Association of Sarcopenia With Toxicity and Survival in Postoperative Recurrent Esophageal Squamous Cell Carcinoma Patients Receiving Chemoradiotherapy.

BACKGROUND: Sarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis. METHODS: One hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models. RESULTS: Sarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p < 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002). CONCLUSIONS: Sarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.

Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8-2.0 Gy per fraction to a total dose of 50-60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. RESULTS: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3-4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). CONCLUSION: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy.

BACKGROUND: Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 286 patients with stage II-IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm3 at diagnosis, and treatment-related lymphopenia was defined as total lymphocyte count <200 cells per mm3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment-related lymphopenia and treatment response. RESULTS: Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m2, and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment-related lymphopenia. Tumor progression and cancer-related death were more frequently observed in treatment-related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment-related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. CONCLUSION: Treatment-related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. IMPLICATIONS FOR PRACTICE: A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment-related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment-related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.

Comparison of efficacy for postoperative chemotherapy and concurrent radiochemotherapy in patients with IIIA-pN2 non-small cell lung cancer: an early closed randomized controlled trial.

OBJECTIVE: The efficacy of postoperative concurrent radiochemotherapy (POCRT) on IIIA-pN2 non-small cell lung cancer (NSCLC) is still unclear. The aim of this randomized controlled trial was to compare POCRT with postoperative chemotherapy (POCT) alone in terms of survival and relapse patterns. METHODS: Patients with completely resected IIIA-pN2 NSCLC were randomized into POCRT or POCT groups. Chemotherapy consisted of paclitaxel (175 mg/m(2)) and cisplatin (60 mg/m(2)) administered intravenously for four cycles on day 1, 22, 43, and 64. Patients in the POCRT group received radiotherapy (50.4 Gy/28 fractions) concurrently with the first 2 cycles of chemotherapy. RESULTS: This study recruited 140 participants and was closed early because of slow accrual. Data were analyzed for 135 of them including 66 cases in the POCRT group and 69 cases in the POCT group. Patients were followed-up for a median period of 45 months. The POCRT group had a median survival (MS) of 40 months and a 5-year overall survival (OS) rate of 37.9%. The POCT group had a MS of 28 months and a 5-year OS rate of 27.5%. The hazard ratio for death in the POCRT group was 0.69 (95% CI: 0.457-1.044, P=0.073). We observed a disease-free survival (DFS) of 28 months and a 5-year DFS rate of 30.3% in the POCRT group. Likewise, we observed a DFS of 18 months and a 5-year DFS rate of 18.8% in the POCT group. The recurrence hazard ratio in the POCT group was 1.49 (95% CI: 1.008-2.204, P=0.041). Subgroup analysis revealed that POCRT significantly increased the OS rate of the patients with ≥2 pN2 lymph nodes (P=0.021). The POCRT group had a significantly lower local relapse (P=0.009) and distant metastasis (P=0.05) rates as compared to that of the POCT group. One case died of pyemia and 9 cases suffered from grade 3 and 4 acute radiation esophagitis. The two groups had similar and tolerable hematologic toxicities. CONCLUSIONS: Compared with POCT, POCRT increased both local/regional and distant DFS rate of the patients with IIIA-pN2 NSCLC, but not the OS rate. Considering the relatively small sample size of the current study, caution should be taken when adopting the conclusions.

[A randomized controlled trial of intensity-modulated radiation therapy plus docetaxel and cisplatin versus simple intensity-modulated radiation therapy in II-III stage esophageal carcinoma].

OBJECTIVE: To compare the efficacy and toxicity of intensity- modulated radiation therapy plus chemotherapy (IMRT-TP) with simple intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced esophageal carcinoma. METHODS: A total of 170 eligible patients with locally advanced esophageal carcinoma were recruited prospectively from September 2004 to April 2008 and randomly divided into IMRT-TP group and IMRT group. Two groups were treated with IMRT of 6MV-X. The radiation dose was 60 Gy in 30 fractions in IMRT-TP group and 66 Gy in 30 fractions in IMRT group. The regimen of chemotherapy consisted of docetaxel and cisplatin in IMRT-TP group for 2 cycles. RESULTS: Of 170 patients, 160 completed the trial, including 75 patients of IMRT-TP group and 85 of IMRT group. As compared to IMRT group, total recurrence rate [69.3% (52/75) vs. 84.7% (72/85), P=0.020] and local recurrence rate [50.7% (38/75) vs. 67.1% (57/85), P=0.035] decreased in IMRT-TP group, the 5-year overall survival (29.3% vs. 15.3%, P=0.031) and 5-year recurrence free survival (24.0% vs. 10.6%, P=0.015) increased in IMRT-TP group. While severe side effect ratio increased obviously in IMRT-TP group [54.7% (41/75) vs. 4.7% (4/85), P=0.000]. CONCLUSION: As compare to simple IMRT, IMRT plus docetaxel and cisplatin can decrease the local recurrence rate, prolong the overall survival and regression-free survival, but bring more side effects.

A randomized controlled study of single-agent cisplatin and radiotherapy versus docetaxel/cisplatin and radiotherapy in high-risk early-stage cervical cancer after radical surgery.

BACKGROUND: This study explored whether docetaxel/cisplatin and radiotherapy (TP-R) increases overall survival (OS) and recurrence-free survival (RFS) compared to single-agent cisplatin and radiotherapy (C-R) in patients with high-risk early-stage cervical cancer post surgery. METHODS: Patients with clinical stage IB and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or the diameter of the primary tumor ≥4 cm and/or depth of interstitial infiltration ≥1/2 and/or lymphovascular space invasion were eligible for this study. Patients were randomized to receive C-R or TP-R. Radiotherapy in both groups was external radiation (46-54 Gy) followed by high-dose rate brachytherapy (12-24 Gy). Patients were given cisplatin (40 mg/m(2)) every week for five cycles (C-R group) or docetaxel (30 mg/m(2)) and cisplatin (30 mg/m(2)) every week for five cycles (TP-R group). RESULTS: Between 2003 and 2008, 320 patients were entered onto the study. Final analyses included 285 patients. One hundred and forty patients comprised the C-R group and 145 were in the TP-R group. The 5-year OS were 74.3 % in the C-R group and 82.8 % in the TP-R group. The hazard ratio (HR) for death was 0.65 in the TP-R group (95 % CI: 0.39-1.09, P = 0.098). The RFS were 69.3 % in the C-R group and 79.3 % in the TP-R group, and the HR for recurrence was 0.64 in the TP-R group (95 % CI: 0.40-1.03, P = 0.061). Recurrence rates were similar in both groups (27 in the C-R group and 18 in the TP-R group, P = 0.112). The seriousness of late side effects was similar in the two groups, with a higher rate of reversible hematological effects in the TP-R group. CONCLUSIONS: Compared with single-agent cisplatin and radiotherapy, docetaxel/cisplatin in combination with radiotherapy does not increase OS but has the trend of increasing RFS in patients with high-risk early-stage cervical cancer. However, docetaxel/cisplatin in combination with radiotherapy is associated with a higher incidence of side effects, this effect was reversible, and the incidence of late side effects was similar in the two treatment groups.

A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection.

BACKGROUND AND PURPOSE: The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established. In this study, we compared postoperative intensity-modulated radiotherapy plus chemotherapy (IMRT-C) with chemotherapy-only in this patient population. MATERIALS AND METHODS: We randomly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups. The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20mg of leucovorin per square meter of body-surface area per day for 5 days, followed by 45 Gy of IMRT for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT. Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group. RESULTS: The median overall survival (OS) in the chemotherapy-only group was 48 months, as compared with 58 months in the IMRT-C group; the hazard ratio for death was 1.24 (95% confidence interval, 0.94-1.65; P=0.122). IMRT-C was associated with increases in the median duration of recurrence-free survival (RFS) (36 months vs. 50 months), the hazard ratio for recurrence was 1.35 (95% confidence interval, 1.03-1.78; P=0.029). COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors. Rates of all grade adverse events were similar in the two treatment groups. CONCLUSIONS: IMRT-C improved RFS, but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer. Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection.