shimizu, T. , Matsunaga, T. , Fukumoto, Y. and Saito, H. (2015) Neoadjuvant Chemotherapy for Clinical Stage II and III Thoracic Esophageal Squamous Cell Carcinoma with Curative Esophagectomy. Journal of Cancer Therapy, 6, 1207-1213. doi: 10.4236/jct.2015.615131.
References
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http://dx.doi.org/10.1097/00000658-200008000-00013 [2] Akiyama, H., Tsurumaru, M., Udagawa, H. and Kajiyama, Y. (1994) Radical Lymph Node Dissection for Cancer of the Thoracic Esophagus. Annals of Surgery, 220, 364-372.
http://dx.doi.org/10.1097/00000658-199409000-00012 [3] Ando, N., Iizuka, T., Ide, H., Ishida, K., Shinoda, M., Nishimaki, T., Takiyama, W., Watanabe, H., Isono, K., Aoyama, N., Makuuchi, H., Tanaka, O., Yamana, H., Ikeuchi, T., Nagai, K., Shimada, Y., Kinjo, Y., Fukuda, H. and Japan Clinical Oncology Group (2003) Surgery plus Chemotherapy Compared with Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204. Journal of Clinical Oncology, 21, 4592-4596.
http://dx.doi.org/10.1200/JCO.2003.12.095 [4] Ando, N., Kato, H., Igaki, H., Shinoda, M., Ozawa, S., Shimizu, H., Nakamura, T., Yabusaki, H., Aoyama, N., Kurita, A., Ikeda, K., Kanda, T., Tsujinaka, T., Nakamura, K. and Fukuda, H. (2012) A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907). Annals of Surgical Oncology, 19, 68-74.
http://dx.doi.org/10.1245/s10434-011-2049-9 [5] Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, L., Verweij, J., Glabbeke, M.V., van Oosterom, A.T., Christian, M.C. and Gwyther, S.G. (2000) New Guidelines to Evaluate the Response to Treatment in Solid Tumors. JNCI, 92, 205-216.
http://dx.doi.org/10.1093/jnci/92.3.205 [6] Sobin, L.H. and Wittekind, C.H. (2002) UICC TNM Classification of Malignant Tumours. 6th Edition, John Wiley & Sons, Hoboken, New Jersey. [7] Japanese Society for Esophageal Diseases (2004) Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus Ninth Edition: Part II. Esophagus, 1, 107-125.
http://dx.doi.org/10.1007/s10388-004-0019-z [8] Hirao, M., Ando, N., Tshujinaka, T., Udagawa, H., Yano, M., Yamana, H., Nagai, K., Mizusawa, J., Nakamura, K. and Japanese Esophageal Oncology Group/Japan Clinical Oncology Group (2011) Influence of Preoperative Chemotherapy for Advanced Thoracic Oesophageal Squamous Cell Carcinoma on Perioperative Complications. British Journal of Surgery, 98, 1735-1741.
http://dx.doi.org/10.1002/bjs.7683 [9] Kumagai, K., Rouvelas, I., Tsai, J.A., Mariosa, D., Klevebro, F., Lindblad, M., Ye, W., Lundell, L. and Nisson, M. (2014) Meta-Analysis of Postoperative Morbidity and Perioperative Mortality in Patients Receiving Neoadjuvant Chemotherapy or Chemoradiotherapy for Resectable Oesophageal and Gastro-Oesophageal Junctional Cancers. British Journal of Surgery, 101, 321-338.
http://dx.doi.org/10.1002/bjs.9418 [10] Yip, C., Goh, V., Davies, A., Gossage, J., Mitchell-Hay, R., Hynes, O., Maisey, N., Ross, P., Gaya, A., Landau, D.B., Cook, G.J., Griffin, N. and Mason, R. (2014) Assessment of Sarcopenia and Changes in Body Composition after Neoadjuvant Chemotherapy and Associations with Clinical Outcomes in Oesophageal Cancer. European Radiology, 24, 998-1005.
http://dx.doi.org/10.1007/s00330-014-3110-4 [11] Ida, S., Watanabe, M., Karashima, R., Imamura, Y., Ishimoto, T., Baba, Y., Iwagami, S., Sakamoto, Y., Miyamoto, Y., Yoshida, N. and Baba, H. (2014) Changes in Body Composition Secondary to Neoadjuvant Chemotherapy for Advanced Esophageal Cancer Are Related to the Occurrence of Postoperative Complications after Esophagectomy. Annals of Surgical Oncology, 21, 3675-3679.
http://dx.doi.org/10.1245/s10434-014-3737-z [12] Yano, M., Takachi, K., Doki, Y., Miyashiro, I., Kishi, K., Noura, S., Eguchi, H., Yamada, T., Ohue, M., Ohigashi, H., Sasaki, Y., Ishikawa, O. and Imaoka, S. (2006) Preoperative Chemotherapy for Clinically Node-Positive Patients with Squamous Cell Carcinoma of the Esophagus. Diseases of the Esophagus, 19, 158-163.
http://dx.doi.org/10.1245/s10434-014-3737-z [13] Konishi, H., Fujiwara, H., Shiozaki, A., Hiramoto, H., Kosuga, T., Komatsu, S., Ichikawa, D., Okamoto, K. and Otsuji, E. (2015) Effects of Neutropenia and Histological Responses in Esophageal Squamous Cell Carcinoma with Neo-Adjuvant Chemotherapy. International Journal of Clinical Oncology, Epub Ahead of Print.
http://dx.doi.org/10.1007/s10147-015-0875-7 [14] Lee, C.T., Chow, N.H., Liu, Y.S., Lin, S.C., Lin, P.C., Wu, Y.H., Lee, J.C. and Tsai, H.M. (2012) Computed Tomography with Histological Correlation for Evaluating Tumor Regression of Rectal Carcinoma after Preoperative Chemoradiation Therapy. Hepatogastroenterology, 59, 2484-2489. [15] Hara, H., Tahara, M., Daiko, H., Kato, K., Igaki, H., Kadowaki, S., Tanaka, Y., Hamamoto, Y., Matsushita, H., Nagase, M. and Hosoya, Y. (2013) Phase II Feasibility Study of Preoperative Chemotherapy with Docetaxel, Cisplatin, and Fluorouracil for Esophageal Squamous Cell Carcinoma. Cancer Science, 104, 1455-1460.
http://dx.doi.org/10.1111/cas.12274 [16] Elliott, J.A., O’Farrell, N.J., King, S., Halpenny, D., Malik, V., Muldoon, C., Johnston, C. and Reynolds, J.V. (2014) Value of CT-PET after Neoadjuvant Chemoradiation in the Prediction of Histological Tumour Regression, Nodal Status and Survival in Oesophageal Adenocarcinoma. British Journal of Surgery, 101, 1702-1711.
http://dx.doi.org/10.1002/bjs.9670 [17] Makuuchi, Y., Honda, K., Osaka, Y., Kato, K., Kojima, T., Daiko, H., Igaki, H., Ito, Y., Hoshino, S., Tachibana, S., Watanabe, T., Furuta, K., Sekine, S., Umaki, T., Watabe, Y., Miura, N., Ono, M., Tsuchida, A. and Yamada, T. (2013) Soluble Interleukin-6 Receptor Is a Serum Biomarker for the Response of Esophageal Carcinoma to Neoadjuvant Chemoradiotherapy. Cancer Science, 104, 1045-1051.
http://dx.doi.org/10.1111/cas.12187
[1] Ando, N., Ozawa, S., Kitagawa, Y., Shinozawa, Y. and Kitajima, M. (2000) Improvement in the Results of Surgical Treatment of Advanced Squamous Esophageal Carcinoma during 15 Consecutive Years. Annals of Surgery, 232, 225-232.
http://dx.doi.org/10.1097/00000658-200008000-00013 [2] Akiyama, H., Tsurumaru, M., Udagawa, H. and Kajiyama, Y. (1994) Radical Lymph Node Dissection for Cancer of the Thoracic Esophagus. Annals of Surgery, 220, 364-372.
http://dx.doi.org/10.1097/00000658-199409000-00012 [3] Ando, N., Iizuka, T., Ide, H., Ishida, K., Shinoda, M., Nishimaki, T., Takiyama, W., Watanabe, H., Isono, K., Aoyama, N., Makuuchi, H., Tanaka, O., Yamana, H., Ikeuchi, T., Nagai, K., Shimada, Y., Kinjo, Y., Fukuda, H. and Japan Clinical Oncology Group (2003) Surgery plus Chemotherapy Compared with Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204. Journal of Clinical Oncology, 21, 4592-4596.
http://dx.doi.org/10.1200/JCO.2003.12.095 [4] Ando, N., Kato, H., Igaki, H., Shinoda, M., Ozawa, S., Shimizu, H., Nakamura, T., Yabusaki, H., Aoyama, N., Kurita, A., Ikeda, K., Kanda, T., Tsujinaka, T., Nakamura, K. and Fukuda, H. (2012) A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907). Annals of Surgical Oncology, 19, 68-74.
http://dx.doi.org/10.1245/s10434-011-2049-9 [5] Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, L., Verweij, J., Glabbeke, M.V., van Oosterom, A.T., Christian, M.C. and Gwyther, S.G. (2000) New Guidelines to Evaluate the Response to Treatment in Solid Tumors. JNCI, 92, 205-216.
http://dx.doi.org/10.1093/jnci/92.3.205 [6] Sobin, L.H. and Wittekind, C.H. (2002) UICC TNM Classification of Malignant Tumours. 6th Edition, John Wiley & Sons, Hoboken, New Jersey. [7] Japanese Society for Esophageal Diseases (2004) Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus Ninth Edition: Part II. Esophagus, 1, 107-125.
http://dx.doi.org/10.1007/s10388-004-0019-z [8] Hirao, M., Ando, N., Tshujinaka, T., Udagawa, H., Yano, M., Yamana, H., Nagai, K., Mizusawa, J., Nakamura, K. and Japanese Esophageal Oncology Group/Japan Clinical Oncology Group (2011) Influence of Preoperative Chemotherapy for Advanced Thoracic Oesophageal Squamous Cell Carcinoma on Perioperative Complications. British Journal of Surgery, 98, 1735-1741.
http://dx.doi.org/10.1002/bjs.7683 [9] Kumagai, K., Rouvelas, I., Tsai, J.A., Mariosa, D., Klevebro, F., Lindblad, M., Ye, W., Lundell, L. and Nisson, M. (2014) Meta-Analysis of Postoperative Morbidity and Perioperative Mortality in Patients Receiving Neoadjuvant Chemotherapy or Chemoradiotherapy for Resectable Oesophageal and Gastro-Oesophageal Junctional Cancers. British Journal of Surgery, 101, 321-338.
http://dx.doi.org/10.1002/bjs.9418 [10] Yip, C., Goh, V., Davies, A., Gossage, J., Mitchell-Hay, R., Hynes, O., Maisey, N., Ross, P., Gaya, A., Landau, D.B., Cook, G.J., Griffin, N. and Mason, R. (2014) Assessment of Sarcopenia and Changes in Body Composition after Neoadjuvant Chemotherapy and Associations with Clinical Outcomes in Oesophageal Cancer. European Radiology, 24, 998-1005.
http://dx.doi.org/10.1007/s00330-014-3110-4 [11] Ida, S., Watanabe, M., Karashima, R., Imamura, Y., Ishimoto, T., Baba, Y., Iwagami, S., Sakamoto, Y., Miyamoto, Y., Yoshida, N. and Baba, H. (2014) Changes in Body Composition Secondary to Neoadjuvant Chemotherapy for Advanced Esophageal Cancer Are Related to the Occurrence of Postoperative Complications after Esophagectomy. Annals of Surgical Oncology, 21, 3675-3679.
http://dx.doi.org/10.1245/s10434-014-3737-z [12] Yano, M., Takachi, K., Doki, Y., Miyashiro, I., Kishi, K., Noura, S., Eguchi, H., Yamada, T., Ohue, M., Ohigashi, H., Sasaki, Y., Ishikawa, O. and Imaoka, S. (2006) Preoperative Chemotherapy for Clinically Node-Positive Patients with Squamous Cell Carcinoma of the Esophagus. Diseases of the Esophagus, 19, 158-163.
http://dx.doi.org/10.1245/s10434-014-3737-z [13] Konishi, H., Fujiwara, H., Shiozaki, A., Hiramoto, H., Kosuga, T., Komatsu, S., Ichikawa, D., Okamoto, K. and Otsuji, E. (2015) Effects of Neutropenia and Histological Responses in Esophageal Squamous Cell Carcinoma with Neo-Adjuvant Chemotherapy. International Journal of Clinical Oncology, Epub Ahead of Print.
http://dx.doi.org/10.1007/s10147-015-0875-7 [14] Lee, C.T., Chow, N.H., Liu, Y.S., Lin, S.C., Lin, P.C., Wu, Y.H., Lee, J.C. and Tsai, H.M. (2012) Computed Tomography with Histological Correlation for Evaluating Tumor Regression of Rectal Carcinoma after Preoperative Chemoradiation Therapy. Hepatogastroenterology, 59, 2484-2489. [15] Hara, H., Tahara, M., Daiko, H., Kato, K., Igaki, H., Kadowaki, S., Tanaka, Y., Hamamoto, Y., Matsushita, H., Nagase, M. and Hosoya, Y. (2013) Phase II Feasibility Study of Preoperative Chemotherapy with Docetaxel, Cisplatin, and Fluorouracil for Esophageal Squamous Cell Carcinoma. Cancer Science, 104, 1455-1460.
http://dx.doi.org/10.1111/cas.12274 [16] Elliott, J.A., O’Farrell, N.J., King, S., Halpenny, D., Malik, V., Muldoon, C., Johnston, C. and Reynolds, J.V. (2014) Value of CT-PET after Neoadjuvant Chemoradiation in the Prediction of Histological Tumour Regression, Nodal Status and Survival in Oesophageal Adenocarcinoma. British Journal of Surgery, 101, 1702-1711.
http://dx.doi.org/10.1002/bjs.9670 [17] Makuuchi, Y., Honda, K., Osaka, Y., Kato, K., Kojima, T., Daiko, H., Igaki, H., Ito, Y., Hoshino, S., Tachibana, S., Watanabe, T., Furuta, K., Sekine, S., Umaki, T., Watabe, Y., Miura, N., Ono, M., Tsuchida, A. and Yamada, T. (2013) Soluble Interleukin-6 Receptor Is a Serum Biomarker for the Response of Esophageal Carcinoma to Neoadjuvant Chemoradiotherapy. Cancer Science, 104, 1045-1051.
http://dx.doi.org/10.1111/cas.12187