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Comment & Response
July 3, 2019

Analysis of Pathologic Complete Response 10 Weeks After Radiotherapy—A Radiobiological Sin—In Reply

Author Affiliations
  • 1Department of Oncology, Western University, London Health Science Centre, London, Ontario, Canada
JAMA Oncol. Published online July 3, 2019. doi:10.1001/jamaoncol.2019.1901

In Reply We thank all the authors for their thoughtful comments on the Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early Stage Non–Small Cell Lung Cancer (MISSILE-NSCLC) study.1 We wish to briefly discuss some of the main points raised.

Dr Scarbrough and others suggest that 10 weeks is insufficient time for a pathologic complete response (pCR) to manifest after stereotactic ablative radiotherapy (SABR), a hypothesis we raised in our article. Perhaps the pCR rates would have been higher if we had waited longer, but in response to Dr Scarbrough’s letter, we examined the pCR rate stratified by the median time from the end of SABR to surgery (<74 vs ≥74 days), and it was 60% in both groups. Plating the cells would not be useful to establish viability because the plating efficiency of such cells is unknown; even viable lung cancer cells usually fail to generate successful cell lines.2 Dr Scarbrough cites local control rates from clinical studies, but those values are subject to bias owing to the competing risk of death from other causes and uncertainty in determining progression after SABR. In some studies,3,4 growth visible on computed tomography does not count as local failure unless confirmed by biopsy or activity greater than baseline on positron emission tomography, an approach that risks underascertainment of local failure.

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