[Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma].

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.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

[Study on safety of adjuvant radiotherapy concurrent with weekly chemotherapy for stage â ¡B-â £A esophageal carcinoma after radical resection].

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions: Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

[The value of the planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of esophageal squamous cell carcinoma].

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions: The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

[Prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in locally advanced non-small cell lung cancer patients treated with thoracic radiation].

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions: Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient's condition and treatment which needs further research.

[A prospective pilot study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas].

Objective: To carry out a prospective cohort study of combined intra-operative radiotherapy for centrally located hepatocellular carcinomas (HCC) and to observe the safety and postoperative complications. Methods: A total of 79 patients with centrally located HCC who underwent hepatectomy were divided into two groups: experimental group (combined with targeted intra-operative radiotherapy, 32 cases) and control group (single surgical operation, 47 cases). Patients in the experimental group received intra-operative electron radiotherapy after tumor resection, while patients in the control group received to intra-operative electron radiotherapy.The haemorrhagia amount and operation time during the operation, intra-operative liver function and the recovery of liver and gastrointestinal tract of patients in these two groups were compared. Results: No postoperative 30-day mortality was observed in all of the patients. The average total operation time of patients in the experimental group was (319±76) min, significantly longer than (233±76) min of the control group (P<0.001). The average aspartate transaminase (AST) level of patients in the experimental group at postoperative day 1 was 562.5 U/L, significantly higher than 347.0 U/L of control group (P=0.031). However, the average prothrombin activity levels of patients in the experimental group at postoperative day 3 and day 7 were (68.3±17.9)% and (73.4±10.2)%, respectively, significantly lower than (78.9±15.9)% and (80.0±10.6)% of control group (both P<0.05). There were no significant differences of tumor volume, differentiation degree, satellite lesion, dorsal membrane invasion, microvascular invasion between these two groups (all P>0.05). There were no significant differences of hospital stay, ventilation time, the incidence of hepatic insufficiency, ascites, pleural effusion, infection, biliary fistula between these two groups (all P>0.05). There were no significant differences of alanine aminotransferase (ALT), albumin, total bilirubin between these two groups at postoperative day 1, 3, 5 and 7 (all of P>0.05). Conclusion: The resection of centrally located HCC combined with intra-operative radiotherapy may increase the total operation time, delay the early postoperative recovery of liver function, but it is still safe and feasible. Trial registration: National Cancer Centre /Cancer Hospital, Chinese Academy of Medical Sciences, ChiCTR-TRC-12002802.

[IMRT-based preoperative neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma (ESCC): an analysis of outcome and prognosis].

OBJECTIVE: To analyze the outcome and prognostic factors of IMRT-based preoperative neoadjuvant chemoradiotherapy in patients with thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 62 patients with thoracic ESCC who received IMRT-based neoajuvant chemoradiotherapy from January 2009 to January 2015 were retrospectively analyzed. The radiation therapy was given 1.8-2 Gy/fraction per day over 5 days per week with 6 MV X-rays, and then all patients underwent esophagectomy and lymphadenectomy. RESULTS: Among the 62 patients, the R0 resection rate was 96.8%. Twenty (32.3%) patients achieved pCR and 56 (90.3%) cases got down-staging. Grade Ⅲ marrow suppression and esophagitis were seen in 8 (12.9%) and 2 (3.2%) patients, respectively. Eleven (17.7%) patients experienced postoperative complications and three died. The median follow-up was 27 months. The 1-, 3- and 5-year overall survival rates were 88.0%, 63.3% and 44.2%, respectively, with a corresponding disease-free survival rate of 68.1%, 54.8%, and 43.9%, respectively.The univariate analysis showed that pre-treatment stage Ⅱ, down-staging, T/N pCR, good tumor response to neoadjuvant chemoradiotherapy, pN0 and R0 resection were favorable prognostic factors (P<0.05). The multivariate analyses indicated that pre-treatment stage was an independent prognostic factor. CONCLUSIONS: For patients with thoracic ESCC, IMRT-based neoadjuvant chemoradiotherapy followed by surgery can achieve a higher R0 resection rate, down-staging rate, higher pCR rate, and a better tolerance. The incidence of postoperative complications is low. Pre-treatment stage, down-staging, pathological tumor response, lymph node status and R0 resection results are prognostic factors, and the pre-treatment stage is an independent prognostic factor.

[Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

OBJECTIVE: This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). METHODS: Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). RESULTS: A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. CONCLUSIONS: Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

Radiation-induced hypoxia may perpetuate late normal tissue injury.

PURPOSE: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. METHODS AND MATERIALS: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. RESULTS: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-beta, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. CONCLUSION: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines.

A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.

PURPOSE: To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery. MATERIALS AND METHODS: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients. RESULTS: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases. CONCLUSION: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.