Biomarker testing strategies in non-small cell lung cancer in the real-world setting: analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP)

Abstract

AimsThe aim of this study is to extend the analysis of the Lung Cancer Biomarker Testing Registry (LungPath), by analysing the techniques used in the determination of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) for the diagnostic of patients with advanced non-small-cell lung cancer (NSCLC).MethodsInformation of the technique used for the determination of EGFR, ALK, ROS1 and PD-L1 was recorded from March 2018 to January 2019 from 44 centres, but only 34 centres matched with the 38 centres previously analysed, allowing to analyse the techniques used in 8970 matched determinations of EGFR, ALK, ROS1 and PD-L1. Therefore, a by-centre analysis studied the level of implementation of the techniques in the 44 centres, while a by-determination analysis made it possible to assess the overall frequency of the techniques used on the 9134 matched samples.ResultsBy-centre analysis showed that only 46.5% and 25.6% of the centres used reflex strategies for ALK and ROS1 determination, respectively. By-determination analysis showed that 94.4% of EGFR determinations were performed by PCR, 80.7% of ALK determinations were performed by IHC with clone D5F3, while 55.7% of ROS1 determinations were performed by IHC with clone D4D6. 22C3 were the PD-L1 clone more used (43.5%) followed by SP263 clone (31.1%).ConclusionsThe real-world evidence obtained from LungPath shows the effort of Spanish hospitals in performing biomarker determination in NSCLC with different methodologies despite that next-generation sequencing (NGS) utilisation in the year of the analysis was low. Biomarker determination results could be optimised with the incorporation of sequencing methods such as NGS in pathology departments.

Prolonged response to entrectinib in an adult patient with recurrent glioblastoma harboring a GOPC::ROS1 fusion

“…Although ROS1 was negative on immunohistochemistry in our case, international guidelines recommend immunohistochemistry (IHC) as a screening method for ROS1 fusions in lung cancer 19 and this technique is usually highly concordant and less expensive than FISH. Confirmation of positive cases is recommended by a cytogenetic or molecular method.…”

“…In addition, it is important to consider that ROS1 expression without underlying rearrangement (false positives) has been described in almost one-third of tumors. 19 In gliomas, although ROS1 rearrangements can be detected by FISH, GOPC::ROS1 fusions can be difficult to detect by FISH analysis because both genes are closely located on 6q22.1 and require a specifically designed probe set to detect them. 20 Therefore, the use of molecular techniques to detect such alterations is justified.…”

Comparison between Immunocytochemistry, FISH and NGS for ALK and ROS1 Rearrangement Detection in Cytological Samples

“…NGS is a technology that requires a level of expertise that most of pathologists do not possess. A recent Spanish publication showed that IHC and FISH remain the most widely used techniques compared to NGS, with only 1 out of 44 centers using the latter [31].…”

Actionable mutational profiling in solid tumors using hybrid‐capture‐based next‐generation sequencing in a real‐world setting in Spain

“…As part of precision oncology, NGS is a technology that can allow integration of molecular tumor profiles into clinical decision‐making and have increasingly replaced conventional techniques 12,13 . However, an analysis of methods in the Central Prospective Registry of Lung Cancer Biomarkers (LungPath) of the Spanish Society of Anatomic Pathology (SEAP) showed that the level of implementation of NGS was still low and mainly single‐gene conventional tests 14,15 . In an approach recently suggested by ESMO, it will increasingly become necessary to deploy multigene testing with NGS‐based techniques for the genomic profiling of cancer 9,16 .…”

“…12,13 However, an analysis of methods in the Central Prospective Registry of Lung Cancer Biomarkers (LungPath) of the Spanish Society of Anatomic Pathology (SEAP) showed that the level of implementation of NGS was still low and mainly single-gene conventional tests. 14,15 In an approach recently suggested by ESMO, it will increasingly become necessary to deploy multigene testing with NGS-based techniques for the genomic profiling of cancer. 9,16 However, such support does not necessarily translate to equitable access to NGS within and across countries due to gaps in its implementation: varying practices in its use and access, which demonstrates different degrees of efficiency and deficiency across each European country.…”