Association of Target Volume Margins with Locoregional Control and Acute Toxicities for Non-Small Cell Lung Cancer Treated with Concurrent Chemoradiation Therapy

Abstract

To investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy. We reviewed records of 82 patients with inoperable NSCLC treated from 2009–2016 with concurrent chemoradiation. All patients received positron emission tomography-based treatment planning, 4-dimensional computed tomography simulation to define an internal target volume, and daily cone beam computed tomography. We quantified variations in target volume margins with a margin deviation index (MDI), calculated as the percentage change in equivalent uniform dose between the original planning target volume (PTV) and a standard reference PTV 10mm beyond the original gross tumor volume (GTV), consistent with the minimum margins mandated by recent NSCLC trials. Greater MDIs equated to smaller effective target volume margins. We dichotomized patients by the upper tercile MDI value (5.8%). Endpoints included time to locoregional progression and time to grade ≥3 radiation esophagitis (RE3) or radiation pneumonitis (RP3), modelled with the Fine-Gray method. Median follow-up was 37.8 months (range, 5.9–58.1 months). Larger MDIs correlated with smaller clinical target volume (CTV)+PTV margins, larger GTVs, later treatment year, and intensity-modulated radiation therapy use. The risk of locoregional progression did not differ for MDI ≥5.8% versus <5.8% (aHR 0.88, P =.76), while the risk of RE3 or RP3 was decreased for MDI ≥5.8% (aHR 0.27, P =.027). Patients with MDI ≥5.8% were treated with smaller CTV+PTV margins (median, 5.6mm versus 8mm, P <.0001) and a marginally lower volume of esophagus receiving ≥50 Gy (median, 31.1% versus 35.3%, P =.069). Smaller margins were used for larger tumors, yet were not associated with an increase in locoregional failures. Additional studies could clarify whether smaller margins, when used alongside modern radiotherapy techniques, decrease treatment-related toxicity for inoperable NSCLC.