PET-Plan: potential for dose escalation by target volume reduction in locally advanced NSCLC

Transl Lung Cancer Res 2020;9(4):1595-1598 | http://dx.doi. org/10.21037/atm-2020-74 The standard treatment for (inoperable) locally advanced (LA) non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT), showing improved survival over sequential chemotherapy and radiotherapy (RT) or RT alone (1). The development of intensity-modulated RT (IMRT) resulted in more conformal treatment plans than three-dimensional conformal RT (3DCRT), thus allowing for increased dose to the target while avoiding surrounding normal tissue. In addition, improvements in treatment planning systems and image-guided RT (IGRT) have contributed to more effective RT. Nevertheless, besides death from the development of distant metastases, local progression is the main issue currently resulting in poor outcomes for LA-NSCLC (2). Therefore, the effectiveness of RT is largely dependent on the accurate assessment of the localization and extend of the target volume. Thus, higher effectiveness of RT to improve local tumor control could be achieved by both reduction of the target volume and dose escalation. In May 2009, a multicenter, randomized controlled trial (RCT) was started to investigate the restriction of RT to F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) positive areas. The results of the RCT were recently presented in an article published in Lancet Oncology (March 12, 2020), entitled “Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial” (3). In this RCT called PET-Plan, a total of 205 patients were eligible for randomization between the PET-based target group, i.e., informed by F-FDG-PET alone, or the conventional target group, i.e., informed by F-FDG-PET and computed tomography (CT) in which elective nodal irradiation was applied as well, to test for non-inferiority of PET-based planning. The primary endpoint of the study was locoregional regression. Secondary endpoints included out-of-field progression, time to in-field progression, time to distant progression, overall survival (OS), progressionfree survival, acute treatment-related toxicity and late treatment-related toxicity. The rationale for this study was to generate prospective evidence for target volume reduction based on F-FDG-PET, offering potential to safe dose escalation, which might lead to improved local control without increased toxicity. Historically, elective nodal irradiation has been performed to eradicate lymph nodes that might contain micrometastases. This approach originates from before non-invasive imaging has been used for treatment planning and the benefits of elective nodal irradiation have never been proven. Locoregional recurrences are predominantly observed within the primary tumor and less frequently in the involved lymph nodes (4). Moreover, the dose distribution outside the planning target volume (PTV) might ‘accidently’ irradiate lymph nodes, therefore reducing the risk of recurrence (5). Since elective nodal irradiation Editorial Commentary