Complication and lung function impairment prediction using perfusion and computed tomography air trapping (CLIPPCAIR): protocol for the development and validation of a novel multivariable model for the prediction of post-resection lung function

Abstract

Background: Recent advancements in computed tomography (CT) scanning and post processing have provided new means of assessing factors affecting respiratory function. For lung cancer patients requiring resection, and especially those with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), the ability to predict post-operative lung function is a crucial step in the lung cancer operability assessment. The primary objective of the CLIPPCAIR study is to use novel CT data to develop and validate an algorithm for the prediction of lung function remaining after pneumectomy/lobectomy.

Methods: Two sequential cohorts of non-small cell lung cancer patients requiring a pre-resection CT scan will be recruited at the Montpellier University Hospital, France: a test population (N=60) on which predictive models will be developed, and a further model validation population (N=100). Enrolment will occur during routine pre-surgical consults and follow-up visits will occur 1 and 6 months after pneumectomy/lobectomy. The primary outcome to be predicted is forced expiratory volume in 1 second (FEV1) six months after lung resection. The baseline CT variables that will be used to develop the primary multivariable regression model are: expiratory to inspiratory ratios of mean lung density (MLDe/i for the total lung and resected volume), the percentage of voxels attenuating at less than ‒950 HU (PVOX‒950 for the total lung and resected volume) and the ratio of iodine concentrations for the resected volume over that of the total lung. The correlation between predicted and real values will be compared to (and is expected to improve upon) that of previously published methods. Secondary analyses will include the prediction of transfer factor for carbon monoxide (TLCO) and complications in a similar fashion. The option to explore further variables as predictors of post-resection lung function or complications is kept open.

Discussion: Current methods for estimating post-resection lung function are imperfect and can add assessments (such as scintigraphy) to the pre-surgical workup. By using CT imaging data in a novel fashion, the results of the CLIPPCAIR study may not only improve such estimates, it may also simplify patient pathways.

Trial registration: Clinicaltrials.gov (NCT03885765).

Keywords: Non-small cell lung cancer; lobectomy; mean lung density; pneumectomy; respiratory function.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-214). Dr. Suehs reports grants from Astra Zeneca, outside the submitted work. Dr. Molinari reports personal fees from Astra Zeneca, grants from GSK, outside the submitted work. Dr. Bourdin reports grants, personal fees, non-financial support and other (Ad Board; participation in congress; investigator) from Astra Zeneca, grants, personal fees and other (Ad Board; participation in congress; investigator) from GSK, grants, personal fees, non-financial support and other (Ad Board; participation in congress; investigator) from Boeringher Ingelheim, personal fees, non-financial support and other (Ad Board; participation in congress; investigator) from Novartis, personal fees and other (Ad Board; investigator) from Teva, personal fees and other (Ad Board; investigator) from Regeneron, personal fees, non-financial support and other (Ad Board; participation in congress; investigator) from Chiesi Farmaceuticals, personal fees, non-financial support and other (Ad Board; participation in congress; investigator) from Actelion, other (Investigator) from Gilead, personal fees, non-financial support and other (Ad Board; investigator) from Roche, outside the submitted work.

2021 Annals of Translational Medicine. All rights reserved.

Figures

Figure 1

Separate “test” and “validation” groups will be recruited.

Figure 2

Computed tomography (CT) scan attenuation forms a gradient from less dense (darker grey) to more dense (lighter grey). Emphysema is visualized on inspiratory CT as relatively darker spots or areas, as seen on Panel A. The proportion of voxels attenuating below a given threshold (PVOX-950:

Figure 3

The visits required during the study correspond to usual care for the study population. Preliminary patient screening is discussed during weekly multidisciplinary team (MDT) meetings, and enrolment takes place during routine visits required during the pre-surgical workup to lung resection. The latter work-up requires that spirometry, a thoracic computed tomography (CT) scan and lung scintigraphy (only for high-risk patients) be performed within 30 days of surgery. Additional data will be acquired during routing follow-up visits at 1- and 6-months following surgery.