Dose and fractionation concepts in the primary radiotherapy of non-small cell lung cancer

At present, radiotherapy alone or in combination with chemotherapy offers t he only chance of cure of medically inoperable or locally advanced unresect able non-small cell lung cancer. The radiobiological basis and clinical res ults of current dose and fractionation concepts in the primary radiotherapy of NSCLC are briefly reviewed. Whenever possible, focus is given to the re sults of randomized phase III trials. With the exception of early disease t reated to doses higher than 60 Gy, the prognosis of inoperable localized NS CLC is very poor. Local recurrence is the major cause of failure after radi ation therapy calling for intensified local treatment. Dose-escalation usin g conventional fractionation or moderate hypofractionation is promising but randomized trials are presently not available. Dose-escalated hyperfractio nation theoretically offers advantages, however, there appears currently no strong evidence from randomized trials supporting this approach in NSCLC. The highly accelerated CHART regimen significantly improved survival by 9% compared to standard radiotherapy. Nevertheless, even when treated with CHA RT, about 80% of all patients will eventually develop local recurrence and 60% distant metastases. Many trials on combined radiochemotherapy have used radiotherapy regimens that are not optimal from a current perspective. Bec ause of the high rate of both, local recurrence and distant metastases, fut ure research should be directed to further intensify radiotherapy as well a s to integrate such protocols with systemic treatment in carefully selected patients. Since toxicity is expected to increase, state-of-the-art 3D conf ormal radiation techniques need to be part of clinical trials testing such strategies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.