Curr. Oncol., Volume 26, Issue 5 (October 2019) – 20 articles

Prostatic yolk sac tumour is a germ cell tumour with a wide range of age of occurrence, unusual anatomic locations, diverse morphologic patterns, and aggressive biologic behavior, posing challenges both to diagnosis and clinical management. We report a rare case of primary yolk sac tumour of the prostate with extensive local and liver metastasis, the latter of which exhibited sheets of small blue cells expressing CD99 and focal sall4 on biopsy. Positivity for CD99 and gata3 in the initial biopsy raised the differential diagnosis of Ewing sarcoma and poorly differentiated carcinoma. The primary tumour demonstrated an admixture of solid and glandular growth patterns and occasional Schiller–Duval bodies. A panel of immunohistochemical stains showing positivity for AE1/3, sall4, cdx2, and focal alpha-fetoprotein, and negativity for oct-4, facilitated the diagnosis. A thorough review of the literature and our current report indicate that a large tumour load, incomplete tumour resection, limited response to preoperative neoadjuvant chemotherapy, and late stage of the disease are predictive factors for a poor clinical outcome. Full article

Gemcitabine is a chemotherapeutic agent used in a wide variety of solid tumours. Known side effects include a dose-limiting myelosuppressive toxicity, mild rash, and radiation-dependent dermatitis. Rarely, localized inflammation in the form of pseudocellulitis has also been observed. We present the case of a 77-year-old woman with a history of a Whipple procedure for pancreatic adenocarcinoma who presented to the emergency department after the start of gemcitabine therapy with increased erythema, swelling, and tenderness in her lower legs. Relevant past medical history included peripheral vascular disease, dyslipidemia, and hypertension. A diagnosis of gemcitabine-induced pseudocellulitis aggravated by venous stasis was confirmed after an extensive workup. This case report and the literature review describe this rare reaction, highlighting the need for increased recognition to avoid unnecessary therapeutic intervention. Full article

Mutations in EGFR have been implicated in the pathogenesis of various types of cancer, and therefore antibody therapy directed against the epidermal growth factor receptor (egfr) is increasingly being used in the management of various cancers. Currently, anti-egfr antibodies are used mainly in the management of cancers of the head and neck and metastatic colorectal cancers. Because of this increasing use, we would like to inform the oncology community in North America of a rare, but life-threatening, toxicity associated with anti-egfr antibody therapy. Although cases in white and Japanese men have been documented, we present the first known North American report of panitumumab-induced pulmonary toxicity in a white woman. Full article

Complete Resolution of Chylopericardium after Chemotherapy for Chronic Lymphocytic Leukemia Nontraumatic chylous pleural effusions (chylothorax) and pericardial effusions (chylopericardium) are rare. They can, however, accompany intrathoracic malignancies and, most commonly, lymphomas. An association of chronic lymphocytic leukemia (CLL) with chylopericardium has rarely been reported. A 68-year-old woman with cll, previously treated with single-agent fludarabine in the community, developed pleuritic chest pain and a new pericardial effusion. Computed tomography (CT) imaging of her chest revealed a large pericardial effusion with progressive lymphadenopathy. Pericardiocentesis identified a chylous effusion, and complete evacuation was achieved by catheter drainage. The CLL was not treated. An asymptomatic pericardial effusion subsequently recurred. Pericardiocentesis was not repeated. Lymph node biopsy and flow cytometry revealed no evidence of large-cell lymphoma transformation. The patient was treated with 6 cycles of chlorambucil and obinutuzumab. Imaging of her chest by CT between cycles 2 and 3 revealed a marked resolution of the intrathoracic lymphadenopathy, with complete disappearance of the pericardial effusion. Repeat imaging at 5 months and again at 3 years after completion of chemotherapy demonstrated no recurrence of either the lymphadenopathy or the pericardial effusion. The mechanism of production and the treatment of chylous effusions are poorly defined. In this case, resolution of the pericardial effusion with effective chemotherapy is postulated to have alleviated obstruction of anterograde lymphatic flow facilitating drainage into the systemic venous system and allowing for spontaneous complete resolution of the pericardial effusion without surgical intervention. Full article

Authorship in biomedical publications is critical for establishing accountability and contribution toward clinical and scientific research. We examined the frequency of discordance in authorship between presentations of clinical trial data at annual meetings of the American Society of Clinical Oncology and the subsequent peer-reviewed publications. We found that more than 70% of subsequent publications had additional authors not originally present on the abstract despite there being no changes in trial accrual or trial design. This pervasive discordance in authorship demonstrates a lack of uniformity and accountability in authorship reporting standards. Full article

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated. Full article

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20–22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology 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 pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including (1) surgical management of pancreatic adenocarcinoma, (2) adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma, (3) the role of radiotherapy in the management of pancreatic adenocarcinoma, (4) systemic therapy in pancreatic neuroendocrine tumours, (5) updates in systemic therapy for patients with advanced hepatocellular carcinoma, (6) optimum duration of adjuvant systemic therapy for colorectal cancer, and (7) sequence of therapy in oligometastatic colorectal cancer. Full article

Multimode tumour ablation therapy is a treatment method that combines cryoablation with radiofrequency ablation, guided by medical imaging technology and based on precise planning, targeting, monitoring, and control of the thermal energy delivered, with the aim of achieving a whole-body antitumour immune response to malignant tumours. To develop standardized criteria for the application of multimode tumour ablation therapy to malignant hepatic tumours, to facilitate actualization of the criteria in various hospitals, and to ensure therapeutic efficacy and safety, the Society of Interventional Therapy of the Chinese Anti-Cancer Association and the Solid Tumor Theranostics Committee of the Shanghai Anti-Cancer Association assembled experts who specialize in oncology to discuss this treatment method and to arrive at a clinical practice consensus guideline for the indications, contraindications, and techniques of multimode tumour ablation therapy for malignant hepatic tumours. Full article

Background: Patients with lung cancer often experience stressful delays throughout the diagnostic phase of care. To address that situation, our multidisciplinary team created a “Navigation Day,” during which patients partake in a single-day visit that comprises nurse-led teaching, social work, smoking cessation counselling, symptom control, and dedicated test slots for integrated positron-emission tomography and computed tomography (PET/CT), pulmonary function tests (PFTS), and magnetic resonance imaging (MRI) of the brain. We evaluated the effects of that program on wait times and patient satisfaction. Methods: Patients with a suspicion of lung cancer on chest ct imaging referred during 3 time periods were reviewed: 1 year before launch of the Navigation Day, 1 year post-launch, and 2 years post-launch. Patients were further stratified according to concordance of their test date with a Navigation Day date. Mean wait times for PET/CT, PFTS, and MRI brain were calculated for each group. Patient satisfaction was measured using a standardized provincial survey. The Student t-test and analysis of variance were used to assess for significance. Results: After implementation, mean wait times in the first year improved to 9.2 days from 15.5 days for PET/CT (p < 0.0001), to 9.6 days from 15.7 days for PFTS (p < 0.0001), and to 10.2 days from 16.0 days for MRI brain (p < 0.0001). Patients who used a dedicated test slot experienced the shortest wait times, at 5.8 days for PET/CT, 5.8 days for pfts, and 6.3 days for mri brain (p < 0.0001). Those improvements were sustained at 2 years post-launch. Conclusions: Patient satisfaction in the categories of assistance, emotional support, and clarity remained high post-launch. Navigation Day significantly improved the timeliness of diagnostic testing services in patients with suspected lung cancer. Full article

Background Prostate cancer (PCa) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (ADT) and radiotherapy (RT). New androgen-receptor-axis targeted therapies (ARATS), which await validation, offer an option to intensify therapy. Methods In this narrative review, we report the relevant history that has supported combining ADT with RT. The literature in PubMed was searched for studies involving PCa and novel ARATS (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored. Results Early results from three phase I/II trials demonstrated that concurrent abiraterone acetate, ADT, and RT is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single in vitro study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available. Full article

Background: Chemotherapy has improved outcomes in early-stage breast cancer, but treatment practices vary, and use of acute care is common. We conducted a pan-Canadian study to describe treatment differences and the incidence of emergency department visits (EDVS), edvs leading to hospitalization (EDVHS), and direct hospitalizations (HS) during adjuvant chemotherapy. Methods: The cohort consisted of women diagnosed with early-stage breast cancer (stages I–III) during 2007–2012 in British Columbia, Manitoba, Ontario, or Nova Scotia who underwent curative surgery. Parallel provincial analyses were undertaken using linked clinical, registry, and administrative databases. The incidences of edvs, edvhs, and hs in the 6 months after treatment initiation were examined for patients treated with adjuvant chemotherapy. Results: The cohort consisted of 50,224 patients. The proportion of patients who received chemotherapy varied by province, with Ontario having the highest proportion (46.4%), and Nova Scotia, the lowest proportion (38.0%). Age, stage, receptor status, comorbidities, and geographic location were associated with receipt of chemotherapy in all provinces. Ontario had the highest proportion of patients experiencing an EDV (36.1%), but the lowest proportion experiencing H (6.4%). Conversely, British Columbia had the lowest proportion of patients experiencing an EDV (16.0%), but the highest proportion experiencing H (26.7%). The proportion of patients having an edvh was similar across provinces (13.9%–16.8%). Geographic location was associated with EDVS, EDVHS, and HS in all provinces. Conclusions: Intra- and inter-provincial differences in the use of chemotherapy and acute care were observed. Understanding variations in care can help to identify gaps and opportunities for improvement and shared learnings. Full article

Cancer is a genetic disease resulting from germline or somatic genetic aberrations. Rapid progress in the field of genomics in recent years is allowing for increased characterization and understanding of the various forms of the disease. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (octane) clinical trial, open at cancer centres across Ontario, aims to increase access to genomic sequencing of tumours and to facilitate the collection of clinical data related to enrolled patients and their clinical outcomes. The study is designed to assess the clinical utility of next-generation sequencing (ngs) in cancer patient care, including enhancement of treatment options available to patients. A core aim of the study is to encourage collaboration between cancer hospitals within Ontario while also increasing international collaboration in terms of sharing the newly generated data. The single-payer provincial health care system in Ontario provides a unique opportunity to develop a province-wide registry of ngs testing and a repository of genomically characterized, clinically annotated samples. It also provides an important opportunity to use province-wide real-world data to evaluate outcomes and the cost of ngs for patients with advanced cancer. The octane study is attempting to translate knowledge to help deliver precision oncology in a Canadian environment. In this article, we discuss the background to the study and its implementation, current status, and future directions. Full article

Background: Ibrutinib is an approved treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The effect of ibrutinib dose reduction compared with discontinuation in a population-based setting is unclear. Methods: To examine the patterns of ibrutinib use in a Canadian population-based setting, we analyzed a retrospective cohort of patients with relapsed or refractory CLL or SLL treated with ibrutinib. Results: The 64 patients diagnosed with cll or sll had a median age of 76.5 years. Most had unmutated ighv (immunoglobulin variable heavy chain). A hematologic response occurred in 39 patients regardless of the ibrutinib dose. The most common toxicities were infection, bruising or bleeding, and musculoskeletal problems, with a median time to first toxicity of 14 days. More than half the cohort experienced a dose reduction, with musculoskeletal problems, cytopenias, and infection being the leading causes; surgery was the most frequent indication for holding treatment. Only 26 of the 64 patients (40.6%) stayed on the recommended maximal dose of ibrutinib. No differences in reported toxicities or hematologic response rates were evident between the patients receiving maximal and submaximal therapy. At the end of the study period, 53 patients from the initial cohort remained on ibrutinib. Conclusions: More than half the study patients received ibrutinib therapy at a submaximal dose without evidence of increased frequency of toxicities or disease progression. The rate of ibrutinib discontinuation was lower in our cohort than has been reported in other settings. Submaximal ibrutinib dosing will have to be further systematically evaluated. Full article

Background: Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location (ptl) in RAS wild-type metastatic colorectal cancer (wtRAS mcrc) might have predictive value with respect to response to drug therapies. Recent studies also show a potential preferential benefit for epidermal growth factor inhibitors (egfris) for left-sided tumours. In the present study, we aimed to determine the incremental cost-effectiveness ratio (icer) for the first-line use of an egfri for patients with left-sided wtRAS mcrc. Methods: We developed a state-transition model to determine the cost effectiveness of alternative treatment strategies in patients with left-sided mcrc: 1. Standard of care; 2. Use of an egfri in first-line therapy. The cohort for the study consisted of patients diagnosed with unresectable wtRAS mcrc with an indication for chemotherapy and previously documented ptl. Model parameters were obtained from the published literature and calibration. The perspective was that of a provincial ministry of health in Canada. We used a 5-year time horizon and an annual discount rate of 1.5%. Results: Selecting patients for first-line egfri treatment based on left-sided location of their colorectal primary tumour was more effective than the standard of care, resulting in an increase in quality-adjusted life-years (qalys) of 0.226 (or 0.644 life-years gained). However, the strategy was also more expensive, costing an average of $60,639 more per patient treated. The resulting icer was $268,094 per qaly. A 35% price reduction in the cost of egfri would be needed to make this strategy cost-effective at a willingness-to-pay threshold (wtp) of $100,000 per qaly. Conclusions: Selective use of an egfri based on ptl was more cost-effective than unselected use of those agents; however, based on traditional wtp thresholds, it was still not cost-effective. While awaiting the elucidation of more precise predictive biomarkers that might improve cost-effectiveness, the price of egfris could be reduced to meet the wtp threshold. Full article

Background: Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods: We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results: A neuroendocrine tumour, mtc arises from parafollicular cells (“C cells”), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism.
Full article

Background: In 2012 in the United States, the American Society of Clinical Oncology and the Society of Surgical Oncology (ASCO/SSO) published a joint guideline about indications for sentinel lymph node biopsy (SLNB) in cutaneous melanoma. The guideline supported completion lymph node dissection (CLND) for all patients with positive sentinel nodes. We examined the rates and predictors of SLNB and CLND for melanoma patients in Ontario (population 13.6 million) after publication of that guideline. Methods: We used the Ontario Cancer Registry to identify patients diagnosed with cutaneous melanoma in 2013. Patient records were linked to prospectively maintained health administrative databases to obtain details for each patient, including surgical procedures. Results: Of the 3298 patients with melanoma identified in Ontario in 2013, 1973 (59.8%) could be analyzed. Most of that group (n = 1227, 62.2%) underwent local excision alone; 746 (37.8%) had a SLNB. The slnb was performed in 13.9%, 67.8%, 62.6%, and 47.2% of patients with T1, T2, T3, and T4 primary melanomas respectively. In multivariate analysis, receipt of slnb was positively associated with younger age (<80 years), higher T stage, and a non-head-and-neck primary. Of the patients who had a SLNB, 136 (18.2%) were found to be node-positive. A CLND was performed in 82 of those patients (60.3%). Conclusions: In Ontario, only two thirds of patients with intermediate-thickness melanomas (T2, T3) underwent SLNB as recommended by the ASCO/SSO guideline. Use of SLNB was less frequent for patients with a head-and-neck primary and higher for younger patients (<80 years). The rate of CLND after a positive SLNB was also low relative to the guideline recommendation. Full article

Background: Outcomes for patients with metastatic colorectal cancer (MCRC) are improving with the introduction of new treatments. Treatment for patients who are still fit after failure of all available therapies represents a significant unmet need. In the present study, we analyzed real-world treatment patterns for patients enrolled in Health Canada’s trifluridine/tipiracil (FTD/TPI) Special Access Program (SAP) and Taiho Pharma Canada’s Patient Support Program (PSP). Methods: Demographic information and clinical treatment data were collected from adults with mcrc who were previously treated with, or were not candidates for, available therapies and who were enrolled in the SAP and PSP. For all patients, FTD/TPI treatment status, discontinuation reasons, and prior therapies were examined. Results: The analysis included 717 Canadian patients enrolled in the FTD/TPI sap and PSP from September 2017 to October 2018. In that cohort, 59.7% were men, median age was 65 years, and median duration of therapy was 77 days (25%–75% interquartile range: 43–106 days). Of treated patients, 67.1% maintained the same dose for the duration of therapy; 28.0% had a dose reduction. On multivariable analysis, duration of therapy was not influenced by sex, age, province, RAS mutation status, or prior therapies. However, prior oxaliplatin-based chemotherapy (CAPOX or FOLFOX) appeared to be associated with higher rates of discontinuation because of death or disease progression. Conclusions: In advanced MCRC, FTD/TPI is a well-tolerated therapy. The large number of patients enrolled in the access programs within a short period of time is reflective of major clinical need in this area, with many patients being eligible and interested in pursuing treatment in the refractory setting. Full article

Background For women with lymph node (LN)–positive, estrogen receptor–positive, and her2 (human epidermal growth factor receptor 2)–negative breast cancer (BCa), current guidelines recommend treatment with both hormonal therapy and chemotherapy. The 21-gene Recurrence Score (RS) assay might be helpful in selecting patients with bca who can be spared chemotherapy when they have 1–3 positive lns and a lower risk of recurrence. In the present study, we performed a cost–utility analysis comparing use of the 21-gene rs assay with current practice from the perspective of a Canadian health care payer. Methods A Markov model was developed to determine costs and quality-adjusted life-years (QALYS) over a patient’s lifetime. Patient outcomes in both study groups were examined based on published clinical trials. Costs were derived primarily from published Canadian sources. Costs and outcomes were discounted at 1.5% annually, and costs are reported in 2016 Canadian dollars. A probabilistic analysis was used, and the model parameters were varied in a sensitivity analysis. Results The results indicate that use of the 21-gene rs assay was less costly ($432 less) and more effective (0.22 qalys) than current practice. The probabilistic analysis revealed that 70% of the 10,000 simulated incremental cost-effectiveness ratios were in the southeast quadrant. The results were sensitive to the probability of a low rs and to the probability of receiving chemotherapy in the low-risk rs category and in current practice. Conclusions Use of the 21-gene rs assay could be a cost-effective strategy for Ontario patients with estrogen receptor–positive, HER2-negative early bca and 1–3 positive LNS. Full article

Background Routine follow-up is a cornerstone of oncology practice, but evidence to support most aspects of follow-up is lacking. Our objective was to investigate the relationship between frequency of routine follow-up and survival. Methods This population-based study used electronic health care data relating to 5310 patients from Ontario diagnosed with squamous-cell head-and-neck cancer during 2007–2012. Treatments included surgery (24.6%), radiotherapy with or without chemotherapy (52.4%), and combined surgery and radiotherapy (23%). We determined the oncologist who was following each patient after treatment; calculated the average follow-up visits to the oncologist during the subsequent 2.5 years for all patients who were doing well; and used Kaplan–Meier and multiple variable regression analysis to compare, by treatment, overall survival for patients in the high, typical, and low follow-up oncologist groups. Results Many oncologists saw patients 40%–80% more often than other oncologists did. No relationship of appointment frequency with survival was observed for patients in any treatment group. Conclusions The practice of routine follow-up varies and is costly both to a health care system and to patients. Without evidence about the effectiveness of current policies, further research is required to investigate new or optimal practices. Full article