Accelerated proliferation of non-small cell lung cancer cells after induction chemotherapy

Induction chemotherapy of non-small cell lung cancer (NSCLC) stage IIIB with gemcitabine and cisplatin for downstaging the tumour with the aim for further treatment with ionising radiation, is one of the treatments for lung cancer employed. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, i.e. the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth. Interval times between end of chemotherapy and day of diagnostic CT, planning CT and first day of radiotherapy were determined. Increase in tumour volume was measured for 23 patients with NSCLC by measuring the primary tumour dimensions on the diagnostic CT made after induction chemotherapy and on the CT used for radiotherapy planning. Volume doubling times were calculated from the time interval between the two CTs and ratio of the volumes on CT planning and CT diagnostic. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, till CT planning 66 days and till first day of radiotherapy 76 (29 - 108) days. Tumour doubling times ranged from 9 to 153 days with a mean of 47 days. This is far less than the mean doubling time of NSCL in untreated patients. This study shows that time interval between chemo- and start of radiotherapy varies between 29 to 108 days. The consequence is fast tumour progression as result of accelerated proliferation: mean tumour-doubling times are decreased by a factor of 2 to 4. The gain obtained with induction chemotherapy with regard to volume reduction was practically lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo- and radiotherapy to as short as possible