Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis

SIMPLE SUMMARY: Non-small cell lung cancer (NSCLC) in stage III is often inoperable and highly heterogeneous. The primary gross tumor volume is prognostically relevant in several types of cancer, including oral carcinoma, B-cell lymphoma, and sarcoma. The planning target volume (PTV), including the primary tumor and involved lymph node stations, can vary widely, and its prognostic value for stage III is unclear. We aimed to evaluate the impact of the PTV for overall survival (OS), progression-free survival, and loco-regional control in 122 consecutive patients treated with definitive chemoradiotherapy (CRT). Median follow-up for the entire cohort was 41.2 (range: 4–108) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. In a multivariate analysis including age, gender, total radiation dose, and histology, PTV ≥ 700 ccm was found to be an independent prognostic factor for OS (hazard ratio (HR): 1.705, 95% confidence interval (CI): 1.071–2.714, p = 0.025). In conclusion, non-operable stage III NSCLC patients with PTV ≥ 700 ccm showed significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC. ABSTRACT: Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7–108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071–2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3–15.9) and 34.5 (95% CI: 25.6–43.4) months vs. 6.2 (95% CI: 3.1–9.3) (p = 0.057) and 12.7 (95% CI: 8.5–16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.