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  • 1
    In: Current Oncology, MDPI AG, Vol. 30, No. 7 ( 2023-07-06), p. 6473-6496
    Abstract: Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2270777-3
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  • 2
    In: Current Oncology, MDPI AG, Vol. 29, No. 7 ( 2022-07-15), p. 4981-4997
    Abstract: Non-small cell lung cancer (NSCLC) has historically been associated with a poor prognosis and low 5-year survival, but the use of targeted therapies in NSCLC has improved patient outcomes over the past 10 years. The pace of development of new targeted therapies is accelerating, with the associated need for molecular testing of new targetable alterations. As the complexity of biomarker testing in NSCLC increases, there is a need for guidance on how to manage the fluid standard-of-care in NSCLC, identify pragmatic molecular testing requirements, and optimize result reporting. An expert multidisciplinary working group with representation from medical oncology, pathology, and clinical genetics convened via virtual meetings to create consensus recommendations for testing of new targetable alterations in NSCLC. The importance of accurate and timely testing of all targetable alterations to optimize disease management using targeted therapies was emphasized by the working group. Therefore, the panel of experts recommends that all targetable alterations be tested reflexively at NSCLC diagnosis as part of a comprehensive panel, using methods that can detect all relevant targetable alterations. In addition, comprehensive biomarker testing should be performed at the request of the treating clinician upon development of resistance to targeted therapy. The expert multidisciplinary working group also made recommendations for reporting to improve clarity and ease of interpretation of results by treating clinicians and to accommodate the rapid evolution in clinical actionability of these alterations. Molecular testing of all targetable alterations in NSCLC is the key for treatment decision-making and access to new therapies. These consensus recommendations are intended as a guide to further optimize molecular testing of new targetable alterations.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 3
    In: Current Oncology, MDPI AG, Vol. 30, No. 7 ( 2023-06-30), p. 6289-6315
    Abstract: Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC). The literature search included guidelines, systematic reviews, and randomized controlled trials. Regular meetings were held from September 2022 to March 2023 to discuss the available evidence to propose and agree upon specific recommendations. The panel addressed biomarkers and histological features that distinguish SCLC from non-SCLC and other neuroendocrine tumours. Evidence for initial and subsequent systemic therapies was reviewed with consideration for patient performance status, comorbidities, and the involvement and function of other organs. The resulting consensus recommendations herein will help clarify evidence-based management of ES-SCLC in routine practice, help clinician decision-making, and facilitate the best patient outcomes.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2270777-3
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Current Oncology Vol. 28, No. 1 ( 2021-01-04), p. 265-272
    In: Current Oncology, MDPI AG, Vol. 28, No. 1 ( 2021-01-04), p. 265-272
    Abstract: The use of lorlatinib, an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer, is associated with dyslipidemia in over 80% of patients. Clinical trial protocols for the management of lorlatinib-associated dyslipidemia differ from clinical practice guidelines for the management of dyslipidemia to prevent cardiovascular disease, in that they are based on total cholesterol and triglyceride levels rather than on the low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels that form the basis of current cardiovascular guideline recommendations. In order to simplify and harmonize the management of cardiovascular risk in patients with lorlatinib, an advisory committee consisting of a medical oncologist, a cardiologist, and two pharmacists with expertise in cardiology and oncology aimed to develop a simplified algorithm, adapted from the Canadian Cardiovascular Society dyslipidemia recommendations. Recommendations for the evaluation and management of hypercholesterolemia and isolated hypertriglyceridemia in patients treated with lorlatinib are outlined. These recommendations are based on data collected in a large number of lipid-lowering therapy trials applicable to individuals with and without cancer. Considering the relatively long life expectancy and improving prognosis of patients with ALK translocations, this specific patient population should be treated as are patients without cancer and are likely to derive the same benefits from lipid-lowering therapy.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2270777-3
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  • 5
    In: Current Oncology, MDPI AG, Vol. 15, No. 1 ( 2008-01-01), p. 36-41
    Abstract: The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2008
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  • 6
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 20 ( 2022-10-13), p. 6032-
    Abstract: Lip bumper (LB) therapy is used as a treatment approach for mild to moderate crowding without extraction of teeth. Previous studies demonstrated that LB increases arch length through molar uprighting and lateral expansion. However, the effects of LB on mandibular incisors are inconclusive. The controversial results from different studies may be due to limitations including absence of a control group and/or use of 2D radiography. To address this issue, the current retrospective longitudinal CBCT study compared a rapid maxillary expansion (RME) group with no lower treatment [16 patients (9 females, 7 males); median age 8.86 years at T1 and 11.82 years at T2] and an RME + LB group [18 patients (13 females, 5 males); median age 9.46 years at T1 and 12.10 years at T2] . The CBCTs taken before and after phase 1 treatment were 3D superimposed based on the mandibular structure and were measured to determine the angular and linear changes of the mandibular incisors over the course of LB treatment. For comparisons between different timepoints within a group, a Wilcoxon matched-pairs signed rank test was used. For intergroup comparisons, a Mann–Whitney U test was used. Both groups showed eruption and protrusion of the mandibular incisors during the observation period, while there was no significant change in proclination of the lower incisors. When comparing the discrepancy of change between groups, there was no statistically significant difference detected. In summary, by utilizing a longitudinal 3D database, the current study demonstrated that the effect of LB on the position of the mandibular incisors is limited.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 8 ( 2021-07-27), p. 900-
    In: Biomedicines, MDPI AG, Vol. 9, No. 8 ( 2021-07-27), p. 900-
    Abstract: Background: The long-term impact of COVID-19 is still unknown. This study aimed to explore post COVID-19 effects on patients chest computed tomography (CT), lung function, respiratory symptoms, fatigue, functional capacity, health-related quality of life (HRQoL), and the ability to return to work beyond 3 months post infection. Methods: A systematic search was performed on PubMed, Web of Science, and Ovid MEDLINE on 22 May 2021, to identify studies that reported persistent effects of COVID-19 beyond 3 months follow-up. Data on the proportion of patients who had the outcome were collected and analyzed using a one-group meta-analysis. Results: Data were extracted from 24 articles that presented information on a total of 5323 adults, post-infection, between 3 to 6 months after symptom onset or hospital discharge. The pooled prevalence of CT abnormalities was 59% (95% CI 44–73, I2 = 96%), abnormal lung function was 39% (95% CI 24–55, I2 = 94%), fatigue was 38% (95% CI 27–49, I2 = 98%), dyspnea was 32% (95% CI 24–40, I2 = 98%), chest paint/tightness was 16% (95% CI 12–21, I2 = 94%), and cough was 13%, (95% CI 9–17, I2 = 94%). Decreased functional capacity and HRQoL were found in 36% (95% CI 22–49, I2 = 97%) and 52% (95% CI 33–71, I2 = 94%), respectively. On average, 8 out of 10 of the patients had returned to work or reported no work impairment. Conclusion: Post-COVID-19 patients may experience persistent respiratory symptoms, fatigue, decreased functional capacity and decreased quality of life up to 6 months after infection. Further studies are needed to establish the extent to which post-COVID-19 effects continue beyond 6 months, how they interact with each other, and to clarify their causes and their effective management.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Current Oncology, MDPI AG, Vol. 28, No. 6 ( 2021-11-09), p. 4552-4576
    Abstract: In Canada, the therapeutic management of patients with advanced non-small cell lung cancer (NSCLC) with rare actionable mutations differs between provinces, territories, and individual centres based on access to molecular testing and funded treatments. These variations, together with the emergence of several novel mesenchymal-epithelial transition (MET) factor-targeted therapies for the treatment of NSCLC, warrant the development of evidence-based consensus recommendations for the use of these agents. A Canadian expert panel was convened to define key clinical questions, review evidence, discuss practice recommendations and reach consensus on the treatment of advanced MET-altered NSCLC. Questions addressed by the panel include: 1. How should the patients most likely to benefit from MET-targeted therapies be identified? 2. What are the preferred first-line and subsequent therapies for patients with MET exon 14 skipping mutations? 3. What are the preferred first-line and subsequent therapies for advanced NSCLC patients with de novo MET amplification? 4. What is the preferred therapy for patients with advanced epidermal growth factor receptor (EGFR)-mutated NSCLC with acquired MET amplification progressing on EGFR inhibitors? 5. What are the potential strategies for overcoming resistance to MET inhibitors? Answers to these questions, along with the consensus recommendations herein, will help streamline the management of MET-altered NSCLC in routine practice, assist clinicians in therapeutic decision-making, and help ensure optimal outcomes for NSCLC patients with MET alterations.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2270777-3
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