Association of primary, nodal and total metabolic tumor volume with response assessment and overall survival in non-surgical non-small-cell lung cancer (NSCLC) patients treated by radical chemo-radiotherapy

Objectives: Volumetric assessment of tumor on FDG PET/CT has emerged as a prognostic factor for patients with non-small-cell lung cancer (NSCLC). However, the contribution of primary and nodal volumes in response assessment and overall survival (OS) is unclear. The aim of this study was to assess whether primary (pMTV), nodal (nMTV), total metabolic tumor volume (tMTV) or their ratio (nMTV/tMTV) are associated with early post-treatment FDG PET/CT response or OS of NSCLC patients treated with radical radiotherapy (RT) or chemo-RT(CRT).

Methods: Between 2004 and 2016, three NSCLC prospective trials included patients who were treated with radical RT or CRT with baseline and post-treatment FDG-PET/CT imaging. On pre-treatment FDG PET/CT (pre-PET), using a semiautomatic gradient-based contouring algorithm, pMTV, nMTV and tMTV of the hypermetabolic lesions were contoured for each patient. For central tumors, where the primary was confluent and indistinguishable from potential adjacent lymph nodes, the entire volume was considered as pMTV. On post-treatment FDG PET/CT (post-PET) visual response criteria (Peter Mac criteria) were reported and categorized as complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD) or progressive metabolic disease (PMD). All pre-PET and post-PET imaging analyses were by consensus of two nuclear medicine physicians blinded to the clinical outcomes. The MTVs were compared between overall CMR and non-CMR using the independent samples t-test. Cox proportional hazard models and Kaplan-Meier methods were used for OS analyses. Results: Eighty-seven NSCLC patients underwent pre-PET and post-PET after radical RT (n=7) or CRT (n=80). Patients’ stage at diagnosis were 8% (7/87) stage I, 11% (10/87) stage II, 52% (45/87) stage IIIA and 29% (25/87) stage IIIB. The radiation dose was 60Gy in 97% (84/87) and 50-56Gy in 3%(3). PET-post scans were performed at a median of 89 days (range 47-123 days) after RT. Median follow-up after PET response imaging was 49 months and overall median OS was 28 months. Post-PET response assessment was prognostic for OS (HR:1.8 (1.4-2.5), p <0.001). The median pMTV, nMTV and tMTV were 17.9±58.7mL (range: 0.6-369), 5±31.6mL (range: 0-169), and 35.5±64.5mL (range: 1-392), respectively. In 22 patients the nMTV was measured zero as there was neither increased uptake in nodal stations nor distinct lymph node from the central confluent tumor. On post-PET 34% (30/87) of patients were categorized as CMR and 66% (57/87) as non-CMR. The patients with CMR had significantly lower mean pMTV and tMTV on pre-PET, 22.9mL (95% CI: 13.5-32.4) and 40.0mL (95% CI: 24.9-55.2) compared to 57.4mL (95% CI: 34.5-80.3) and 67.2mL (95% CI: 47.9-86.5) with p-value of 0.007 and 0.028, respectively. However, nMTV and nMTV/tMTV did not differ between CMR and non-CMR groups. No significant association was found between pMTV, nMTV, tMTV, nMTV/tMTV and OS. Conclusion: NSCLC patients treated with radical RT/CRT with smaller pMTV and tMTV have higher rate of CMR on early follow-up FDG PET/CT. Although delineation of pMTV from nMTV may be difficult in a subset of centrally located tumor, nodal volumetric assessment alone may not be associated with response on early follow-up PET/CT. In this study volumetric assessments are not associated with OS.