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Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies. [ABSTRACT FROM AUTHOR]

Background Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (NSCLC) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. Methods We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. Results In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; RAS/RAF/MEK, AKT/MTOR, Wnt, and NOTCH pathway activation; and overexpression of RET, ERBB2 (HER2), ERBB3, MET, and cell cycle regulators. Summary We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information. [ABSTRACT FROM AUTHOR]

Nurse navigation is a developing facet of oncology care. The concept of patient navigation was originally created in 1990 at the Harlem Hospital Center in New York City as a strategy to assist vulnerable and socially disadvantaged populations with timely access to breast cancer care. Since the mid-1990s, navigation programs have expanded to include many patient populations that require specialized management and prompt access to diagnostic and clinical resources. Advanced non-small-cell lung cancer is ideally suited for navigation to facilitate efficient assessment in this fragile patient population and to ensure timely results of molecular tests for first-line therapy with appropriately targeted agents. At the BC Cancer Agency, nurse navigator involvement with thoracic oncology triage has been demonstrated to increase the proportion of patients receiving systemic treatment, to shorten the time to delivery of systemic treatment, and to increase the rate of molecular testing and the number of patients with molecular testing results available at time of initial consultation. Insights gained through the start-up process are briefly discussed, and a framework for implementation at other institutions is outlined. [ABSTRACT FROM AUTHOR]

Background The importance of histologic classification in selecting the appropriate systemic therapy for nonsmall- cell lung cancer (nsclc) came to attention in 2007. In British Columbia, that information was communicated through international and national meetings, our centralized cancer care program, and to the medical community at large in multidisciplinary forums. We examined the effects of those education programs on the categorization of nsclc and associated systemic treatment practices. Methods The BC Cancer Agency provides cancer care to 4.6 million residents of British Columbia. A retrospective review of all stage iiib and iv nsclc patients referred in 2007 and 2011 collected baseline characteristics, treatment, and outcomes. Histology was classified using the International Classification of Diseases for Oncology, 3rd edition, for the Canadian Cancer Registry. Results In 2007, 671 patients were referred, and 170 received chemotherapy; in 2011, the relevant figures were 680 and 197 respectively. Baseline characteristics in the cohorts were not statistically significantly different in 2007 and 2011. Histologic classifications in 2007 were 41% nonsquamous, 13% squamous, and 46% not otherwise specified (nos); in 2011, they were 63%, 17%, and 20% respectively. Exposure to pemetrexed in any line of therapy in 2007 was 22% for nonsquamous, 17% for squamous, and 10% for nos; in 2011, exposure was 39%, 3%, and 37% respectively. Exposure to epidermal growth factor receptor tyrosine kinase inhibitor (egfr tki) in 2007 was 36%, 22%, and 33%; in 2011, it was 64%, 60%, and 63%. Median overall survival duration, 2007 versus 2011, was 3.25 months versus 3.57 months with best supportive care, and 11.31 months versus 11.54 months with chemotherapy. Conclusions The specificity of nsclc histologic categorization improved in 2011 compared with 2007, with a reduction of 26 percentage points in the rate of nos disease. The proportion of patients treated with chemotherapy over time remained the same, but the use of pemetrexed and egfr tki increased. The increased accuracy in histologic classification resulted in more appropriate utilization of systemic drugs. [ABSTRACT FROM AUTHOR]

Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.

(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in EGFR or HER2 were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan-Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the EGFR cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not ( p < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; p = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST ( p = 0.744). For the HER2 cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not ( p = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not ( p = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST ( p = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among HER2 ex20ins patients who received ex20ins-specific TKIs.

Background: non-small cell lung cancer (NSCLC) outcomes remain suboptimal for early-stage disease despite emerging advances in systemic therapy for the peri-operative period. Next-generation sequencing (NGS) identifies driver mutations for which targeted therapies have been developed that improve survival. The BC lung cancer screening program, which was initiated in May 2022, is expected to identify people with early and late stages of NSCLC. It is crucial to first understand the molecular epidemiology and patterns of time to initiate treatment across its five health authorities (HA) to optimize the delivery of care for NSCLC in BC. In this way, we may harness the benefits of targeted therapy for more people with NSCLC as novel advances in therapy continue to emerge. Objective: to compare (a) the frequency of actionable NSCLC molecular alterations among HAs and (b) the time to treatment initiation. Methods: a retrospective observational study was conducted with prospectively collected data from the BC CGL Database. Adults with late stage NSCLC who underwent targeted NGS were included for the time period from May 2020 to June 2021. Demographics, actionable molecular alterations, PDL-1 expression, and time to treatment across HAs were examined. Using appropriate statistical tests for comparison among HAs, p>0.05 was deemed significant. Results: 582 patients underwent NGS/IHC and analysis during the study period. The mean age was 71 (10.1), and 326 (56%) patients were female. A significantly higher proportion of all EGFRm+ were identified within Vancouver Coastal Health (VCHA) and Fraser Health Authority (FHA) compared to the other health authorities (p < 0.001). This also holds true for common sensitizing EGFRm+ alone (p < 0.001) and for sensitizing EGFRm+ when adjusted for females and smoker status (OR 0.75; 95% CI 0.62, 0.92; p = 0.005). Patients residing within the Northern, Interior, and Island HAs were less likely to receive treatment at the same rate as those in VCHA and FHA HAs. Conclusion: actionable NSCLC driver mutations are present in all regional HAs, with disparity noted in time to initiate treatment between HAs. This provides evidence for the importance of molecular testing for patients in all BC HAs to guide personalized and timely NSCLC treatment.

Background: Combined positron-emission tomography and computed tomography (pet-ct) reduces futile thoracotomy (ft) rates in patients with non-small-cell lung cancer (nsclc). We sought to identify preoperative risk factors for ft in patients staged with pet-ct., Methods: We retrospectively reviewed all patients referred to the BC Cancer Agency during 2009-2010 who underwent pet-ct and thoracotomy for nsclc. Patients with clinical N2 disease were excluded. An ft was defined as any of a benign lesion; an exploratory thoracotomy; pathologic N2 or N3, stage iiib or iv, or inoperable T3 or T4 disease; and recurrence or death within 1 year of surgery., Results: Of the 108 patients who met the inclusion criteria, ft occurred in 27. The main reason for ft was recurrence within 1 year (14 patients) and pathologic N2 disease (10 patients). On multivariate analysis, an Eastern Cooperative Oncology Group performance status greater than 1, a pet-ct positive N1 status, a primary tumour larger than 3 cm, and a period of more than 16 weeks from pet-ct to surgery were associated with ft. N2 disease that had been negative on pet-ct occurred in 21% of patients with a pet-ct positive N1 status and in 20% of patients with tumours larger than 3 cm and non-biopsy mediastinal staging only. The combination of pet-ct positive N1 status and a primary larger than 3 cm had 85% specificity, and the presence of either risk factor had 100% sensitivity, for ft attributable to N2 disease., Conclusions: To reduce ft attributable to N2 disease, tissue biopsy for mediastinal staging should be considered for patients with pet-ct positive N1 status and with tumours larger than 3 cm even with a pet-ct negative mediastinum.