Inflammatory non-tumor FDG uptake in the lung on early follow-up PET/CT in non-small-cell lung cancer patients treated by chemo-radiotherapy: association with response and overall survival

Objectives: Inflammatory FDG uptake in the lung (PET pneumonitis) is frequently seen during the first 6 month of radiotherapy (RT) or chemo-RT (CRT) in non-small cell lung cancer (NSCLC) patients, and its finding correlates with clinical radiation pneumonitis. The aim of this study was to assess whether PET pneumonitis on early follow-up FDG-PET/CT is associated with tumor response and overall survival (OS).

Methods: Between 2004 and 2016, three NSCLC prospective trials included patients treated with radical RT or CRT with baseline and post-treatment FDG-PET/CT imaging. For each patient, FDG-PET/CT visual response criteria (Peter Mac criteria) were categorised as complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD) or progressive metabolic disease (PMD). FDG PET pneumonitis was assessed based on the relative intensity and distribution pattern of uptake in the lung parenchyma. Based on the intensity of uptake, the following scores were defined: 1) no increased uptake, 2-4) Increased uptake above background with intensity higher than background, mediastinum, moderately above liver or markedly above liver, respectively. Patterns of PET pneumonitis were defined as: A) patchy/pleural/sub-pleural (none larger than a segment of the lung), B) diffuse (involving more than a segment and/or including the site of tumor), and C) in the peripheral distribution surrounding a photopenic region (treated tumor). Consensus was reached between two nuclear medicine physicians in all studies blinded to the clinical outcome. The association between the score, presence or pattern of PET pneumonitis and overall response (OR) or response at the primary site (PR) was tested by linear-by-linear test, Fisher exact test and Kruskal-Wallis test, respectively. Cox proportional hazard models and Kaplan-Meier methods were used in OS analyses. Results: Eighty-seven NSCLC patients underwent FDG-PET/CT before and after radical RT (n=7) or CRT (n=80). Median radiation dose was 60Gy (range: 50-60Gy). Follow-up FDG-PET/CT scans were performed at a median of 89 days (47-123) after RT. Response assessment was as follows: 34.5% (30/87) CMR, 44.8% (39/87) PMR, 1.2% (1/87) SMD and 19.5% (17/87) PMD. Early FDG-PET/CT visual response assessment was prognostic for OS (HR:1.8 (1.4-2.5), p <0.001). No increased uptake (score 1) in lung parenchyma was seen in 29% (25/87) of patients and any increased uptake (score 2-4) was noted in 71% (62/87). Frequency of patterns of PET pneumonitis was as follows: pattern A, 31% (19/62); B, 32% (20/62); and C, 37% (23/62). The proportion of patients with PET pneumonitis was 64% (11/17) in patients with PMD, 69% (27/39) in PMR and 80% (24/30) in CMR. There was no significant association between the score of PET pneumonitis and PR, OR or OS with p-value of 0.07, 0.27 and 0.84, respectively. Also, presence or pattern of PET Pneumonitis was not associated with PR, OR or OS.

Conclusions: Although PET pneumonitis is frequently present in early FDG-PET/CT after CRT for NSCLC, by careful visual assessment its presence does not interfere with response evaluation or predictive ability of follow-up FDG PET/CT and does not independently prognosticate for OS.