Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma.

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535-6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.

Phase II study of preoperative concurrent chemoradiotherapy with oxaliplatin for locally advanced esophageal cancer.

BACKGROUND: We investigated preoperative concurrent chemoradiotherapy (CCRT) with oxaliplatin for locally advanced, potentially operative esophageal cancer in this Phase II study. METHODS: Between October 2009 and October 2011, 35 consecutive patients with newly diagnosed esophageal cancer clinical stage T3-4, N0-1, M0 were enrolled into this study. One dose of chemotherapy with oxaliplatin (35 mg/m2) on Day 1 and Day 2, leucovorin (200 mg/m2) on Day 1, and 5-fluorouracil [5-FU; 2400 mg/m2 intravenously (i.v.) administered continuously for 48 hours] on Day 1 was administered 2 weeks before preoperative CCRT. During preoperative CCRT, radiation dose of 4500 cGy in 25 fractions was administered to the clinical target volume and 5000 cGy to 5040 cGy in 25 fractions was administered to the gross tumor volume; chemotherapy is administered concomitantly with oxaliplatin (45 mg/m2) on Day 1 of radiation therapy (R/T) every 14 days; 5-FU (400 mg/m2 i.v. bolus for 1 hour) for 5 days on Weeks 1 and 5 of R/T. Operation was performed 4-6 weeks after preoperative CCRT. Acute toxicity profile, overall survival rate, disease-free survival rate, distant metastasis failure-free survival rate, and local recurrence rate were evaluated. RESULTS: Four patients withdrew from the study. The total number of patients in this analysis was 31. The resection rate was 64.5%. The pathologic complete response rate was 15%. The overall median survival was 19.3 months. The 5-year overall survival rate was 37.8%. The 5-year disease-free survival rate was 31.1%. The 5-year distant metastasis failure-free survival rate was 40.7% (50.56% for patients with operation; 27.2% for patients without operation, p=0.0298). The acute toxicities were mild, and no Grade 3 or above hematologic toxicity was noted. There was only one patient with Grade 3 esophagus toxicity. Grade 3 lung toxicity occurred in only three patients. CONCLUSION: Preoperative chemoradiotherapy with oxaliplatin in the treatment of locally advanced, potentially resectable esophageal cancer is feasible and safe.

Feasibility of intensity-modulated radiotherapy for esophageal cancer in definite chemoradiotherapy.

BACKGROUND: Esophageal cancer is a highly lethal malignancy, and its treatment has undergone a major evolution over the past 15 years. The objective of this study was to report our experience on the efficacy of definite chemoradiotherapy with the intensity-modulated radiotherapy (IMRT) technique in treating locally advanced esophageal cancer. METHODS: From September 2004 to November 2011, 39 patients with biopsy-proven esophageal cancer, clinical stage T1-4N0-3M0 according to the American Joint Committee on Cancer 7(th) edition were enrolled. In these enrolled cases, either the tumor was unresectable or the patients refused surgery. All patients received a total radiation dose of 40-56 Gy in 20-28 fractions using IMRT planning. Five to seven radiation beam angles were designed according to the specific shape of the clinical target volume (CTV) and were delivered by a linear accelerator with photons of 6-10 MV energy. The gross tumor volume, CTV, planning target volume, and the organs at risk were outlined, and the homogeneity index (HI) and the conformity index (CI) were calculated. The treatment-related toxicities were also reviewed. RESULTS: The mean follow-up time was 22.4 months (range, 2.0-91.0 months). The 2- and 3-year overall survival rates were 30% and 28%, respectively. The most common Grade 3/4 toxicity was hematologic toxicity (43.6%). The IMRT plans showed high-dose homogeneity to the target, with a calculated HI of 0.9. The calculated CI of 0.8 also showed high conformity treatment dose to target within an acceptable dose range. For the total lungs, the average mean dose was 1313.7 cGy. The V5 and V20 of the total lungs were 67.8% and 23.4%, respectively. For the heart, the average mean dose was 2319.2 cGy. The V30 and V35 of the heart were 30.2% and 21.5%, respectively. CONCLUSION: Concurrent chemoradiotherapy using the IMRT technique for treating locally advanced unresectable esophageal cancer is feasible, with better conformity of target volume as well as improved sparing of organs at risk.

To evaluate the treatment response of locally advanced esophageal cancer after preoperative chemoradiotherapy by FDG-PET/CT scan.

BACKGROUND: This study was designed to gauge the effectiveness of evaluation of tumor response and prognosis by positron emission tomography with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) before and after preoperative chemoradiotherapy in patients with esophageal cancer. METHODS: Forty-nine patients from October 2008 to September 2012 with locally advanced stage esophageal carcinoma, clinical stage T2-4N0-3M0, who underwent preoperative chemoradiotherapy (pre-CRT) followed by esophagectomy were enrolled in our study. All patients underwent two FDG-PET scans to compare those results with the pathologic results. Metabolic response of the primary tumor by the percentage change of the SUVmax/1 hour (ΔSUV) before and after pre-CRT (ΔSUV was calculated as the difference between pre-CRT SUVmax/1 hour and post-CRT SUVmax/1 hour divided by pre-CRT SUVmax/1 hour at esophageal tumor) was evaluated for overall survival (OS), disease free survival (DFS), local recurrence rate, and distant failure free survival (DFFS). Prognostic factors such as age, different regimen of chemotherapy, pathologic stage, FDG-PET stage, endoscopic esophageal tumor length, and ΔSUV were analyzed. The number of highly suspect malignant lymph nodes was calculated by PET when SUVmax/1 hour ≥2.5 and by surgical removal. Sensitivity and specificity of regional lymph node detection by PET were also recorded. RESULTS: Upon univariate analysis, overall survival rate was related to ΔSUV >60% (p = 0.045), pathological N stage (p = 0.001), and endoscopic total length of esophageal tumor (p = 0.005). The result of FDG-PET scan after pre-CRT had high specificity (96.7%) but low sensitivity (45.8%) in predicting the residual malignant lymph node numbers. The positive and the negative prediction rates were 44% and 96%, respectively. The result of the FDG-PET after pre-CRT showed upstaged in 16 patients (32.6%), downstaged in nine patients (18.3%), and the same stage in 24 patients (48.9%) when compared with the pathologic stage [corrected]. CONCLUSION: The change of SUVmax can be a tool for evaluating tumor response after pre-CRT. There is also a trend of good prognosis in overall survival rate when ΔSUV value is >60%.