Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study

Abstract

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer

“…Apart from dosimetric investigations, an increase in the number of clinical trials has also demonstrated the feasibility and efficacy of the DE-IMRT technique for EC patients, with encouraging improvement in local control and well tolerated acute toxicities, although the escalated dose was slightly different. Both Yu et al and Chen et al initiated a phase II study to investigate the efficacy of radiation dose escalation using the DE-IMRT technique combined with chemotherapy, for the treatment of EC patients 11,13. The results showed a similar trend of improvement in local-regional control and overall survival, indicating that the method of theoretical evaluation could obtain results that were similar to those obtained in clinical practices.…”

“…1) Extensive publications have developed dosimetric predictors or predicting models to estimate the incidence of AET or LET in NSCLC patients; however, none of these studies have yet developed models derived from EC cases. Our group completed a phase II study, and the establishment of an esophagitis-predicting model first derived from EC patients is still ongoing 13. 2) There is no consensus on the contouring of the esophagus in EC patients.…”

“…Dose escalation using a simultaneous integrated boost (SIB) is a novel technique in which an accelerated higher dose, and a conventional lower dose can be delivered to the primary tumor and the subclinical disease simultaneously 10. Recently, an increasing number of studies have demonstrated its feasibility, efficacy, and safety for the treatment of EC patients with the combination of IMRT and dose escalation techniques 11–13. However, to the best of our knowledge, only several studies investigated the potential benefits of dose-escalated IMRT (DE-IMRT) to offer a dose escalation to the primary tumor, and improve the sparing of normal tissues compared with non-escalated IMRT (NE-IMRT) for EC patients 14–16.…”

Definitive chemoradiotherapy

“…Modern radiation techniques like IMRT and VMAT using simultaneous integrated boost radiotherapy have been shown to considerably decrease the dose to critical organs like heart and lungs (27,28). Excellent results have been reported from a phase II trial (n=60) using these technologies to administer 66 Gy in 30 fractions in combination with 2 cycles of cisplatin and 5-FU (29). Randomized trials using modern radiation techniques and escalated doses are ongoing and will hopefully clarify this issue.…”

Do We Need to Add Postoperative Radiotherapy in Patients Undergoing Trimodality Therapy for Esophageal Squamous Cell Carcinoma with Positive Lymph Nodes Disease?

“…To date, it has been reported that 7.2-18.3% of esophageal cancer patients, who received CCRT, experience late toxicities of grade 3 or greater [13][14][15]. Therefore, this study was aimed at investigating a large database of patients undergoing esophagectomy for cancer of the esophagus, esophagogastric (GE) junction, and gastric cardia after preoperative CCRT to determine the effects of positive LN in these patients and explore the benefits of PORT for survival in patients with pathologically confirmed positive LN.…”