Prevalence of the EGFR T790M and other resistance mutations in the Australian population and histopathological correlation in a small subset of cases.

We sought to review the prevalence of EGFR T790M and other EGFR mutations associated with either proven or probable tyrosine kinase inhibitor (TKI) resistance in the Australasian lung cancer population and to perform histopathological correlation in a subset of cases. Retrospective statistical analysis was performed on a set of targeted lung cancer gene mutation tests (FIND IT gene panel) performed at Sonic Healthcare during 2018 and early 2019. A total of 1833 lung adenocarcinoma tumour samples underwent somatic mutation testing. EGFR mutations were found in 28% (n=514) of patients, in whom 9.3% (n=48) T790M mutations were present (always combined with other EGFR mutations) and 4.8% (n=25) exon 20 insertions were found. We also compared the prevalence of EGFR mutations identified in our population with that of the four largest publicly available lung cancer cohorts (total n=576 samples). Finally, a subset of 38 samples of primary/and or metastatic lung adenocarcinomas from 23 patients, including five with serial biopsies, underwent detailed morphological analysis. No reproducible morphological correlates were found to be associated with T790M, exon 20 resistance mutations or rarer co-occurring EGFR mutations. Although this may be subject to referral bias towards patients with resistant disease, the incidence of EGFR and T790M mutations is higher in this series from an Australasian population than in other similar publicly available lung adenocarcinoma cohorts. We conclude that histopathological features cannot be used to predict the acquisition of EGFR resistance.

Assessment of Tumor-infiltrating Lymphocytes Using International TILs Working Group (ITWG) System Is a Strong Predictor of Overall Survival in Colorectal Carcinoma: A Study of 1034 Patients.

The presence of increased tumor-infiltrating lymphocytes (TILs) is established as a positive prognostic factor in many malignancies including colorectal carcinoma (CRC). However, multiple different approaches have been used to assess TILs. In 2014, the International TILs Working Group (ITWG) proposed a standardized methodology for evaluating TILs, initially in the context of breast cancer, but subsequently expanded to other malignancies. To date, the efficacy of the ITWG system has not been investigated in a large cohort of all-stage CRC. We, therefore, sought to validate this system in CRC. We used the ITWG system to assess the density of stromal TILs in an unselected cohort of 1034 CRC patients undergoing primary tumor resection at our institution. The percentage TILs' score was categorized into 3 groups: low (0% to 10%), intermediate (15% to 50%), and high (55% to 100%). The mean survival was 53, 67, and 75 months, respectively (P=0.0001). This survival benefit remained statistically significant in multivariate analyses (P=0.0001) and subgroup analyses of mismatch repair-proficient CRCs (P=0.0001), mismatch repair-deficient CRCs (P=0.031), BRAFV600E-mutant CRCs (P=0.0001), and BRAF wild-type CRCs (P=0.001). The predictive value of TILs assessed using the ITWG system was superior to the assessment of intraepithelial lymphocyte performed prospectively using a standard system requiring ≥5 lymphocytes per high-powered field in direct contact with tumor cells or between tumor clusters. We conclude that the ITWG system for assessing TILs is a powerful predictor of all-cause survival in CRC independent of many prognostic factors and superior to the assessment of intraepithelial lymphocytes using a traditional system.