The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. METHODS: Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. RESULTS: Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08-0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33-0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33-0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38-1.02, p = 0.06). CONCLUSIONS: In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

The oncology ribbon of reflection: a novel tool to encourage trainee self-reflection.

The field of oncology presents a number of emotionally challenging situations for a trainee to navigate which might not have been previously encountered in training. With the assistance of a guide, reflecting on such situations can be helpful; however, no tool exists in the literature specifically for clinical oncology situations and tailored to provide trainees guidance through the reflective process. Consequently, we present a self-guided reflection tool design using four established reflection models and improved over three iterations of feedback.

Le domaine de l'oncologie présente un certain nombre de situations émotionnellement difficiles à gérer pour un stagiaire qui n'a peut-être jamais été confronté à de telles situations au cours de sa formation. Avec l'aide d'un guide, il peut être utile de réfléchir à ces situations. Cependant, il n'existe pas dans la littérature d'outil adapté aux situations cliniques en oncologie et conçu pour guider les stagiaires tout au long du processus de réflexion. Par conséquent, nous présentons un outil d'autoréflexion conçu à partir de quatre modèles de réflexion établis et amélioré au cours de trois rondes de rétroaction.

Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers.

INTRODUCTION: Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice. MATERIALS AND METHODS: Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified. Landmark four-month logistic regression analysis compared the odds of developing irAE or sequelae amongst patients aged <75 years to those aged 75-84 or ≥ 85. Objective responses were determined using Response Evaluation Criteria in Solid Tumors version 1.1. Univariable Cox proportional hazard (PH) regression modelling of factors associated with overall survival (OS) was performed. RESULTS: Of 106 patients, the proportions aged <75, 75-84, and ≥ 85 years were 34%, 45%, and 21%, respectively. Overall, the proportion of patients with irAE ≥ grade 3, cemiplimab discontinuation, and hospitalization for immune toxicity was 27.4%, 31.1%, and 11.3%, respectively. There was no clear association between age and the odds of high grade irAE. However, increased odds of cemiplimab discontinuation was observed in patients aged 75-84 years (p = 0.05). Patients ≥85 years had increased hospitalizations due to irAE (OR = 5.00, 95% CI = 0.97-37.52) with two treatment-related deaths. Objective responses were similar across age cohorts (50.0%, 60.4%, and 54.5%) but progressive disease was higher in the age ≥ 85 group (22.2%, 18.8%, and 31.8%). On Cox PH regression analysis, age ≥ 85 years (vs. <75), Eastern Cooperative Oncology Group performance status 2-3 (vs. 0-1), and neutrophil to lymphocyte ratio (NLR) ≥7.80 (vs. <7.80) were associated with shorter survival. DISCUSSION: While the odds of high grade irAE were similar across age groups, significant age-related differences in treatment discontinuation and hospitalization due to immune toxicity were observed. Despite a higher incidence of primary progression and shorter OS in the oldest cohort, cemiplimab yielded robust objective responses regardless of age. Higher pre-treatment NLR was associated with shorter survival and the cut-point identified requires further study.

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer.

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan-Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively.

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic.

Background: The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively. Kaplan-Meier curves of OS and progression-free survival (PFS) from the start of osimertinib were plotted. The associations of baseline characteristics with PFS, and development of pneumonitis or dose reductions due to toxicity with OS were evaluated with hazard ratios estimated using univariable and multivariable Cox models. Results: The cohort comprised 231 individuals. 58.7% of patients with de novo advanced NSCLC were initially diagnosed after presentation to the Emergency Room. At osimertinib initiation, 31.6% were aged ≥75 years and 45.5% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Median PFS and OS were 18.0 months [95% confidence interval (CI): 16.1-26.2] and 25.4 months (95% CI: 20.3-not reached), respectively. On multivariable analysis, age ≥75 years (vs. <75), ECOG PS 2/3 (vs. 0/1), ECOG PS 4 (vs. 0/1), current smokers (vs. never smokers), programmed death ligand 1 (PD-L1) expression ≥50% (vs. <1%), and L858R mutation (vs. exon 19 deletion) were associated with shorter PFS. Among 110 patients who progressed, 33.6% received subsequent therapy. A proportion of 16.5% of the cohort developed grade ≥3 adverse events. Pneumonitis from osimertinib (3.9% incidence) was weakly associated with shorter OS (hazard ratio: 2.59, 95% CI: 0.94-7.12, P=0.066); dose reductions were not associated with worse OS. 10.8% of patients developed COVID-19. Conclusions: In a cohort receiving first-line osimertinib during the COVID-19 pandemic, ECOG PS ≥2 was observed in nearly half of patients at treatment initiation contributing to a median OS shorter than in FLAURA. The incidence of severe adverse events was low and dose reduction for drug toxicity did not impact OS. Identifying and reducing barriers to the diagnosis of NSCLC during the COVID-19 pandemic are required.

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis.

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX) (5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.