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Circulating Lymphocyte Count During Neoadjuvant Chemoradiation Therapy for Esophageal Cancer as a Predictive Biomarker of Pathologic Complete Response
Oral Scientific Sessions S151
Volume 96 Number 2S Supplement 2016
340 Role of Postoperative Concurrent Chemoradiation Therapy (CCRT) for Esophageal Carcinoma: A Meta-Analysis of 1445 Patients J. Kang,1 Z. Hui,2 X. Sun,1 and Y. Men2; 1Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China, 2Department of Radiation Oncology, Cancer Institute & Hospital, Chinese Academic of Medical Sciences(CIH-CAMS), Peking Union Medical College (PUMC), Beijing, China Purpose/Objective(s): The role of postoperative CCRT for esophageal carcinoma remains controversial. This meta-analysis aimed to evaluate the effect of CCRT on overall survival (OS) and tumor control of esophageal cancer patients after surgery. Materials/Methods: We systematically searched PubMed, EMBASE, CNKI and Wanfang databases for all randomized controlled trials (RCTs) and nonrandomized controlled trials (NRCTs) with computer and manual retrieval. Studies published before December 2015 which compared CCRT with non-CCRT treatment in esophageal cancer after surgery were included. The quality of RCTs was assessed using the Jadad scale based on only three evaluation items (description of randomization, the right method of randomization, and the dropouts and withdrawals). NRCTs were evaluated according to the MINORS. Meta-analysis was performed with the software of Review Manager Version 5.3. The primary endpoint was the pooled odds ratio (OR) about OS. The Begg’s test and Egger’s test in STATA version 12 were used to assess the potential publication bias. Results: Eleven studies were eligible which consisted of three RCTs and eight NRCTs. The total number of patients was 1445. Six hundred thirtyeight patients were treated with postoperative CCRT and the rest 807 patients received non-CCRT treatment after surgery. The overall methodological quality of included studies was relatively high, with the average Jadad score of 2.3 for the RCTs and average MINORS score of 18.3 for the NRCTs. Comparing the CCRT group with the non-CCRT one, the OR value was 1.49 (95% CI Z 1.05-2.13, P Z 0.03) for the 1-year OS, 1.54 (95% CI Z 1.23-1.94, P Z 0.0002) for the 3-year OS, and 1.60 (95% CI Z 1.24-2.05, P Z 0.0003) for the 5-year OS. There was no publication bias for the pooled estimates of 1-year and 3-year OS. Although publication bias was detected for the result of 5-year OS (Begg’s test, P Z 0.032; Egger’s test, P Z 0.022), further trim and fill analysis certified that the publication bias had little influence on the pooled result (imputed OR Z 1.327, 95% CI Z 1.093e1.696, P Z 0.024). Survival benefits were also observed in the comparisons of postoperative CCRT with surgery alone (OR for 5-year OS Z 1.87, 95% CI Z 1.28e2.75, P Z 0.001) or with postoperative radiotherapy (OR for 5-year OS Z 1.67, 95% CI Z 1.10e2.53, P Z 0.02). The local-regional recurrence rate was significantly reduced in the CCRT group (OR Z 0.59, 95% CI Z 0.46-0.75, P < 0.0001; Begg’s test, P Z 0.573; Egger’s test, P Z 0.898), but there was no significant difference of the distant metastasis rate between the CCRT and non-CCRT groups (OR Z 0.92, 95% CI Z 0.75-1.13, P Z 0.42; Begg’s test, P Z 0.127; Egger’s test, P Z 0.698). Conclusion: For patients with esophageal carcinoma, postoperative CCRT can significantly improve the OS and local-regional control, but has no effect on distant metastasis. Author Disclosure: J. Kang: None. Z. Hui: None. X. Sun: None. Y. Men: None.
Houston, TX, 5University of Arizona Department of Radiation Oncology, Tucson, AZ Purpose/Objective(s): Lymphocytopenia is associated with worse survival outcomes in patients with multiple cancer types. Recent studies have demonstrated a critical role of lymphocytes in promoting systemic immune response against tumors. However, whether circulating lymphocyte levels is predictive of locoregional treatment response in esophageal cancer patients after neoadjuvant chemoradiotherapy is unknown. Materials/Methods: Patients (N Z 320) who underwent trimodality therapy between 2007 and 2013 with stage I-IVa (AJCC 6th edition) esophageal cancer treated from 2007e2013 were analyzed. Absolute lymphocyte count (ALC) was obtained prior to, during (weekly), and one month after CRT. All surgical specimens were centrally reviewed. Complete pathologic response(pCR) was defined no viable tumor cells at surgical resection. High ALC was defined as nadir of 0.35 x 103 mL-1 assessed during CRT weeks 1-6, consistent with the highest tertile, with remaining patients classified as having low ALC. Comparison of continuous and categorical variables by pCR was assessed by ANOVA and Pearson chi-square, respectively. Logistic regression was used to provide an odds ratio (OR) for predictors of pCR. Results: A total of 130 (40.6%) patients received induction chemotherapy prior to chemoradiation, while 190 (59.4%) had neoadjuvant chemoradiation alone. Histologically, 305 (95.3%) tumors were adenocarcinomas and 15 (4.7%) were squamous cell carcinomas. pCR was achieved in 89 patients (27.8%). ALC nadir during CRT was significantly higher in patients with pCR compared to those with viable tumor (mean 0.35 x 103 mL1 vs 0.29 x 103 mL-1, P Z 0.007). Rate of pCR was increased with high as compared to low ALC at 38.4% vs 23.9%, respectively (P Z 0.011). The increased association of high ALC with pCR persisted (OR Z 1.87, 95% CI Z 1.03-3.37, P Z 0.037) after adjusting for sex, age, KPS, stage, histology, radiation modality, induction chemotherapy, and concurrent systemic regimens. No other risk factors were significantly associated with pCR in this model. When analyzing adenocarcinoma patients exclusively, high ALC remained a significant predictor for pCR after neoadjuvant chemoradiotherapy on multivariate analysis (OR Z 2.02, 95% CI Z 1.093.73, P Z 0.025). Conclusion: Esophageal cancer patients with a higher ALC level are more likely to achieve a pCR after neoadjuvant therapy. Since there is currently a lack of predictive tools for pCR, the impact of neoadjuvant therapy on ALC levels may serve as an indicator, along with other potential factors such as tumor gene expression and imaging characteristics of treatment response, to form a multiparametric predictor of pCR. Our result further suggests the importance of maintaining a functional immune system status in the control of locoregional disease. Author Disclosure: W. Jiang: None. R. Davuluri: None. P. Fang: None. C. Xu: None. J.W. Welsh: Advisor; Reflexion Medical, Checkmate Pharmaceuticals. Co-founder; Molecular Match, OncoResponse. cofounder; Healios. Research Grant; BMS, Merck, Varian, GSK. Stock; Healios, Molecular Match. Stock Options; OncoResponse, Reflexion Medical, Checkmate Pharmaceuticals. C.H. Crane: Honoraria; Vertex, EMD Serono. R.U. Komaki: None. J.D. Cox: None. C.C. Hsu: None. S.H. Lin: Research Grant; STCube Pharmaceuticals, Roche/Genentech, Peregrine Pharmaceuticals, Bayer, Elekta. Honoraria; US Oncology, AstraZeneca.
342 341 Circulating Lymphocyte Count During Neoadjuvant Chemoradiation Therapy for Esophageal Cancer as a Predictive Biomarker of Pathologic Complete Response W. Jiang,1 R. Davuluri,2 P. Fang,1 C. Xu,3 J.W. Welsh,4 C.H. Crane,1 R.U. Komaki,4 J.D. Cox,1 C.C. Hsu,5 and S.H. Lin1; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2University of Arizona, Tucson, AZ, 3MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center,
Cardiac Toxicity With Radiation Therapy in Esophageal Cancer N. Panjwani, K.E. Fero, and J.D. Murphy; University of California, San Diego, La Jolla, CA Purpose/Objective(s): Radiation therapy plays a central role in the multimodality treatment of locally advanced esophageal cancer. The close proximity of the esophagus and heart puts patients at risk for cardiovascular complications from radiation; however, the competing risk of cancer mortality may reduce the risk of late treatment-related toxicity. The purpose of this study was to evaluate the impact of radiation on cardiac events
Volume 96 Number 2S Supplement 2016
340 Role of Postoperative Concurrent Chemoradiation Therapy (CCRT) for Esophageal Carcinoma: A Meta-Analysis of 1445 Patients J. Kang,1 Z. Hui,2 X. Sun,1 and Y. Men2; 1Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing, China, 2Department of Radiation Oncology, Cancer Institute & Hospital, Chinese Academic of Medical Sciences(CIH-CAMS), Peking Union Medical College (PUMC), Beijing, China Purpose/Objective(s): The role of postoperative CCRT for esophageal carcinoma remains controversial. This meta-analysis aimed to evaluate the effect of CCRT on overall survival (OS) and tumor control of esophageal cancer patients after surgery. Materials/Methods: We systematically searched PubMed, EMBASE, CNKI and Wanfang databases for all randomized controlled trials (RCTs) and nonrandomized controlled trials (NRCTs) with computer and manual retrieval. Studies published before December 2015 which compared CCRT with non-CCRT treatment in esophageal cancer after surgery were included. The quality of RCTs was assessed using the Jadad scale based on only three evaluation items (description of randomization, the right method of randomization, and the dropouts and withdrawals). NRCTs were evaluated according to the MINORS. Meta-analysis was performed with the software of Review Manager Version 5.3. The primary endpoint was the pooled odds ratio (OR) about OS. The Begg’s test and Egger’s test in STATA version 12 were used to assess the potential publication bias. Results: Eleven studies were eligible which consisted of three RCTs and eight NRCTs. The total number of patients was 1445. Six hundred thirtyeight patients were treated with postoperative CCRT and the rest 807 patients received non-CCRT treatment after surgery. The overall methodological quality of included studies was relatively high, with the average Jadad score of 2.3 for the RCTs and average MINORS score of 18.3 for the NRCTs. Comparing the CCRT group with the non-CCRT one, the OR value was 1.49 (95% CI Z 1.05-2.13, P Z 0.03) for the 1-year OS, 1.54 (95% CI Z 1.23-1.94, P Z 0.0002) for the 3-year OS, and 1.60 (95% CI Z 1.24-2.05, P Z 0.0003) for the 5-year OS. There was no publication bias for the pooled estimates of 1-year and 3-year OS. Although publication bias was detected for the result of 5-year OS (Begg’s test, P Z 0.032; Egger’s test, P Z 0.022), further trim and fill analysis certified that the publication bias had little influence on the pooled result (imputed OR Z 1.327, 95% CI Z 1.093e1.696, P Z 0.024). Survival benefits were also observed in the comparisons of postoperative CCRT with surgery alone (OR for 5-year OS Z 1.87, 95% CI Z 1.28e2.75, P Z 0.001) or with postoperative radiotherapy (OR for 5-year OS Z 1.67, 95% CI Z 1.10e2.53, P Z 0.02). The local-regional recurrence rate was significantly reduced in the CCRT group (OR Z 0.59, 95% CI Z 0.46-0.75, P < 0.0001; Begg’s test, P Z 0.573; Egger’s test, P Z 0.898), but there was no significant difference of the distant metastasis rate between the CCRT and non-CCRT groups (OR Z 0.92, 95% CI Z 0.75-1.13, P Z 0.42; Begg’s test, P Z 0.127; Egger’s test, P Z 0.698). Conclusion: For patients with esophageal carcinoma, postoperative CCRT can significantly improve the OS and local-regional control, but has no effect on distant metastasis. Author Disclosure: J. Kang: None. Z. Hui: None. X. Sun: None. Y. Men: None.
Houston, TX, 5University of Arizona Department of Radiation Oncology, Tucson, AZ Purpose/Objective(s): Lymphocytopenia is associated with worse survival outcomes in patients with multiple cancer types. Recent studies have demonstrated a critical role of lymphocytes in promoting systemic immune response against tumors. However, whether circulating lymphocyte levels is predictive of locoregional treatment response in esophageal cancer patients after neoadjuvant chemoradiotherapy is unknown. Materials/Methods: Patients (N Z 320) who underwent trimodality therapy between 2007 and 2013 with stage I-IVa (AJCC 6th edition) esophageal cancer treated from 2007e2013 were analyzed. Absolute lymphocyte count (ALC) was obtained prior to, during (weekly), and one month after CRT. All surgical specimens were centrally reviewed. Complete pathologic response(pCR) was defined no viable tumor cells at surgical resection. High ALC was defined as nadir of 0.35 x 103 mL-1 assessed during CRT weeks 1-6, consistent with the highest tertile, with remaining patients classified as having low ALC. Comparison of continuous and categorical variables by pCR was assessed by ANOVA and Pearson chi-square, respectively. Logistic regression was used to provide an odds ratio (OR) for predictors of pCR. Results: A total of 130 (40.6%) patients received induction chemotherapy prior to chemoradiation, while 190 (59.4%) had neoadjuvant chemoradiation alone. Histologically, 305 (95.3%) tumors were adenocarcinomas and 15 (4.7%) were squamous cell carcinomas. pCR was achieved in 89 patients (27.8%). ALC nadir during CRT was significantly higher in patients with pCR compared to those with viable tumor (mean 0.35 x 103 mL1 vs 0.29 x 103 mL-1, P Z 0.007). Rate of pCR was increased with high as compared to low ALC at 38.4% vs 23.9%, respectively (P Z 0.011). The increased association of high ALC with pCR persisted (OR Z 1.87, 95% CI Z 1.03-3.37, P Z 0.037) after adjusting for sex, age, KPS, stage, histology, radiation modality, induction chemotherapy, and concurrent systemic regimens. No other risk factors were significantly associated with pCR in this model. When analyzing adenocarcinoma patients exclusively, high ALC remained a significant predictor for pCR after neoadjuvant chemoradiotherapy on multivariate analysis (OR Z 2.02, 95% CI Z 1.093.73, P Z 0.025). Conclusion: Esophageal cancer patients with a higher ALC level are more likely to achieve a pCR after neoadjuvant therapy. Since there is currently a lack of predictive tools for pCR, the impact of neoadjuvant therapy on ALC levels may serve as an indicator, along with other potential factors such as tumor gene expression and imaging characteristics of treatment response, to form a multiparametric predictor of pCR. Our result further suggests the importance of maintaining a functional immune system status in the control of locoregional disease. Author Disclosure: W. Jiang: None. R. Davuluri: None. P. Fang: None. C. Xu: None. J.W. Welsh: Advisor; Reflexion Medical, Checkmate Pharmaceuticals. Co-founder; Molecular Match, OncoResponse. cofounder; Healios. Research Grant; BMS, Merck, Varian, GSK. Stock; Healios, Molecular Match. Stock Options; OncoResponse, Reflexion Medical, Checkmate Pharmaceuticals. C.H. Crane: Honoraria; Vertex, EMD Serono. R.U. Komaki: None. J.D. Cox: None. C.C. Hsu: None. S.H. Lin: Research Grant; STCube Pharmaceuticals, Roche/Genentech, Peregrine Pharmaceuticals, Bayer, Elekta. Honoraria; US Oncology, AstraZeneca.
342 341 Circulating Lymphocyte Count During Neoadjuvant Chemoradiation Therapy for Esophageal Cancer as a Predictive Biomarker of Pathologic Complete Response W. Jiang,1 R. Davuluri,2 P. Fang,1 C. Xu,3 J.W. Welsh,4 C.H. Crane,1 R.U. Komaki,4 J.D. Cox,1 C.C. Hsu,5 and S.H. Lin1; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2University of Arizona, Tucson, AZ, 3MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center,
Cardiac Toxicity With Radiation Therapy in Esophageal Cancer N. Panjwani, K.E. Fero, and J.D. Murphy; University of California, San Diego, La Jolla, CA Purpose/Objective(s): Radiation therapy plays a central role in the multimodality treatment of locally advanced esophageal cancer. The close proximity of the esophagus and heart puts patients at risk for cardiovascular complications from radiation; however, the competing risk of cancer mortality may reduce the risk of late treatment-related toxicity. The purpose of this study was to evaluate the impact of radiation on cardiac events