Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer-A Cost-Efficient Strategy in a Public Healthcare System.

Maisam Makarem,Doreen A Ezeife,Adam C Smith,Jennifer H Law,Ming-Sound Tsao,Janice J N Li,Natasha B Leighl

doi:10.3390/curroncol28050284

Abstract

ROS1 rearrangements are identified in 1–2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing costs and turnaround time (TAT). Eight diagnostic strategies were compared, including reflex single gene testing via immunohistochemistry (IHC) screening, fluorescence in-situ hybridization (FISH), next-generation sequencing (NGS), and biomarker-informed (EGFR/ALK/KRAS wildtype) testing initiated by pathologists and clinician-initiated strategies. Reflex IHC screening with FISH confirmation of positive cases yielded the best results for TAT, TP detection rate, and cost. IHC screening saved CAD 1,000,000 versus reflex FISH testing. NGS was the costliest reflex strategy. Biomarker-informed testing was cost-efficient but delayed TAT. Clinician-initiated testing was the least costly but resulted in long TAT and missed TP cases, highlighting the importance of reflex testing. Thus, reflex IHC screening for ROS1 with FISH confirmation provides a cost-efficient strategy with short TAT and maximizes the number of TP cases detected.

Highlights

Advances in targeted therapies in lung cancer have changed the management and subsequent disease trajectory of lung cancer patients
fluorescence in-situ hybridization (FISH) was assumed to be the gold standard for this analysis, upfront next-generation sequencing (NGS) and IHC screening with FISH confirmation yielded a high rate of TP cases
We found that reflex ROS1 testing with IHC followed by FISH confirmation in positive cases is a cost-efficient approach with a high yield of true-positive cases and favorable result turnaround time (TAT) (3 days or less for negative cases)

Summary

Introduction

Advances in targeted therapies in lung cancer have changed the management and subsequent disease trajectory of lung cancer patients. There are several genomic aberrations contributing to tumorigenesis that have shown improved patient outcomes with targeted therapy; these include mutations in EGFR, BRAF, and MET and rearrangements in ALK, NTRK, RET, and ROS1, among others [1]. ROS1 gene rearrangements are present in 1–2% of all NSCLC [2,3] and are more commonly found in adenocarcinoma, younger patients, and never-smokers [3]. Crizotinib and entrectinib have been approved for the treatment of patients with ROS1-rearranged advanced non-squamous NSCLC [4,5] and have markedly improved outcomes in this patient population [6]

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Discussion

Conclusion