Current Oncology

Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt’s lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician. Full article

Stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation (TA) are alternatives to surgery for the management of pulmonary oligometastases. In this collaborative work, we retrospectively analyzed patients who had undergone iterative focal ablative treatments of pulmonary oligometastases. We hypothesized that repeated ablative therapies could benefit patients with consecutive oligometastatic relapses. Patients treated with SBRT and/or TA for pulmonary oligometastases in two French academic centers between October 2011 and November 2016 were included. A total of 102 patients with 198 lesions were included; 45 patients (44.1%) received repeated focal treatments at the pulmonary site for an oligorecurrent disease (the “multiple courses” group). Median follow-up was 22.5 months. The 3-year overall survival rates of patients who had a single treatment sequence (the “single course” group) versus the “multiple courses” were 73.9% and 78.8%, respectively, which was not a statistically significant difference (p = 0.860). The 3-year systemic therapy-free survival tended to be longer in the “multiple courses” group (50.4%) than in the “single course” group (44.7%) (p = 0.081). Tolerance of repeated treatments was excellent with only one grade 4 toxicity. Thereby, multimodality repeated ablative therapy is effective in patients with pulmonary oligorecurrent metastases. This strategy may delay the use of more toxic systemic therapy. Full article

Bone metastases induce pain, risk of fracture, and neural compression, and reduced mobility and quality of life. Electrochemotherapy (ECT) is a minimally invasive local treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies have supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Since 2009, 88 patients with bone metastasis have received ECT at the Rizzoli Institute. 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. We share the Rizzoli Institute experience of 38 patients treated with ECT for a bone metastasis, excluding patients not included in the registry (before 2014) and those treated with bone fixation. Mean follow-up was 2 months (1–52). Response to treatment using RECIST criteria was 29% objective responses, 59% stable disease, and 16% progressive disease. Using PERCIST, the response was 36% OR, 14% SD, and 50% PD with no significant differences between the two criteria. A significant decrease in pain and better quality of life was observed at FU. Full article

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar–suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of this tumor makes complete resection a challenge and contributes to its recurrence. Additionally, these tumors are bimodally distributed, being treated with surgery, and are followed by other adjuncts, such as focused radiation therapy, e.g., Gamma knife. Advances in surgical techniques, imaging tools, and instrumentations have resulted in the evolution of surgery using endoscopic techniques, with residual components being treated by radiotherapy to target the residual tumor. Advances in molecular biology have elucidated the main pathways involved in tumor development and recurrence, but presently, no other treatments are offered to patients, besides surgery, radiation, and endocrine management, as the disease and tumor evolve. We review the contemporary management of these tumors, from the evolution of surgical treatments, utilizing standard open microscopic approaches to the more recent endoscopic surgery, and discuss the current recommendations for care of these patients. We discuss the developments in radiation therapy, such as radiosurgery, being used as treatment strategies for craniopharyngioma, highlighting their beneficial effects on tumor resections while decreasing the rates of adverse outcomes. We also outline the recent chemotherapy modalities, which help control tumor growth, and the immune landscape on craniopharyngiomas that allow the development of novel immunotherapies. Full article

The oncology setting may give rise to significant feelings of helplessness among oncologists via patients’ inevitable deaths or suffering. The current study examines whether and how oncologists’ sense of control (locus of control; LOC) influences their compassion fatigue and satisfaction. Methods: Seventy-three oncologists completed the following questionnaires: the Professional Quality of Life scale; Levenson’s Internal, Powerful Others, and Chance scale; the Guilt Inventory, State Guilt subscale; and the Learned Helplessness scale. Results: Oncologists reported high levels of secondary traumatic stress and burnout and moderate levels of compassion satisfaction. A positive association between oncologists’ external LOC and compassion fatigue, and a negative association between oncologists’ internal LOC and compassion fatigue, were found. Helplessness, but not guilt, had a mediating role in these associations. Internal LOC was also positively associated with compassion satisfaction. Conclusions: The current study highlights oncologists as a population at risk of experiencing compassion fatigue and emphasizes oncologists’ locus of control as a predisposition that plays a role in the development of this phenomenon. Additionally, the cognitive as well as the emotional aspects of control were found to be important factors associated with compassion fatigue. Full article

Background: OncoSim-Breast is a Canadian breast cancer simulation model to evaluate breast cancer interventions. This paper aims to describe the OncoSim-Breast model and how well it reproduces observed breast cancer trends. Methods: The OncoSim-Breast model simulates the onset, growth, and spread of invasive and ductal carcinoma in situ tumours. It combines Canadian cancer incidence, mortality, screening program, and cost data to project population-level outcomes. Users can change the model input to answer specific questions. Here, we compared its projections with observed data. First, we compared the model’s projected breast cancer trends with the observed data in the Canadian Cancer Registry and from Vital Statistics. Next, we replicated a screening trial to compare the model’s projections with the trial’s observed screening effects. Results: OncoSim-Breast’s projected incidence, mortality, and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and from Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial. Conclusions: OncoSim-Breast’s ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer. Full article

Background: In 2019, cancer patients comprised over 65% of all individuals who requested and received Medical Assistance in Dying (MAID) in Canada. This descriptive study sought to understand the self-reported symptom burden and complexity of cancer patients in the 12 months prior to receiving MAID in Alberta. Methods: Between July 2017 and January 2019, 337 cancer patients received MAID in Alberta. Patient characteristics were descriptively analyzed. As such, 193 patients (57.3%) completed at least one routine symptom-reporting questionnaire in their last year of life. Mixed effects models and generalized estimating equations were utilized to examine the trajectories of individual symptoms and overall symptom complexity within the cohort over this time. Results: The results revealed that all nine self-reported symptoms, and the overall symptom complexity of the cohort, increased as patients’ MAID provision date approached, particularly in the last 3 months of life. While less than 20% of patients experienced high symptom complexity 12 months prior to MAID, this increased to 60% in the month of MAID provision. Conclusions: Cancer patients in this cohort experienced increased symptom burden and complexity leading up to their death. These findings could serve as a flag to clinicians to closely monitor advanced cancer patients’ symptoms, and provide appropriate support and interventions as needed. Full article

This study sought to explore the existence and clinical significance of intratumoral heterogeneity of proliferative potential in vestibular schwannoma (VS). Rapid intraoperative flow cytometry was utilized with raw samples to measure the proliferative ability of VS. The proliferation index (PI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. A total of 66 specimens (26 from the intrameatal portion and 40 from the cisternal portion) were obtained from 34 patients with VS. There was a moderate correlation between the PI and MIB-1 labelling index values (R = 0.57, p < 0.0001). In contrast, the patterns of heterogeneity, represented by the proportion of intrameatal PI to cisternal PI, were associated with tumor size (p = 0.03). In addition, preoperative hearing tended to be poor in cases where the intrameatal PI was higher than the cisternal PI (p = 0.06). Our data demonstrated the presence of intratumoral heterogeneity of proliferative potential in VS and its relationship with tumor characteristics. The results of this study may advocate the resection of the intrameatal portion of large VSs treated with planned subtotal resection, especially in cases of poor preoperative hearing function. Full article

High survival rates in adolescent cancer patients have shifted the medical focus to the long-term outcomes of cancer treatments. Surgery, chemotherapy, and radiation increase the risk of infertility and infertility-related distress in adolescent cancer patients and survivors. The aims of this narrative review were to (1) describe the psychosocial impacts of cancer-related infertility in adolescents, (2) identify multilevel barriers to fertility preservation (FP) conversations and referrals, and (3) conclude with evidence-based clinical solutions for improving the oncofertility support available to Canadian adolescents. The results of this review revealed that FP decisions occur within the patient, parent, and health care provider (HCP) triad, and are influenced by factors such as parent attitudes, patient maturity, and HCP knowledge. Decision tools and HCP education can promote the occurrence of developmentally appropriate fertility discussions. At the systems level, cost and resource barriers prevent patients from receiving sufficient fertility information and referrals. Clinical models of care (MOCs) can define interdisciplinary roles and referral pathways to improve the integration of oncofertility services into adolescent cancer care. The continued integration of oncofertility care will ensure that all Canadian adolescents receive the exemplary medical and psychological support necessary to make empowered decisions about their own fertility. Full article

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76–7.07) and 5.36 months (95% CI, 3.75–6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50–19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98–19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM. Full article

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC. Full article

Smoking during cancer treatment is associated with reduced treatment response and cancer recurrence in patients with tobacco-related cancers. The purpose of this study was to examine smoking characteristics in head and neck cancer patients (n = 503) with a history of smoking and examine the impact of an intensive clinical tobacco intervention to patients who were currently smoking. All participants completed an interviewer-administered questionnaire at study enrollment which examined smoking behaviours, motivations to quit, and strategies used to cessate smoking. Follow-up assessments were completed at 6- and 12-months which monitored whether patients had quit smoking, remained cessated, or continued to smoke since study recruitment. For those who were currently smoking (n = 186, 37.0%), an intensive clinical tobacco intervention that utilized the 3A’s—Ask, Advise, Arrange—and the Opt-Out approach was offered to assist with smoking cessation at their new patient visit and followed-up weekly during their head and neck radiation therapy for 7 weeks. At 6 months, 23.7% (n = 41) of those who were smoking successfully quit; 51.2% quit ‘cold turkey’ (defined as using no smoking cessation assistance, aids or pharmacotherapy to quit), while 34.9% used pharmacotherapy (varenicline (Champix)) to quit. On average, it took those who were smoking 1–5 attempts to quit, but once they quit they remained cessated for the duration of the study. Although the head and neck cancer patients in this study reported high levels of nicotine dependence, many were able to successfully cessate. Full article

Lesions commonly associated with HIV infection include oral candidiasis, herpes simplex infection, oral Kaposi’s sarcoma, hairy leukoplakia, periodontal diseases (linear gingival erythema and necrotizing ulcerative periodontitis), xerostomia, human papillomavirus-associated warts, aphthous ulcers, non-Hodgkin’s lymphoma, histoplasmosis, carcinoma, exfoliative cheilitis, and HIV salivary gland disease. Non-Hodgkin’s lymphoma (NHL) is the most common cancer in people living with HIV (PLWH), and the incidence is increased for aggressive B-cell NHL. Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy that is often unresponsive to chemotherapy and usually has a poor prognosis. We hereby present the case of a patient with a recent history of COVID-19 infection who was diagnosed with HIV and NHL, with manifestations in the oral cavity and a favorable evolution after the introduction of antiviral therapy, specific chemotherapy, and radiotherapy. Dental expertise is necessary for the appropriate management of oral manifestations of HIV infection or AIDS, and lymphoma should be included in the differential diagnosis of any oral lesions. Full article

The Serious Illness Care Program (SICP), designed by Ariadne Labs, is a multicomponent intervention to improve conversations about values and goals for patients with a life-limiting illness. In oncology, implementation of the SICP achieved more, earlier, and better-quality conversations and reduced anxiety and depression among patients with advanced cancer. In this commentary, we describe the SICP, including results from the cluster-randomized trial, provide examples of real-world implementation of this program, and highlight ongoing challenges and barriers that are preventing widespread adoption of this intervention into routine practice. For the SICP to be successfully embedded into routine patient care, it will require significant effort, including ongoing leadership support and training opportunities, champions from all sectors of the interdisciplinary team, and adaptation of the program to a wider range of patients. Future research should also investigate how early conversations can be translated into personalized care plans for patients. Full article

Public reimbursement systems face the challenge of balancing provision of needed treatments and the reality of limited resources. Canada has a complex system for drug approval and public reimbursement, with jurisdiction divided between the federal government and the provinces/territories. A pivotal role is that of health technology assessment (HTA), which relies primarily on health economic principles to analyze the value of drugs on a population health basis and make recommendations about public reimbursement. The Canadian Agency for Drugs and Technologies in Health (CADTH) provides recommendations to all provinces but Quebec. This article provides an overview of Canada’s approval and public reimbursement pathway, including the role of HTA and the economic principles on which it relies. Starting in late 2020, CADTH reduced the cost per quality-adjusted life year (QALY) threshold, the metric relied upon in making recommendations to public payers. An analysis of all 56 oncology drug final recommendations issued from January 2020 to January 2022 was conducted and confirms this reduction in the cost per QALY threshold. As a result of this threshold reduction, recommendations to the provinces include, in a number of cases, substantially greater price reductions. The potential implications for successful price negotiation with the pan-Canadian Pharmaceutical Alliance (pCPA), the public negotiating body for the provinces, are discussed. Full article

Aim: To evaluate optimal systemic therapy sequencing (first-line targeted therapy (1L-TT) vs. first-line immunotherapy (1L-IO)) in patients with BRAF-mutated metastatic melanoma. Methods: Nation-wide prospective data of patients with newly diagnosed BRAF-mutated metastatic melanoma were retrieved from the Canadian Melanoma Research Network. Results: Our study included 79 and 107 patients in the 1L-IO and 1L-TT groups, respectively. There were more patients with ECOG 0–1 (91% vs. 72%, p = 0.023) in the 1L-IO group compared to the 1L-TT group. Multivariable Cox analysis suggested no OS differences between the two groups (HR 0.838, 95%CI 0.502–1.400, p = 0.500). However, patients who received 1L-TT then 2L-IO had the longest OS compared to 1L-IO without 2L therapy, 1L-IO then 2L-TT, and 1L-TT without 2L therapy (38.3 vs. 32.2 vs. 16.9 vs. 6.3 months, p < 0.001). For patients who received 2L therapy, those who received 2L-IO had a trend towards OS improvement compared with the 2L-TT group (21.7 vs. 8.9 months, p = 0.053). Conclusions: Our nation-wide prospective study failed to establish any optimal systemic therapy sequencing in advanced BRAF-mutant melanoma patients. Nevertheless, we provided evidence that immunotherapy has durable efficacy in advanced BRAF-mutant melanoma patients, regardless of treatment line, and that Canadian medical oncologists were selecting the appropriate treatment sequences in a real-world setting, based on patients’ clinical and tumour characteristics. Full article

Purpose: to determine management problems of ovarian masses in girls in order to form a baseline for prospective randomized studies of the established topics and quality improvement of our management. Materials and Methods: We performed a national analysis of clinical aspects of ovarian masses in girls operated on in Poland, analyzed retrospectively medical files of all consecutive patients aged 0–18 who underwent surgeries for ovarian lesions between 2012 and 2017 at 17 pediatric surgical departments and complemented the analysis with a scoping review of a recent primary research related to ovarian masses in children. Results: The study group comprised 595 patients. Forty-four (7.39%) girls were diagnosed with malignant tumors. The overall preservation rate was 64.54%. The analysis revealed that positive tumor markers (OR = 10.3), lesions larger than 6 cm (OR = 4.17) and solid mass on ultrasound examination (OR = 5.34) are interdependent variables differentiating malignant tumors from non-malignant lesions (${\mathcal{X}}_4^2$ = 79.1; p = 0.00000). Our scoping review revealed 10 major branches of research within the topic of ovarian masses in pediatric population. Conclusions: We have developed an overview of the field with the emphasis on the local environment. Our next step is a multi-institutional prospective study of a quality improvement project implementation based on the obtained knowledge. Full article

The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We retrospectively reviewed 128 patients who underwent hepatic resection for HCC at a tertiary academic centre (2007–2019). Patient data were modelled by regression analysis, and platelet count was treated as a continuous variable. 89 patients had BCLC 0/A tumours and 39 had BCLC B tumours. Platelet count was higher in patients with larger tumours and lower in patients with higher MELD scores, advanced fibrosis, and portal hypertension (p < 0.001 for all listed variables). After adjusting for BCLC stage and tumour diameter, low platelet count associated with reduced overall survival (hazard ratio 1.25 per 50/nL decrease in platelet count, 95% confidence interval (CI) 1.02–1.53, p = 0.034) and increased perioperative mortality (odds ratio 1.96 per 50/nL decrease in platelet count, 95% CI 1.19–3.53, p = 0.014). Overall, low platelet count correlates with increased liver disease severity, inferior survival, and excess perioperative mortality in resectable HCC. These insights might be applied in clinical practice to better select patients for resection. Full article

Health professionals working in oncology face the challenge of a stressful work environment along with impacts of providing care to those suffering from a life-threatening illness and encountering high levels of patient loss. Longitudinal exposure to loss and suffering can lead to grief, which over time can lead to the development of compassion fatigue (CF). Prevalence rates of CF are significant, yet health professionals have little knowledge on the topic. A six-week continuing education program aimed to provide information on CF and support in managing grief and loss and consisted of virtual sessions, case-based learning, and an online community of practice. Content included personal, health system, and team-related risk factors; protective variables associated with CF; grief models; and strategies to help manage grief and loss and to mitigate against CF. Participants also developed personal plans. Pre- and post-course evaluations assessed confidence, knowledge, and overall satisfaction. A total of 189 health professionals completed the program (90% nurses). Reported patient loss was high (58.8% > 10 deaths annually; 12.2% > 50). Improvements in confidence and knowledge across several domains (p < 0.05) related to managing grief and loss were observed, including use of grief assessment tools, risk factors for CF, and strategies to mitigate against CF. Satisfaction level post-program was high. An educational program aiming to improve knowledge of CF and management of grief and loss demonstrated benefit. Full article