Tri-Modality Therapy For Esophageal Cancer: Mucinous Histology Is Associated With Decreased Pathologic Response Rates To Neoadjuvant Chemoradiation Therapy

Purpose/Objective(s)Complete pathologic response to pre-operative chemoradiation therapy for locally advanced esophageal cancer occurs only 25% of the time. Complete and near complete response to chemoradiation therapy is associated with improved overall survival. Mucinous histology has been associated with improved outcomes in patients treated with neo-adjuvant radiochemotherapy but worse outcomes in patients treated with surgery alone. We reviewed the relationship between mucinous histology and pathologic response to chemoradiation therapy.Materials/MethodsFrom 1/1/00–3/1/06, 175 patients were treated for esophageal cancer at Wake Forest University. Of these, 49 were treated curatively with combined chemoradiation therapy followed by attempted esophagectomy. Chemotherapy consisted of 5 Fluorouracil alone or in combination with cisplatin or carboplatin and concurrent with radiotherapy. Median radiation dose was 50.4 Gy. Response to chemoradiation was determined by an experienced pathologist as observed in the esophagectomy specimen. Patients experiencing either pathologic complete response or microscopic residual disease only were scored as a responder to chemoradiation. Mucinous histology was detemined by the pathologist and the extent of mucin was quantified as either intracellular (signet ring) or extracellular (colloidal). Overall survival was estimated using Kaplan-Meier methods.ResultsMean age was 62, 86% were male, 92% were Caucasian, 8% black, and 2% other. Median pre-treatment ECOG was 1 and 37% experienced greater than 10% weight loss prior to starting therapy. GE junction tumors were found in 51% with lower esophageal location in 43% and middle or cervical location in 6%. Adenocarcinoma was the histologic subtype in 88%. A total of 13 (27%) had either signet ring histology or mucin in the specimen. Signet ring histology was found in 10 (20%) and 8 were found to have mucin in the specimen. Significant response to chemoradiation was found in 16 (33%) and the remaining 33 (67%) did not experience significant response. Only 1/16 (6%) of patients with either mucin in the specimen or signet ring histology experienced significant response compared to 12/33 (36%) who had no mucin or signet ring histology (p = 0.03). No patient with mucin in the specimen experienced significant response but 8/33 (24.2%) without mucin experienced significant response (p = 0.04). Patients with mucin in the histologic specimen had a median survival of 13.6 months compared to 21.2 months in patients who did not have mucin in the specimen (p = 0.16).ConclusionsIf contrast to existing reports, mucinous histology, whether intracellular or extracellular, is associated with decreased rates of pathologic response after radiochemotherapy for esophageal cancer. There was a trend towards decreased survival in this population which did not reach significance. This pathologic parameter should be tested in the pre-treatment setting to identify patients with a low likelihood of response to radiochemotherapy.Supported, in part, by a grant from the National Cancer Institute, award 1R-21 CA 089410. Purpose/Objective(s)Complete pathologic response to pre-operative chemoradiation therapy for locally advanced esophageal cancer occurs only 25% of the time. Complete and near complete response to chemoradiation therapy is associated with improved overall survival. Mucinous histology has been associated with improved outcomes in patients treated with neo-adjuvant radiochemotherapy but worse outcomes in patients treated with surgery alone. We reviewed the relationship between mucinous histology and pathologic response to chemoradiation therapy. Complete pathologic response to pre-operative chemoradiation therapy for locally advanced esophageal cancer occurs only 25% of the time. Complete and near complete response to chemoradiation therapy is associated with improved overall survival. Mucinous histology has been associated with improved outcomes in patients treated with neo-adjuvant radiochemotherapy but worse outcomes in patients treated with surgery alone. We reviewed the relationship between mucinous histology and pathologic response to chemoradiation therapy. Materials/MethodsFrom 1/1/00–3/1/06, 175 patients were treated for esophageal cancer at Wake Forest University. Of these, 49 were treated curatively with combined chemoradiation therapy followed by attempted esophagectomy. Chemotherapy consisted of 5 Fluorouracil alone or in combination with cisplatin or carboplatin and concurrent with radiotherapy. Median radiation dose was 50.4 Gy. Response to chemoradiation was determined by an experienced pathologist as observed in the esophagectomy specimen. Patients experiencing either pathologic complete response or microscopic residual disease only were scored as a responder to chemoradiation. Mucinous histology was detemined by the pathologist and the extent of mucin was quantified as either intracellular (signet ring) or extracellular (colloidal). Overall survival was estimated using Kaplan-Meier methods. From 1/1/00–3/1/06, 175 patients were treated for esophageal cancer at Wake Forest University. Of these, 49 were treated curatively with combined chemoradiation therapy followed by attempted esophagectomy. Chemotherapy consisted of 5 Fluorouracil alone or in combination with cisplatin or carboplatin and concurrent with radiotherapy. Median radiation dose was 50.4 Gy. Response to chemoradiation was determined by an experienced pathologist as observed in the esophagectomy specimen. Patients experiencing either pathologic complete response or microscopic residual disease only were scored as a responder to chemoradiation. Mucinous histology was detemined by the pathologist and the extent of mucin was quantified as either intracellular (signet ring) or extracellular (colloidal). Overall survival was estimated using Kaplan-Meier methods. ResultsMean age was 62, 86% were male, 92% were Caucasian, 8% black, and 2% other. Median pre-treatment ECOG was 1 and 37% experienced greater than 10% weight loss prior to starting therapy. GE junction tumors were found in 51% with lower esophageal location in 43% and middle or cervical location in 6%. Adenocarcinoma was the histologic subtype in 88%. A total of 13 (27%) had either signet ring histology or mucin in the specimen. Signet ring histology was found in 10 (20%) and 8 were found to have mucin in the specimen. Significant response to chemoradiation was found in 16 (33%) and the remaining 33 (67%) did not experience significant response. Only 1/16 (6%) of patients with either mucin in the specimen or signet ring histology experienced significant response compared to 12/33 (36%) who had no mucin or signet ring histology (p = 0.03). No patient with mucin in the specimen experienced significant response but 8/33 (24.2%) without mucin experienced significant response (p = 0.04). Patients with mucin in the histologic specimen had a median survival of 13.6 months compared to 21.2 months in patients who did not have mucin in the specimen (p = 0.16). Mean age was 62, 86% were male, 92% were Caucasian, 8% black, and 2% other. Median pre-treatment ECOG was 1 and 37% experienced greater than 10% weight loss prior to starting therapy. GE junction tumors were found in 51% with lower esophageal location in 43% and middle or cervical location in 6%. Adenocarcinoma was the histologic subtype in 88%. A total of 13 (27%) had either signet ring histology or mucin in the specimen. Signet ring histology was found in 10 (20%) and 8 were found to have mucin in the specimen. Significant response to chemoradiation was found in 16 (33%) and the remaining 33 (67%) did not experience significant response. Only 1/16 (6%) of patients with either mucin in the specimen or signet ring histology experienced significant response compared to 12/33 (36%) who had no mucin or signet ring histology (p = 0.03). No patient with mucin in the specimen experienced significant response but 8/33 (24.2%) without mucin experienced significant response (p = 0.04). Patients with mucin in the histologic specimen had a median survival of 13.6 months compared to 21.2 months in patients who did not have mucin in the specimen (p = 0.16). ConclusionsIf contrast to existing reports, mucinous histology, whether intracellular or extracellular, is associated with decreased rates of pathologic response after radiochemotherapy for esophageal cancer. There was a trend towards decreased survival in this population which did not reach significance. This pathologic parameter should be tested in the pre-treatment setting to identify patients with a low likelihood of response to radiochemotherapy.Supported, in part, by a grant from the National Cancer Institute, award 1R-21 CA 089410. If contrast to existing reports, mucinous histology, whether intracellular or extracellular, is associated with decreased rates of pathologic response after radiochemotherapy for esophageal cancer. There was a trend towards decreased survival in this population which did not reach significance. This pathologic parameter should be tested in the pre-treatment setting to identify patients with a low likelihood of response to radiochemotherapy.