The evolution of Radiation Therapy Oncology Group (RTOG) protocols for nonsmall cell lung cancer.

Over the past 2 decades, the Radiation Therapy Oncology Group (RTOG) has played a significant role in clarifying the role of radiation therapy (RT) in the treatment of nonsmall cell lung cancer (NSCLC). RTOG lung cancer research has evolved over this time period through a systematic succession of investigations. For unresectable NSCLC, the dependence of local tumor control and survival on total dose of standard fractionation RT, as well as pretreatment performance characteristics, was demonstrated in initial RTOG trials. Subsequently, further radiation dose intensification was tested using altered fractionation RT to total doses up to 32% higher than standard RT to 60 Gy, given as either hyperfractionation or accelerated fractionation, while attempting to retain acceptable normal tissue toxicity. These higher doses required rethinking of established RT techniques and limitations, as well as careful surveillance of acute and late toxicity. A survival advantage was shown for hyperfractionation to 69.6 Gy, in favorable performance patients, compared to 60 Gy. Further testing of high dose standard RT will use three-dimensional, conformal techniques to minimize toxicity. RTOG further extended the theme of treatment intensification for unresectable NSCLC by evaluating combined chemotherapy (CT) and RT. Improved local control and survival was shown for induction CT followed by standard RT to 60 Gy, compared to standard RT (60 Gy) and altered fractionation RT (69.6 Gy). The intent of current studies is to optimize dose and scheduling of combined CT and standard RT, as well as combined CT and altered fractionation RT. Noncytotoxic RT adjuvants, such as hypoxic cell sensitizers, nonspecific immune stimulants, and biologic response modifiers have also been studied. Resectable NSCLC has also been an RTOG focus, with studies of preoperative and postoperative RT, CT, and CT/RT, including the prognostic value of serum and tissue factors. RTOG studies have yielded incremental improvements in treatment outcome for NSCLC, better understanding of the disease dynamics, and a strong foundation for future investigations.