Rechallenge Strategy in Cancer Therapy.

Drug resistance is one of the most important factors limiting the success of systemic anticancer therapy in achieving cure or prolonged overall survival. In clinical practice, resistant disease describes cancer that is found to have progressed since the time of treatment initiation. The term "drug resistant" is often used synonymously with "progressive disease" when referring to a treated tumour. Stopping a treatment at the time of disease progression is the current dominant approach of clinical trial conduct; therefore, available data from clinical trials are routinely not able to provide any information that could challenge this concept of permanent drug resistance. However, drug rechallenge and treatment continuation beyond progression have emerged as potential strategies in the past decade, especially for molecularly targeted agents and immunotherapy. In this review we focussed on rechallenge strategies for chemotherapy, immune therapy and targeted therapy in the main types of cancer.

Patterns of recurrence following selective intraoperative radiofrequency ablation as an adjunct to hepatic resection for colorectal liver metastases.

BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze the patterns of recurrence following intraoperative radiofrequency ablation (RFA) combined with hepatic resection for patients with colorectal liver metastases (CLM). METHODS: Patients undergoing liver resection (with or without RFA) for CLM were examined. Rates and patterns of disease recurrence, as well as overall survival were assessed using Kaplan-Meier and Cox analyses. RESULTS: A total of 174 patients underwent liver resection for CLM (150 without and 24 with intraoperative RFA). RFA was used to treat 41 tumors (median 1.6 cm). The 3-year overall survival was 65.5% and 61.4% (adjusted HR 1.02, 95% CI 0.55-1.88). Median recurrence-free survival was 7.4 versus 12.7 months with RFA versus non-RFA, respectively (adjusted HR 1.51, 95% CI 0.94-4.42). On multivariate analysis, neither survival nor recurrence-free survival was significantly associated with RFA. In total, there were two RFA ablation zone local failures. An ablation site recurrence was the sole site in one patient (4.2%). CONCLUSION: RFA was used as an adjunct to resection in patients with greater disease burden. Despite this, RFA was not significantly associated with a higher risk of local failure and was not associated with worse survival, when compared with liver resection alone.

Virtual Care for Patients with Advanced Well Differentiated Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET).

INTRODUCTION: The COVID-19 pandemic resulted in an unprecedent shift towards virtual cancer care, including the care of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aim of this study was to evaluate the use of virtual care for GEP-NETs during the COVID-19 pandemic at a high-volume academic cancer center. METHODS: This retrospective, observational study performed at the Ottawa Hospital Cancer Center in Canada evaluated adult patients with GEP-NETs seen in consultation by medical oncology between 1 June 2019 and 31 December 2022. Demographic, clinicopathologic, cancer treatment and visit data were collected. Univariable and multivariable analyses assessed the relationship between patient characteristics and virtual care use. RESULTS: A total of 103 patients with well-differentiated GEP-NETS were included. Overall, 18/103 (17.5%) consults and 594/781 (76.1%) follow-ups were performed virtually. All consultation visits returned to in-person assessment by 2022, while 67.0% and 41.4% follow-ups remained virtual in 2022 and 2023, respectively. The year of follow-up, sex, employment and Charlston comorbidity index were associated with virtual follow-up use in the multivariable analysis. DISCUSSION: Virtual care remained a predominant method of GEP-NET patient assessment in the peri-pandemic period. These results highlight an opportunity to improve access to subspecialty neuroendocrine cancer care through the continued use of virtual care.

Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms.

High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.

Models of Follow-Up Care and Secondary Prevention Measures for Survivors of Colorectal Cancer: Evidence-Based Guidelines and Systematic Review.

OBJECTIVE: To provide recommendations for preferred models of follow-up care for stage I-IV colorectal (CRC) cancer survivors in Ontario; to identify signs and symptoms of potential recurrence and when to investigate; and to evaluate patient information and support needs during the post-treatment survivorship period. METHODS: Consistent with the Program in Evidence-Based Medicine's standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases were systematically searched. The authors drafted recommendations and revised them based on the comments from internal and external reviewers. RESULTS: Four guidelines, three systematic reviews, three randomized controlled trials, and three cohort studies provided evidence to develop recommendations. CONCLUSIONS: Colorectal cancer follow-up care is complex and requires multidisciplinary, coordinated care delivered by the cancer specialist, primary care provider, and allied health professionals. While there is limited evidence to support a shared care model for follow-up, this approach is deemed to be best suited to meet patient needs; however, the roles and responsibilities of care providers need to be clearly defined, and patients need to know when and how to contact them. Although there is insufficient evidence to recommend any individual or combination of signs or symptoms as strong predictor(s) of recurrence, patients should be educated about these and know which care provider to contact if they develop any new or concerning symptoms. Psychosocial support and empathetic, effective, and coordinated communication are most valued by patients for their post-treatment follow-up care. Continuing professional education should emphasize the importance of communication skills and coordination of communication between the patient, family, and healthcare providers.

An Evidence-Based Guideline for Surveillance of Patients after Curative Treatment for Colon and Rectal Cancer.

OBJECTIVE: To provide recommendations for a surveillance regimen that leads to the largest overall survival benefit for patients after curative treatment for Stage I-IV colon and rectal cancer. METHODS: Consistent with the Program in Evidence-Based Care's standard approach, guideline databases, i.e., MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO, were systematically searched. Then, we drafted recommendations and methodology experts performed an internal review of the resulting draft recommendations, which was followed by an external review by targeted experts and intended users. RESULTS: Four systematic reviews and two randomized controlled trials were identified that provided evidence for recommendations. CONCLUSIONS: For patients with stage I-III colon cancer, a medical history and physical examination should be performed every six months for three years; computed tomography (CT) of the chest-abdomen-pelvis (CT CAP) should be performed at one and three years, or one CT CAP could be performed at 18 months; the use of carcinoembryonic antigen (CEA) is optional if CT imaging is being performed; and surveillance colonoscopy should be performed one year after the initial surgery. The frequency of subsequent surveillance colonoscopy should be dictated by previous findings, but generally, colonoscopies should be performed every five years if the findings are normal. There was insufficient evidence to support these recommendations for patients with rectal cancer, Stage IV colon cancer, and patients over the age of 75 years. Patients should be informed of current recommendations and the treating physician should discuss the specific risks and benefits of each recommendation with their patients.

Intervention Development Process for a Pragmatic Randomized Controlled Trial: The Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial.

BACKGROUND: Use of complementary therapies is high among people with cancer despite research gaps. The Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial will evaluate the impact of an integrative care intervention delivered by naturopathic doctors (NDs) in conjunction with usual care for patients undergoing surgery for lung, gastric, and esophageal cancer. OBJECTIVES: To describe the multistep, multidisciplinary process of defining the integrative care intervention to be used in the Thoracic POISE trial using a principle-based approach that is pragmatic, holistic, safe, feasible, evidence driven, and consensus based. METHODS: An Intervention Development Committee (IDC) made up of a multidisciplinary team of health care providers (NDs, surgeons, oncologists, nurses, dietitians, physiotherapists, pharmacists, and psychologists), researchers, and patients was established to oversee the process. Potential intervention components were identified through a clinical practice survey and expert opinion. Systematic literature reviews were conducted and scores assigned based on the following criteria: usage, safety, goals, feasibility/scalability, and evidence. The IDC selected an intervention to be piloted that consists of a standard palette including core and optional components. Safety, known risks, and interactions with pharmaceuticals were evaluated using industry and professional monographs, a scoping literature review, and consultations with hospital pharmacists. RESULTS: The clinical practice survey and expert opinion identified 28 components for consideration. Following literature reviews, scoring, consensus from the IDC, and safety and interaction considerations, an intervention palette consisting of core and optional components was defined. The intervention options vary based on the patient's phase of treatment and symptom-specific needs. The intervention includes supplements, physical recommendations (exercise), nutritional counseling, and psychological support (audio scripts). CONCLUSION: Through a multistep, multidisciplinary process an integrative care intervention was developed for the Thoracic POISE trial. The intervention will be piloted in a single-arm feasibility study, followed by a single-center randomized controlled trial (RCT), and finally a multicenter RCT.

Ottawa Hospital Patient Safety Study: incidence and timing of adverse events in patients admitted to a Canadian teaching hospital.

BACKGROUND: Adverse events are poor patient outcomes that are due to medical care. Studies of hospital patients have demonstrated that adverse events are common, but few data describe the timing of them in relation to hospital admission. We evaluated characteristics of adverse events affecting patients admitted to a Canadian teaching hospital, paying particular attention to timing. METHODS: We randomly selected 502 adults admitted to the Ottawa Hospital for acute care of nonpsychiatric illnesses over a 1-year period. Charts were reviewed in 2 stages. If an adverse event was judged to have occurred, a physician determined whether it occurred before or during the index hospitalization. The reviewer also rated the preventability, severity and type of each adverse event. RESULTS: Of the 64 patients with an adverse event (incidence 12.7%, 95% confidence interval [CI] 10.1%-16.0%), 24 had a preventable event (4.8%, 95% CI 3.2%-7.0%), and 3 (0.6%, 95% CI 0.2%-1.7%) died because of an adverse event. Most adverse events were due to drug treatment, operative complications or nosocomial infections. Of the 64 patients, 39 (61%, 95% CI 49%-72%) experienced the adverse event before the index hospitalization. INTERPRETATION: Adverse events were common in this study. However, only one-third were deemed avoidable, and most occurred before the hospitalization. Interventions to improve safety must address ambulatory care as well as hospital-based care.