We thank Manoharan et al for their interest in our recent publication.1 Further, their recent analysis detailing the impact of FDG-PET/CT on outcomes of patients with limited-stage small cell lung cancer (LS-SCLC) in the context of the CONVERT trial (evaluating the utility of once- vs twice-daily radiation) is a helpful contribution to the literature.2 We agree that, for a number of reasons, level 1 evidence supporting the use of FDG-PET/CT in staging for SCLC is unlikely, and therefore, retrospective and longitudinal data such as our analyses are likely the best data sources.
Overall, we recommend that patients be staged as comprehensively as possible at diagnosis and that available resources be maximized to allow for the best treatment decisions for individual patients. Our analysis of a mandatory audited database of the largest integrated US health system suggests that all patients with SCLC may benefit from PET staging. In their analysis of patients enrolled on the CONVERT trial, Manoharan et al were unable to identify a significant survival difference based on FDG-PET/CT in a small cohort of patients with good performance status. It is worth noting that their study may have been underpowered to identify this difference. As they point out, retrospective studies such as theirs and ours are subject to a number of sources of bias. We note that several important factors that could contribute to bias were accounted for in our analysis as much as possible, with multivariate adjustment and multiple iterations of propensity matching. Our most stringent match included the use of treating facility in addition to year and time-based factors in an attempt to minimize bias.
Importantly in the CONVERT trial, patients staged with FDG-PET/CT had additional benefits, including lower radiation doses to critical tissues such as the lung, heart, and esophagus, which may offer alternative avenues to improved overall survival with further data maturation. Radiation doses delivered to these critical structures, particularly the heart, impacted survival outcomes in patients with non–small cell lung cancer in the landmark RTOG 0617 study.3 Manoharan et al additionally point out that a proportion of patients with low-burden metastatic disease not detected on CT but identified on FDG-PET/CT may benefit from curative intent thoracic chemoradiation. However, this contrasts with the findings of RTOG 0937, which randomized patients with extracranial oligometastatic extensive-stage SCLC to prophylactic cranial irradiation (PCI) alone versus PCI plus consolidative radiation therapy to intrathoracic and extracranial metastases after response to chemotherapy.4 This study crossed the futility boundary for survival. These patients were staged with either CT or PET/CT.
We thank Manoharan et al for their contribution and insights. We additionally anticipate the results of CALGB 30610 (ClinicalTrials.gov identifier: NCT00632853), another phase III trial randomizing patients with LS-SCLC to once- versus twice-daily radiation treatments and which encourages use of PET/CT for staging, to further contribute to this literature.
Hong JC, Boyer MJ, Spiegel DY, . Increasing PET use in small cell lung cancer: survival improvement and stage migration in the VA Central Cancer Registry. J Natl Compr Canc Netw 2019;17:127–139.
Manoharan P, Salem A, Mistry H, . 18F-fludeoxyglucose PET/CT in SCLC: analysis of the CONVERT randomized controlled trial. J Thorac Oncol 2019;14:1296–1305.
Chun SG, Hu C, Choy H, . Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol 2017;35:56–62.
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)| false . , Chun SG , Hu C , Choy H Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol 2017; 35: 56– 62. 28034064 10.1200/JCO.2016.69.1378
Gore EM, Hu C, Sun AY, . Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive-disease small cell lung cancer (ED SCLC): NRG Oncology RTOG 0937. J Thorac Oncol 2017;12:1561–1570.
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)| false . , Gore EM , Hu C , Sun AY Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive-disease small cell lung cancer (ED SCLC): NRG Oncology RTOG 0937. J Thorac Oncol 2017; 12: 1561– 1570. 10.1016/j.jtho.2017.06.015 28648948