Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: a phase II, multi-institutional clinical trial

J Thorac Cardiovasc Surg. 2014 Jan;147(1):36-44, 46.e1. doi: 10.1016/j.jtcvs.2013.08.061. Epub 2013 Oct 15.

Abstract

Objective: To determine the response rate, toxicity, and rate of complete resection after induction chemoradiotherapy for locally advanced thymic tumors, which were defined by specific radiographic criteria.

Methods: A single-arm, pilot trial was conducted at 4 institutions. Patients with thymoma or thymic carcinoma who met specific criteria on computed tomography were accrued. Induction therapy consisted of 2 cycles of cisplatin and etoposide combined with 45 Gy of thoracic radiotherapy. Patients underwent computed tomography and positron emission tomography before and after induction therapy and then resection was attempted. Postoperative chemoradiotherapy was administered in selected patients. The primary endpoint was the pathologic response to induction therapy. The secondary endpoints were toxicity, surgical complications, radiographic response, and the rate of R0 resection.

Results: A total of 22 patients were accrued during a 5-year period (1 patient withdrew before starting induction therapy). Of the 22 patients, 21 completed induction therapy, and 9 (41%) experienced grade 3 or 4 toxicity. A total of 10 patients had a partial radiographic response and 11 had stable disease. Of the 21 patients, 17 (77%) underwent an R0 resection, 3 (14%) an R1 resection, and 1 (5%) underwent debulking. Eight patients sustained surgical complications (36%), and two patients (9%) died postoperatively. Of the 21 patients, 13 (62%) had either thymic carcinoma or B3 thymoma and 15 (71%) had either Masaoka stage III or IV disease. No patient had a complete pathologic response, but 5 specimens (24%) had <10% viable tumor.

Conclusions: The present induction chemoradiotherapy protocol, which used specific computed tomography inclusion criteria to successfully select locally advanced thymic tumors, appeared to be tolerable and resulted in a high rate of complete surgical resection.

Trial registration: ClinicalTrials.gov NCT00387868.

Keywords: 13; CPR; CT; ITMIG; International Thymic Malignancy Interest Group; PET; SUV(max); WHO; World Health Organization; complete pathologic response; computed tomography; maximum standardized uptake value; positron emission tomography.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / diagnostic imaging
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / therapy*
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chemoradiotherapy, Adjuvant* / mortality
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Humans
  • Kaplan-Meier Estimate
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Neoplasm Invasiveness
  • North America
  • Pilot Projects
  • Postoperative Complications / etiology
  • Prospective Studies
  • Radiotherapy Dosage
  • Thymectomy* / adverse effects
  • Thymectomy* / mortality
  • Thymoma / diagnostic imaging
  • Thymoma / mortality
  • Thymoma / pathology
  • Thymoma / therapy*
  • Thymus Neoplasms / diagnostic imaging
  • Thymus Neoplasms / mortality
  • Thymus Neoplasms / pathology
  • Thymus Neoplasms / therapy*
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Etoposide
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT00387868