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Background Immunotherapy in the presence of COVID-19 infections raises concerns because of potential overlapping clinical complications and immune system enhancement. Further investigation is warranted to establish its safety and to improve clinical decisions. Methods We conducted a retrospective cohort study using linked health administrative data from Ontario, Canada to assess 30-day mortality in patients with solid tumors who were treated with immunotherapy within 120 days before testing positive for COVID-19. A stepwise multivariable logistic regression model was used to identify clinical factors associated with 30-day mortality. Results Between January 2020 and April 2023, 281 patients tested positive for COVID-19 and were included in our study. The mean age was 68 (Standard Deviation: 10.3), 45% (127/281) were females and 58% (163/281) had lung cancer. 59% of patients (167/281) were treated with single agent immunotherapy, and almost 80% received at least one dose of COVID-19 vaccine. The 30-day mortality was 22% (63/281) and < 5% of patients were admitted to ICU or required ventilation. Factors associated with higher mortality were older age (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 1.07–2.39), prior radiation therapy (OR 2.38, 95%CI 1.08–5.28), lower hemoglobin (< 10 g/dl) (OR 4.08, 95%CI 1.89–8.82) and higher leucocytes count (> 11,000/mm 3 ) (OR 3.63, 95%CI 1.55–8.52). Conclusions Immunotherapy does not seem to increase the risk of 30-day mortality in patients with COVID-19 infections compared to published outcomes of patients with cancer and COVID-19. Mortality was associated with certain clinical characteristics that need to be carefully examined when prescribing immunotherapy during future comparable pandemics.

Background: Docetaxel, following progression on immunotherapy and platinum-based chemotherapy, remains the standard of care for advanced non-small-cell lung cancer (NSCLC) but offers limited promise. Antibody–drug conjugates (ADCs) may improve outcomes in this population. Objectives: Data from the literature, mainly randomized controlled trials (RCTs), have shown discrepancies. This report evaluates the efficacy and safety of ADCs versus docetaxel in previously treated advanced NSCLC. Design: The systematic review and meta-analysis was conducted focusing on phase II/III RCTs to synthesize available evidence regarding efficacy outcomes and safety of ADCs compared to docetaxel. Data resources and methods: Databases (PubMed (MEDLINE), EMBASE, and Cochrane Library), clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened comparing ADC versus docetaxel. Two researchers independently completed data retrieval and screening work using Covidence. The Cochrane Risk of Bias Tool (RoB 2.0) was used to assess the methodological quality of the included RCTs. The primary outcomes include progression-free survival (PFS) and overall survival (OS), while the secondary outcomes include objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The pooled hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed using the appropriate generic variance and Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates. Results: Of the 212 records screened, three RCTs involving 1597 patients were included. ADCs did not significantly improve PFS (pooled HR: 0.91, 95% CI: 0.73–1.13). For OS, the pooled HR was 0.88 (95% CI: 0.78–1.00, p = 0.06), reflecting a borderline significant trend favoring ADCs, with negligible heterogeneity (I2 = 0%). Furthermore, subgroup analysis demonstrated a significant OS benefit in the nonsquamous cohort (HR: 0.85, 95% CI: 0.74–0.98, p = 0.03). In addition, no difference was observed in ORR (OR: 1.16, 95% CI: 0.54–2.51) and DCR (OR: 1.39, 95% CI: 0.75–2.57). Grade ⩾ 3 treatment-related AEs were significantly lower (pooled OR: 0.49, 95% CI: 0.26–0.90, p = 0.02) with ADCs, despite high heterogeneity (I2 = 87%). Conclusion: Overall, there was no difference between the docetaxel and the ADC treatment arms; however, our findings report a significant survival benefit in the subgroup of patients with nonsquamous NSCLC pathology treated with ADCs compared to docetaxel with a manageable safety profile. Further research is needed to address heterogeneity, refine patient selection, and obtain more mature survival data with predictive biomarkers.

Background Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. Methods We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. Results CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p =0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p =0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65; p =0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p =0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p =0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p =0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p =0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p <0.001). Conclusion The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Background We compared the health‐related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I‐III esophageal cancer. Methods A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5‐fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5‐fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. Results There was no significant difference in the functional assessment of cancer therapy‐esophageal (FACT‐E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre‐treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT‐E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‐OG25), and EuroQol 5‐D‐3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30‐day mortalities and 2% vs. 10% 90‐day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5‐year: 35% vs. 32%, p = 0.409) or disease‐free survival (DFS) (5‐year: 31% vs. 30%, p = 0.710). Conclusion Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed. This randomized trial assessed the health related quality of life in esophageal cancer patients undergoing neoadjuvant versus adjuvant trimodality therapy. Every patient experienced at least one adverse event. The quality of life was worse for patients undergoing neoadjuvant compared to adjuvant chemoradiation with no significant difference in either overall survival or disease‐free survival. More effective therapy is needed.

Overall survival (OS) has been debated as the most important clinical endpoint in metastatic breast cancer (MBC) trials mainly because survival could be influenced by treatment after progression in an era of effective subsequent-line agents. We conducted a search strategy using PubMed for all the phase 3 trials in the last two decades evaluating survival outcome in MBC. We investigated the frequency of trials reporting survival outcome and response/resistance to treatment beyond progression. One hundred fifteen trials met our eligibility criteria: 69 (60 %) evaluated chemotherapy regimens (group A), 32 (28 %) evaluated targeted therapies (group B), and 14 (12 %) focused on endocrine treatment (group C). An OS benefit was demonstrated in approximately 22 % of the trials in each group. Less than 10 % of the trials in group A and B reported response data after progression on trial therapy. Post-progression treatment resistance was only reported in group A in 3 % (2/69) of the trials. In addition, the number of lines of treatment used post-progression was reported in 14 % (10/69), 9.4 % (3/32), and 14 % (2/14) of the trials in group A, B, and C, respectively. Post-progression survival and its effect on OS was reported in only 1 % (1/69), 3 % (1/32), and 7 % (1/14) of the trials for group A, B, and C respectively. A clear paucity of post-progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS can be affected partially or directly by treatments used after progression. In order to assess the true clinical benefit of a new drug and to have a complete evaluation of OS outcome, a detailed collection of post-progression treatment information is required and should be mandated in MBC trials.

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

Overall survival (OS) has been debated as the most important clinical endpoint in metastatic breast cancer (MBC) trials mainly because survival could be influenced by treatment after progression in an era of effective subsequent-line agents. We conducted a search strategy using PubMed for all the phase 3 trials in the last two decades evaluating survival outcome in MBC. We investigated the frequency of trials reporting survival outcome and response/resistance to treatment beyond progression. One hundred fifteen trials met our eligibility criteria: 69 (60 %) evaluated chemotherapy regimens (group A), 32 (28 %) evaluated targeted therapies (group B), and 14 (12 %) focused on endocrine treatment (group C). An OS benefit was demonstrated in approximately 22 % of the trials in each group. Less than 10 % of the trials in group A and B reported response data after progression on trial therapy. Post-progression treatment resistance was only reported in group A in 3 % (2/69) of the trials. In addition, the number of lines of treatment used post-progression was reported in 14 % (10/69), 9.4 % (3/32), and 14 % (2/14) of the trials in group A, B, and C, respectively. Post-progression survival and its effect on OS was reported in only 1 % (1/69), 3 % (1/32), and 7 % (1/14) of the trials for group A, B, and C respectively. A clear paucity of post-progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS can be affected partially or directly by treatments used after progression. In order to assess the true clinical benefit of a new drug and to have a complete evaluation of OS outcome, a detailed collection of post-progression treatment information is required and should be mandated in MBC trials.

Abstract Introduction The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited. Methods We conducted a retrospective cohort study using provincial health administrative data from Ontario, Canada to: (1) assess the extent of IO use from 2011 (pre-IO funding) to 2019; and (2) identify factors associated with IO use in patients with advanced cancers for which IO is reimbursed including melanoma, bladder, lung, head and neck, and kidney tumors. The datasets were linked using a unique encoded identifier. A Fine and Gray regression model with death as a competing risk was used to identify factors associated with IO use. Results Among 59 510 patients assessed, 8771 (14.7%) received IO between 2011 and 2019. Use of IO increased annually from 2011 (3.3%) to 2019 (39.2%) and was highest in melanoma (52%) and lowest in head and neck cancer (6.6%). In adjusted analysis, factors associated with lower IO use included older age (hazard ratio (HR) 0.91 (95% CI, 0.89-0.93)), female sex (HR 0.85 (95% CI, 0.81-0.89)), lower-income quintile, hospital admission (HR 0.78 (95% CI, 0.75-0.82)), high Charlson score and de novo stage 4 cancer. IO use was heterogeneous across cancer centers and regions. Conclusion IO utilization for advanced cancers rose substantially since initial approval albeit use is associated with patient characteristics and system-level factors even in a universal healthcare setting. To optimize IO utilization in routine practice, survival estimates and potential inequity in access should be further investigated and addressed. Since the advent of immunotherapy (IO), the treatment paradigm for cancer has dramatically changed for multiple tumor sites. This study used provincial administrative health data to estimate the proportion of patients with advanced cancer for which IO had been approved received the treatment and explored factors associated with IO use.

Purpose Estrogen receptor (ER) negative (−) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database “Biomatrix” to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes. Methods Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified. Results 304 patients were included with a median follow-up of 43.3 months (Q1–Q3 28.7–61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99–1.00, p  = 0.027 and 0.98 95% CI 0.97–0.99, p  < 0.0001, respectively). A cut-off of 60 and 80% predicted best the association with tumor size reduction and pCR, respectively. pCR was shown to be an independent predictor of RFS (HR 0.17, 95% CI 0.07–0.43, p  = 0.0002) in all patients. At 5 years, 93% of patients with pCR and 72% of patients with residual tumor were recurrence-free, respectively ( p  = 0.0012). Conclusions Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.

In May 2013, Angelina Jolie revealed to the media that she had undergone preventive double mastectomy after testing positive for a BRCA1 gene mutation. Media coverage has been extensive, but it is not clear how such a personal story affected the public and cancer genetics clinics. We conducted a retrospective review using data from the clinical database of the Familial Cancer Program at our centre. The impact of Ms. Jolie’s story on genetic counseling referrals and the appropriateness of such referrals were assessed and reported. The number of women referred for genetic counseling increased by 90 % after 6 months and remained high one year after AJ’s story with an increase of 88 % from baseline. The number of women who qualified for genetic testing increased by 105 % after 6 months; this increase persisted but was somewhat lower after one year with an increase of 68 % from baseline. Furthermore the number of BRCA1 / 2 carriers identified increased by 110 % after 6 months and by 42 % after one year. The effect of Mrs. Jolie’s story persisted one year after its release; however in the latter half of the year, the hereditary cancer risk of referred women was significantly lower than initially observed. The next challenge for our health care system will not only be to meet the increased demand for cancer genetic services in our region, but also to ensure that referrals and hence use of genetic counseling resources are appropriate.