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Gagnon R, Kish EK, Cook S, Takemura K, Cheng BYC, Bressler K, Heng DYC, Alimohamed N, Ruether D, Lee-Ying RM, Bose P, Kolinsky MP, Vasquez C, Samuel D, Lewis J, Faridi R, Borkar M, Fairey A, Bismar T, Yip S
Abstract:
BACKGROUND: Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians. METHODS: This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases. Median overall survival (OS) was calculated by stage and castration sensitivity. Prognostic factors were assessed via multivariate analysis. OS and progression-free survival on first-line metastatic systemic treatment were also evaluated. RESULTS: Of 135 NEPC cases, 25.9% had NEPC documented in the original pathological report. Mixed pathology was found in 91.9% of cases. Median OS from NEPC diagnosis was 59.2, 42.3, 14.3, 17.6 and 9.6 months for localized, nonmetastatic castration-sensitive, nonmetastatic castration-resistant, metastatic castration-sensitive and metastatic castration-resistant prostate cancer, respectively. Anemia (hazard ratio [HR]: 1.66; 95% CI 1.05-2.16; P = .031) and elevated neutrophil-lymphocyte ratio (NLR) (HR: 1.51; 95% CI 1.01-2.52; P = .045), were associated with increased risk of death on multivariate analysis. 67 patients received first-line metastatic treatment beyond androgen deprivation, with a median progression-free survival of 5.2 months and OS of 15 months. Of these, 50.7% received more than 1 line of systemic treatment. CONCLUSION: We observed underdiagnosis of NEPC in pathology specimens. NEPC is associated with poorer prognosis than would be expected in pure adenocarcinoma populations, with rapid progression on first-line metastatic treatment and sharp drop-off between subsequent treatment lines. Anemia and elevated NLR were associated with poor survival.
Patil T, Gao D, Watson A, Sakamoto M, Nie Y, Gibson A, Dean ML, Yoder BA, Miller E, Stalker M, Aisner DL, Bunn PA, Schenk EL, Marmarelis ME, Bennati C, Navani V, Zhang Y, Camidge DR
Abstract:
INTRODUCTION: For patients with EGFR mutant NSCLC who progress on osimertinib, the clinical benefit of continuing osimertinib with next line platinum pemetrexed chemotherapy remains unknown. METHODS: In this international, multi-center, retrospective cohort study, a total of 159 patients with EGFR mutant NSCLC who progressed on osimertinib and received platinum-pemetrexed therapy on progression from 2013 to 2023 were included. The data cutoff was December 31, 2023. Data analysis was conducted from January 2024 to June 2024. The primary endpoints were progression free survival (PFS) and overall survival (OS), analyzed using Kaplan-Meier methods. Multivariable Cox regression adjusting for patient-specific and cancer-specific factors was performed. RESULTS: 421 patients with EGFR mutant NSCLC with progression on osimertinib were identified, of which159 patients who met pre-specified inclusion criteria were divided into two groups: Cohort 1 (osimertinib + platinum-pemetrexed) included 50 patients (median [IQR] age, 59 [30 - 83] years; 36 [72.0 %] female; 11 [22.4 %] Asian) and Cohort 2 (platinum-pemetrexed alone) included 109 patients (median [IQR] age, 54 [25 - 80] years; 62 [56.9 %] female; 74 [64.9 %] Asian). Most patients were never smokers (Cohort 1, 37 [74.0 %]; Cohort 2, 66 [60.6 %]). One third of patients had baseline brain metastases (Cohort 1, 19 [38.0 %]; Cohort 2, 36 [38.3 %]). Both cohorts had a median of two prior lines of anti-cancer therapy. The addition of bevacizumab or immune checkpoint inhibitors (ICI) to next-line platinum-pemetrexed chemotherapy was more common in Cohort 2 (bevacizumab use, 30.3 % vs 8.0 %, p = 0.002; ICI use, 33.0 % vs 2.0 %, p = 0.001). With a median duration of follow up of 30 months, there was a significant PFS benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy (9.0 vs 4.5 months; HR 0.49, 95 % CI 0.32 - 0.74, p = 0.0032), also seen in subset analyses of patients who received first line osimertinib (n = 55, 11.0 vs 6.2 months; HR 0.41, 95 % CI 0.25 - 0.73, p = 0.002). Among patients with EGFR mutant NSCLC without brain metastases after progression on osimertinib, we found that continuing osimertinib with next line platinum pemetrexed significantly reduced the median time to CNS progression (n = 38; 7.0 vs 4.1 months; HR 0.47, 95 % CI 0.48 - 0.98, p = 0.01). After adjusted analysis, there was no significant OS difference between Cohorts 1 and 2 (19 months vs 13 months; HR 0.92, 95 % CI 0.60 - 1.39, p = 0.68). CONCLUSIONS AND RELEVANCE: For patients with EGFR mutant NSCLC who progress on osimertinib, there is a significant PFS, but not OS, benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy. The continuation of osimertinib with next line platinum pemetrexed chemotherapy appears to reduce the risk of CNS progression.
Harsanyi H, Yang L, Lau J, Cheung WY, Cuthbert C
Abstract:
No Data
Tavares VDO, Schuch FB, de Sousa GM, Hallgren M, Oliveira Neto L, Cabral DAR, Nóbrega de Almeida R, Barbosa DC, de Almeida VRN, Tinoco H, Lira RA, Hallak JE, Arcoverde E, Cuthbert C, Patten S, Galvão-Coelho NL
Abstract:
This randomized controlled trial investigated the effectiveness of an affect-adjusted, supervised, multimodal, online, and home-based exercise group protocol as an adjunct therapy to antidepressants on depressive symptoms, cardiorespiratory fitness, and side effects related to antidepressants in adults with major depression (MDD, diagnosed by a clinician). Depressive symptom scales were administered by a psychiatrist and self-reported. A health-related measure (i.e., cardiorespiratory fitness), was also administered. The exercise intervention was adjusted by perceived effort and affect (pleasure and enjoyment) toward exercise and lasted 12 weeks. In total, 59 adults with MDD were divided into two groups: the exercise-group (EG; exercise + pharmacotherapy) with 26-patients (76.9 % females, mean age 28.5 years) and the control-group (CG, pharmacotherapy) with 33-patients (78.7 % females, mean age 25.6 years). The EG had a lower dropout rate (15.3 %) than CG and an increase in cardiorespiratory fitness (CRF), which was not observed in the CG. Both groups showed a decrease in self-reported depressive symptoms. However, the EG had significantly lower depressive symptom scores at t1 and t2. The EG also had higher remission rates (t1, EG: = 42.3 % and CG = 27.2 %) and remission rates (t2, EG: = 72.7 % and CG = 48.1 %) than CG, which were maintained during the four month follow-up. Side effects from anti-depressant medication were larger in the EG compared to CG. Complementing usual care for MDD with exercise resulted in better clinical outcomes and supports the use of this type of exercise protocol in the clinical management of depression.
Phillips WJ, Jackson A, Kidane B, Lim G, Navani V, Wheatley-Price P
Abstract:
The role of immunotherapy as systemic therapy for nonmetastatic non-small cell lung cancer (NSCLC) has evolved rapidly over the last decade. There are several well-conducted phase 3 clinical trials evaluating immunotherapy in the neoadjuvant, perioperative, adjuvant and nonoperative setting. In this narrative review, we summarize the data from these studies and discuss ongoing controversies in applying these data to clinical practice. These controversies relate to the value of the adjuvant component of perioperative immunotherapy, treatment of patients with PDL1 negative tumors, defining resectability, optimal use of operative versus nonoperative management, the role of stereotactic radiation therapy for very early lung cancers, and management of tumors with an oncogenic driver.
Warkentin MT, Cheung WY, Brenner DR, O'Sullivan DE
Abstract:
BACKGROUND: Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada. METHODS: We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), in which E is a weighted sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up. RESULTS: The risk of developing a SPC up to 15 years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR = 1.50) and females (SIR = 1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than five-fold increase for survivors diagnosed between ages 18 and 39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPC among females and males, respectively. CONCLUSIONS: Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared with the cancer risk in the general population. IMPACT: Screen-detectable cancers were common SPC sites and highlight the need to investigate optimal strategies for screening the growing population of cancer survivors.
Gotto GT, Yip SM, Shayegan B, O'Sullivan DE, Wallis CJD, Basappa NS, Cagiannos I, Hamilton RJ, Ferrario C, Fernandes R, Danielson B, Saad F, Hotte SJ, Cheung WY, Boyne DJ, Chan K, Osborne B, Zardan A, Malone S
Abstract:
INTRODUCTION: Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice. METHODS: Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated on ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation. RESULTS: A total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. Three percent of patients were intensified in 2010-2013; this increased to 67% in 2020. From 2014-2017, docetaxel was the most used approach, although it was supplanted by abiraterone acetate, apalutamide, and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). CONCLUSIONS: There has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.
Gupta M, Wells C, Regan MM, Xie W, Navani V, Saliby RM, Basappa NS, Donskov F, Yuasa T, Takemura K, Kollmannsberger CK, Crumbaker M, Lalani AA, Powles T, Ebrahimi H, McKay RR, Lee JL, Kanesvaran R, Choueiri TK, Heng DYC
Abstract:
BACKGROUND AND OBJECTIVE: Patients receiving immune checkpoint blockade (ICB) therapy may experience periods of prolonged disease control without a need for systemic therapy. Treatment-free survival (TFS) is an important measure for this period, but no data are available for patients with metastatic renal cell carcinoma (mRCC) starting first-line agents. Our aim was to analyze TFS outcomes for patients with mRCC starting first-line therapy. METHODS: We analyzed data for patients with mRCC starting first-line systemic therapy with VEGFR-targeted monotherapy, an ICB + VEGFR combination, or an ICB doublet from February 1, 2014 to February 1, 2023 from the multicenter International Metastatic RCC Database Consortium (IMDC) database. We estimated 36-mo TFS as the difference in restricted mean survival time between (1) the time to first-line therapy discontinuation and (2) the time to subsequent systemic therapy initiation. KEY FINDINGS AND LIMITATIONS: The study population included 3758 patients receiving either first-line VEGFR monotherapy (n = 2635), an ICB + VEGFR combination (n = 354), or doublet ICB (n = 769) were included. For the IMDC favorable-risk cohort, the 36-mo TFS estimate was 3.1 mo (95% confidence interval [CI] 1.5-4.6) for the VEGFR monotherapy group and 3.7 mo (95% CI 0.2-7.2) for the ICB + VEGFR group. For the IMDC intermediate-/poor-risk cohort, TFS was 2.1 mo (95% CI 1.4-2.8) for the VEGFR monotherapy group, 3.7 mo (95% CI 1.0-6.4) for the ICB + VEGFR group, and 5.3 mo (95% CI 3.8-6.8) for ICB doublet group. Limitations include the retrospective design and an inability to quantify time spent with adverse events. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study demonstrates that patients with IMDC intermediate or poor risk treated with ICB doublet therapy experienced longer TFS than those treated with VEGFR monotherapy in the first-line setting. These results emphasize the utility of TFS as an informative endpoint and provide survival estimates to inform decision-making in mRCC. PATIENT SUMMARY: For patients with metastatic kidney cancer, we compared the survival time free from a second treatment line for different first-line treatment options. The results show that the time free from second-line treatment was longer when first-line treatment was with a combination of two immunotherapy drugs (ipilimumab and nivolumab) in comparison to other treatment options.
Warkentin MT, Tammemägi MC, Vakil E, Bedard ELR, Cheung WY, Brenner DR, Tremblay A
Abstract:
INTRODUCTION: Older individuals have an elevated lung cancer risk but may also have substantial comorbidities that preclude curative treatment options and limit the survival benefits of screening. The objective of this study was to assess early stage lung cancer survival patterns among those at the upper age limit for screening and identify older individuals who have the potential to benefit from lung cancer screening. METHODS: We identified all early stage (I or II) lung cancers diagnosed in Alberta, Canada between 2010 and 2020. Overall survival (OS) was based on the time from the date of lung cancer diagnosis to the date of death (from any cause) or censoring. We estimated OS using the Kaplan-Meier method. We present OS with 95% confidence intervals (CIs) for each age group and sex and stratified by presence of comorbidities (Charlson Comorbidity Index) and receipt of surgery. RESULTS: There were 6401 early stage lung cancers (71% stage I, 29% stage II), of which 43% and 57% were among males and females, respectively. For females, the 5-year OS was 54.7% (95% CI: 50.6-58.8), 47.2% (95% CI: 42.7-51.7), and 33.7% (95% CI: 28.4-38.9) for ages 70 to 74 years, 75 to 79 years, and 80 to 84 years, respectively. For males, the 5-year OS was 47.7% (95% CI: 43.1-52.3), 38.0% (95% CI: 33.2-42.8), and 24.2% (95% CI: 19.2-29.3) for ages 70 to 74 years, 75 to 79 years, and 80 to 84 years, respectively. Across all age groups, the 5-year OS was higher for those with fewer comorbidities and for those who received surgery as part of their treatment strategy, usually surpassing that in younger cohorts with more comorbidities or those who did not receive surgical treatment. CONCLUSIONS: Age limits for lung cancer screening should consider comorbidity and fitness for curative treatment because these can significantly influence the survival after diagnosis and treatment of early lung cancer.
Hutchinson JM, Chow J, Farah E, Warkentin MT, Ruan Y, Hilsden RJ, Brenner DR
Abstract:
PURPOSE: There is limited evidence regarding body mass index (BMI) as an early marker of high-risk adenoma (HRA) at the time of screening colonoscopy. Because high-risk adenomas (HRA) can develop into colorectal cancer (CRC), BMI could serve as an important clinical predictor of future risk of CRC. METHODS: We examined data from 1831 adults undergoing screening colonoscopy at the Forzani & MacPhail Colon Cancer Screening Center in Alberta, Canada. We fit multivariable logistic regression models to examine the association between BMI and HRA. Non-linear relationships for BMI on HRA were also evaluated using restricted cubic splines. RESULTS: The mean BMI in patients with HRA was 28.2 kg/m2 compared to 27.4 kg/m2 in patients without adenomas (t test: p = 0.003). In the adjusted models, those with a BMI over 30 kg/m2 had 1.45 (95% CI 1.05-2.00) times the odds of HRA detected during colonoscopy compared to those with a BMI below 25 kg/m2. Examining BMI as continuous, the odds of HRA were 1.20 (95% CI 1.04-1.37) times higher for every 5 kg/m2 increase in BMI. CONCLUSION: The findings of this study suggest that excess body mass is associated with higher risk of HRA among a screening population and may be useful an early marker of future disease.
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