A Pan-Canadian Validation Study for the Detection of EGFR T790M Mutation Using Circulating Tumor DNA From Peripheral Blood

Introduction: Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the EGFR T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing. Methods: In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection. Baseline performance characteristics were established using known and blinded engineered plasma samples spiked with predetermined concentrations of T790M, L858R, and exon 19 deletion variants. In phase II, peripheral blood collected from local patients with known EGFR activating mutations and progressing on treatment were assayed for the presence of EGFR variants and concordance with a clinically validated test at the reference laboratory. Results: All laboratories in phase 1 detected the variants at 0.5 % and 5.0 % allele frequencies, with no false positives. In phase 2, the concordance with the reference laboratory for detection of both the primary and resistance mutation was high, with next-generation sequencing and droplet digital polymerase chain reaction exhibiting the best overall concordance. Data also suggested that the ability to detect mutations at clinically relevant limits of detection is generally not platform-specific, but rather impacted by laboratory-specific practices. Conclusions: Discrepancies among sending laboratories using the same assay suggest that laboratory-specific practices may impact performance. In addition, a negative or inconclusive ctDNA test should be followed by tumor testing when possible

COVID-19 Impact on Diagnosis and Staging of Colorectal Cancer: A Single Tertiary Canadian Oncology Center Experience

Background: Public health measures have imposed drastic reductions in cancer screening programs at the beginning of the COVID-19 pandemic, with an unknown impact on the diagnosis and staging of colorectal cancer (CRC). Methods: Newly diagnosed CRC cases at the Centre Hospitalier de l’Université de Montréal (CHUM) were divided into two groups according to the timeline: pre-pandemic (1 January 2018–12 March 2020), and pandemic (13 March 2020–30 June 2021) periods. Colonoscopy, surgery, and staging at diagnosis during the pandemic period were compared to the pre-pandemic period. Results: 254 CRC diagnoses were made during the pre-pandemic period in comparison to 125 during the pandemic period. Mean diagnosis rates were lower in the pandemic period (7.8 vs. 9.8 diagnoses/month, p = 0.048). Colonoscopy deadlines were less respected in the pandemic period (51.7% vs. 38.3%, p = 0.049). The rate of elective surgery did not differ (2.9 vs. 3.5 surgeries/month, p = 0.39) and mean delays were similar (58.6 vs. 60.4 days, p = 0.77). Stages at diagnosis did not differ (p = 0.17). Most of the delayed colonoscopies led to a stage 0 or I CRC (p = 0.2). Conclusion: In our center, the COVID-19 pandemic resulted in a decreased rate of CRC diagnosis and increased endoscopic delays without affecting the rate of advanced stage disease. Delays to surgery were quite similar once the CRC diagnosis was established

The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and their influence on the NLR in NSCLC patients treated with immunotherapy

Background: PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Patients & methods: This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method. Results: From 100 patients with known KRAS status, 50 were mutated (KRASMut). Mutation in TP53, STK11 and KEAP1 were present, and their status known in, respectively, 19/40 (47.5 %), 8/39 (20.5 %) and 4/38 (10.5 %) patients. STK11Mut and KEAP1Mut were associated with shorter overall survival when compared with wild type tumors (respectively median OS of 3.3 vs 20.4, p = 0.0001 and 10.1 vs 17.7, p = 0.24). When KRAS status was compounded with STK11/KEAP1, KRASMut trended to a better prognosis in STK11+KEAP1WT tumors (median OS 21.1 vs 15.8 for KRASWT, p = 0.15), but not for STK11+/-KEAP1Mut tumors. The NLR was strongly impacted by STK11 (6.0Mut vs 3.6WT, p = 0.014) and TP53 (3.2Mut vs 4.8WT, p = 0.048), but not by KEAP1 or KRAS mutations. Conclusion: STK11Mut and KEAP1Mut are adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11Mut but not by KEAP1Mut, suggesting differences in their resistance mechanism. In STK11-KEAP1WT tumors, KRASMut seem associated with improved survival in NSCLC patients treated with ICIs. MicroAbstract: Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19–21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer