Radiotherapy Alone: Early attempts to use non-surgical treatment modalities for unresectable locally advanced disease (our stage IIIA4) involved single modality chest radiotherapy, yielding poor survivals at 5 years of 5 to 10% with traditional dose and fractionation schedules (1.8 to 2.0 Gy per fraction per day to 60 to 70 Gy in 6 to 7 weeks). Patterns of failure for patients treated with radiotherapy alone included both locoregional and distant failures. Attempts to improve on locoregional control tested alternative radiotherapy doses and schedules, applying radiotherapy at escalating doses at shortened intervals (hyperfractionation) that, in theory, would maximize cell killing in lung cancers with relatively short doubling times. A hyperfractionated, higher-dose radiotherapy trial utilized from 60.0 to 79.2 Gy, delivered in smaller-than-standard fractions administered in two fractions per day rather than one. Hyperfractionation of radiotherapy yielded an improved but still poor 2-year survival of 20%, with an apparent benefit for patients treated at 69.6 Gy. There appeared to be acceptable acute or late toxicity using the hyperfractionated schedule. add comment
Further alterations of standard dose and fractionation led to testing accelerated hyperfractionation. In the United Kingdom, three radiotherapy fractions were delivered per day in a continuous schedule (7 days rather than 5 days per week) over 12 days to a total dose of 50.4 Gy or 54 Gy. This continuous hyperfractionated accelerated radiation therapy (CHART) regimen yielded good radiographic responses in tumors with an acceptable early and late toxicity profile. In a randomized trial comparing CHART with a standard dose and fractionation radiotherapy regimen in locally advanced NSCLC, there was a survival advantage for CHART. American groups have utilized versions of CHART that eliminate the weekend doses and deliver multiple daily fractions within an 8-h time period, referred to as hyperfractionated accelerated radiation therapy (HART).