Curr. Oncol., Volume 26, Issue s1 (November 2019) – 7 articles

The term “real-world evidence” (rwe) describes the analysis of data that are collected beyond the context of clinical trials. The use and application of rwe have become increasingly common and relevant, especially in oncology, because there is growing recognition that randomized controlled trials (rcts) might not be sufficiently representative of the entire patient population that is affected by cancer, and that specific clinical research questions might be best addressed by real-world data. In this brief review, our main aim is to highlight the role of rwe in informing cancer care, particularly focusing on specific examples from colorectal cancer. Our hope is to illustrate the ways in which rwe can complement rcts in improving the understanding of cancer management and how rwe can facilitate cancer treatment decisions for real-world patients encountered in routine clinical care. Full article

Background: To date, the role of adjuvant systemic therapy in stages ii and iii colon cancer remains a topic of interest and debate. The objective of the present review was to assess the most recent data, specifically addressing methods of risk stratification, duration of therapy, and future directions. Methods: PubMed and medline were searched for literature pertinent to adjuvant chemotherapy in either stage ii or stage iii colorectal cancer. Summary: Locoregional disease, histopathology, age, laterality, and a number of other biologic and molecular markers appear to have a role in disease risk stratification. The duration of adjuvant therapy for stage iii disease can vary based on risk factors, but use of adjuvant therapy and duration of therapy in stage ii disease remain controversial. Future directions should include genomic assays and improved study design to provide concrete evidence about the duration of adjuvant folfox or capox and about other types of chemotherapy and immunotherapy. Full article

Significant advances in the treatment of metastatic colorectal cancer (mcrc) since the early 2000s have led to improved clinical outcomes, including overall survival (os). When fluorouracil was the sole treatment agent for mcrc, os in phase iii studies was approximately 12 months. Now, in 2019, the median os (mos) in the most recent mcrc clinical trials has been approaching 3 years. The biologic agents that target the vascular endothelial growth factor (vegf), epithelial growth factor receptor (egfr), human epidermal growth factor receptor 2 (her2), PD-1, ctla-4, ntrk, and braf pathways play important roles in the mcrc treatment algorithm, given their significant—sometimes dramatic—activity. Emerging data indicate that the choice of a specific biologic at a particular time (line of treatment) for specific patient populations (based on tumour characteristics) is critical. In the present review, we discuss the available evidence for optimal biologic sequencing in the management of mcrc. Full article

Therapeutic options for chemorefractory metastatic colorectal cancer (mcrc) have significantly expanded since 2009. The oral targeted therapies regorafenib and trifluridine/tipiracil have been established to be efficacious and safe in patients with mcrc who have progressed beyond 2 or more lines of chemotherapy. Evidence for the use of immunotherapy in a subgroup of this patient population is also encouraging, particularly in patients with mcrc that exhibits high microsatellite instability or deficient mismatch repair. Those significant advances have led to Health Canada approval of 3 novel therapeutic options for the treatment of patients with chemorefractory mcrc. However, the limited clinical efficacy of those treatments underscores the need for ongoing development of systemic therapy options for this unique cohort of patients. Here, we review the current and emerging treatment landscape for chemorefractory mcrc. Full article

Background: Total mesorectal excision (tme) is the current standard of care for the treatment of rectal cancer. However, that surgery is associated with significant morbidity and mortality. Clinicians and patients are seeking alternatives to radical resection. Currently, prevalent organ-sparing strategies under investigation include local excision and nonoperative management (nom). Methods: We reviewed the current evidence in the literature to create an overview of the use of transanal endoscopic surgery and watch-and-wait strategies in the modern management of rectal cancer. Results: Compared with radical resection, transanal endoscopic surgery in patients with early rectal cancer (cT1) having favourable histopathologic features is associated with an increased risk of local recurrence, but no difference in 5-year survival. In patients with T2 or early T3 cancer, strategies that use neoadjuvant or adjuvant therapy as adjuncts to local excision are under evaluation. Nonoperative management is a new option for patients who experience a complete clinical response after neoadjuvant chemoradiotherapy (ncrt). The selection criteria that will appropriately identify patients for whom nom will succeed are not established. Conclusions: Local excision is appropriate for early rectal cancer with favourable histopathologic features. Although organ-preserving strategies are promising, the quality of the evidence to date is insufficient to replace the current standard care in most patients. Patients should be offered nom in the safe setting of a clinical trial or registry. Rigorous follow-up, including endoscopy and imaging at frequent intervals is recommended when radical resection is forgone. Full article

Background: The incorporation of novel biomarkers into therapy selection for patients with metastatic colorectal cancer (mcrc) has significantly improved outcomes. Optimal treatment planning now takes into account diverse characteristics of patients and their tumours to create personalized therapeutic plans. Discussion: This review is split into two sections. In the first section, we review the prognostic and predictive significance of expanded RAS mutation testing, BRAF mutations, ERBB₂ (her2) amplification, microsatellite instability (msi) and deficient mismatch repair (dmmr) protein, NTRK fusions, PIK₃CA mutations, and met amplifications. The therapeutic implication of each of those biomarkers for personalizing therapies for each patient with mcrc is discussed. In the second section, we touch on testing methods and considerations of relevance to clinicians when they interpret companion diagnostics meant to guide therapy selection. The advantages and pitfalls of various methods are evaluated, and we also look at the potential of liquid biopsies and circulating tumour dna (ctdna) to change the landscape of therapeutic choice and biologic understanding of the disease. Summary: Routine testing for extended RAS, BRAF, dmmr or high msi, and NTRK fusions is necessary to determine the best sequencing of chemotherapy and biologic agents for patients with mcrc. Although next-generation sequencing and ctdna are increasingly being adopted, other techniques such as immunohistochemistry retain their relevance in detection of her2 amplification, NTRK fusions, and dmmr. Full article