The association between neighborhood-level income and cancer stage at diagnosis and survival in Alberta.

BACKGROUND: Socioeconomic status (SES) is associated with a range of health outcomes, including cancer diagnosis and survival. However, the evidence for this association is inconsistent between countries with and without single-payer health care systems. In this study, the relationships between neighborhood-level income, cancer stage at diagnosis, and cancer-specific mortality in Alberta, Canada, were evaluated. METHODS: The Alberta Cancer Registry was used to identify all primary cancer diagnoses between 2010 and 2020. Average neighborhood income was determined by linking the Canadian census to postal codes and was categorized into quintiles on the basis of income distribution in Alberta. Multivariable multinomial logistic regression was used to model the association between income quintile and stage at diagnosis, and the Fine-Gray proportional subdistribution hazards model was used to estimate the association between SES and cancer-specific mortality. RESULTS: Out of the 143,818 patients with cancer included in the study, those in lower income quintiles were significantly more likely to be diagnosed at stage III (odds ratio [OR], 1.07; 95% CI [confidence interval], 1.06-1.09) or IV (OR, 1.12; 95% CI, 1.11-1.14) after adjusting for age and sex. Lower income quintiles also had significantly worse cancer-specific survival for breast, colorectal, liver, lung, non-Hodgkin lymphoma, oral cavity, pancreas, and prostate cancers. CONCLUSIONS: Disparities were observed in cancer outcomes across neighborhood-level income groups in Alberta, which demonstrates that health inequities by SES exist in countries with single-payer health care systems. Further research is needed to better understand the underlying causes and to develop strategies to mitigate these disparities.

Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland.

PURPOSE: Early phase clinical studies are ongoing to evaluate the role of immune checkpoint inhibitors in adenoid cystic carcinoma (ACC) despite a paucity of information on the immune microenvironment. This study aims to better characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on tumour infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression. METHODS: Patient characteristics, treatment and outcome data were collected for 24 ACC patients. The CD8+(cluster of differentiation 8) TIL and PD-L1 expression were quantified by immunohistochemistry. Marker expression and survival outcomes were evaluated by Kaplan-Meier analysis. RESULTS: All cases were negative for PD-L1 expression; four cases had focal high, eight cases had focal moderate and 12 cases had low TIL expression. Based on TIL expression, there was no difference in disease-free or overall survival. CONCLUSION: Adenoid cystic carcinoma tumours were found to be associated with a poor immunogenic microenvironment, with absent PD-L1 expression and low CD8+ TILs. There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.

Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study.

Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment ≥10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov).

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship.

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual's physical and mental health. There are many factors that impact an individual's risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of 'dysbiosis' can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.

Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study.

Aims: Overall survival (OS) and updated time to treatment failure (TTF) analysis of patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer who received sequential afatinib/osimertinib in the real-world GioTag study. Patients & methods: Patients had T790M-positive disease following first-line afatinib and received osimertinib treatment (n = 203). Primary outcome was TTF. The OS analysis was exploratory. Results: Median OS was 41.3 months (90% CI: 36.8-46.3) overall and 45.7 months (90% CI: 45.3-51.5) in patients with Del19-positive tumors (n = 149); 2-year survival was 80 and 82%, respectively. Updated median TTF with afatinib and osimertinib was 28.1 months (90% CI: 26.8-30.3). Conclusion: Sequential afatinib/osimertinib was associated with encouraging OS/TTF in patients with EGFR T790M-positive non-small-cell lung cancer, especially in patients with Del19-positive tumors. Trial registration number: NCT03370770.

Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study.

AIM: To assess outcomes in patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer receiving sequential afatinib and osimertinib in a real-world clinical setting. Materials & methods: In this retrospective, observational, multicenter study, patients (n = 204) had T790M-positive disease following first-line afatinib and started osimertinib treatment ≥10 months prior to data entry. Primary outcome was time on treatment. RESULTS: Overall median time on treatment was 27.6 months (90% CI: 25.9-31.3), 30.3 months (90% CI: 27.6-44.5) in Del19-positive patients and 46.7 months (90% CI: 26.8-not reached) in Asians. The 2-year overall survival was 78.9%. CONCLUSION: In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M acquired resistance, and is a potentially attractive strategy, especially for Del19-positive tumors. TRIAL REGISTRATION NUMBER: NCT03370770.

Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.

Distress levels in patients with oropharyngeal vs. non-oropharyngeal squamous cell carcinomas of the head and neck over 1 year after diagnosis: a retrospective cohort study.

BACKGROUND: Human papillomavirus (HPV)-related cancers have been associated with different demographic profiles and disease characteristics than HPV-unrelated cancers in head and neck patients, but distress and other symptoms have not been compared. The aim of this study was to assess whether distress levels, fatigue, pain, anxiety, depression, and common psychological and practical problems differ between head and neck cancer patients with HPV-related vs. HPV-unrelated carcinomas (using oropharyngeal carcinoma (OPC) and non-OPC cancers as surrogates for HPV status). METHODS: Distress, depression, anxiety, fatigue, pain, and common problems were examined in 56 OPC and 90 non-OPC patients at 4 timepoints during the first year following diagnosis. Two-level hierarchical linear modeling was used to examine effects. RESULTS: The HPV-related OPC group was more likely to be younger (p = 0.05), Caucasian (p = 0.001), non-smokers (p = 0.01), earn more (p = 0.04), and present with more advanced stage (p < 0.0001). At baseline, OPC patients reported only higher pain scores (p = 0.01) than non-OPC patients. Total problems decreased more in the OPC group (p = 0.08) than the non-OPC group from baseline to 12-month follow-up. In both groups, scores on distress, depression, psychosocial problems, and practical problems decreased similarly over time. CONCLUSIONS: Despite a difference in the clinico-demographic characteristics of HPV-related vs. HPV-unrelated patients, only baseline pain levels and total problems over time differed between the two groups.

Evaluation of E-cadherin, ß-catenin and vimentin protein expression using quantitative immunohistochemistry in nasopharyngeal carcinoma patients.

PURPOSE: Aberrant expression of proteins involved in epithelial-to-mesenchymal transition have been described in various cancers. In this retrospective study, we sought to evaluate E-cadherin, ß-catenin and vimentin protein expression in non-metastatic nasopharyngeal (NPC) patients treated with curative intent, examine their relationship with each other, and with clinical outcome measures. METHODS: Pre-treatment formalin-fixed paraffin-embedded biopsies of 140 patients treated between January 2000 and December 2007 were assembled into a tissue microarray (TMA). Automated quantitative immunohistochemistry (AQUA®) was performed on sequential TMA sections stained with fluorescent-labeled antibodies against E-cadherin, ß-catenin and vimentin. Cox proportional hazards regression was used to estimate the effect of cytoplasmic vimentin, cytoplasmic E-cadherin, ß-catenin nuclear/cytoplasmic ratio expression on overall survival and disease-free survival. RESULTS: The average age of the patients was 51.7 years (SD=12.1; range 18-85), 66% were male, 71% had a KPS ≥ 90% at the start of treatment and 65% had stage III/IV disease. After adjusting for performance status, WHO and stage, high E-cadherin levels over the 75th percentile were found to produce a significantly increased risk for both a worse overall survival (HR = 2.53, 95% CI 1.21, 5.27) and disease free survival (DFS; HR = 2.14, 95%CI 1.28, 3.59). Vimentin levels over the first quartile produced an increased risk for a worse DFS (HR = 2.21, 95% CI 1.11, 4.38). No association was seen between ß-catenin and survival. CONCLUSION: In this cohort of NPC patients, higher levels of E-cadherin and higher levels of vimentin were associated with worse outcomes. Further work is needed to understand the role of these epithelial mesenchymal transition proteins in NPC.

Acceptability of automatic referrals to supportive and palliative care by patients living with advanced lung cancer: qualitative interviews and a co-design process.

PURPOSE: Timely access to supportive and palliative care (PC) remains a challenge. A proposed solution is to trigger an automatic referral process to PC by pre-determined clinical criteria. This study sought to co-design with patients and providers an automatic PC referral process for patients newly diagnosed with stage IV lung cancer. METHODS: In Step 1 of this work, nine one on one phone interviews were conducted with advanced lung cancer patients on their perspectives on the acceptability of phone contact by a specialist PC provider triggered by an automatic referral process. Interviews were thematically analysed. Step 2: Patient advisors, healthcare providers (oncologists, nurses from oncology and PC, clinical social worker, psychologist), and researchers were invited to join a working group to provide input on the development and implementation of the automatic referral process. The group met biweekly (virtually) over the course of six months. RESULTS: From interviews, the concept of an automatic referral process was perceived to be acceptable and beneficial for patients. Participants emphasized the need for timely support, access to peer and community resources. Using these findings, the co-design working group identified eligibility criteria for identifying newly diagnosed stage IV lung cancer patients using the cancer centre electronic health record, co-developed a telephone script for specialist PC providers, handouts on supportive care, and interview and survey guides for evaluating the implemented automatic process. CONCLUSION: A co-design process ensures stakeholders are involved in program development and implementation from the very beginning, to make outputs relevant and acceptable for stage IV lung cancer patients.

Abstracts of the 2023 Canadian Association of Medical Oncologists Annual Scientific Meeting.

On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the abstracts of the 2023 Annual Scientific Meeting. The CAMO Annual Scientific Meeting (ASM) took place on 27 April 2023 in an in-person event in Toronto, ON. Thirty-two (32) abstracts were selected for presentation as oral presentations, in-person poster presentations, and virtual poster presentations. Awards for the top four (4) abstracts were presented during the ASM; they have been marked as "Award Recipient". We congratulate all presenters on their research work and contribution.

Durvalumab-Associated Pneumonitis in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Real-World Population Study.

The PACIFIC trial led to a new standard of care for patients with locally advanced lung cancer, but real-world practice has demonstrated that immune checkpoint inhibitor (ICI) pneumonitis can lead to significant clinical complications. This study aimed to examine the clinical predictors, outcomes, and healthcare utilization data in patients who received consolidation durvalumab. Using the Alberta Immunotherapy Database, NSCLC patients who received durvalumab in Alberta, Canada, from January 2018 to December 2021 were retrospectively evaluated. We examined incidence and predictive values of severe pneumonitis, with overall survival (OS) and time-to-treatment failure (TTF) using exploratory multivariate analyses. Of 189 patients, 91% were ECOG 0-1 and 85% had a partial response from chemoradiation prior to durvalumab. Median TTF and OS were not reached; 1-year OS was 82%. An amount of 26% developed any grade of pneumonitis; 9% had ≥grade 3 pneumonitis. Male gender and a pre-existing autoimmune condition were associated with severe pneumonitis. V20 was associated with any grade of pneumonitis. Pneumonitis development was found to be an independent risk factor for worse OS (p = 0.038) and TTF (p = 0.007). Our results suggest clinical and dosimetric predictive factors of durvalumab-associated pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population.

Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as 'partial response', with 3.9% reporting 'complete response'. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients.

Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171).

Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase 2 trial (120 patients planned) comparing progression-free survival of standard platinum and pemetrexed (CP) versus CP + pembrolizumab (pembro) versus pembro. Accrual to the pembro arm was discontinued on the basis of interim analysis (IA-16 wk disease control rate). CP + pembro was tolerable, with progression-free survival similar between arms and median survival and overall response rate higher than those of CP alone (19.8 mo [95% confidence interval or CI: 8.4-41.36] versus 8.9 mo [95% CI: 5.3-12.8] and 47% [95% CI: 24%-71%] versus 19% [95% CI: 5%-42%], respectively). The subsequent phase 3 trial has completed accrual; results are expected in 2023.

TRK Inhibition with Entrectinib in Metastatic Salivary Secretory Carcinoma (SC): A Case Report.

NTRK gene fusions are rare oncogenic driver mutations that can be found in a broad range of neoplasms. In secretory carcinoma (SC), ETV6-NTRK3 gene fusion is seen in a majority of the cases and represents a druggable target for patients with advanced disease in the absence of a currently accepted standard of care. In our case, we describe a patient with recurrent, metastatic SC treated with first line entrectinib with clinically meaningful, durable ongoing response after 49 months. The patient experienced grade 1 fatigue, dysgeusia, skin sensitivity, arthralgias, an increase in serum creatinine, and weight-gain as well as grade 2 hypotension which resolved after a dose reduction. Entrectinib is a well-tolerated treatment with the potential for durable responses and TRK inhibition should be considered the standard of care in SC and other NTRK gene fusion-positive advanced neoplasms without acceptable alternative treatment options.

Abstracts of the 2022 Canadian Association of Medical Oncologists Annual Scientific Meeting.

On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the abstracts of the 2022 Annual Meeting. The CAMO Virtual Annual Scientific Meeting (ASM) took place on 28 April 2022. Twenty-five (25) abstracts were selected for presentation as oral presentations and poster presentations. Awards for the top three (3) abstracts were presented during the ASM. All of them are marked as "Award Recipient". We congratulate all the presenters on their research work and contribution.

Real-World Management and Outcomes of Crizotinib-Treated ROS1-Rearranged NSCLC: A Retrospective Canadian Cohort.

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.

The economic value of liquid biopsy for genomic profiling in advanced non-small cell lung cancer.

Background: Liquid biopsy (LB) can detect actionable genomic alterations in plasma circulating tumor circulating tumor DNA beyond tissue testing (TT) alone in advanced non-small cell lung cancer (NSCLC) patients. We estimated the cost-effectiveness of adding LB to TT in the Canadian healthcare system. Methods: A cost-effectiveness analysis was conducted using a decision analytic Markov model from the Canadian public payer (Ontario) perspective and a 2-year time horizon in patients with treatment-naïve stage IV non-squamous NSCLC and ⩽10 pack-year smoking history. LB was performed using the comprehensive genomic profiling Guardant360™ assay. Standard of care TT for each participating institution was performed. Costs and outcomes of molecular testing by LB + TT were compared to TT alone. Transition probabilities were calculated from the VALUE trial (NCT03576937). Sensitivity analyses were undertaken to assess uncertainty in the model. Results: Use of LB + TT identified actionable alterations in more patients, 68.5 versus 52.7% with TT alone. Use of the LB + TT strategy resulted in an incremental cost savings of $3065 CAD per patient (95% CI, 2195-3945) and a gain in quality-adjusted life-years of 0.02 (95% CI, 0.01-0.02) versus TT alone. More patients received chemo-immunotherapy based on TT with higher overall costs, whereas more patients received targeted therapy based on LB + TT with net cost savings. Major drivers of cost-effectiveness were drug acquisition costs and prevalence of actionable alterations. Conclusion: The addition of LB to TT as initial molecular testing of clinically selected patients with advanced NSCLC did not increase system costs and led to more patients receiving appropriate targeted therapy.

A real-world comparison of cisplatin vs cetuximab used concurrently with radiation in the treatment of locally advanced oropharyngeal carcinoma.

BACKGROUND: This population-based retrospective study compares the efficacy of cisplatin (cis-RT) vs cetuximab (cetux-RT) with concurrent radiation as definitive treatment in patients with oropharyngeal carcinoma (OPC). METHODS: Patients with OPC treated in Alberta with cis-RT or cetux-RT between 2006 and 2016 were evaluated. Median disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method. Multivariable analysis (MVA) was completed with a Cox proportional hazards model. RESULTS: Among 546 patients with OPC, 431 (78.9%) received cis-RT and 115 (21.1%) cetux-RT. Patients treated with cetux-RT were more likely to develop a recurrence after treatment compared to cis-RT (25% vs 15%, P = .01). On MVA, current smoking, human papillomavirus (HPV)-negative status, higher Charlson comorbidity index (CCI), T-stage, and cetux-RT predicted for worse DFS and OS. Outcomes in older patients with a higher CCI still favored cis-RT. CONCLUSIONS: Our data reaffirm results from randomized studies showing better survival outcomes with cis-RT compared to cetux-RT even among those who are >65 with CCI ≥3.

Abstracts of the 2021 Canadian Association of Medical Oncologists Annual Meeting.

On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the Abstracts of the 2021 Annual Meeting. The National CAMO Residents Research Day was held virtually on 1 April 2021 and the CAMO Virtual Annual Scientific Meeting (ASM) & Annual General Meeting (AGM) took place on 22 April 2021. Twenty (20) abstracts were selected for presentation as oral presentations and rapid-fire presentations. Awards for the top three (3) abstracts were presented during the ASM and AGM. All of them were marked as "Award Recipient". We congratulate all the presenters on their research work and contribution.