BACKGROUNDThe effectiveness of neoadjuvant chemoradiotherapy (NCRT) treatment for patients with esophageal carcinoma (EC) remains controversial. The aim of this study was to compare the effect of NCRT followed by surgery (NCRTS) with surgery alone (SA) for EC.

METHODSThe PubMed, EMBASE, and the Cochrane Library databases were electronically searched up to August 2015 for all the published studies that investigated EC patients receiving either NCRTS or SA, and the reference lists were also manually examined for the eligible studies. The risk ratio (RR) with 95% confidence intervals (CI s) as effective size was determined to assess the 1-, 3-, 5-year survival rates (SRs), postoperative morbidity, and postoperative mortality. Heterogeneity was determined using the Q-test. The Begg's test and Egger's test were used for assessing any potential publication bias.

RESULTSOf 1120 identified studies, 16 eligible studies were included in this analysis (involving 2549 patients). Overall, the pooled results suggested that NCRTS was associated with significantly improved 1-year (RR: 1.07, 95% CI: 1.02-1.13), 3-year (RR: 1.26, 95% CI: 1.14-1.39), and 5-year (RR: 1.36, 95% CI: 1.18-1.56) SRs. However, the results also indicated that NCRTS had no or little effect on postoperative morbidity (RR: 0.93, 95% CI: 0.82-1.05) and postoperative mortality (RR: 1.17, 95% CI: 0.56-2.44).

CONCLUSIONSCompared with SA, NCRTS can increase 1-, 3-, and 5-year SRs in patients with EC.

Esophageal cancer is a malignant tumor with a high incidence in China. At pesent, advanced esophageal cancer patients are still frequently encountered. The primary treatment for resectable advanced esophageal cancer is surgery-based multimodality therapy, including preoperative neoadjuvant therapy, such as chemotherapy, chemoradiotherapy or chemotherapy plus immunotherapy, followed by radical esophagectomy with thoraco-abdominal two-field or cervico-thoraco-abdominal three-field lymphadenectomy via minimally invasive approach or thoracotomy. In addition, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy, or immunotherapy may also be administered if suggested by postoperative pathological results. Although the treatment outcome of esophageal cancer has improved significantly in China, many clinical issues remain controversial. In this article, we summarize the current hotspots and important issues of esophageal cancer in China, including prevention and early diagnosis, treatment selection for early esophageal cancer, surgical approach selection, lymphadenectomy method, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and nutritional support treatment.
Humans ; Esophageal Neoplasms/surgery* ; Combined Modality Therapy ; Neoadjuvant Therapy/methods* ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Esophagectomy/methods*

BACKGROUNDThe effectiveness and influence of surgery followed by adjuvant chemoradiotherapy (CRT) on the survival of patients with resectable esophageal carcinoma are still under debate. The outcomes of clinical trials have not been consistent. This study aimed to perform a meta-analysis of eligible published clinical trials to compare CRT with surgery without adjuvant chemoradiotherapy (non-CRT) for resectable esophageal carcinoma.

METHODSComputerized bibliographic and manual searches were undertaken to identify all eligible literature between 1990 and 2012. PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were our primary sources for published clinical trials. The quality of the methodology and reliability of the data from all of the clinical trials were assessed. All data were extracted by three independent researchers.

RESULTSSeven studies that included a total of 523 patients were selected. It was found that CRT significantly improved survival. The odds ratio (OR) in comparing CRT and non-CRT groups was 1.75 (95% confidence intervals (CI): 1.17 - 2.60, P = 0.006) for 1-year survival, 2.07 (95%CI: 1.45 - 2.96, P < 0.0001) for 3-year survival, and 2.17 (95%CI: 1.45 - 3.26, P = 0.0002) for 5-year survival. There have been no CRT treatment-related deaths reported in the literature. The incidence of related complications was high in the cases with CRT. Patients treated with CRT had a lower incidence of local-regional cancer recurrence (OR: 0.49, 95%CI: 0.31 - 0.76, P = 0.002) and a similar incidence of distant cancer recurrence (OR: 0.90, 95%CI: 0.60 - 1.34, P = 0.60).

CONCLUSIONSIt was found that patients with resectable esophageal carcinoma could gain a survival benefit from CRT. However, CRT was associated with a high incidence of related complications.

The prognosis of patients with locally advanced esophageal cancer treated by surgery alone is poor. The neoadjuvant chemoradiotherapy is considered to improve the long-term survival of patients with locally advanced esophageal cancer. The combination of neoadjuvant chemoradiotherapy and surgery has been recommended to be the standard treatment for the locally advanced esophageal cancer in China even in Europe and America countries. However, available evidence suggests that only those who had histopathologic response seemed to benefit the most from neoadjuvant chemotherapy while non-responders even had rather worse outcome compared to patients with surgery alone. Therefore, predictive markers of response to neoadjuvant chemoradiotherapy in locally advanced esophageal cancer are highly significant and needed. These markers would allow a tailored treatment to guide non-responders to alternative preoperative therapies and ultimately avoid ineffective, costly and seriously cytotoxic treatments. Results of most studies on biomarkers for predicting response to neoadjuvant chemoradiotherapy in esophageal cancer are promising. The potential utilization of biomarkers in clinical practice is urgently expected and needed, which plays an important role in guiding and improving the individualization of multimodality therapy in locally advanced esophageal cancer.
Biomarkers, Tumor ; Chemoradiotherapy ; Esophageal Neoplasms ; drug therapy ; radiotherapy ; surgery ; Humans ; Neoadjuvant Therapy ; methods ; Treatment Outcome

Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.
Chemoradiotherapy ; Humans ; Magnetic Resonance Imaging ; Methods ; Neoadjuvant Therapy ; Quality of Life ; Rectal Neoplasms

PURPOSE: Insistence that total regression of primary tumor would not represent long-term oncologic outcomes has been raised. Therefore, this study aimed to evaluate the outcomes of these patients after preoperative chemoradiotherapy (PCRT) and radical surgery and to evaluate the associated risk factors. METHODS: We included 189 patients with rectal cancer who showed total regression of the primary tumor after PCRT, followed by radical resection, between 2001 and 2012. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the results were compared with 77 patients with Tis rectal cancer who received only radical resection. Factors associated with RFS were evaluated using Cox regression analysis. RESULTS: Sphincter-saving resection was performed for 146 patients (77.2%). Adjuvant chemotherapy was administered to 168 patients (88.9%). During the follow-up period, recurrence occurred in 17 patients (9%). The 5-year RFS was 91.3%, which was significantly lower than that of patients with Tis rectal cancer without PCRT (P = 0.005). In univariate analysis, preoperative CEA and histologic differentiation were associated with RFS. However, no factors were found to be associated with RFS. CONCLUSION: RFS was lower in patients with total regression of primary rectal cancer after PCRT than in those with Tis rectal cancer without PCRT, and it would not be considered as the same entity with early rectal cancer or “disappeared tumor” status.
Chemoradiotherapy ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Methods ; Rectal Neoplasms ; Recurrence ; Risk Factors

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

PURPOSE: This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR). METHODS: Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes. RESULTS: A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0). CONCLUSION: Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.
Carcinoembryonic Antigen ; Chemoradiotherapy ; Classification ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Methods ; Polymerase Chain Reaction ; Proportional Hazards Models ; Rectal Neoplasms

PURPOSE: The response to neoadjuvant chemoradiotherapy (CRT) for rectal cancer can be assessed using digital rectal examination, endoscopy and magnetic resonance imaging (MRI). Precise assessment of clinical complete response (CR) after CRT is essential when deciding between optimizing surgery or organ-preserving treatment. The objectives of this study were to correlate the CR finding in endoscopy and MRI with pathologic CR and to determine the appropriate approach for combining endoscopy and MRI to predict the pathologic CR in patients with rectal cancer after neoadjuvant CRT. METHODS: This retrospective cohort study included 102 patients with rectal cancer who underwent endoscopy and MRI at 2–4 weeks after CRT. We assigned a confidence level (1–4) for the endoscopic and MRI assessments. Accuracy, sensitivity, and specificity were analyzed based on the endoscopy, MRI, and combination method findings. Diagnostic modalities were compared using the likelihood ratios. RESULTS: Of 102 patients, 17 (16.7%) had a CR. The accuracy, sensitivity, and specificity for the prediction CR of endoscopy with biopsy were 85.3%, 52.9%, and 91.8%, while those of MRI were 91.2%, 70.6%, and 95.3%, and those of combined endoscopy and MRI were 89.2%, 52.9%, and 96.5%, respectively. No significant differences were noted in the sensitivity and specificity of any each modality. The prediction rate for CR of the combination method was 92.6% after the posttest probability test. CONCLUSION: Our study demonstrated that combining the interpretation of endoscopy with biopsy and MRI could provide a good prediction rate for CR in patients with rectal cancer after CRT.
Biopsy ; Chemoradiotherapy ; Cohort Studies ; Digital Rectal Examination ; Endoscopy ; Humans ; Magnetic Resonance Imaging ; Methods ; Rectal Neoplasms ; Retrospective Studies ; Sensitivity and Specificity

PURPOSE: The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). MATERIALS AND METHODS: A total of 194 locoregionally advanced nasopharyngeal carcinoma patients youngerthan 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. RESULTS: One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. CONCLUSION: This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.
Adolescent* ; Chemoradiotherapy* ; Child* ; Cohort Studies* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Induction Chemotherapy* ; Methods ; Neutropenia ; Radiotherapy