Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

Abstract

SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263–22.942, p = 0.023)). Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

Risk factors for brain metastases in locally advanced non-small cell lung cancer patients treated with radical radiotherapy

“…Increasing tumor volumes have long been thought to indicate a poor prognosis. Previous studies found that PTV and GTV had an impact on prognosis of inoperable LA-NSCLC patients ( 26 - 29 ). There were also reports that primary tumor size was associated with BM incidence ( 30 - 32 ).…”

Chemoradiotherapy Combined with Immunotherapy in Stage III Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes

“…38 studies [6, 8, 12‒47] involving 5,348 patients were included. There were 11 clinical trials and 27 real-world studies.…”

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice

“…Because RP also had a relationship with the size of the PTV, the prognostic value of the PTV might be strengthened by immune checkpoint inhibitors. In fact, a larger PTV had already related to significantly shorter PFS and extracranial DMFS after chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibitors [ 36 ]. In this study, grade 2 or higher RP on DMFS and lung V20 on PFS were significant prognostic factors.…”