Scheduling of Radiation and Chemotherapy for Limited-Stage Small-Cell Lung Cancer: Repopulation As a Cause of Treatment Failure?

Themeta-analystcancastabroadnettogainstatisticalpower, possibly obtaining results clouded by the combining of heterogeneous trials, or can focus on more homogeneous data, thereby sacrificingpower.Inthisissue,DeRuysscheretal 1 havechosenthe latter approach to test the plausible hypothesis that initial chemotherapy or protracted radiotherapy can trigger repopulation of surviving cells in limited-stage small-cell lung cancer (LSCLC), thus decreasing the effectiveness of treatment. Repopulation of cells in critical normal tissues between individual dose fractions of either radiotherapy or chemotherapy is important for recovery or retention of normal organ function, thereby improving tolerance to treatment. Thus, a schedule of radiotherapy administered over 6 to 7 weeks leads to less normal tissuereactionthanasimilartotaldoseadministeredoverashorter time, and the kinetics of repopulation in the bone marrow allow repetitive scheduling of cycle-active chemotherapy at approximately 3-week intervals. However, repopulation of surviving tumor cells also occurs between dose fractions of either radiation or chemotherapy and effectively decreases tumor-cell kill (Fig 1). 2,3 There is evidence in several tumor types for an increase in the rate of repopulation during the latter part of a course of radiation treatment, which is an effect long recognized as a mechanism of clinicallysignificantresistancetotreatment. 4 Therearefewdataon the role of repopulation in the longer intervals between cycles of chemotherapy, but accelerating repopulation probably occurs and can lead to clinical resistance, even if there is no change in the inherent sensitivity of the cancer cells. 2