Current Oncology

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges.

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy.

Standard treatment for glioblastoma multiforme is surgery followed by radiotherapy and chemotherapy, generally with temozolomide. However, disease recurs in almost all patients. Diagnosis of progression is complex given the possibility of pseudoprogression. The Response Assessment in Neuro-Oncology criteria increase the sensitivity for detecting progression. Most patients will not be candidates for new surgery or re-irradiation, and anticancer drugs are the most common approach for second-line treatment, if the patient’s condition allows. Antiangiogenics, inhibitors of the epidermal growth factor receptor, nitrosoureas, and re-treatment with temozolomide have been studied in the second line, but a standard therapy has not yet been established. This review considers currently available medical treatment options for patients with glioblastoma recurrence.

Background: The prognosis of patients with brain metastases from non-small-cell lung cancer (NSCLC) is poor. However, some reports suggest that patients with brain metastases at the time of initial diagnosis have a more favourable survival than do patients with advanced NSCLC without brain metastases. Methods: In a retrospective cohort of all new lung cancer patients seen at a Canadian tertiary centre between July 2005 and June 2007, we examined survival after a diagnosis of brain metastases for patients with brain metastases at initial diagnosis and patients who developed brain metastases later in their illness. Results: During the 2-year period, 91 of 878 patients (10.4%) developed brain metastases. Median age in this cohort was 64 years. In 45, brain metastases were present at initial diagnosis, and in 46, brain metastases developed later in the course of the illness. Median survival in the entire cohort was 7.8 months. Survival after the diagnosis of brain metastases was similar for patients with brain metastases at diagnosis and later in the illness (4.8 months vs. 3.7 months, p = 0.53). As a result, patients who developed brain metastases later in their illness had a longer overall survival than did patients with brain metastases at diagnosis (9.8 months vs. 4.8 months). Among patients who received chemotherapy, the survival of patients with brain metastases at diagnosis was still poor (6.2 months). Conclusions: Our data show limited survival in patients with brain metastases from NSCLC. Careful patient selection for more aggressive treatment approaches is necessary.

Metastatic non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality in Canada. Although treatment outcomes in advanced disease remain modest, with paradigm shifts in the approach to treatment, they are steadily improving. Customizing treatment based on histology and molecular typing has become the standard of care. EGFR genotyping and pathology subtyping should be considered routine in new diagnoses of metastatic NSCLC. Treatment options for those with somatic EGFR activating mutations include gefitinib until progression, followed by standard chemotherapy. For patients with wild-type EGFR, or in patients whose EGFR genotype is unknown, platinum-based chemotherapy remains the first-line standard, with single-agent chemotherapy as an option for older patients and those who are unfit for platinum-doublet therapy. Patients with nonsquamous histology may receive treatment regimens incorporating pemetrexed or bevacizumab. In patients with squamous cell carcinoma, the latter agents should be avoided because of concerns about enhanced toxicity or decreased efficacy. Second-line chemotherapy is offered to a selected subgroup of patients upon progression and may include pemetrexed in non-squamous histology and docetaxel or erlotinib (or both) in all histologies. Currently, only erlotinib is offered as a third-line option in unselected NSCLC patients after failure of first- and second-line chemotherapy. Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of NSCLC, such as crizotinib in tumours harbouring the EML4–ALK gene rearrangement.

Purpose: Multidisciplinary cancer conferences (mccs) are designed to optimize patient outcomes. It appears intuitive that mccs are essential to clinical decision-making and patient management; however, it is unclear whether that belief is supported by evidence. Our objectives were to assess the currently published literature addressing the impact of mccs on clinical decision-making and patient outcomes. Methods: Ovid medline was searched from 1950 to June 2010 using these keywords: “multidisciplinary/interdisciplinary/clinical meeting$/conference$/round$/team$,” “decision making,” “neoplasms$/cancer$/oncology/tumo(u)r conference$/board$/meeting$,” “multidisciplinary/interdisciplinary cancer conference$/meeting$.” All trials, guidelines, metaanalyses, reviews, and prospective and retrospective studies were included. Results: The keywords retrieved 595 abstracts, and 30 manuscripts were obtained. Most of the studies assessed the impact of mccs on clinical decision-making rather than on patient outcomes. Conclusions: Available evidence supports the belief that mccs significantly influence clinical decision-making and treatment recommendations. In contrast, scant evidence suggests that mccs improve patient outcomes. Unfortunately, the current literature is substantially heterogeneous and therefore does not allow for firm conclusions.

Venous thromboembolism (VTE) represents a major challenge in the management of patients with cancer. The malignant phenotype is associated with derangements in the coagulation cascade that can manifest as thrombosis, hemorrhage, or disseminated intravascular coagulation. The risk of VTE is increased by a factor of approximately 6 in patients with cancer compared with non-cancer patients, and cancer patients account for approximately 20% of all newly diagnosed cases of VTE. Postmortem studies have demonstrated rates of VTE in patients with cancer to be as high as 50%. Despite that prevalence, VTE prophylaxis is underused in hospitalized patients with cancer. Studies have demonstrated that hospitalized patients with cancer are less likely than their non-cancer counterparts to receive VTE prophylaxis. Consensus guidelines address the aforementioned issues and emerging concepts in the area, including the use of risk-assessment models, biomarkers to identify patients at highest risk of VTE, and use of anticoagulants as anticancer therapy. Despite those guidelines, a gulf exists between current recommendations and clinical practice; greater efforts are thus required to ensure effective implementation of strategies to reduce the incidence of VTE in patients with cancer.

Objectives: In cancer patients, chemotherapy-induced peripheral neuropathy (cipn) is a common complication, characterized by pain, loss of sensation, and numbness. Medical treatment for peripheral neuropathies has been shown to be ineffective for cipn. Acupuncture has been shown to be safe and effective in treating cancer-related symptoms and other peripheral neuropathies. For the present review, we aimed to evaluate the efficacy of acupuncture for the treatment of cipn. Design: Comprehensive searches for relevant studies were conducted in Ovid embase, the Web of Science, Ovid medline, the Cochrane Central Register of Controlled Trials (central), cinahl (ebsco Information Services, Ipswich, MA, U.S.A.), and the ClinicalTrials.gov Web site. References from previous systematic reviews were also searched. Additional trials were found in the reference lists of relevant papers and in searches of Google Scholar and acupuncturespecific Web sites. Included studies were randomized controlled trials (rcts) of any type of acupuncture used to treat patients with cipn. Results: Three clinical trials (203 participants) were included. Two studies found acupuncture to be effective in alleviating cipn pain and improving quality of life. One study found no benefit in improving neuropathic pain, symptoms, or quality of life. Study quality was variable and included a moderate overall risk of bias. Conclusions: The evidence is insufficient to recommend acupuncture for the treatment or prevention of cipn. Further research is needed to evaluate the effects of acupuncture in the treatment of cipn. Given that acupuncture is considered safe and might provide relief for patients, it can be considered at the clinician’s discretion.

The treatment of advanced non-small-cell lung cancer (NSCLC) has undergone a paradigm shift since the early 2000s. The identification of molecular subtypes of the disease, based on oncogenic drivers, has led to the development of personalized medicine and the ability to deliver molecularly targeted therapies to patients. In the 10 years that have elapsed since the discovery of the ALK gene in a patient with NSCLC, several active drugs have moved rapidly from bench to bedside, and multiple others are currently in clinical trials. Those developments have led to important improvements in patient outcomes, while simultaneously raising key questions about the optimal treatment for ALK-positive NSCLC. The inevitable emergence of resistance to ALK-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive NSCLC, with a focus on Canadian practice.

Background: We investigated whether preoperative anemia and perioperative blood transfusion (PBT) are associated with overall survival and recurrence-free survival in patients with nonmetastatic colorectal cancer. Methods: From 1 January 2009 to 31 December 2014, 1003 patients with primary colorectal cancer were enrolled in the study. Perioperative clinical and oncologic outcomes were analyzed based on the presence of preoperative anemia and PBT. Results: Preoperative anemia was found in 468 patients (46.7%). In the anemia and no-anemia groups, PBT was performed in 44% and 15% of patients respectively. Independent predictors for PBT were preoperative anemia, higher American Society of Anesthesiologists score, laparotomy, lengthy operative time, advanced TNM stage, T4 stage, and 30-day morbidity. The use of PBT, but not preoperative anemia, was found to be an independent adverse prognostic factor for overall survival. In terms of recurrence-free survival, the presence of preoperative anemia was similarly not a significant prognostic factor, but the use of PBT was an independent factor for an unfavourable prognosis. Conclusions: The use of PBT, but not preoperative anemia, was independently associated with worse overall and recurrence-free survival in nonmetastatic colorectal cancer. For better oncologic outcomes, our findings indicate a need to reduce the use of blood transfusion during the perioperative period.