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

{"title":"Sex Disparities in Postoperative Outcomes Among Patients With Spine Tumors: A Systematic Review.","authors":"Tobechukwu Ndika, Anushka Peer, Kristina Schaufele, Chinelo Agwuegbo, Seeley Yoo, Ellen O'Callaghan, Alyssa Bartlett, Samantha Kaplan, Samantha Spellicy, Tara Dalton, Julia Duvall, Andrea N Goodwin, Melissa Erickson, C Rory Goodwin","doi":"10.1097/COC.0000000000001356","DOIUrl":"10.1097/COC.0000000000001356","url":null,"abstract":"<p><strong>Objectives: </strong>Sex-based differences in postoperative outcomes have been reported in nononcologic spine surgery, but their impact among patients undergoing surgery for spine tumors remains poorly understood. We conducted a systematic review to evaluate the impact of patient sex on postoperative length of stay (LOS) and nonroutine discharge (NRD).</p><p><strong>Methods: </strong>A systematic literature search was performed according to PRISMA guidelines. Independent reviewers screened studies for eligibility. Studies were included if they evaluated adult patients undergoing spine tumor surgery and reported postoperative LOS and/or NRD stratified by patient sex. Study quality was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence and the Methodological Index for Non-Randomized Studies (MINORS).</p><p><strong>Results: </strong>Twelve retrospective cohort studies comprising 250,648 patients met the inclusion criteria. All studies were classified as moderate quality based on MINORS criteria. Nine studies evaluated LOS, with 3 demonstrating significant associations with patient sex. Two studies reported higher odds of prolonged LOS among female patients, whereas one reported higher odds among male patients. Nine studies evaluated NRD of which 4 found significantly higher odds of NRD among female patients, while 5 found no association.</p><p><strong>Conclusions: </strong>Evidence regarding sex-based differences in postoperative LOS and NRD was mixed, although female sex was more consistently associated with prolonged hospitalization and nonroutine discharge. These findings suggest that sex-based disparities in postoperative resource utilization may exist in spine oncology and should be considered in perioperative risk stratification and discharge planning.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609750","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":"Outcomes and Toxicities of Radiation Therapy in HIV-Positive Patients With Head and Neck Cancer: A Systematic Review.","authors":"Linden A Lechner, Florence Mutua, Vivek Ghosh, Carlton Johnny","doi":"10.1097/COC.0000000000001351","DOIUrl":"https://doi.org/10.1097/COC.0000000000001351","url":null,"abstract":"<p><p>People living with HIV (PLWH) have an increased incidence of head and neck cancer (HNC), yet the impact of HIV on radiation therapy (RT) outcomes remains poorly defined. To our knowledge, no prior systematic review has synthesized this evidence. A systematic review was conducted following PRISMA 2020 guidelines and prospectively registered on PROSPERO (CRD420251075908). PubMed was searched from inception to July 2025, with an updated search in May 2026 yielding no additional studies. Eight retrospective studies comprising 185 patients were included, all from the United States. Tumor subsites included the oral cavity, oropharynx, larynx, paranasal sinus, and facial skin, with squamous cell carcinoma and Kaposi sarcoma as the predominant histologies. Treatment techniques ranged from conventional radiotherapy in earlier series to intensity-modulated radiotherapy in more contemporary cohorts. In curative-intent cohorts, 3-year overall survival ranged from 55% to 78% and local control from 69% to 92%. Grade ≥3 acute toxicity, including mucositis, dermatitis, and dysphagia, was common but not clearly disproportionate to HIV-negative populations. Treatment interruption rates appeared elevated, with up to 42% of patients experiencing breaks exceeding 10 cumulative days in one series. Reporting of CD4 count, viral load, and HPV/p16 status was inconsistent. Methodological quality was low to moderate, and clinical heterogeneity precluded meta-analysis. These findings suggest that curative-intent RT for HNC in PLWH is feasible with meaningful disease control. Antiretroviral therapy optimization and multidisciplinary co-management are essential. Prospective, multicenter studies with standardized reporting, matched controls, and inclusion of high HIV-prevalence settings are needed to define optimal treatment strategies.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609711","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":"Vitamin C as an Adjunctive Therapy in Cancer: A Systematic Review and Meta-Analysis of Outcomes in Solid and Hematologic Malignancies.","authors":"Moazzam Shahzad, Muhammad Kashif Amin, Hafiz Muhammad Hannan Javed, Amir Kasaeian, Zeeshan Sattar, Jehad Zeidkilani, Iman Menbari Oskouie, Sohaib Irfan, Ruhma Sehar, Sarmad Zaman Warraich, Muhammad Umair Mushtaq, Michael Jaglal","doi":"10.1097/COC.0000000000001353","DOIUrl":"10.1097/COC.0000000000001353","url":null,"abstract":"<p><strong>Objectives: </strong>Vitamin C has gained interest as an adjunctive treatment in oncology due to its antioxidant effects, potential to enhance cancer therapy, and ability to improve quality of life. This systematic review and meta-analysis aimed to assess the therapeutic impact of vitamin C in patients with solid and hematologic malignancies.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Cochrane, Embase, ClinicalTrials.gov, and Google Scholar from inception to August 2025, in accordance with PRISMA guidelines. A total of 43 studies were included, with 19 focusing on hematologic malignancies (695 patients) and 24 on solid tumors (827 patients). Data were extracted and analyzed using Kaplan-Meier survival plots via the MetaSurvival package (R version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria). Selected studies were also described narratively.</p><p><strong>Results: </strong>In hematologic malignancies, the median age was 60.92 years, and 49.07% were male. The pooled median overall survival (mOS) was 34.42 months, and median progression-free survival (mPFS) was 14.09 months (95% CI: 9.54-20.50). The estimated mean OS and PFS were 27.80 months (95% CI: 22.78-31.58) and 19.63 months (95% CI: 15.97-22.53), respectively. Among solid tumors, pancreatic cancer showed a mOS of 15.2 months and lung cancer 13.4 months. Vitamin C was also associated with reduced inflammation, oxidative stress, and radiotherapy-related side effects, as well as improved quality of life.</p><p><strong>Conclusions: </strong>Vitamin C may enhance tolerability and patient-reported outcomes in cancer therapy. While survival benefits were observed in hematologic malignancies, evidence remains inconsistent in solid tumors, underscoring the need for larger, well-designed trials.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609714","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":"Anaplastic Thyroid Carcinoma in the Modern Era: A Population-Based Provincial Analysis.","authors":"Lindsay Barr, Richard Musoke, Alexa Dang, Eric Berthelet, Matthew Chan, Daegan Sit, Nicole Chau, Sarah N Hamilton","doi":"10.1097/COC.0000000000001355","DOIUrl":"https://doi.org/10.1097/COC.0000000000001355","url":null,"abstract":"<p><strong>Objectives: </strong>Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy. The purpose of this study was to update the outcomes of ATC in a large provincial database in a modern cohort.</p><p><strong>Methods: </strong>All patients diagnosed with ATC in British Columbia between 2000 and 2022 were included in this retrospective analysis. Charts were reviewed for demographic, staging, treatment, and outcomes data. Statistical analysis was performed using the Kaplan-Meier method for overall survival. The Fine and Gray method was used to determine factors associated with progression.</p><p><strong>Results: </strong>A total of 127 patients were included, with a median age of 73 years. At diagnosis, 22% had stage IVA, 42% stage IVB, and 36% stage IVC disease. Surgery was performed in 43% of patients, and 66% received radiotherapy. Molecular testing was conducted in 13%, with 5 patients testing positive for BRAF mutations. Chemotherapy was used in 15 patients, either concurrently with radiotherapy or palliatively. Median OS was 5.7 months (stage IVA), 4.3 months (IVB), and 2.5 months (IVC). Improved OS was associated with better ECOG performance status, surgery, radiotherapy, and higher radiation doses (P<0.05). Improved progression-free survival was linked to better ECOG status, absence of metastases, and higher radiation dose (P<0.05). Only 3% of patients survived longer than 3 years.</p><p><strong>Conclusions: </strong>In this large population-based cohort, ATC remains associated with poor survival, with outcomes strongly influenced by stage and performance status at diagnosis. Surgery and radiotherapy, particularly higher radiation doses, were associated with improved survival outcomes in selected patients.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609744","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":"PD-1 Inhibition With Camrelizumab in Cervical Cancer: A Systematic Review and Meta-Analysis.","authors":"Adeena Musheer, Muhammad S Mannan, Muhammad W Khan, Aribah Bhatti, Tuba Basit, Ali Shan Hafeez, Hadiya Javed, Safwan Muhammad","doi":"10.1097/COC.0000000000001352","DOIUrl":"10.1097/COC.0000000000001352","url":null,"abstract":"<p><strong>Objectives: </strong>Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. PD-L1 is expressed in 34.4% to 96% of cervical cancers. Camrelizumab is an anti-PD-1 IgG4 antibody with antitumor activity. This study evaluates the efficacy and safety of camrelizumab in cervical cancer.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, Web of Science, Cochrane Library, Ovid MEDLINE, and Scopus was performed to identify studies of pathologically confirmed cervical cancer treated with camrelizumab alone or in combination with chemotherapy or VEGFR-TKIs, including apatinib or famitinib. Eligible studies included randomized trials, single-arm trials, cohort studies, and case-control studies. Pooled proportions with 95% CIs were calculated using R version 4.4.1. Heterogeneity was assessed using I2 , and evidence certainty was evaluated using GRADE.</p><p><strong>Results: </strong>Eight studies comprising 382 patients were included. Camrelizumab was evaluated as monotherapy, with chemotherapy, or with VEGFR-TKIs. The pooled objective response rate (ORR) was 0.62 (95% CI: 0.32-0.85). The disease control rate (DCR), assessed in 7 studies including 297 patients, was 0.83 (95% CI: 0.60-0.94). The pooled partial response (PR) rate was 0.45 (95% CI: 0.29-0.62), while the complete response (CR) rate was 0.15 (95% CI: 0.10-0.23). Progressive disease (PD) outcomes were reported in a cohort of 297 patients, corresponding to a proportion of 0.16 (95% CI: 0.06-0.36), and stable disease (SD) demonstrated a pooled proportion of 0.30 (95% CI: 0.19-0.44). Commonly reported adverse events included neutropenia, anemia, leukopenia, hypertension, lymphopenia, and myelosuppression.</p><p><strong>Conclusions: </strong>Camrelizumab demonstrates clinically meaningful antitumor activity in cervical cancer, particularly in combination regimens, though toxicity requires careful monitoring.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563376","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":"Targeting HCC With SBRT: Practical Strategies and Immunologic Synergies.","authors":"Vedin Barve, Neil Newman","doi":"10.1097/COC.0000000000001342","DOIUrl":"https://doi.org/10.1097/COC.0000000000001342","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, characterized by high recurrence rates despite curative-intent therapies. While surgical resection, ablation, transarterial therapies, and systemic agents form the backbone of current management, advances in radiation technology have positioned stereotactic body radiotherapy (SBRT) as an increasingly important modality across the HCC disease spectrum. Historically limited by concerns for hepatic toxicity and presumed radioresistance, modern SBRT enables precise delivery of ablative doses while sparing functional liver parenchyma, resulting in excellent local control with acceptable toxicity. This review summarizes contemporary evidence supporting SBRT in early-stage, intermediate, and advanced HCC, including its roles as definitive therapy, salvage after transarterial chemoembolization, cytoreduction in macrovascular invasion, palliation, and as a bridge to liver transplantation. Practical considerations are emphasized, including dose selection, biologically effective dose thresholds, volumetric liver sparing, functional imaging, and the delayed radiographic response characteristics of post-SBRT HCC, which challenges conventional response assessment criteria. In addition, emerging insights into the radiobiology of HCC suggest that high-dose hypofractionation overcomes prior assumptions of radio resistance through direct cytotoxicity and microenvironmental modulation. Finally, this review explores the immunologic synergy between SBRT and immune checkpoint inhibitors, highlighting early clinical data and ongoing trials combining SBRT with immunotherapy. As multimodal strategies evolve, SBRT is poised to become a cornerstone of personalized, liver-directed therapy in HCC.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551323","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":"Safety and Efficacy of Palbociclib and Endocrine Therapy Versus Endocrine Therapy Alone in HR+/HER 2- Breast Cancer Patients; a Systematic Review and Meta-Analysis.","authors":"Faiza Fatima, Muhammad I Bhatti, Ahmed Raza, Aeliya Mirza, Fatima Hussain, Ali T Khan","doi":"10.1097/COC.0000000000001354","DOIUrl":"https://doi.org/10.1097/COC.0000000000001354","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel agents in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. Palbociclib, when used in combination with endocrine therapy (ET), has shown promising results in this domain; however, conclusive evidence is still inadequate. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, comparing palbociclib plus ET with ET alone in HR+/HER2- advanced breast cancer patients. A total of 15 studies comprising 13,827 patients were included. Palbociclib plus ET significantly improved overall survival (HR=0.83, 95% CI: 0.76-0.91; P<0.0001) and progression-free survival (HR=0.60, 95% CI: 0.54-0.67; P<0.0001) compared with ET alone. Significant differences were also observed in objective response rate (OR=1.85, 95% CI: 1.45-2.35; P<0.0001), partial response (OR=1.89, 95% CI: 1.43-2.48; P<0.0001), disease control rate (OR=2.42, 95% CI: 1.77-3.29; P<0.0001), and progressive disease (OR=0.37, 95% CI: 0.21-0.64; P=0.0005). No significant differences were observed for complete response or stable disease. In addition, palbociclib plus ET was associated with significantly increased adverse events, including neutropenia, leukopenia, thrombocytopenia, anemia, and febrile neutropenia. Palbociclib plus ET exhibits supremacy over ET alone in terms of survival and disease-control outcomes in HR+/HER2- advanced or metastatic breast cancer. However, there exists a significant trade-off in terms of increased adverse events, especially hematological toxicity, in the palbociclib plus ET group as compared with the ET group.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537643","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":"Real-World Outcomes of Adjuvant Immunotherapy and Radiation Therapy for Stage III Merkel Cell Carcinoma.","authors":"Natalie N Chakraborty, Trisha Lal, Iris Sheng, Ankit Mangla, Richard S Hoehn, Luke D Rothermel","doi":"10.1097/COC.0000000000001349","DOIUrl":"https://doi.org/10.1097/COC.0000000000001349","url":null,"abstract":"<p><strong>Objectives: </strong>Immune checkpoint inhibitors demonstrate meaningful promise in advanced unresectable Merkel cell carcinoma (MCC), but their role in the adjuvant setting is evolving. We assessed the association between adjuvant immunotherapy (IO), radiation therapy (RT), or their combination and overall survival (OS) in a real-world cohort.</p><p><strong>Methods: </strong>Using the National Cancer Database (NCDB), we identified 2538 stage III MCC patients diagnosed between 2017 and 2022 with known adjuvant IO and RT status. Patients were stratified into clinically (n=720) and occult node-positive (n=1818) subgroups. Multivariable logistic regression identified predictors of receipt of adjuvant therapy, while Cox proportional hazards models assessed factors associated with OS.</p><p><strong>Results: </strong>Overall, 25% of patients received neither adjuvant IO nor RT, 6% received both therapies, 5% received IO alone, and 66% received RT alone. Adjuvant IO utilization increased from 4.3% to 13.1% of patients between 2017 and 2022. Receipt of combined IO and RT, as well as RT alone, was associated with improved OS in clinically and occult node-positive patients. Treatment at high-volume centers was associated with improved OS in occult node-positive patients.</p><p><strong>Conclusions: </strong>In this retrospective cohort, adjuvant IO combined with RT showed the strongest association with improved survival. This OS benefit was particularly pronounced in clinically node-positive patients. These real-world findings complement emerging randomized trial data and suggest that multimodal treatment strategies warrant further investigation in MCC.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474004","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":"Hepatobiliary Toxicity Following Ablative Radiation for Centrally Located Hepatocellular Carcinoma.","authors":"Sarah Feldkamp, Bailey Nelson, Kyle Wang, Darren Lee, Nedas Semaska, Ismael Assi, Jordan Kharofa","doi":"10.1097/COC.0000000000001323","DOIUrl":"https://doi.org/10.1097/COC.0000000000001323","url":null,"abstract":"<p><strong>Objectives: </strong>Centrally located hepatocellular carcinoma (CL-HCC) poses a therapeutic challenge due to proximity to the central hepatobiliary tract (cHBT) and concern for radiation-related toxicity. We evaluated hepatobiliary toxicity, liver function changes, and oncologic outcomes following ablative external beam radiotherapy (EBRT) for CL-HCC across multiple modalities.</p><p><strong>Methods: </strong>We retrospectively reviewed 103 patients treated with ablative EBRT for HCC from 2014 to 2024. Tumors were classified as central if the planning target volume overlapped a 1-cm expansion around the portal vein. Modalities included stereotactic body radiotherapy (SBRT), intensity-modulated radiation therapy (IMRT), and proton therapy. The primary endpoint was Grade ≥3 CTCAE hepatobiliary toxicity. Secondary endpoints included change in albumin-bilirubin (ALBI) score at 6 months, local control (LC), and overall survival (OS). Dose-volume parameters were converted to EQD2 for comparison.</p><p><strong>Results: </strong>Forty-eight patients (47%) had CL-HCC. Among central tumors, treatment included SBRT (29%), proton therapy (58%), and IMRT (13%), with a median EQD2 of 82 Gy. No EBRT-attributable biliary strictures were observed; 1 patient developed possible treatment-related portal vein thrombosis. The cumulative incidence of Grades 1 to 2 ALBI worsening at 6 months was 52% in CL-HCC (57% SBRT, 46% proton, 50% IMRT) versus 44% in peripheral tumors. LC exceeded 90% in both groups without differences in local progression-free survival. Median OS was 28 months for central versus 42 months for peripheral tumors (HR=1.62, P=0.07).</p><p><strong>Conclusions: </strong>Ablative EBRT for CL-HCC achieved excellent local control with low rates of clinically significant hepatobiliary toxicity, supporting its use in this high-risk population.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426174","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":"Targeted CysLTR1 Blockade Rescues Myeloid-Mediated Resistance to Immune Checkpoint Inhibition in Solid Malignancies: A Combined Genomic, Emulated Clinical Trial, and Epidemiological Negative-Control Analysis.","authors":"Steven Lehrer, Peter Rheinstein","doi":"10.1097/COC.0000000000001348","DOIUrl":"https://doi.org/10.1097/COC.0000000000001348","url":null,"abstract":"<p><strong>Objectives: </strong>Myeloid-driven inflammation contributes to resistance to immune checkpoint inhibitors (ICIs) in solid tumors, partly through neutrophil-mediated immunosuppressive mechanisms. Experimental evidence suggests cysteinyl leukotriene receptor 1 (CysLTR1) signaling promotes tumor-supportive myelopoiesis. We evaluated whether pharmacologic CysLTR1 blockade with montelukast could mitigate myeloid-mediated resistance to anti-PD-1 immunotherapy.</p><p><strong>Methods: </strong>A triangulated translational framework was applied using 3 independent data sets. First, CYSLTR1 and ELANE transcript expression were analyzed in The Cancer Genome Atlas (TCGA; n=9907). Second, a propensity-matched emulated clinical trial was conducted in the Mount Sinai TriNetX network, comparing pembrolizumab plus montelukast versus pembrolizumab alone in advanced solid malignancies (n=70 per arm). Third, a negative-control analysis was performed in UK Biobank cancer patients (n=19,443) using multivariable Cox proportional hazards models.</p><p><strong>Results: </strong>High concurrent CYSLTR1 and ELANE expression was associated with significantly poorer long-term survival in TCGA (P<0.0001). In TriNetX, concurrent montelukast exposure was associated with improved overall survival during pembrolizumab treatment (HR=0.505; 95% CI: 0.256-0.995; P=0.0441). In the UK Biobank, baseline neutrophil-to-lymphocyte ratio independently predicted mortality, but montelukast showed no survival interaction (P=0.957), supporting immunotherapy-specific rather than generalized oncologic benefit.</p><p><strong>Conclusion: </strong>CysLTR1 blockade with montelukast may represent a low-cost companion strategy to overcome myeloid-mediated ICI resistance. These findings support prospective validation of combined anti-PD-1 and anti-CysLTR1 therapy in advanced solid tumors.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413453","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}