Clinical trials are increasingly supported by industries while previous studies have shown that industry-supported studies have more favorable results than studies with other sources of funding. In the present study, we investigated the association of industrial funding on the results of clinical trials regarding chemotherapy in prostate cancer.
Methods
A systematic literature search was performed in the Cochrane Library, MEDLINE, and EMBASE to identify clinical trials comparing chemotherapy with treatments such as hormone therapy, surgery, radiotherapy, and placebo in patients with metastatic or non-metastatic prostate cancer. Data were extracted by two reviewers on the financial resources and the positive or negative results of chemotherapy in each study. The quality of articles was evaluated and compared based on Cochrane Critical Appraisal Tool. The trials were divided into two groups; industry funded and those not funded by industry. Association of industry funding and positive outcome was presented as odds ratio.
Results
In this study, out of the 91 studies, 80.2% were funded by pharmaceutical companies and 19.8% were funded by government agencies. The end result of 61.6% of the studies funded by pharmaceutical companies was an increase in survival due to chemotherapy, whereas only 27.8% of the studies sponsored by government agencies reported positive results (P-value=0.010). In fact, industry-funded trials more often presented statistically significant positive results for survival (OR: 4.17; CI, 1.34–12.99). In general, there was no significant difference in the degree of bias between the two groups.
Conclusion
According to this study, despite of the similar quality of studies funded by pharmaceutical companies and government agencies, positive results were more common in studies related to pharmaceutical companies. Therefore, this point should be taken into account when making a decision on the best treatment approach.
{"title":"Pharmaceutical industry funding and chemotherapy trials for prostate cancer: A systematic review","authors":"Amirreza Heydari , Behnam Shakiba , Asaad Moradi , Saeed Esmaeil Soofian , Nasrollah Abian , Kazem Heidari , Robab Maghsoudi","doi":"10.1016/j.ctarc.2023.100739","DOIUrl":"10.1016/j.ctarc.2023.100739","url":null,"abstract":"<div><h3>Introduction</h3><p>Clinical trials are increasingly supported by industries while previous studies have shown that industry-supported studies have more favorable results than studies with other sources of funding. In the present study, we investigated the association of industrial funding on the results of clinical trials regarding chemotherapy in prostate cancer.</p></div><div><h3>Methods</h3><p>A systematic literature search was performed in the Cochrane Library, MEDLINE, and EMBASE to identify clinical trials comparing chemotherapy with treatments such as hormone therapy, surgery, radiotherapy, and placebo in patients with metastatic or non-metastatic prostate cancer. Data were extracted by two reviewers on the financial resources and the positive or negative results of chemotherapy in each study. The quality of articles was evaluated and compared based on Cochrane Critical Appraisal Tool. The trials were divided into two groups; industry funded and those not funded by industry. Association of industry funding and positive outcome was presented as odds ratio.</p></div><div><h3>Results</h3><p>In this study, out of the 91 studies, 80.2% were funded by pharmaceutical companies and 19.8% were funded by government agencies. The end result of 61.6% of the studies funded by pharmaceutical companies was an increase in survival due to chemotherapy, whereas only 27.8% of the studies sponsored by government agencies reported positive results (P-value=0.010). In fact, industry-funded trials more often presented statistically significant positive results for survival (OR: 4.17; CI, 1.34–12.99). In general, there was no significant difference in the degree of bias between the two groups.</p></div><div><h3>Conclusion</h3><p>According to this study, despite of the similar quality of studies funded by pharmaceutical companies and government agencies, positive results were more common in studies related to pharmaceutical companies. Therefore, this point should be taken into account when making a decision on the best treatment approach.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.ctarc.2023.100723
Pedro Augusto Reck dos Santos , Yalun Li , Vinicius Ernani , Jonathan D'Cunha , Marie-Christine Aubry , Ping Yang
Introduction
Non-Small Cell Lung Cancer (NSCLC) diagnosed at a younger age have patterns of care, responses to treatment, and outcomes not entirely clear. A particular feature includes more advanced stages at diagnosis. Our objective was to characterize these young patients with advanced disease and evaluate the impact of targeted therapies.
Methods
Analyzing our cohort of 18,252 newly diagnosed NSCLC patients, we defined Young-age versus Norm-age based on the age distribution at the time of diagnosis. Stage-IV patients were investigated on their clinical information and outcomes; deaths were considered lung cancer-related. Primary outcome was overall survival (OS). Multivariate Cox models were built to evaluate independent prognostic factors in comparative age groups.
Results
We found 4,267 patients with stage-IV NSCLC (359 Young-age; 3,908 Norm-age). Young patients had predominance of females (52.6% vs. 43.3%, P = 0.001), never-smokers (43.2% vs. 14.8%, P < 0.001), and adenocarcinoma (73.5% vs. 62.5%, P < 0.001). Mean OS was 21.1 months in the Young and 15.1 months in Norm, respectively (P < 0.001). Young patients were more often treated with surgery (6.7% vs. 5.0%), chemotherapy (53.2% vs. 44.1%), and targeted therapy (10.6% vs. 5.7%). Molecular studies were assessed in patients when the mutation tests became clinically available (93 Young, 875 Norm) and revealed a critical role of targeted therapy in the improved survival of both age groups.
Discussion
Young patients with stage-IV NSCLC have a specific profile and benefit more when treated with surgery and targeted therapy. Molecular testing is critical in this population, where improved survival was identified. A more aggressive approach to this population needs to be considered.
{"title":"Clinical outcomes of stage-IV non–small-cell lung cancer in young patients and the impact of tumor markers","authors":"Pedro Augusto Reck dos Santos , Yalun Li , Vinicius Ernani , Jonathan D'Cunha , Marie-Christine Aubry , Ping Yang","doi":"10.1016/j.ctarc.2023.100723","DOIUrl":"10.1016/j.ctarc.2023.100723","url":null,"abstract":"<div><h3>Introduction</h3><p>Non-Small Cell Lung Cancer (NSCLC) diagnosed at a younger age have patterns of care, responses to treatment, and outcomes not entirely clear. A particular feature includes more advanced stages at diagnosis. Our objective was to characterize these young patients with advanced disease and evaluate the impact of targeted therapies.</p></div><div><h3>Methods</h3><p>Analyzing our cohort of 18,252 newly diagnosed NSCLC patients, we defined Young-age versus Norm-age based on the age distribution at the time of diagnosis. Stage-IV patients were investigated on their clinical information and outcomes; deaths were considered lung cancer-related. Primary outcome was overall survival (OS). Multivariate Cox models were built to evaluate independent prognostic factors in comparative age groups.</p></div><div><h3>Results</h3><p>We found 4,267 patients with stage-IV NSCLC (359 Young-age; 3,908 Norm-age). Young patients had predominance of females (52.6% vs. 43.3%, <em>P</em> = 0.001), never-smokers (43.2% vs. 14.8%, <em>P</em> < 0.001), and adenocarcinoma (73.5% vs. 62.5%, <em>P</em> < 0.001). Mean OS was 21.1 months in the Young and 15.1 months in Norm, respectively (<em>P</em> < 0.001). Young patients were more often treated with surgery (6.7% vs. 5.0%), chemotherapy (53.2% vs. 44.1%), and targeted therapy (10.6% vs. 5.7%). Molecular studies were assessed in patients when the mutation tests became clinically available (93 Young, 875 Norm) and revealed a critical role of targeted therapy in the improved survival of both age groups.</p></div><div><h3>Discussion</h3><p>Young patients with stage-IV NSCLC have a specific profile and benefit more when treated with surgery and targeted therapy. Molecular testing is critical in this population, where improved survival was identified. A more aggressive approach to this population needs to be considered.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.ctarc.2023.100745
Ahmed K. Awad , Rehmat Ullah Awan , Ayman K. Awad , Ambreen Nabeel , Sophia Dar , Ayokunle T. Abegunde
Background
Enteropathy-Associated T-Cell Lymphoma (EATL) is a rare lymphoma of T-cell origin associated with celiac disease. There is limited evidence in the literature about the incidence and causes of death in patients with EATL.
Methods
We performed a retrospective study through analyzing the Surveillance, Epidemiology, and End Results (SEER) data base to determine the incidence, trends and causes of death of patients with EATL in the U.S from 2000 to 2018. Baseline characteristics with treatment options (surgery, radiotherapy, and chemotherapy), status of patients either alive, dead due to cancer itself or other non-cancerous causes with listing of those non-cancerous causes was retrieved. Sub-group analysis based on sex was also done. Multiple latency periods (<2 year, 2–5, 6–10, 11–15, and more than 15 years) were analyzed following EATL diagnosis.
Results
There were 259 EATL patients, majority were aged 70–74 years old (n = 36, 13.9%), predominantly males 155 (59.8%), most common in whites, (76.4%, n = 198), EATL was the only primary tumor in 177 (68.3%) cases, most common site was small bowel at different sites 84 (32.4%) followed by jejunum specifically 57 (22%), majority went for surgical resection (69.9%, n = 181) followed by chemotherapy (47.5%, n = 123), 217 (83.7%) died during follow-up in this study,
Conclusion
EATL is a rare entity, mostly seen in males, between 70 and 74 years, and mostly originated in the small bowel. With over 80% death in five-year follow up period, EATL patients showed better survival if they underwent chemotherapy. More studies are needed for further understanding of this rare entity.
{"title":"Patients with enteropathy-associated T-cell lymphoma in the United States from 2000 to 2018: SEER data-base analysis","authors":"Ahmed K. Awad , Rehmat Ullah Awan , Ayman K. Awad , Ambreen Nabeel , Sophia Dar , Ayokunle T. Abegunde","doi":"10.1016/j.ctarc.2023.100745","DOIUrl":"10.1016/j.ctarc.2023.100745","url":null,"abstract":"<div><h3>Background</h3><p>Enteropathy-Associated T-Cell Lymphoma (EATL) is a rare lymphoma of T-cell origin associated with celiac disease. There is limited evidence in the literature about the incidence and causes of death in patients with EATL.</p></div><div><h3>Methods</h3><p>We performed a retrospective study through analyzing the Surveillance, Epidemiology, and End Results (SEER) data base to determine the incidence, trends and causes of death of patients with EATL in the U.S from 2000 to 2018. Baseline characteristics with treatment options (surgery, radiotherapy, and chemotherapy), status of patients either alive, dead due to cancer itself or other non-cancerous causes with listing of those non-cancerous causes was retrieved. Sub-group analysis based on sex was also done. Multiple latency periods (<2 year, 2–5, 6–10, 11–15, and more than 15 years) were analyzed following EATL diagnosis.</p></div><div><h3>Results</h3><p>There were 259 EATL patients, majority were aged 70–74 years old (<em>n</em> = 36, 13.9%), predominantly males 155 (59.8%), most common in whites, (76.4%, <em>n</em> = 198), EATL was the only primary tumor in 177 (68.3%) cases, most common site was small bowel at different sites 84 (32.4%) followed by jejunum specifically 57 (22%), majority went for surgical resection (69.9%, <em>n</em> = 181) followed by chemotherapy (47.5%, <em>n</em> = 123), 217 (83.7%) died during follow-up in this study,</p></div><div><h3>Conclusion</h3><p>EATL is a rare entity, mostly seen in males, between 70 and 74 years, and mostly originated in the small bowel. With over 80% death in five-year follow up period, EATL patients showed better survival if they underwent chemotherapy. More studies are needed for further understanding of this rare entity.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.ctarc.2023.100715
Beung-Chul Ahn , Seoyoung Lee , Jiyun Lee , Jii Bum Lee , Min Hee Hong , Sun Min Lim , Suyog Jain , Steve Olsen , Byoung Chul Cho
Objectives: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC.
Patients and methods: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently.
Results: aNSCLC patients with cfDNA test results (n = 405) were categorized into three groups: treatment naïve (n = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (n = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (n = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (n = 221) with common EGFR mutations or ALK/ROS1 fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment.
Conclusions: In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC.
{"title":"Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea","authors":"Beung-Chul Ahn , Seoyoung Lee , Jiyun Lee , Jii Bum Lee , Min Hee Hong , Sun Min Lim , Suyog Jain , Steve Olsen , Byoung Chul Cho","doi":"10.1016/j.ctarc.2023.100715","DOIUrl":"10.1016/j.ctarc.2023.100715","url":null,"abstract":"<div><p><strong><em>Objectives:</em></strong> Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC.</p><p><strong><em>Patients and methods:</em></strong> This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently.</p><p><strong><em>Results:</em></strong> aNSCLC patients with cfDNA test results (<em>n</em> = 405) were categorized into three groups: treatment naïve (<em>n</em> = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (<em>n</em> = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (<em>n</em> = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (<em>n</em> = 221) with common <em>EGFR</em> mutations or <em>ALK</em>/<em>ROS1</em> fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment.</p><p><strong><em>Conclusions:</em></strong> In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human p38γ protein kinase, or MAPK12, is a crucial signaling protein that is important in channelizing membrane signals to the nucleus in the MAPK cascade pathway, associated with breast and colorectal cancer, besides other forms of malignancies and atherosclerotic lesions too. P38γ has a significant contribution to the progression of breast carcinoma due to its multifaceted functions. Targeting p38γ for defining potent antagonists against p38γ can turn out to be an attractive and novel means of breast cancer therapeutics. Novel and potent lead molecules were designed utilizing computational drug design methodologies. Using high-throughput virtual screening, 1909 geometrically similar analogs of known inhibitors were generated, primarily using BIRB796, SB202190, ANP, CHEBI: 620708, and CHEBI: 524699. Chemical correctness was ensured using LigPrep for the standalone library, and Prep Wizard for p38γ using Maestro v.11.5. Using the Glide v5.5 flexible docking procedure on a standalone library of p38γ binding sites, we defined 18 potential leads and assessed their ADMET properties. Lead "1", among the proposed four p38γ antagonists with high-scoring and favorable interactions, was considered for 100 ns molecular dynamics simulations. Among the four proposed leads, Lead '1′ displayed consistent and stable bonding interactions with p38γ throughout the 100 ns molecular dynamics (MD) simulations. Additionally, it formed water bridges, contributing to its strong association with the protein. Notably, Lead '1′ (3-deazaadenosine) exhibited favorable root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) within the acceptable range of pharmacological properties. Thus, 3-deazaadenosine and its mimetic might be promising new directions for developing a novel class of antagonists for breast cancer treatment.
{"title":"3-deazaadenosine: A promising novel p38γ antagonist with potential as a breast cancer therapeutic agent","authors":"Pradeep Natarajan , Munikumar Manne , Swetha Kumari Koduru , Teja Sree Bokkasam","doi":"10.1016/j.ctarc.2023.100744","DOIUrl":"10.1016/j.ctarc.2023.100744","url":null,"abstract":"<div><p>Human p38γ protein kinase, or MAPK12, is a crucial signaling protein that is important in channelizing membrane signals to the nucleus in the MAPK cascade pathway, associated with breast and colorectal cancer, besides other forms of malignancies and atherosclerotic lesions too. P38γ has a significant contribution to the progression of breast carcinoma due to its multifaceted functions. Targeting p38γ for defining potent antagonists against p38γ can turn out to be an attractive and novel means of breast cancer therapeutics. Novel and potent lead molecules were designed utilizing computational drug design methodologies. Using high-throughput virtual screening, 1909 geometrically similar analogs of known inhibitors were generated, primarily using BIRB796, SB202190, ANP, CHEBI: 620708, and CHEBI: 524699. Chemical correctness was ensured using LigPrep for the standalone library, and Prep Wizard for p38γ using Maestro v.11.5. Using the Glide v5.5 flexible docking procedure on a standalone library of p38γ binding sites, we defined 18 potential leads and assessed their ADMET properties. Lead \"1\", among the proposed four p38γ antagonists with high-scoring and favorable interactions, was considered for 100 ns molecular dynamics simulations. Among the four proposed leads, Lead '1′ displayed consistent and stable bonding interactions with p38γ throughout the 100 ns molecular dynamics (MD) simulations. Additionally, it formed water bridges, contributing to its strong association with the protein. Notably, Lead '1′ (3-deazaadenosine) exhibited favorable root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) within the acceptable range of pharmacological properties. Thus, 3-deazaadenosine and its mimetic might be promising new directions for developing a novel class of antagonists for breast cancer treatment.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.ctarc.2023.100767
Francis Proulx-Rocray , Bertrand Routy , Rami Nassabein , Wiam Belkaid , Danh Tran-Thanh , Julie Malo , Marion Tonneau , Omar El Ouarzadi , Marie Florescu , Mustapha Tehfe , Normand Blais
Background
PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs.
Patients & methods
This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method.
Results
From 100 patients with known KRAS status, 50 were mutated (KRASMut). Mutation in TP53, STK11 and KEAP1 were present, and their status known in, respectively, 19/40 (47.5 %), 8/39 (20.5 %) and 4/38 (10.5 %) patients. STK11Mut and KEAP1Mut were associated with shorter overall survival when compared with wild type tumors (respectively median OS of 3.3 vs 20.4, p = 0.0001 and 10.1 vs 17.7, p = 0.24). When KRAS status was compounded with STK11/KEAP1, KRASMut trended to a better prognosis in STK11+KEAP1WT tumors (median OS 21.1 vs 15.8 for KRASWT, p = 0.15), but not for STK11+/-KEAP1Mut tumors. The NLR was strongly impacted by STK11 (6.0Mutvs 3.6WT, p = 0.014) and TP53 (3.2Mutvs 4.8WT, p = 0.048), but not by KEAP1 or KRAS mutations.
Conclusion
STK11Mut and KEAP1Mut are adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11Mut but not by KEAP1Mut, suggesting differences in their resistance mechanism. In STK11-KEAP1WT tumors, KRASMut seem associated with improved survival in NSCLC patients treated with ICIs.
MicroAbstract
Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism.
背景:PD-L1的表达用于预测NSCLC对ICIs的反应,但其性能并不理想。KRAS突变对这些患者的影响尚不清楚。评估TP53、STK11和KEAP1以及NLR的共突变的研究表明,它们可以预测ICIs的益处。患者和方法:这是一项对2015年7月至2020年6月在CHUM接受ICIs治疗的NSCLC患者的回顾性研究。使用Kaplan-Meier和logrank方法比较OS和PFS。说明了TP53、STK11和KEAP1以及NLR的共突变。用Wald法比较ORR和安全性。结果:在100例已知KRAS状态的患者中,有50例发生了突变(KRASMut)。TP53、STK11和KEAP1存在突变,其状态分别在19/40(47.5%)、8/39(20.5%)和4/38(10.5%)患者中已知。与野生型肿瘤相比,STK11Mut和KEAP1Mut的总生存期较短(中位OS分别为3.3 vs 20.4,p=0.001和10.1 vs 17.7,p=0.024)。当KRAS状态与STK11/KEAP1相结合时,KRASMut在STK11+KEAP1WT肿瘤中的预后更好(KRASWT的中位OS 21.1 vs 15.8,p=0.015),但在STK11+/-KEAP1Mout肿瘤中则不然。NLR受到STK11(6.0Mut对3.6WT,p=0.014)和TP53(3.2Mut对4.8WT,p=0.048)的强烈影响,但不受KEAP1或KRAS突变的影响。结论:STK11Mut和KEAP1Mut是ICI治疗获益的不良预测因素。NLR受到STK11Mut的强烈影响,但不受KEAP1Mut的影响,这表明它们的抗性机制存在差异。在STK11-KEAP1WT肿瘤中,KRASMut似乎与ICIs治疗的NSCLC患者的生存率提高有关。微观结论:NSCLC对免疫疗法的反应不容易预测。我们对100名非小细胞肺癌和已知KRAS状态的患者进行了回顾性研究。通过考虑不同的共突变,KRAS突变被发现与STK11和KEAP1野生型肿瘤更好的中位总生存率相关(21.1比15.8,p=0.15)。NLR受到STK11的影响,但没有受到KEAP1突变的影响,这表明它们的抗性机制存在差异。
{"title":"The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and their influence on the NLR in NSCLC patients treated with immunotherapy","authors":"Francis Proulx-Rocray , Bertrand Routy , Rami Nassabein , Wiam Belkaid , Danh Tran-Thanh , Julie Malo , Marion Tonneau , Omar El Ouarzadi , Marie Florescu , Mustapha Tehfe , Normand Blais","doi":"10.1016/j.ctarc.2023.100767","DOIUrl":"10.1016/j.ctarc.2023.100767","url":null,"abstract":"<div><h3>Background</h3><p>PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of <em>KRAS</em> mutations in these patients is unclear. Studies evaluating co-mutations in <em>TP53, STK11</em> and <em>KEAP1</em> as well as the NLR showed that they may predict the benefit of ICIs.</p></div><div><h3>Patients & methods</h3><p>This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in <em>TP53, STK11</em> and <em>KEAP1</em> as well as the NLR were accounted for. ORR and safety were compared using Wald method.</p></div><div><h3>Results</h3><p>From 100 patients with known <em>KRAS</em> status, 50 were mutated (<em>KRAS</em><sup>Mut</sup>). Mutation in <em>TP53, STK11</em> and <em>KEAP1</em> were present, and their status known in, respectively, 19/40 (47.5 %), 8/39 (20.5 %) and 4/38 (10.5 %) patients. <em>STK11</em><sup>Mut</sup> and <em>KEAP1</em><sup>Mut</sup> were associated with shorter overall survival when compared with wild type tumors (respectively median OS of 3.3 <em>vs</em> 20.4, <em>p</em> = 0.0001 and 10.1 <em>vs</em> 17.7, <em>p</em> = 0.24). When <em>KRAS</em> status was compounded with <em>STK11</em>/<em>KEAP1, KRAS</em><sup>Mut</sup> trended to a better prognosis in <em>STK11+KEAP1</em><sup>WT</sup> tumors (median OS 21.1 <em>vs</em> 15.8 for <em>KRAS</em><sup>WT</sup>, <em>p</em> = 0.15), but not for <em>STK11+/-KEAP1</em><sup>Mut</sup> tumors. The NLR was strongly impacted by <em>STK11</em> (6.0<sup>Mut</sup> <em>vs</em> 3.6<sup>WT</sup>, <em>p</em> = 0.014) and <em>TP53</em> (3.2<sup>Mut</sup> <em>vs</em> 4.8<sup>WT</sup>, <em>p</em> = 0.048), but not by <em>KEAP1</em> or <em>KRAS</em> mutations.</p></div><div><h3>Conclusion</h3><p><em>STK11</em><sup>Mut</sup> and <em>KEAP1</em><sup>Mut</sup> are adverse predictors of ICI therapy benefit. The NLR is strongly impacted by <em>STK11</em><sup>Mut</sup> but not by <em>KEAP1</em><sup>Mut</sup>, suggesting differences in their resistance mechanism. In <em>STK11-KEAP1</em><sup>WT</sup> tumors, <em>KRA</em>S<sup>Mut</sup> seem associated with improved survival in NSCLC patients treated with ICIs.</p></div><div><h3>MicroAbstract</h3><p>Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known <em>KRAS</em> status. By accounting for different co-mutations, <em>KRAS</em> mutation was found to be associated with a better median overall survival in <em>STK11</em> and <em>KEAP1</em> wild-type tumors (21.1 <em>vs</em> 15.8, <em>p</em> = 0.15). NLR was impacted by <em>STK11</em>, but not <em>KEAP1</em> mutation, suggesting a difference in their resistance mechanism.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41192157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC.
Methods
Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022.
Results
Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27–123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients.
Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4–542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31–90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively.
Conclusion
One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.
{"title":"Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report","authors":"Aakash Desai , Sagar Rakshit , Radhika Bansal , Yash Ashara , Ashley Potter , Rami Manochakian , Yanyan Lou , Yujie Zhao , Vinicius Ernani , Panos Savvides , Anna Schwecke , Nicole Moffett , Craig Hocum , Konstantinos Leventakos , Alex Adjei , Randolph Marks , Julian Molina , Aaron S. Mansfield , Zong-Ming Chen , Anastasios Dimou","doi":"10.1016/j.ctarc.2023.100743","DOIUrl":"10.1016/j.ctarc.2023.100743","url":null,"abstract":"<div><h3>Introduction</h3><p>We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in <em>KRAS</em> G12C mutated NSCLC.</p></div><div><h3>Methods</h3><p>Retrospective review of medical records of patients with <em>KRAS</em> G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022.</p></div><div><h3>Results</h3><p>Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27–123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients.</p><p>Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4–542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31–90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively.</p></div><div><h3>Conclusion</h3><p>One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cissus quadrangularis plant from Vitaceae family, native in India. Many parts of this plant have medicinal values but most precious is stem of this plant. In past years number of studies reported their activities and secondary metabolites in Cissus quadrangularis plant and their pharmacological activities and uses in traditional medicine system. It is reported to possess excellent medicinal properties and potent fracture healing properties, antimicrobial, antiulcer, antioxidative, cholinergic activity and beneficial effect on cardiovascular diseases, possesses antiulcer and cytoprotective property in indomethacin-induced gastric mucosal injury. The aim of this study was to determine the qualitative phytochemical analysis, antimicrobial activity, cell viability and in vitro anticancer activity of a potential of Cissus quadrangularis stem extract against A549 human lung cancer cell line. The disc diffusion method was employed to determine the antimicrobial activity of Cissus quadrangularis stem extract and showed potential antibacterial and antifungal activity against various microorganisms. Results have shown that Stem methanolic extract induced a significant decrease of tumour cell viability. The cell viability assay clearly showed that the cells treated with Cissus quadrangularis methanolic extract has significantly reduced the lung cancer cell viability in a dose dependant manner. The stem methanolic extract was tested for the in vitro antiproliferative potential on A549 human lung cancer cell line using different concentrations, namely 1000, 62.5 and 7.8 µg/ml. We observed the IC50 dose at 65.2 μg/ml concentration. In cell culture A549 cells treated with Cissus quadrangularis stem methanolic extract in 24 h the cells growth is controlled.
{"title":"A study on antimicrobial and anticancer properties of Cissus quadrangulris using lung cancer cell line","authors":"Sholapuri Payani , Matcha Bhaskar , Gandham Sandeep Kumar , Jangampalli Adi Pradeepkiran","doi":"10.1016/j.ctarc.2023.100732","DOIUrl":"10.1016/j.ctarc.2023.100732","url":null,"abstract":"<div><p><em>Cissus quadrangularis</em> plant from Vitaceae family, native in India. Many parts of this plant have medicinal values but most precious is stem of this plant. In past years number of studies reported their activities and secondary metabolites in <em>Cissus quadrangularis</em> plant and their pharmacological activities and uses in traditional medicine system. It is reported to possess excellent medicinal properties and potent fracture healing properties, antimicrobial, antiulcer, antioxidative, cholinergic activity and beneficial effect on cardiovascular diseases, possesses antiulcer and cytoprotective property in indomethacin-induced gastric mucosal injury. The aim of this study was to determine the qualitative phytochemical analysis, antimicrobial activity, cell viability and <em>in vitro</em> anticancer activity of a potential of <em>Cissus quadrangularis</em> stem extract against A549 human lung cancer cell line. The disc diffusion method was employed to determine the antimicrobial activity of <em>Cissus quadrangularis</em> stem extract and showed potential antibacterial and antifungal activity against various microorganisms. Results have shown that Stem methanolic extract induced a significant decrease of tumour cell viability. The cell viability assay clearly showed that the cells treated with <em>Cissus quadrangularis</em> methanolic extract has significantly reduced the lung cancer cell viability in a dose dependant manner. The stem methanolic extract was tested for the <em>in vitro</em> antiproliferative potential on A549 human lung cancer cell line using different concentrations, namely 1000, 62.5 and 7.8 µg/ml. We observed the IC50 dose at 65.2 μg/ml concentration. In cell culture A549 cells treated with <em>Cissus quadrangularis</em> stem methanolic extract in 24 h the cells growth is controlled.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10179594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Synchronous endometrial and ovarian cancer (SEOC) is a relatively rare entity with indistinct clinical manifestation but have a better prognosis compared to metastatic malignancy of each organ. The aim of the study is to determine the prognosis and factors associated with recurrence of SEOC.
Methods
This case-series study was performed on 37 histologically confirmed SEOC, diagnosed and treated in our tertiary hospital from March 2009 to September 2021. Disease-free survival (DFS) and overall survival (OS) rates following indicated procedure were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to determine risk factors of recurrence.
Results
The mean age of participants was 49.38 (age range: 26–78). The most common complaints and symptoms were abdominal pain (40.5%), followed by abnormal uterine bleeding (29.7%). Most common histological presentation was endometroid type for both ovarian (46%) and endometrial (97.3%) cancers. Over the mean follow-up period of 85.54 months, 11 patients developed recurrence without mortality. Non-endometrioid histology of ovarian cancer, higher grade and stage of ovarian cancer, and omentum invasion were significantly associated with worse DFS in unvariate analysis. Lymphovascular invasion was the sole predictor of DFS in multivariate analysis.
Conclusion
While this study was not able to investigate the risk factors of overall survival associated with SEOC, the results of this study provides an overview of clinicopathological presentation of the disease and emphasizes the importance of lymphovascular invasion in determining prognosis and DFS in SEOC.
{"title":"Synchronous endometrial and ovarian cancer and its recurrent risk factors: Case series","authors":"Niloufar Hoorshad , Saina Nassiri , Shaparak Najibi , Elham Feizabad , Narges Zamani","doi":"10.1016/j.ctarc.2023.100731","DOIUrl":"10.1016/j.ctarc.2023.100731","url":null,"abstract":"<div><h3>Background</h3><p>Synchronous endometrial and ovarian cancer (SEOC) is a relatively rare entity with indistinct clinical manifestation but have a better prognosis compared to metastatic malignancy of each organ. The aim of the study is to determine the prognosis and factors associated with recurrence of SEOC.</p></div><div><h3>Methods</h3><p>This case-series study was performed on 37 histologically confirmed SEOC, diagnosed and treated in our tertiary hospital from March 2009 to September 2021. Disease-free survival (DFS) and overall survival (OS) rates following indicated procedure were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to determine risk factors of recurrence.</p></div><div><h3>Results</h3><p>The mean age of participants was 49.38 (age range: 26–78). The most common complaints and symptoms were abdominal pain (40.5%), followed by abnormal uterine bleeding (29.7%). Most common histological presentation was endometroid type for both ovarian (46%) and endometrial (97.3%) cancers. Over the mean follow-up period of 85.54 months, 11 patients developed recurrence without mortality. Non-endometrioid histology of ovarian cancer, higher grade and stage of ovarian cancer, and omentum invasion were significantly associated with worse DFS in unvariate analysis. Lymphovascular invasion was the sole predictor of DFS in multivariate analysis.</p></div><div><h3>Conclusion</h3><p>While this study was not able to investigate the risk factors of overall survival associated with SEOC, the results of this study provides an overview of clinicopathological presentation of the disease and emphasizes the importance of lymphovascular invasion in determining prognosis and DFS in SEOC.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10179624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.ctarc.2023.100696
Mark Sorin , Sophie Camilleri-Broët , Emilie Pichette , Justin-Pierre Lorange , Nasim Haghandish , Laurie-Rose Dubé , André Lametti , Caroline Huynh , Leora Witkowski , George Zogopoulos , Yifan Wang , Hangjun Wang , Jonathan Spicer , Logan A. Walsh , Roni Rayes , Guy Rouleau , Alan Spatz , Andrea Liliam Gomez Corredor , Pierre Olivier Fiset
Background
Lung cancer is the leading cause of cancer death in both men and women. Quebec has the highest lung cancer mortality out of all provinces in Canada, believed to be caused by higher smoking rates. Molecular testing for lung cancer is standard of care due to the discovery of actionable driver mutations that can be targeted with tyrosine kinase inhibitors. To date, no detailed molecular testing characterization of Quebec patients with lung cancer using next generation sequencing (NGS) has been performed.
Materials and methods
The aim of this study was to describe the genomic landscape of patients with lung cancer (n = 997) who underwent NGS molecular testing at a tertiary care center in Quebec and to correlate it with clinical and pathology variables.
Results
Compared to 10 other NGS studies found through a structured search strategy, our cohort had a higher prevalence of KRAS mutations (39.2%) compared to most geographical locations. Additionally, we observed a significant positive association between decreasing age and a higher proportion of KRAS G12C mutations.
Conclusion
Overall, it remains important to assess institutional rates of actionable driver mutations to help guide governing bodies, fuel clinical trials and create benchmarks for expected rates as quality metrics.
{"title":"Next-generation sequencing of non-small cell lung cancer at a Quebec health care cancer centre","authors":"Mark Sorin , Sophie Camilleri-Broët , Emilie Pichette , Justin-Pierre Lorange , Nasim Haghandish , Laurie-Rose Dubé , André Lametti , Caroline Huynh , Leora Witkowski , George Zogopoulos , Yifan Wang , Hangjun Wang , Jonathan Spicer , Logan A. Walsh , Roni Rayes , Guy Rouleau , Alan Spatz , Andrea Liliam Gomez Corredor , Pierre Olivier Fiset","doi":"10.1016/j.ctarc.2023.100696","DOIUrl":"10.1016/j.ctarc.2023.100696","url":null,"abstract":"<div><h3>Background</h3><p>Lung cancer is the leading cause of cancer death in both men and women. Quebec has the highest lung cancer mortality out of all provinces in Canada, believed to be caused by higher smoking rates. Molecular testing for lung cancer is standard of care due to the discovery of actionable driver mutations that can be targeted with tyrosine kinase inhibitors. To date, no detailed molecular testing characterization of Quebec patients with lung cancer using next generation sequencing (NGS) has been performed.</p></div><div><h3>Materials and methods</h3><p>The aim of this study was to describe the genomic landscape of patients with lung cancer (<em>n</em> = 997) who underwent NGS molecular testing at a tertiary care center in Quebec and to correlate it with clinical and pathology variables.</p></div><div><h3>Results</h3><p>Compared to 10 other NGS studies found through a structured search strategy, our cohort had a higher prevalence of KRAS mutations (39.2%) compared to most geographical locations. Additionally, we observed a significant positive association between decreasing age and a higher proportion of KRAS G12C mutations.</p></div><div><h3>Conclusion</h3><p>Overall, it remains important to assess institutional rates of actionable driver mutations to help guide governing bodies, fuel clinical trials and create benchmarks for expected rates as quality metrics.</p></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}