80IN - What is the optimal radiotherapy combined with chemotherapy for stage III disease?

Date 30 September 2012
Event ESMO Congress 2012
Session Hot topics in early stage NSCLC
Topics Non-Small-Cell Lung Cancer, Early Stage
Surgery and/or Radiotherapy of Cancer
Presenter Dirk De Ruysscher
Authors D. De Ruysscher
  • Radiation Oncology, Maastricht University Medical Centre, 6229ET - Maastricht/NL

Abstract

For most stage III (T4, N2/3) NSCLC concurrent chemo-radiotherapy is the first choice treatment. Many series used a “standard” radiotherapy schedule of 60-66 Gy in 2 Gy QD fractions, combined with cisplatin and etoposide or vinorelbin or carboplatin-paclitaxel (CP). However, local recurrences (LR) occur in 30-50 % of the patients. The observation that an improvement of local control (LC) leads to higher overall survival (OS) rates even at 5 years, has fuelled research aiming at increasing LC. Based on a phase II trial suggesting OS with 74 Gy/ 35 QD fractions over 60 Gy/ 30 QD fractions given concurrently with CP followed by two cycles adjuvant CP, and the possible beneficial effect of cetuximab as well, the RTOG embarked with the randomised phase III trial RTOG 0617. Patients were treated with weekly CP and either 60 Gy or 74 Gy in 2 Gy QD fractions, either with or without cetuximab, followed by two cycles of consolidation CP ± cetuximab. At a planned interim analysis at 11 months median follow-up and including 213 patients in the 60 Gy arm and 204 having received 74 Gy, the high-dose arm had a worse OS (20.7 months vs. 21.7 months, p = 0.02) and was closed. However, dose escalation can also be achieved by increasing biological intensification, rather than by adding fractions and thus increasing the overall treatment time. Most ongoing clinical trials on radiation dose intensification thus use individualised, accelerated iso-toxic radiotherapy (INDAR), based on organ at risk (OAR) constraints as their backbone. Obviously, much more knowledge needs to be obtained on the complex interactions between systemic treatments and radiotherapy and their effects on malignant tissues and OARs. RTOG 0617 nevertheless illustrates that with current standard radiotherapy doses and fractionation, when delivered in well selected patients and when the whole treatment chain is of high quality, much better long-term survival can be achieved than in historical series. In view of the preliminary data of RTOG 0617 and ongoing dose intensification trials, radiation dose intensification is certainly not obsolete. For standard practice, current protocols and guidelines should not be changed but emphasis on quality assessment and if needed adjustment of the entire diagnostic, treatment and supportive care process should be the main goal.

Disclosure

The author has declared no conflicts of interest.