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Concurrent radiotherapy and weekly chemotherapy of 5-fluorouracil and platinum agents for postoperative locoregional recurrence of oesophageal squamous cell carcinoma.

ABSTRACT: The most optimal management for postoperative locoregional recurrence of oesophageal squamous cell carcinoma is still controversial. Several studies have reported the feasibility and efficacy of concurrent chemoradiotherapy (CCRT), mostly with three-weekly or four-weekly schedule of chemotherapy. However, treatment compliance was not quite satisfactory, probably due to treatment-related toxicities. Since CCRT with weekly chemotherapy regimens have demonstrated a favorable toxicity profile as well as promising survival in certain types of cancer, we aimed to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly chemotherapy with 5-fluorouracil (5-FU) and platinum agents for patients with postoperative locoregional recurrence of oesophageal squamous cell carcinoma in our center. Twenty-seven consecutive patients who were diagnosed with postoperative locoregional recurrence of oesophageal squamous cell carcinoma and received CCRT with weekly chemotherapy of 5-FU and platinum agents were retrospectively analyzed. Our data showed that the present protocol of radiotherapy combined concurrently with weekly chemotherapy of 5-FU and platinum agents was a safe and effective salvage treatment for postoperative locoregional recurrence of oesophageal squamous cell carcinoma.

SUBMITTER: Zhang WW

PROVIDER: S-EPMC4308707 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:A phase II study was performed to investigate the safety and efficacy of weekly doses of combined paclitaxel and 5-fluorouracil (5-FU) with concurrent radiation therapy, followed by 2 cycles of consolidation chemotherapy to treat patients with advanced oesophageal carcinoma.The eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; an Eastern Cooperative Oncology Group (ECOG) score of???2; and adequate organ function. Patients received chemoradiotherapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and 5-FU (300 mg/m2) for 96 h on days 1, 8, 15, 22, and 29. The two-cycle consolidation chemotherapy protocol included paclitaxel (175 mg/m2) plus continuously infused 5-FU (1800 mg/m2) for 72 h administered on days 57 and 85, after concurrent chemoradiotherapy.Between February 2012 and August 2013, 53 patients with oesophageal carcinoma were enrolled in the study. Among these patients, 33 (62.2%) were newly diagnosed and 20 (37.7%) had postoperative local regional lymph node metastasis. The median overall survival (OS) time was 17.9 months (95% CIs?=?11.9-23.9), and the median progression-free survival (PFS) time was 12.4 months (95% CIs?=?8.6-16.1). Approximately 84.9% (45/53) and 50.9% (27/53) of the patients completed???5 cycles and all 7 cycles of chemotherapy, respectively. Approximately 86.7% (46/53) of patients completed radiation therapy. The 1-, 2-, and 3-year OS rates were 66.0%, 37.7%, and 35.8%, respectively. The 1-, 2-, and 3-year local control rates were 76.9%, 66.4%, and 66.4%, respectively. Seventeen patients (32%) experienced grade 3 or higher toxicity. Grade 3 to 5 toxicity during chemoradiotherapy included neutropaenia (7.5%), thrombocytopaenia (1.8%), fatigue (7.5%), anaemia (1.8%), dermatitis radiation (1.8%), pneumonitis (5.6%), oesophagitis (9.4%) and vomiting (3.7%).The combination of weekly doses of paclitaxel and 5-FU was well tolerated and produced comparable results among patients with locally advanced oesophageal cancer. A randomised phase III trial (NCT01591135) comparing paclitaxel plus 5-FU with cisplatin plus 5-FU is on-going at our hospital.

Project description:INTRODUCTION:In this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis. METHODS:Two comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF. RESULTS:A total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods. CONCLUSION:Our results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.

Project description:Background and purposeChemoradiotherapy is the standard treatment for moderate and advanced oesophageal cancer. The aim of this study was to establish a predictive model based on enhanced computed tomography examination, and to evaluate its clinical value for detecting locoregional recurrence-free survival (LRFS) in cases of oesophageal squamous cell carcinoma after radiotherapy.Materials and methodsIn total, 218 patients with pathologically diagnosed oesophageal squamous cell carcinoma who received radical chemoradiotherapy from July 2016 to December 2017 were collected in this study. Patients were randomly divided into either a training group (n=153) or a validation group (n=65) in a 7:3 ratio. Clinical patient information was then recorded. The enhanced computed tomography scan images of the patients were imported into 3D-slicer software (version 4.8.1), and the radiomic features were extracted by the Python programme package. In the training group, the dimensionality reduction of the radiomic features was implemented by Lasso regression, and then a radiological label, the model of predicting LRFS, was established and evaluated. To achieve a better prediction performance, the radiological label was combined with clinical risk factor information to construct a radiomics nomogram. A receiver operating characteristic curve was used to evaluate the efficacy of different models. Calibration curves were used to assess the consistency between the predicted and observed recurrence risk, and the Hosmer-Lemeshow method was used to test model fitness. The C-index evaluated the discriminating ability of the prediction model. Decision curve analysis was used to determine the clinical value of the constructed prediction model.ResultsOf the 218 patients followed up in this study, 44 patients (28.8%) in the training group and 21 patients (32.3%) in the validation group experienced recurrence. There was no difference in LRFS between the two groups (χ2 = 0.525, P=0.405). Lasso regression was used in the training group to select six significant radiomic features. The radiological label established using these six features had a satisfactory prediction performance. The C-index was 0.716 (95% CI: 0.645-0.787) in the training group and 0.718 (95% CI: 0.612-0.825) in the validation group. The radiomics nomogram, which included the radiological label and clinical risk factors, achieved a better prediction than the radiological label alone. The C-index was 0.742 (95% CI: 0.674-0.810) in the training group and 0.715 (95% CI: 0.609-0.820) in the validation group. The results of the calibration curve and decision curve analyses indicated that the radiomics nomogram was superior in predicting LRFS of oesophageal carcinoma after radiotherapy.ConclusionsA radiological label was successfully established to predict the LRFS of oesophageal squamous cell carcinoma after radiotherapy. The radiomics nomogram was complementary to the clinical prognostic features and could improve the prediction of the LRFS after radiotherapy for oesophageal cancer.

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Concurrent radiotherapy and weekly chemotherapy of 5-fluorouracil and platinum agents for postoperative locoregional recurrence of oesophageal squamous cell carcinoma.

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