American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

{"title":"Trends and Disparities in Acute Lymphoblastic Leukemia-Related Mortality in the United States from 1999 to 2020: Insights From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Database.","authors":"Shahzaib Ahmed, Eeman Ahmad, Hamza Ashraf, Haider Ashfaq, Umar Akram, Shoaib Ahmad","doi":"10.1097/COC.0000000000001162","DOIUrl":"10.1097/COC.0000000000001162","url":null,"abstract":"<p><strong>Objectives: </strong>The incidence of acute lymphoblastic leukemia (ALL) shows a bimodal distribution, with the first peak in children under 10 years old and the second in adults. It is imperative to understand disparities in ALL-related mortality.</p><p><strong>Methods: </strong>ALL-related mortality trends in the United States from 1999 to 2020 were studied by extracting age-adjusted mortality rates (AAMRs) from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Changes in AAMR were evaluated by calculating annual percentage change (APC) and average APC using Joinpoint regression.</p><p><strong>Results: </strong>A total of 35,056 ALL-related deaths were reported. The AAMR declined from 1999 to 2020 (APC: -0.65). Men exhibited a higher AAMR (0.59) than women (0.43). Hispanic or Latinos exhibited the highest AAMR (0.75), followed by non-Hispanic (NH) whites (0.47), NH black or African Americans (0.37), and NH Asian or Pacific Islanders (0.35). Among census regions, the West was observed to have the highest AAMR (0.59), followed by the South (0.49), the Midwest (0.47), and the Northeast (0.45). California had the highest AAMR (0.64), while the District of Columbia had the lowest (0.40). Stratification by urbanization revealed a higher overall AAMR in rural areas (0.52) than in urban areas (0.48). A majority of the deaths occurred in medical facilities (63.52%).</p><p><strong>Conclusions: </strong>Even though a decrease was observed in ALL-related mortality in the United States from 1999 to 2020, disparities were identified in trends stratified by sex, race, census regions, and urbanization. It is essential to direct efforts towards high-risk populations to ensure a decrease in ALL-related mortality across the board.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"215-221"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton Tyrosine Kinase Degraders: Current Concepts.","authors":"Giorgi Sabakhtarishvili, Mouza Alshebli, Omer Bajwa, Imad A Tabbara","doi":"10.1097/COC.0000000000001170","DOIUrl":"10.1097/COC.0000000000001170","url":null,"abstract":"<p><p>Bruton tyrosine kinase (BTK) is a key enzyme involved in B-cell development and signaling, making it a crucial target in the treatment of B-cell malignancies, such as chronic lymphocytic leukemia and non-Hodgkin lymphoma. While BTK inhibitors (BTKi), such as ibrutinib, have been effective, resistance-both intrinsic and acquired-poses a significant challenge, often associated with BTK mutations like C481S. To address this, novel BTK degraders have been developed, leveraging proteolysis-targeting chimeras to selectively degrade both wild-type and mutant BTK forms. This approach offers a promising strategy to overcome BTKi resistance. Agents such as NRX-0492, BGB-16673, NX-5948, NX-2127, HZ-Q1060, ABBV-101, and AC676 have shown significant BTK degradation in preclinical and early clinical trials. NRX-0492 demonstrated over 90% BTK degradation with sustained pharmacodynamic effects, whereas BGB-16673 achieved clinical responses in 67% of patients with relapsed/refractory B-cell malignancies. Similarly, NX-5948 and NX-2127 showed potent BTK degradation, with NX-2127, in addition, targeting immunomodulatory proteins, resulting in partial and stable responses in chronic lymphocytic leukemia and non-Hodgkin lymphoma patients. HZ-Q1060, a preclinical candidate, displayed rapid and sustained BTK degradation in vivo. Early-phase trials of ABBV-101 and AC676 are also showing promising results. These BTK degraders have demonstrated favorable safety profiles, with manageable adverse events, and offer a novel therapeutic avenue for patients with BTKi-resistant malignancies. As clinical trials progress, these degraders hold the potential to significantly enhance treatment outcomes, offering a new frontier in personalized cancer therapy.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"257-261"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Risk Profile of Nivolumab Anti-cancer Therapy: A Review of Current Literature.","authors":"Zaheer Qureshi, Zaofashan Zaheer, Zoha Asghar, Muhammad Bakhtiar, Eeshal Fatima, Faryal Altaf","doi":"10.1097/COC.0000000000001166","DOIUrl":"10.1097/COC.0000000000001166","url":null,"abstract":"<p><strong>Objectives: </strong>Immune checkpoint inhibitors (ICI) upregulate host antitumor immunity, proving efficacy across diverse tumor types. Currently approved ICI treatment primarily targets the programmed cell death receptor 1 (PD-1) and its ligand PD-L1, and cytotoxic T lymphocyte-antigen 4 (CTLA-4). Nivolumab is a monoclonal antibody that targets the human PD-1 receptor and is an entirely human immunoglobulin G4 (IgG4), approved by the FDA for various cancers like advanced melanoma, metastatic renal cell carcinoma, Hodgkin lymphoma, and advanced lung carcinoma. This review will summarise and discuss the recent literature on cardiotoxicity associated with nivolumab therapy.</p><p><strong>Methods: </strong>We searched online databases like PubMed, Scopus, Google Scholar, and Embase for articles related to Nivolumab.</p><p><strong>Results: </strong>Cardiotoxicity with ICI use is most commonly represented as myocarditis. Patients present with complaints of shortness of breath, palpitations, edema, and fatigue. Takotsubo cardiomyopathy, or broken heart syndrome, is characterized by systolic dysfunction of the left ventricle, mimicking a myocardial infarction but without associated coronary ischemia and with minimal elevation of cardiac enzymes. In the CHECKMATE-037 trial, ventricular arrhythmias occurred in <10% of those who received nivolumab. In a retrospective analysis of patients treated with ICI (predominantly nivolumab monotherapy) for lung cancer, 11% of the patients developed major adverse cardiac events, including myocarditis, non-ST-segment elevated myocardial infarction, supraventricular tachycardia, and pericardial disorders.</p><p><strong>Conclusion: </strong>Close collaboration between cardiology and oncology specialists is crucial for early detection and effective management of cardiac complications, enhancing the safety of nivolumab anticancer therapy.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"235-241"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of Therapeutic Approaches in Acute Myeloid Leukemia: Unveiling Trends and Predictors of Treatment Response.","authors":"Zaheer Qureshi, Abdur Jamil, Faryal Altaf, Rimsha Siddique","doi":"10.1097/COC.0000000000001169","DOIUrl":"10.1097/COC.0000000000001169","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate emerging trends and predictors for optimizing treatment strategies for acute myeloid leukemia (AML).</p><p><strong>Method: </strong>A literature search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases. Bias assessment was conducted using Cochrane's risk of bias tool, while statistical analyses were performed using Review Manager and Comprehensive Meta-Analysis software.</p><p><strong>Results: </strong>We included 44 studies and the pooled results showed that high-dose cytarabine (HDAC) in induction therapy significantly improved the complete remission (CR) rate than standard-dose cytarabine (SDAC) in younger adults but not older adults (OR: 1.29, 95% CI: 1.12-1.49, P =0.0004 and OR: 1.02, 95% CI: 0.80-1.29, P =0.87, respectively). In consolidation therapy, HDAC showed a significant benefit in event-free survival (EFS) over SDAC (RR: 1.30, 95% CI: 1.04-1.62, P =0.02). The pooled analysis also revealed that idarubicin (IDR) was associated with improved CR rates than daunorubicin (DNR) (OR: 1.34, 95% CI: 1.02-1.76, P =0.04). However, the results do not substantiate the claim that IDR is better than mitoxantrone (MTZ) or that DNR is superior to MTZ in inducing CR (OR: 0.88, 95% CI: 0.72-1.08, P =0.22 and OR: 0.85, 95% CI: 0.72-1.01, P =0.06, respectively). The evidence has also shown that the pooled composite complete response (CRc) rates for FLT3 inhibitors such as sorafenib, gilteritinib, and quizartinib were 56%, 31%, and 36%, respectively. The pooled results further showed that the overall CRc for patients receiving IDH inhibitors and immune checkpoint inhibitors were 49.6% (95% CI: 37-63) and 26% (95% CI: 18.7-35), respectively.</p><p><strong>Conclusion: </strong>Chemotherapy, targeted therapy, and immunotherapy are valuable treatment options for AML patients. However, the efficacy of these AML treatments may vary depending on AML status and patient characteristics such as age and cytogenetic risk.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"242-256"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Consensus Guidelines, Clinical Trials, and COVID-19 on Fractionation Practices for Node-negative Intact Breast Cancer.","authors":"Jessica Cruttenden, Jonathan Grant, Jaden Evans, George Cannon, David K Gaffney, Matthew Poppe, Lindsay M Burt, Vilija Avizonis, Dustin Boothe","doi":"10.1097/COC.0000000000001167","DOIUrl":"10.1097/COC.0000000000001167","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate whether hypofractionated radiotherapy (HF-RT) in node-negative intact breast cancer significantly increased after guideline updates, trial publications, and COVID-19.</p><p><strong>Methods: </strong>Patients with node-negative breast cancer undergoing lumpectomy and adjuvant RT were identified in the National Cancer Database. Receiving ≥25 and <50 Gy in 5-20 fractions defined HF-RT. Receiving 50 to 66 Gy in >20 fractions defined conventional RT (CF-RT). Patient characteristics were compared with X 2 testing. Joinpoint analysis identified when fractionation significantly changed. Variables associated with HF-RT were identified by univariate and multivariate (MVA) logistic regression. Two-sided P -value <0.05 was significant.</p><p><strong>Results: </strong>Patients meeting criteria totaled 236,336; 54.8% received CF-RT and 45.2% HF-RT. HF-RT and 5-fraction RT significantly increased after 2015 and 2019, respectively ( P <0.05). On MVA, HF-RT was positively associated with: age older than or equal to 65 years (OR 2.14, P <0.001); private insurance (OR 1.27, P =0.03); treatment in Midwest (OR 1.66, P <0.001) or Western United States (US) (OR 3.77, P <0.001); distance ≥50 miles (OR 1.16, P =0.001); later year of diagnosis (OR 1.44, P <0.001); and partial breast irradiation (OR 2.08, P <0.001). HF-RT was negatively associated with: community (OR 0.49, P <0.001) or integrated network (0.55, P <0.001) centers; grade 2 (OR 0.83, P <0.001) or 3 (OR 0.49, P <0.001), hormone receptor negative (OR 0.66, P <0.001), and HER2+ (OR 0.74, P <0.001) disease; positive surgical margins (OR 0.61, P <0.001); and presence of lympho-vascular invasion (OR 0.86, P <0.001).</p><p><strong>Conclusions: </strong>HF-RT in node-negative intact breast cancer increased after 2015, coinciding with US and European guideline updates. Five-fraction RT increased after 2019, coinciding with COVID-19 and FAST-Forward trial results.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"222-229"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Control Arm Quality in Recent Radiation Oncology Randomized Clinical Trials.","authors":"Ifeanyi O Ekpunobi, Laura E Flores, Reshma Jagsi, Shearwood McClelland","doi":"10.1097/COC.0000000000001168","DOIUrl":"10.1097/COC.0000000000001168","url":null,"abstract":"<p><strong>Background: </strong>For randomized controlled trials (RCTs) to provide the highest levels of evidence for clinical practice, it is ethically imperative for patients assigned to the control arm to receive standard-of-care treatment. Oncologic medical trials investigating new systemic agents have demonstrated a high proportion of RCTs with inadequate control arms. It is unknown whether this finding is prevalent in oncologic trials investigating radiation therapy (RT) for cancer.</p><p><strong>Methods: </strong>ClinicalTrials.gov was queried for registered clinical trials investigating RT in patients with cancer from 2013 to 2023. Each control arm was analyzed, with the standard of care determined by National Comprehensive Cancer Center Network (NCCN) guidelines at the time of initial trial posting.</p><p><strong>Results: </strong>Five hundred eight interventional studies with results registered were included, of which 12 met inclusion criteria for final analysis. Two trials each investigated RT usage in central nervous system, prostate, head and neck, and breast disease sites, and 1 each for lung, hepatobiliary, rectal, and bone disease sites. Most trials were industry-funded (83%); 75% of studies took place in the United States. Hundred percent of trials had an adequate control arm per the corresponding NCCN guidelines.</p><p><strong>Conclusion: </strong>All recently completed oncologic RCTs investigating RT for cancer involved an adequate control arm. This finding contrasts with the high proportion of inadequate control arms in medical oncology trials. These findings suggest that adequate control arm treatments are feasible to achieve in trial design, emphasizing both the need for continued focus on improving the quality of ethical oncologic research trials and a possible subspecialty that may serve as an exemplar.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"230-234"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Safety and Efficacy of Adding Liver-Directed Radiation Therapy to Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma: A Single-Center Retrospective Cohort Analysis.","authors":"Timothy J Brown, Uri Amit, Rohi Gheewala, Edgar Ben-Josef, Thomas B Karasic","doi":"10.1097/COC.0000000000001214","DOIUrl":"https://doi.org/10.1097/COC.0000000000001214","url":null,"abstract":"<p><strong>Objectives: </strong>Radiation therapy (RT) may potentiate an antitumor immune response when combined with immunotherapy in advanced hepatocellular carcinoma (HCC) but carries the potential risk of bowel toxicity and impaired liver function. We describe our single-center experience of adding liver-directed RT to atezolizumab and bevacizumab (A/B) in patients with advanced HCC.</p><p><strong>Methods: </strong>This was a single-center retrospective cohort study of patients with HCC naive to systemic therapy who received A/B with or without liver-directed RT from January 1, 2020 until May 1, 2023. We assessed safety outcomes, the real-world response rate (rwRR), overall survival (OS), and time-to-progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by Kaplan-Meier methodology. Given anticipated baseline imbalances between cohorts, no formal comparisons were performed.</p><p><strong>Results: </strong>We identified 49 patients (n=34 control, n=15 RT) who met the inclusion criteria. The cohorts differed in the presence of ascites, baseline liver dysfunction, infection with hepatitis B, and alcoholic liver disease. Two patients in the control group (5.8%) and 1 patient in the RT group (6.7%) experienced clinically significant bleeding. One patient (6.7%) developed possible RT-induced liver disease. The rwRR in the RT group was 73.3% (11/15) compared with 17.6% (6/34) in the control group. The median OS in the RT group was 14.4 months, and 10.8 months in the control group. Median TTP was 6.4 months with RT compared with 5.8 months in the control group.</p><p><strong>Conclusions: </strong>The addition of liver RT to A/B resulted in limited additional toxicity with increased response rates, although significant differences in baseline characteristics limit a full interpretation of this data. Ongoing trials and trials under development will provide informative data regarding the addition of RT to A/B, particularly to assess the impact on OS and TTP.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of Impact of Expansion Size From Gross Tumor Volume to Planning Target Volume on Control Rates and Patterns of Recurrence in Fractionated Radiotherapy for WHO Grade 1 Meningiomas.","authors":"Christopher R Weil, Calvin B Rock, Vikren Sarkar, Nicholas Gravbrot, Felicia H Lew, Christian B Rock, Lindsay M Burt, Cristina M DeCesaris, Randy L Jensen, Dennis C Shrieve, Donald M Cannon","doi":"10.1097/COC.0000000000001193","DOIUrl":"https://doi.org/10.1097/COC.0000000000001193","url":null,"abstract":"<p><strong>Objectives: </strong>For single-fraction stereotactic radiosurgery (SRS) for WHO grade I meningiomas, no-GTV or minimal-GTV to PTV margin is an accepted practice. We evaluated whether there is a control difference based on GTV to PTV expansion size for fractionated RT.</p><p><strong>Methods: </strong>Eighty-seven patients with WHO grade 1 meningioma were identified from an institutional database, treated with either conventional immobilization and radiation treatment delivery techniques (cRT) with 5 to 20 mm PTV expansions or fractionated stereotactic radiotherapy (fSRT) with ≤3 mm GTV to PTV expansions. Kaplan-Meier estimators were used for local failure-free survival (LFFS), marginal-failure-free survival (MFFS), and distant failure-free survival (DFFS) analysis.</p><p><strong>Results: </strong>The median follow-up duration was 9.0 years. Twenty-five patients (29%) received cRT and 62 patients (71%) received fSRT. The median dose was 54 Gray. There were 4 local (5%), 1 marginal (1%), and 1 distant failure (1%). The fSRT and cRT groups each had 2 local failures; 3/4 local failures occurred in areas near critical organs at risk. For cRT versus fSRT, 5-year and 10-year LFFS were 100% versus 98% (P=0.46) and 94% versus 96% (P=0.34), 5-year and 10-year MFFS were 100% versus 100% and 100% versus 92% (P=0.004), and 5-year and 10-year DFFS were 100% versus 98% at both time points (P=0.65 and P=0.67, respectively).</p><p><strong>Conclusions: </strong>In this patient cohort, there was no local control benefit for larger GTV-to-PTV expansions. For patients with tumors not eligible for SRS, fractionated stereotactic treatment workflow with ≤3 mm PTV expansions is an effective approach for WHO grade 1 meningiomas.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Adjuvant Chemotherapy in Endometrial Cancer Following Preoperative Neoadjuvant Chemoradiation Therapy.","authors":"Margaret R Flanigan, Michelle Ertel, John A Vargo, Li Wang, Michelle M Boisen, Sarah Taylor, Shannon K Rush, Paniti Sukumvanich, Jamie L Lesnock","doi":"10.1097/COC.0000000000001205","DOIUrl":"https://doi.org/10.1097/COC.0000000000001205","url":null,"abstract":"<p><strong>Objectives: </strong>In patients with surgically unresectable disease who undergo neoadjuvant chemoradiation (CRT) or neoadjuvant radiation therapy (RT) before surgical staging, little is known about whether adjuvant chemotherapy confers a survival benefit. We aim to explore the survival impact of adjuvant chemotherapy in patients with locally advanced endometrial cancer who undergo neoadjuvant CRT or RT.</p><p><strong>Methods: </strong>A retrospective, single-institution review of all patients from April 2008 to October 2021 who underwent neoadjuvant RT or CRT before surgical resection of endometrial cancer was performed. Kaplan-Meier method with log-rank test was used to determine differences in overall survival (OS) and disease-free survival (DFS) between the group that received adjuvant chemotherapy and the group that did not. Subgroup analysis was performed to assess whether specific subgroups benefited from adjuvant chemotherapy.</p><p><strong>Results: </strong>Eighty-nine patients, 48 (54%) of whom received adjuvant chemotherapy, were identified. There was no statistically significant difference in OS (P=0.062) between those who received adjuvant chemotherapy and those who did not. Adjuvant chemotherapy had a significant association with worse DFS (P=0.037). On subgroup analysis, there were no statistically significant differences in OS or DFS in any subgroups when examining the impact of adjuvant chemotherapy.</p><p><strong>Conclusions: </strong>After receiving neoadjuvant CRT or RT for advanced and high-grade endometrial cancers, adjuvant chemotherapy was not predictive of improved OS, but was predictive of worse DFS. A larger cohort and longer follow-up are needed to ascertain whether certain high-risk subgroups of patients benefit from adjuvant chemotherapy.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Lasting Cigarette Smoking Alterations in Immune Function Occur in Cannabis Smokers, Possibly Rendering Them Vulnerable to Smoking-Related Tumors in Later Life.","authors":"Steven Lehrer, Peter Rheinstein","doi":"10.1097/COC.0000000000001203","DOIUrl":"https://doi.org/10.1097/COC.0000000000001203","url":null,"abstract":"<p><strong>Objectives: </strong>Active cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5 levels are associated with various inflammatory diseases and tumorigenesis. In addition, smoking is linked to an increase in the level of the cytokine CEACAM6 in the bloodstream of smokers. CEACAM6 is increased in pancreatic adenocarcinoma, breast cancer, non-small-cell lung cancer, gastric cancer, colon cancer, and other cancers and promotes tumor progression, invasion, and metastasis. Although cytokine secretion in the innate immune response returns to nonsmoker levels after quitting smoking, the effects on the adaptive response appear to persist for years or decades due to epigenetic memory. As a result, epigenetic changes induced by smoking may contribute to long-lasting alterations in immune function, including elevated CXCL5 and CEACAM6. The effects of cannabis smoking might be similar.</p><p><strong>Methods: </strong>In the current study we used UK Biobank (UKB) data to assess the relationship of CXCL5, CEACAM6, and pulmonary function to cigarette and cannabis smoking. Our UK Biobank application was approved as UKB project 57245 (S.L. and P.H.R.). Our analysis included all subjects with smoking and/or marijuana use data in the UK Biobank database. Circulating levels of CXCL5 and CEACAM6 were from UKB Olink data. Individual CXCL5 and CEACAM6 levels are NPX, Normalized Protein expression, Olink arbitrary unit in Log2 scale (Olink Proteomics AB, Uppsala, Sweden; http://www.olink.com).</p><p><strong>Results: </strong>Current smokers and past smokers had elevated circulating levels of CXCL5 and CECAM6. In multivariate analysis, current, past, or no smoking history was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex. Frequency of cannabis use had a similar effect. In multivariate analysis, frequency of cannabis use was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex, and years between last cannabis use and enrollment in study.</p><p><strong>Conclusions: </strong>We can confirm a previous report of epigenetic changes induced by cigarette smoking that may contribute to long-lasting alterations in immune function related to CXCL5 and CEACAM6. In addition, we have found that these same long-lasting smoking alterations in immune function related to CXCL5 and CEACAM6 occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}