Is clinical target volume necessary?-a failure pattern analysis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy using intensity-modulated radiotherapy technique

Background: Our previous dosimetric study showed that for locally advanced non-small cell lung cancer (LA-NSCLC), radiotherapy with intensity-modulated radiotherapy (IMRT) technique could deliver sufficient dose coverage to subclinical regions and reduce the dose to normal tissues with the omission of clinical target volume (CTV). To further clinically validate this strategy, we conducted the current study to analyze the failure pattern for patients with LA-NSCLC treated with concurrent chemotherapy and CTV-omitted IMRT. We also investigated the effects of target volumes on lymphopenia during radiotherapy to further test the potential benefits of CTV omission in anti-tumor immunotherapy. Methods: A total of 63 patients with LA-NSCLC treated with CTV-omitted IMRT with concurrent chemotherapy were enrolled in this study. Their planning target volume (PTV) (also PTV-g) was expanded directly from gross tumor volume (GTV). A virtual CTV was expanded from GTV, and the PTV generated from virtual CTV was named planning target volume with CTV expansion (PTV-c). Treatment failures were divided into local, regional, and distant failures, and local-regional recurrences were classified into inside PTV-g (IN-PTV-g), between PTV-g and PTV-c (PTV-g-c), and outside PTV-c (OUT-PTV-c). The relationship between lymphopenia during radiotherapy and the target volumes was also evaluated using Spearman's correlation analysis. Results: Among the 60 patients with detailed follow-up data for recurrences, 46 (76.7%) experienced recurrences, with 18 (30.0%) being local recurrence, 5 (8.4%) being regional failure, and 33 (55.0%) being distant failure. For the 21 patients with local-regional recurrences, 16, 6, and 1 were IN-PTV-g, OUTPTV-c, and PTV-g-c recurrences, respectively. Lymphopenia during radiotherapy was associated with both GTV and PTV, with larger volumes linked to severe lymphopenia. Conclusions: CTV omission is feasible for LA-NSCLC treated with concurrent chemoradiotherapy and does not compromise failure inside the subclinical region. The radiation volumes were associated with lymphopenia during radiotherapy, with larger volumes related to severe lymphopenia. This finding supports the further exploration of CTV omission for immunotherapy.