Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials.

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy-effectiveness gap whereby patients in the 'real world' seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics.

Treating anaplastic lymphoma kinase (ALK) fusion-driven metastatic non-small cell lung cancer (NSCLC) with alectinib through pregnancy.

Management of cancer during pregnancy requires careful consideration of risks and benefits from maternal and fetal perspectives. For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin-paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy.

Impact of age, comorbidity, and polypharmacy on receipt of systemic therapy in advanced cancers: A retrospective population-based study.

Introduction: Cancer incidence, comorbidity, and polypharmacy increase with age, but the interplay between these factors on receipt of systemic therapy (ST) in advanced cancer has rarely been studied.

Materials And Methods: A retrospective cohort study was conducted including patients aged ≥18 years diagnosed from 2004 to 2015 with multiple myeloma (MM) (all stages), lung cancer (stage IV), and stage III-IV non-Hodgkin's lymphoma (NHL), breast, colorectal (CRC), prostate, or ovarian cancer in Manitoba, Canada. Clinical and administrative health data were used to determine demographic and cancer characteristics, treatment history, comorbidity (Charlson Comorbidity Index [CCI] and Resource Utilization Band [RUB]), and polypharmacy (≥6 medications).

Real-world predictors of survival in patients with limited-stage small-cell lung cancer in Manitoba, Canada.

Background: Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential.

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions.

Objective: This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada.

Real-World Outcomes of Stage IV NSCLC with PD-L1 ≥ 50% Treated with First-Line Pembrolizumab: Uptake of Second-Line Systemic Therapy.

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.

Real World Patient Eligibility for Second Line Lurbinectedin Based Treatment in Small Cell Lung Cancer: Understanding Epidemiology and Estimating Health Care Utilization.

Background: In the ATLANTIS study, second-line lurbinectedin/doxorubicin did not improve overall survival (OS), however patients with a chemotherapy-free interval (CTFI) of ≥180 days had an improved progression free survival (PFS). The objective of this retrospective study was to identify the proportion of real-world small cell lung cancer (SCLC) patients who are suitable for lurbinectedin-based therapy based on these criteria.

Methods: A retrospective study of all SCLC referred to BC Cancer between 2012 and 2017 was conducted.

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing.

Background: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules.

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer.

Introduction: Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.

Acute Onset of a Life-Threatening Skin Toxicity Due to Osimertinib: Severe Psoriasis Versus Toxic Epidermal Necrolysis.

Osimertinib is a third-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor currently used as first-line systemic therapy for advanced EGFR mutant non-small cell lung cancer. Osimertinib is generally very well tolerated with only a 1% risk of grade 3-4 skin toxicity. Here we present a case of a 68-year-old Asian male with advanced EGFR exon 19 deletion non-small cell lung cancer.

Radiation Induced Abscopal Effect in a Patient With Malignant Pleural Mesothelioma on Pembrolizumab.

Abscopal effect is a rare phenomenon in which treatment benefit from radiotherapy (RT) is seen outside the target field due to activation of the immune system inducing an anti-tumor effect. This phenomenon has been reported in cancer patients receiving immune checkpoint inhibitors (ICI). Here we report a case of presumed abscopal effect in malignant mesothelioma.

Treatment Patterns, Toxicity, and Outcomes of Older Adults With Advanced Pancreatic Cancer Receiving First-line Palliative Chemotherapy.

Objectives: Advanced pancreatic cancer (APC) disproportionately impacts older adults. Randomized trials demonstrate improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine compared with gemcitabine alone, but with increased toxicity. Older adults are at increased risk of side effects from chemotherapy.

Treatment and Prevention of Brain Metastases in Small Cell Lung Cancer.

Central nervous system (CNS) metastasis will develop in 50% of small cell lung cancer (SCLC) patients throughout disease course. Development of CNS metastasis poses a particular treatment dilemma due to the accompanied cognitive changes, poor permeability of the blood-brain barrier to systemic therapy and relatively advanced state of disease. Survival of patients with untreated SCLC brain metastases is generally <3 months with whole brain radiotherapy used as first-line management in most SCLC patients.

Feasibility of Randomized Controlled Trials for Cancer Drugs Approved by the Food and Drug Administration Based on Single-Arm Studies.

Background: The US Food and Drug Administration (FDA) introduced an Accelerated Approval (AA) pathway to expedite patient access to new drugs. AA accepts less rigorous trial designs, including single-arm studies (SAS), owing to perceived lack of feasibility of timely randomized controlled trials (RCTs).

Methods: We designed hypothetical RCTs with endpoints of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) for FDA approvals based on SAS for solid tumors during 2010-2019.

Canadian Cancer Centre Response to COVID-19 Pandemic: A National and Provincial Response.

Background: COVID-19 has spread rapidly, requiring health delivery systems to undertake dramatic transformations. To evaluate these system changes, we undertook one of the first Canadian health delivery system reviews and the first Canadian cancer centre evaluation of pandemic system modifications.

Methods: Questionnaires were distributed to the Canadian Association of Provincial Cancer Agencies (CAPCA) members in order to assess changes to cancer centre services and patient management.

Immune Checkpoint Inhibition as Primary Adjuvant Therapy for an -Mutant Anaplastic Astrocytoma in a Patient with CMMRD: A Case Report-Usage of Immune Checkpoint Inhibition in CMMRD.

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive hereditary cancer syndrome due to biallelic germline mutation involving one of the four DNA mismatch repair genes. Here we present a case of a young female with CMMRD, homozygous for the c.2002A>G mutation in the gene.

Immunotherapy Benefit in a Patient With Non-Small Cell Lung Cancer and a Rare BRAF Mutation.

Immunotherapy is less effective in non-small cell lung cancer (NSCLC) with driver mutations in epidermal growth factor receptor or anaplastic lymphoma kinase and some may extrapolate this trend to other driver mutations. Up to 4% of NSCLC cases contain a mutation. Most mutations are V600E, and little is known about the impact of treatment in rare G469A mutations.

Utility of the modified frailty index in predicting toxicity and cancer outcomes for older adults with advanced pancreatic cancer receiving first-line palliative chemotherapy.

Background: Pancreatic cancer primarily affects older adults and is associated with a high morbidity and mortality. Identifying frail patients with advanced pancreatic cancer (APC) helps to mitigate the risks of chemotherapy (CT). The modified Frailty Index (mFI) is an 11-point deficit measure used to identify frail patients.

Effect of Hospitalization During First Chemotherapy and Performance Status on Small-cell Lung Cancer Outcomes.

Introduction: Small-cell lung cancer (SCLC) is highly responsive to chemotherapy (CT) and one of the few malignancies treated in hospitalized patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS). Because of the little current information available on the outcomes experienced by hospitalized patients with SCLC receiving CT, we explored the outcomes for these patients to improve the evidence base for practice.

Materials And Methods: We conducted a retrospective cohort study to evaluate patients with a diagnosis of SCLC and treated with CT during a 10-year period.

Salvage HIFU for biopsy confirmed local prostate cancer recurrence after radical prostatectomy and radiation therapy: Case report and literature review.

High-intensity focused ultrasound (HIFU) is a treatment option for low- and intermediate-risk prostate cancer and more recently has been used as salvage therapy after failed radiation therapy. We present a case of local recurrence with biochemical failure after radical prostatectomy and salvage external beam radiation therapy with salvage HIFU without biochemical recurrence at 20 months.

A qualitative analysis of methotrexate self-injection education videos on YouTube.

The aim of this study is to identify and evaluate the quality of videos for patients available on YouTube for learning to self-administer subcutaneous methotrexate. Using the search term "Methotrexate injection," two clinical reviewers analyzed the first 60 videos on YouTube. Source and search rank of video, audience interaction, video duration, and time since video was uploaded on YouTube were recorded.

Angiomyolipoma with caval extension and regional nodal involvement: Aggressive behaviour or just rare natural history? Case report and review of literature.

Renal angiomyolipoma (AML) is predominantly a non-aggressive benign tumour. Cases of more aggressive AMLs are present in the literature. We present 2 cases of aggressive AML behaviour.