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.

The clinical utility of baseline cardiac assessments prior to adjuvant anthracycline chemotherapy in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Cardiac assessment with multi-gated acquisition scan (MUGA) or echocardiography (ECHO) is commonly employed prior to adjuvant anthracycline-based chemotherapy (AA). However, the clinical utility of routine baseline cardiac assessments prior to AA for early-stage breast cancer (EBC) is unknown. OBJECTIVES: To determine: (i) the clinical utility of routine baseline cardiac assessments prior to AA for EBC and (ii) identify patients in whom baseline cardiac assessments may not be warranted. METHODS: A systematic review of the literature was conducted to identify all relevant studies that met predefined criteria. The clinical utility was defined by: (i) the rates of abnormal baseline left ventricular ejection fraction (LVEF) and (ii) the rates of change in chemotherapy decisions prompted by baseline LVEF results. RESULTS: Eight studies met our criteria, of whom six (n = 2545) reported rates of abnormal LVEF and six (n = 1713) reported rates of change in chemotherapy decision. Overall, 2.5% (95% CI 2.0-4.0%) of patients had abnormal baseline LVEF and 1.6% (95% CI 1.0-3.0%) had a change in chemotherapy decision. In subset analyses, the underlying imaging modality (ECHO vs. MUGA) or inclusion of patients with metastatic disease (YES vs. NO) did not significantly affect these rates. There were no consistently identified underlying predictors of abnormal baseline LVEF across studies. CONCLUSIONS: Routine baseline cardiac assessments prior to AA in all EBC patients have low yield and infrequently affect clinical management. Future studies should further examine potential predictors of abnormal cardiac functions in an attempt to identify low risk patients in whom routine baseline LVEF assessment may not be warranted and prevent delay in chemotherapy administration.

Trastuzumab beyond progression for HER2 positive metastatic breast cancer: progression-free survival on first-line therapy predicts overall survival impact.

Trastuzumab beyond first progression in the metastatic setting has been adopted based on limited data suggesting improved outcomes compared to second-line chemotherapy alone although predictive factors for preferential benefit remain elusive. We conducted a retrospective review of all patients receiving trastuzumab for HER2 + metastatic disease between Jan 1, 1999-June 15, 2011. Univariate and time to event analyses described treatment and survival patterns. Median duration of each line of therapy and overall survival times for covariates, including treatment era (pre versus post Jan 1, 2005), lines of trastuzumab-based therapy (1 versus 2 versus 3 + ), first-line chemotherapy partner (docetaxel/paclitaxel versus other) and median exposure to first-line trastuzumab-based therapy (=/> versus < cohort median) were estimated. A total of 119 patients received a median of two lines of trastuzumab-based therapy (range 1-8). Median overall survival was 21.8 months (95% CI = 14.5-27.1 m), by era was 15.6 m (95% CI = 9.7-24.8 m) versus 26.1 m (95% CI = 20.0-39.3 m; p = 0.11) and by lines of trastuzumab-based therapy received was 10.6 m (95% CI = 5.3-17.4 m) versus 13.9 m (95% CI = 9.5-27.6 m) versus 32.5 m (95% CI = 25-49.4 m) (p = 0.0014). Median overall survival was significantly longer for those receiving taxanes with trastuzumab compared to other first line partners (26.1 m, 95% CI = 17.8-31.4 m versus 14.5 m, 95% CI = 9.4-21.9 m, p = 0.02). Median overall survival with duration of first-line trastuzumab-based therapy =/> cohort median was 31.9 m (95% CI = 26.2-52.2 m) versus 10.3 m for shorter durations (95% CI = 6.9-15.6 m; p < 0.0001). Our observations support progression-free survival on first-line trastuzumab-based therapy as a clinically relevant predictive factor for overall survival benefit with the adoption of a trastuzumab beyond progression treatment strategy.

Trastuzumab for HER2-Positive Metastatic Breast Cancer: Clinical and Economic Considerations.

Trastuzumab is a recombinant humanized monoclonal antibody that selectively targets the extra-cellular domain of the HER2 receptor. It was approved by the FDA in September 1998 as the first targeted therapy for HER2-positive metastatic breast cancer, and has since led to significant improvements in the overall prognosis for patients with HER2-positive metastatic disease. The favourable benefit/risk profile associated with palliative trastuzumab has been demonstrated in a number of clinical trials that examined trastusumab as monotherapy or in combination with chemotherapy, endocrine therapy and other HER2 targeted agents. The clinical benefits of trastuzumab, however should also be examined within the context of its significant drug acquisition costs. This review highlights the significant findings from the landmark clinical trials of trastuzumab for metastatic HER2-positive breast cancer, and the potential "value for money" associated with its use in clinical practice.

Routine cardiac evaluation in patients with early-stage breast cancer before adjuvant chemotherapy.

INTRODUCTION: This population-based study of women diagnosed with early-stage breast cancer aimed to (i) determine the current utilization pattern of multigated acquisition (MUGA) scans before adjuvant chemotherapy (AdjC) treatment, and (ii) examine the impact of MUGA scan results on AdjC decision making. METHODS: All women who underwent curative-intent surgery for stage I-III breast cancer between October 2005 and September 2006 in Nova Scotia, Canada, were identified through the provincial cancer registry. A retrospective chart review was performed to abstract all relevant clinical-pathologic variables, including baseline cardiac risk factors. The association between MUGA scan utilization and clinical-pathologic variables, as well as receipt and type of AdjC, was examined through univariate and multivariate analyses. RESULTS: The study included 593 women, of whom 238 (40%) received AdjC (94% anthracycline vs. 6% nonanthracycline) and 198 (33%) underwent baseline MUGA scans. Of those received AdjC, 80% underwent MUGA scans. MUGA scan utilization was associated with AdjC treatment (yes vs. no; P < .0001), Her-2/neu status (positive vs. negative vs. not tested; P < .0001), and AdjC regimen (anthracycline vs. nonanthracycline; P < .0001). Abnormal MUGA results were observed in 5 (2.5%) of 198; all were smokers, and 4 were >65 years of age. In the 1 patient <50 years old, subsequent echocardiograms indicated normal cardiac function. CONCLUSIONS: Routine baseline MUGA scans before AdjC were abnormal and changed the AdjC treatment decision in only 2.5% and 2.0% of patients, respectively. Routine MUGA scans before anthracycline-based AdjC without trastuzumab, however, did not influence AdjC decisions for younger patients <65 years of age without underlying cardiac risk factors.

Review of nasopharyngeal carcinoma.

We review the literature on nasopharyngeal carcinoma that has been published within the past 5 years. Nasopharyngeal carcinoma is a highly morbid disease, and survival is poor. Its management remains extremely difficult, not just for otolaryngologists but for radiation oncologists and medical oncologists, as well. A clear understanding of its etiology is still lacking, but nasopharyngeal carcinoma is widely suspected to be the result of both a genetic susceptibility and exposure to environmental factors or Epstein-Barr virus infection. With no clear cause, treatment is controversial. For example, an optimal radiation regimen has not been determined, reports in the literature regarding the role of chemotherapy for advanced disease are conflicting, and treatment of local recurrences is unsettled. Still, advances in immunologic research and chemotherapy offer hope for better control of the disease. We hope that our assessment of the recent literature will provide otolaryngologists with a more clear understanding of the etiology and management of nasopharyngeal carcinoma.