TY - JOUR
T1 - Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma
AU - Lin, Wei Cheng
AU - Ding, Yi Fang
AU - Hsu, Han Lin
AU - Chang, Jer Hwa
AU - Yuan, Kevin Sheng Po
AU - Wu, Alexander T.H.
AU - Chow, Jyh Ming
AU - Chang, Chia Lun
AU - Chen, Shee Uan
AU - Wu, Szu Yuan
N1 - Funding Information:
This work was supported by Taipei Medical University (TMU105-AE1-B26) and Wan Fang Hospital (106-eva-01). The cohort for this study was established using data from the Taiwan Cancer Registry database. We enrolled patients who received a diagnosis of TESCC between January 1, 2006, and December 31, 2014. The index date was of date of surgery in the surgery and trimodality groups and the date on which treatment was started in the definitive CCRT group. The follow-up duration was from the index date to December 31, 2014. The cancer registry database of the Collaboration Center of Health Information Application contains detailed cancer-related information, including the clinical stage, treatment modalities, pathology, radiation doses, and regimens used (CCRT or neoadjuvant CCRT). Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University(TMU-JIRB no. 201402018). The diagnoses of enrolled patients were confirmed according to their pathologic data, and it was confirmed that patients who received a new diagnosis of TESCC had no other cancer or distant metastasis. The inclusion criteria were a TESCC diagnosis, age ≥20 years, and AJCC clinical cancer stages IA through IIIC (without metastasis). Exclusion criteria were a history of cancer before TESCC diagnosis, distant metastasis, unknown esophageal locations, missing sex data, age <20 years, unclear staging, and non-SCC histology. TESCC was defined as esophageal SCC (ESCC) with pathologic confirmation in the thoracic area recorded in the cancer registry database. In addition, we excluded patients with TESCC who did not receive any treatments, did not receive sufficient RT doses (≥4500 centigrays [cGy]) in the trimodality or CCRT groups after TESCC diagnosis, did not receive cisplatin-based CT regimens, received sequential CT and RT, received CT alone, received RT alone, received adjuvant therapy after surgery or adjuvant CCRT, or underwent surgery >12 weeks after CCRT. Finally, we enrolled patients with TESCC and categorized them into the following groups on the basis of treatment modality to compare their outcomes: group 1, those who underwent surgery alone; group 2, those who received neoadjuvant CCRT followed by surgery (trimodality); and group 3, those who received definitive CCRT. The median total RT dose and fraction size was 5040 cGy in 180-cGy fractions for groups 2 and 3, respectively. Comorbidities were scored using the Charlson comorbidity index (CCI). Only comorbidities observed 6 months before and after the index date were included; comorbid conditions were identified and included according to the main International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for the first admission or more than 2 repeated main diagnosis codes for visits to the outpatient department. Significant independent predictors, such as age, sex, CCI score, AJCC clinical stage, year of diagnosis, RT dose, alcohol consumption, and cigarette smoking, were determined using multivariate Cox regression analysis to determine the hazard ratio (HR); the independent predictors were controlled for adjustment or were stratified in the analysis, and the endpoint was the mortality rate among treatments, with group 1 as the control arm. The cumulative incidence of death was estimated using the Kaplan-Meier method, and differences among treatment modalities were determined using the log-rank test. After adjustment for confounders, the Cox proportional-hazards method was used to model the time from the index date to all-cause mortality among patients receiving treatment. In the multivariate analysis, HRs were adjusted for age, sex, CCI score, clinical AJCC stage, year of diagnosis, RT modality, RT dose, alcohol consumption, and cigarette smoking. Stratified analyses were performed to evaluate the mortality risk associated with different treatment modalities and different AJCC clinical stages. All analyses were performed using SAS software (version 9.3; SAS, Cary, NC). A 2-tailed P value <.05 was considered statistically significant.
Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/10/15
Y1 - 2017/10/15
N2 - BACKGROUND: Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS: Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients.
AB - BACKGROUND: Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS: Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients.
KW - concurrent chemoradiotherapy (CCRT)
KW - squamous cell carcinoma
KW - surgery alone
KW - thoracic esophageal cancer
KW - trimodality therapy
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U2 - 10.1002/cncr.30823
DO - 10.1002/cncr.30823
M3 - Article
C2 - 28608916
AN - SCOPUS:85020410112
SN - 0008-543X
VL - 123
SP - 3904
EP - 3915
JO - Cancer
JF - Cancer
IS - 20
ER -
