Notable variation of molecular testing in metastatic lung cancer in the Netherlands

Oncology, infection and vascular disease (English)

Chantal Kuijpers
UMC Utrecht, Pathologie
Background/objective: Adequate and timely testing for molecular alterations in non-small cell lung cancer (NSCLC) is necessary to enable treatment with tyrosine kinase inhibitors (TKI) when a certain molecular alteration is present. On a nationwide basis, we aimed to assess the performance of molecular testing for EGFR and/or KRAS mutation, and ALK and ROS-1 rearrangement in a cohort of metastatic NSCLC.

Methods: All stage IV non-squamous NSCLC with incidence year 2013 or 2015 were identified from the Netherlands Cancer Registry, and matched to the Dutch pathology registry (PALGA). Using information extracted from pathology excerpts, proportions of tumors tested for EGFR and/or KRAS mutation, ALK rearrangement, and in 2015 also for ROS-1 rearrangement within 3 months after diagnosis were determined, and variation between 48 laboratories was assessed. In a best practice session with 4 laboratories with highest testing proportions, we tried to identify a process for the best possible flow and highest possible testing proportions.

Results: In total, 6,619 tumors were included (2013: N=3,195; 2015: N=3,424). In 2013, EGFR and/or KRAS testing was performed in 73.1% (variation between laboratories 30.6-91.7%) and was significantly higher in 2015: 78.9% (40.0-91.0%). Of the EGFR/KRAS wildtype (wt) tumors, 49.5% underwent ALK testing in 2013 (6.3-100%) and 77.4% in 2015 (32.5-100%), which was significantly higher. ROS-1 testing was performed in 50.9% (0-100%) of the EGFR/KRASwt tumors from 2015. In 2015, 6 (12.5%), 7 (14.6%), and 10 (20.8%) laboratories tested significantly less often for EGFR/KRAS, ALK, and ROS-1 respectively, than the national proportion. Insufficient tumor tissue was the most stated reason for not testing (~60% of these cases had only cytological specimen(s) available), followed by inappropriate specimen. The best practice session showed that, among other, dedicated specialized professionals, good communication with short lines, and a work culture of critical openness and honesty are essential for adequate molecular testing.

Conclusion: Although testing proportions significantly increased, improvement remains possible in some laboratories/hospitals, as some patients were possibly unjustly not eligible for TKI. The percentage of ROS-1 tested tumors in 2015 was comparable to that for ALK in 2013, which implies that testing for ROS-1 follows the same curve as ALK. Results were fed back to individual laboratories, so they can improve their practice, if necessary. Initiatives will be taken to share the best practice session outcomes nationwide. Very preliminary results on 2017 data (currently ~7% of tumors analyzed) show further increases in proportions of EGFR/KRAS, ALK and ROS-1 tested tumors.
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