Definitive Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Dose and Fractionation

Abstract

Lung cancer is the leading cause of cancer-related mortality for both men and women. Among all cases, non-small cell lung cancer (NSCLC) accounts for 70-80% and almost half of the cases are considered to be locally advanced (LA) or unresectable disease at first presentation (1). Until only a decade ago, conventional fractionated radiotherapy (RT) alone applied at a dose of 60 Gy in 2 Gy fractions over 6 weeks was accepted as the standard nonsurgical treatment for these patients. However, the results were discouraging as the median survival obtained was less than a year and the 2-year survival rate did not go above 15-20% (2).After the impact of RT dose for lung cancer was established (3), a number of trials were structured in the quest for better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents.This review summarises the results of significant trials on dose and altered fractionation in the treatment of LA-NSCLC with an emphasis on possible future perspectives. The included trials were evaluated under two main titles as "Dose and Dose Escalation" and "Treatment Duration and Altered Fractionation". It should be noted that there is not always a distinct differentiation among the trials as some of the studies address both aspects. In the case of overlap, trials were grouped according to the main hypothesis which they were designed to answer. DOSE AND DOSE ESCALATIONSeveral studies have confirmed the relationship for dose and tumour response that led to an ameliorated local control and survival (Table 1).The first trial that validated the advantage of dose escalation for LA-NSCLC was the Radiation Therapy Oncology Group (RTOG) 73-01 trial, where 376 patients were randomised into four arms (2). Three arms included standard fractionation with doses of 40, 50 and 60 Gy in 2 Gy fractions and the fourth arm included a split course RT that was applied in 4 Gy fraction size to a total dose of 40 Gy over 5 weeks with a 3 week interruption in the middle. The overall 3 year intrathoracic failure rate was 33% for patients treated in the 60 Gy arm; this was significantly lower when compared to the other arms, with reDefinitive radiotherapy plays a major role in the treatment of locally advanced non-small cell lung cancer (LA NSCLC). After the impact of RT dose for lung cancer was established, a number of trials were structured with the aim of better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents. In spite of the increased number of these studies, the optimal dose or fractionation still remains to be determined. Another aspect questioned is the incorporation of these higher doses and shorter treatment times with chemotherapy or targeted agents. This review summarises the results of significant trials on d...

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