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A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in limited disease small cell lung cancer patients Accelerated
proliferation of tumor clonogens is a well-recognized cause of failure
after radiotherapy and chemotherapy in several malignancies. These
considerations stimulated us to look for time factors reflecting
both chemotherapy and radiotherapy associated accelerated proliferation of
tumor clonogens. Such factors could facilitate a more rational design of
combined modality treatment, optimizing anti-tumor effect and normal tissue
sparing. Limited disease small cell lung cancer (LD-SCLC) was chosen
because this is a rapidly growing tumor where both chemotherapy and chest
radiotherapy play a role. Only trials where platinum-based chemotherapy
was delivered concurrently with chest radiotherapy were included, as this
is at present the standard treatment. A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the SER (Start of any treatment till the End of Radiotherapy) on local tumor control, survival, and esophagitis were analyzed in our study. The
SER was the most important predictor of outcome. There
was a significantly higher 5-year survival in the shorter SER arms (RR:0.62;
95% CI: 0.49-0.80; p=0.0003) which was more than 20% when the SER
was less than 30 days (upper bound 95 % CI: 90 days).
A low SER was associated with a higher incidence of severe esophagitis (RR:0.55;
95% CI: 0.42-073; p<0.0001). Each week of extension of the SER beyond
that of the study arm with the shortest SER, resulted in an overall
absolute decrease of the 5-year survival of 1.83 % ± 0.18 % (95 % CI). In
conclusion, a low time between the first day of chemotherapy and the last day of chest
radiotherapy is associated with improved survival in LD-SCLC patients. The
parameter SER, that takes into account accelerated proliferation of
tumour clonogens during both radiotherapy and chemotherapy, may facilitate
a more rational design of combined modality treatment in rapidly
proliferating tumors.
Bibliographical reference: Dirk
De Ruysscher, Madelon Pijls-Johannesma, Søren M Bentzen, André Minken,
Rinus Wanders, Ludy Lutgens, Monique Hochstenbag, Liesbeth Boersma, Bradly
Wouters, Guido Lammering, Johan Vansteenkiste and Philippe Lambin;
"The
time between the first day of chemotherapy and the last day of chest
radiation is the most important predictor of survival in limited disease
small cell lung cancer", J Clin Oncol 2006 24:1057-1063 Anthony M. Brade and Ian F. Tannock.: "Scheduling of Radiation and Chemotherapy for Limited-Stage Small-Cell Lung Cancer: Repopulation As a Cause of Treatment Failure?", J Clin Oncol 2006 24:1020-1022
Dirk de Ruysscher Department of Radiotherapy, University Hospital Maastricht, University Maastricht, Groel en Ontwikkeling, The Netherlands
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