Carbon Monoxide Diffusing Capacity (DLCO) Correlates with CT Morphology after Chemo-Radio-Immunotherapy for Non-Small Cell Lung Cancer Stage III

Abstract

Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DLCO) and FEV1, which may contribute to a better understanding of radiation-induced lung disease. Methods: Eighty-five patients with NSCLC III were included. All of them received two cycles of platinum-based induction chemotherapy followed by high dose radiation. Thereafter, durvalumab was administered for one year in 63/85 patients (74%). Pulmonary function tests (PFTs) were performed three months and six months after completion of radiotherapy (RT) and compared to baseline. At the same time points, patients underwent diagnostic CT (dCT). These dCTs were matched to the planning CT (pCT) using RayStation® Model Based Segmentation and deformable image registration. Differential volumes defined by specific isodoses were generated to correlate them with the PFTs. Results: In general, significant correlations between PFTs and differential volumes were found in the mid-dose range, especially for the volume of the lungs receiving between 65% and 45% of the dose prescribed (V65−45%) and DLCO (p<0.01). This volume range predicted DLCO after RT (p-value 0.03) as well. In multivariate analysis, DLCO (p-value 0.040) and FEV1 (p-value 0.014) predicted pneumonitis. Conclusions: The current analysis revealed a strong relation between the dynamics of DLCO and CT morphology changes in the mid-dose range, which convincingly indicates the importance of routinely used PFTs in the context of a curative treatment approach.

Chemo-Radio-Immunotherapy for NSCLC III: ESR/ATS Thresholds for DLCO Correlate with Radiation Dosimetry and Pneumonitis Rate

“…While in a previous study, we correlated CT morphology changes with DL CO dynamics after RT [ 16 ], the current study shows that a clinically relevant DL CO decline > 10% is significantly correlated with a higher percentage of the differential volume V 65–45% . Figure 3 visualizes the relation between V 65–45% and a DL CO decline > 10% three months after RT (one-sided Pearson correlation coefficient = 0.143, p -value = 0.089) with the cutoff point at 5.1%.…”

“…All patients provided informed consent. The detailed selection criteria were described elsewhere [ 16 ]. In brief, patients with a suitable performance score (ECOG 0-1) were obligatorily staged with 18F-FDG-PET-CT and cranial MRI.…”

“…Based on the assumption that the anatomical substrate of CT density increase is fibrotic lung tissue that does not participate in gas exchange, we correlated DL CO and CT morphology changes in a previous analysis [ 16 ]. Dose volumes with reference to the PTV were delineated on the planning CT in 10% decrements from V 105% , which is the volume receiving at least 105% of the prescription dose, to V 5% .…”

“…In a previous publication by our group, we established a correlation between irradiated volumes and PF dynamics after high-dose radiation therapy. The volume receiving between 45% and 65% of the prescribed total radiation dose (V 65–45% ) was shown to be most prominently correlated with a DL CO decline [ 16 ]. This is in line with the notion that radiation therapy may cause pulmonary fibrosis, which secondarily leads to PF impairment.…”

Radiation-Induced Lung Injury: Prevention, Diagnostics and Therapy in the Era of the COVID-19 Pandemic

“…Concurrent systemic treatment should only be used if robust evidence through large prospective trials is established, with comorbidities such as interstitial lung disease needing to be considered to estimate the risk of RILI [ 12 ]. The longitudinal monitoring of the diffusing capacity for carbon monoxide (DLCO) after TRT could serve as an early predictive marker [ 13 ].…”