Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2002-03-01
INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.
Abstract
Purpose
To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer.
Patients and methods
A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m(2)/24 hours for 4 days) and cisplatin (75 mg/m(2) bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive.
Results
For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less.
Conclusion
The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.
Related Questions
What dose regimen would you use to treat a patient with locally advanced esophageal SCC of the mid-esophagus who refuses chemo and surgery, agreeing only to radiation alone?
The 5Y survival of RTOG 8501’s RT alone arm was 0%. They used 64/32 Gy. So... I tend to think that RT alone is purely palliative and generally stick with 40/15 to provide palliation and hopefully some local control. 50/25 not unreasonable, but please don’t use the RT alone arm of the chemoRT vs RT s...
How do you treat localized esophageal carcinoma in patients who are unwilling or unable to undergo chemotherapy or surgery?
This is a question that comes up occasionally in clinic. My viewpoint is generally based on the prospective data that we have. Of course, the RTOG 85-01 study showed 0% long-term OS with definitive RT vs CRT. Additionally, the Intergroup 0123 study showed no evidence of improvement with higher dose...
Would you consider induction chemotherapy prior to starting chemoradiation therapy in squamous cell carcinoma of the esophagus?
Time and again, studies have shown that induction therapy for squamous cell carcinoma, seemingly regardless of primary tumor origin, probably does not improve the outcomes for patients compared to upfront chemoradiation therapy. For example in Head & Neck squamous cell cancers, the use of induction ...
What is your preferred dose for definitive radiation of squamous cell cancer of the thoracic esophagus that will be combined with chemothererapy?
We normally plan for 50.4 Gy to 59.4 Gy based on tolerance, realizing the fact that RTOG didn't show a benefit for more than 50.4 Gy. The European studies which compared triple modality to chemo RT delivered dose in 60s and, although they showed feasibility, they did report high stricture rates.
What dose do you use for definitive treatment of squamous cell carcinoma of the cervical esophagus?
Our institutional preference is to employ a total dose to 70 Gy with concurrent chemotherapy for squamous cell carcinoma of the cervical esophagus, because a local failure in would require salvage surgery with pharyngo-laryngo-esophagectomy. The role of dose escalation in squamous cell carcinomas of...