Therapeutic Advances in Medical Oncology最新文献

{"title":"Advancing treatment efficacy: combined therapy of eribulin, anlotinib, and camrelizumab in advanced or metastatic retroperitoneal liposarcoma.","authors":"Weiwei Jia,Jianhui Wu,Hongtao Zhang,Yan Wu,Daoning Liu,Zhen Wang,Xiaopeng Wang,Chengpeng Li,Chunyi Hao","doi":"10.1177/17588359241276968","DOIUrl":"https://doi.org/10.1177/17588359241276968","url":null,"abstract":"BackgroundRetroperitoneal liposarcoma (RLPS) typically shows limited response to standard chemotherapy, presenting a challenge in treating advanced or metastatic RLPS.ObjectiveThis study aimed to evaluate the potential advantages of a combined therapeutic strategy utilizing eribulin, anlotinib, and camrelizumab.DesignBetween December 2020 and March 2023, this retrospective study enrolled patients with advanced or metastatic RLPS who received treatment at Peking University Cancer Hospital Sarcoma Center. The treatment regimen involved eribulin plus anlotinib and camrelizumab administered every 3 weeks (Q3W).MethodsEfficacy was assessed following the Response Evaluation Criteria in Solid Tumors version 1.1, while safety was evaluated using the Common Terminology Criteria for Adverse Events version 5.0.ResultsThe study included 47 patients with RLPS with a median age of 55.5 years. Patients received a median of 4.5 (range, 2-21) cycles of treatment. Notably, partial response was observed in 8 patients (18.2%), while 25 (56.8%) exhibited stable disease. The objective response rate (ORR) and disease control rate were 18.2% and 75%, respectively. Significant differences in ORR were observed among histological subtypes (well-differentiated vs de-differentiated vs myxoid: 0 vs 17.9% vs 50%; p = 0.039). Six patients underwent surgery before disease progression, and one patient with myxoid liposarcoma (MLPS) had a pathological complete response. With a median follow-up of 21.8 (range, 2.7-30.7) months, the median progression-free survival (mPFS) was 6.9 (95% confidence interval (CI), 4.7-9.1) months, and the 6-month PFS rate was 60.5%. Based on various histological subtypes, the mPFS was 8.4 (95% CI, 4.1-12.7) months with well-differentiated liposarcoma, 5.8 (95% CI, 3.3-8.3) months with de-differentiated liposarcoma and not reached with MLPS, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 36 (76.6%) patients, with grade 3 or higher TRAEs in 21 (44.7%) patients. The most common TRAEs were neutropenia (53.2%), proteinuria (21.3%), and anorexia (21.3%).ConclusionThe combined treatment strategy involving eribulin, anlotinib, and camrelizumab showed promising efficacy and manageable safety in patients with advanced or metastatic RLPS, particularly in those with MLPS.","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"3 1","pages":"17588359241276968"},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inetetamab-based therapy in real-world treatment patterns with HER2-positive advanced breast cancer patients: a retrospective single-center study.","authors":"Mingxia Jiang,Jiaxuan Liu,Maiyue He,Mengqi Zhang,Shihan Zhou,Shanshan Chen,Ruigang Cai,Hongnan Mo,Bo Lan,Pin Zhang,Binghe Xu,Qiao Li","doi":"10.1177/17588359241275422","DOIUrl":"https://doi.org/10.1177/17588359241275422","url":null,"abstract":"BackgroundInetetamab is a novel antibody targeting human epidermal growth factor receptor 2 (HER2) developed in China. Due to its optimized antibody-dependent cell-mediated cytotoxicity effect compared with trastuzumab, it has shown good efficacy and safety in the treatment of HER2-positive advanced breast cancer (ABC).ObjectivesThis study aimed to investigate the efficacy and safety of inetetamab combination therapy in the treatment of HER2-positive ABC in real-world clinical practice.DesignRetrospective study.MethodsA total of 133 patients with HER2-positive ABC who were treated with inetetamab-based regimens between March 2020 and January 2024 were retrospectively included in this study. The main endpoint was median progression-free survival (mPFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety.ResultsThe study included 133 HER2-positive ABC patients, and the median age was 55 years. The mPFS was 8.0 (6.7-9.3) months. The ORR was 50.4%, while the DCR was 88.7%. The mPFS for patients receiving inetetamab-based therapy as first to second, third to fourth, and later lines of metastatic treatment were 14.0, 7.0, and 6.0 months, respectively. Patients treated with inetetamab plus pyrotinib plus chemotherapy, especially with capecitabine, had the best outcomes (mPFS = 14.0 months). Multivariate analysis revealed that prior HER2-TKI treatment was significantly associated with worse PFS (hazard ratios 2.829, 95% confidence interval 1.265-6.328, p = 0.011). Subgroup analysis indicated that patients without visceral metastases had significantly better PFS (14.0 months vs 8.0 months, p = 0.003). The overall incidence of any grade adverse events (AEs) was 100%, with most being grades 1-2. Severe complications included neutropenia (37.6%) and leukopenia (33.1%).ConclusionsInetetamab-based combination therapy shows promising efficacy and good safety in patients with HER2-positive ABC. It is one of the late-line treatment options for Chinese patients with HER2-positive ABC.","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"41 1","pages":"17588359241275422"},"PeriodicalIF":4.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic landscape of homologous recombination repair and practical outcomes of PARPi therapy in ovarian cancer management.","authors":"Mengyu Chen, Ningjing Lei, Ruixia Guo, Liping Han, Qinghe Zhao, Yang Zhao, Luojie Qiu, Fengling Wu, Shan Jiang, Ningyao Tong, Kunmei Wang, Siyu Li, Lei Chang","doi":"10.1177/17588359241271845","DOIUrl":"10.1177/17588359241271845","url":null,"abstract":"<p><strong>Background: </strong>Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients.</p><p><strong>Objectives: </strong>Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi.</p><p><strong>Design: </strong>A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed.</p><p><strong>Methods: </strong>The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi.</p><p><strong>Results: </strong>Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols.</p><p><strong>Conclusion: </strong>Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241271845"},"PeriodicalIF":4.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2 becomes a novel survival biomarker for gastric cancer patients: a pooled analysis.","authors":"Ji Cheng,Ming Cai,Guobin Wang,Kaixiong Tao","doi":"10.1177/17588359241271913","DOIUrl":"https://doi.org/10.1177/17588359241271913","url":null,"abstract":"BackgroundAlthough anti-HER2 therapies have been widely used against gastric carcinoma, the prognostic significance of HER2 overexpression remains unclear. Previous studies failed to provide convincible evidence due to inconsistent HER2 evaluation criteria and heterogeneous clinical characteristics.ObjectivesTo figure out the prognostic significance of HER2 expression in gastric cancer, we rigorously designed and conducted this study.DesignMeta-analysis.Data sources and methodsRecord retrieval was performed by searching PubMed, Web of Science, Cochrane Library, Embase, ASCO, and ESMO meeting libraries from inception to November 2022. Cohort studies investigating overall survival comparison between HER2-positive and HER2-negative gastric cancer patients were included. Both resectable and advanced cases were separately collected while HER2 evaluation standards should be consistent across eligible studies. Newcastle-Ottawa Scale was used for quality assessment. Overall survival was the only endpoint and effect size was presented by hazard ratio (HR) with its 95% confidence interval. The pooled calculation was conducted on Review Manager 5.4.ResultsThirty studies were eligible, including 9945 patients. Eligible studies were mostly high quality (n = 31). Regarding resectable cases (n = 22), HER2-positive groups had significantly worse prognosis than HER2-negative counterparts (HR 1.56, 95%CI 1.32-1.85, p < 0.00001). For HER2-positive patients with advanced gastric cancer (n = 10), HER2 overexpression was also an unfavorable survival indicator (HR 1.70, 95%CI 1.23-2.35, p = 0.001). Potential heterogeneous studies had been eliminated while outcomes remained stable by sensitivity analysis. Subgroup analysis suggested HER2-positive patients had a poorer prognosis in both East Asian (resectable: HR 1.56; advanced: HR 1.32) and non-East Asian countries (HR 1.58; HR 3.27).ConclusionAs a novel survival biomarker in gastric cancer, HER2 overexpression indicates unfavorable prognosis among both resectable and advanced patients, irrespective of East Asian or non-East Asian populations.Trial registrationPROSPERO (CRD42020168051).","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"75 1","pages":"17588359241271913"},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Criteria for assessing evidence for biomarker-targeted therapies in rare cancers-an extrapolation framework.","authors":"Doah Cho, Sarah J Lord, Robyn Ward, Maarten IJzerman, Andrew Mitchell, David M Thomas, Saskia Cheyne, Andrew Martin, Rachael L Morton, John Simes, Chee Khoon Lee","doi":"10.1177/17588359241273062","DOIUrl":"10.1177/17588359241273062","url":null,"abstract":"<p><strong>Background: </strong>Advances in targeted therapy development and tumor sequencing technology are reclassifying cancers into smaller biomarker-defined diseases. Randomized controlled trials (RCTs) are often impractical in rare diseases, leading to calls for single-arm studies to be sufficient to inform clinical practice based on a strong biological rationale. However, without RCTs, favorable outcomes are often attributed to therapy but may be due to a more indolent disease course or other biases. When the clinical benefit of targeted therapy in a common cancer is established in RCTs, this benefit may extend to rarer cancers sharing the same biomarker. However, careful consideration of the appropriateness of extending the existing trial evidence beyond specific cancer types is required. A framework for extrapolating evidence for biomarker-targeted therapies to rare cancers is needed to support transparent decision-making.</p><p><strong>Objectives: </strong>To construct a framework outlining the breadth of criteria essential for extrapolating evidence for a biomarker-targeted therapy generated from RCTs in common cancers to different rare cancers sharing the same biomarker.</p><p><strong>Design: </strong>A series of questions articulating essential criteria for extrapolation.</p><p><strong>Methods: </strong>The framework was developed from the core topics for extrapolation identified from a previous scoping review of methodological guidance. Principles for extrapolation outlined in guidance documents from the European Medicines Agency, the US Food and Drug Administration, and Australia's Medical Services Advisory Committee were incorporated.</p><p><strong>Results: </strong>We propose a framework for assessing key assumptions of similarity of the disease and treatment outcomes between the common and rare cancer for five essential components: prognosis of the biomarker-defined cancer, biomarker test analytical validity, biomarker actionability, treatment efficacy, and safety. Knowledge gaps identified can be used to prioritize future studies.</p><p><strong>Conclusion: </strong>This framework will allow systematic assessment, standardize regulatory, reimbursement and clinical decision-making, and facilitate transparent discussions between key stakeholders in drug assessment for rare biomarker-defined cancers.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241273062"},"PeriodicalIF":4.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study.","authors":"Qingyuan Zhang, Pin Zhang, Min Yan, Xi Yan, Xian Wang, Yuanting Gu, Xiujuan Qu, Shaorong Li, Guoying Xu, Xiaoyu Zhu, Binghe Xu","doi":"10.1177/17588359241273026","DOIUrl":"10.1177/17588359241273026","url":null,"abstract":"<p><strong>Background: </strong>Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC).</p><p><strong>Objectives: </strong>To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC.</p><p><strong>Design: </strong>A multicenter, open-label, phase Ib trial.</p><p><strong>Methods: </strong>Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1-2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3-5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety.</p><p><strong>Results: </strong>A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%-93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%-87.5% for lower doses; grade 4, 46.7% and 4.2%-20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%-54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5-82.6) and patients progressing after ET (53.3%; 95% CI 26.6-78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9-46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9-24.1) with fulvestrant.</p><p><strong>Conclusion: </strong>Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03481998.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241273026"},"PeriodicalIF":4.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials.","authors":"Sara A Almansour, Mohammad A Y Alqudah, Ziad Abuhelwa, Humaid O Al-Shamsi, Ahmad Alhuraiji, Mohammad H Semreen, Yasser Bustanji, Karem H Alzoubi, Natansh D Modi, Ross A Mckinnon, Michael J Sorich, Ashley M Hopkins, Ahmad Y Abuhelwa","doi":"10.1177/17588359241275387","DOIUrl":"10.1177/17588359241275387","url":null,"abstract":"<p><strong>Background: </strong>Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations.</p><p><strong>Design: </strong>A posthoc analysis of individual-participant level data (IPD).</p><p><strong>Methods: </strong>IPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark.</p><p><strong>Results: </strong>Among 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26-0.77), <i>p</i> = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations.</p><p><strong>Conclusion: </strong>This study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM.</p><p><strong>Trial registration: </strong>MAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241275387"},"PeriodicalIF":4.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On cost-effectiveness analysis, quality-adjusted life years, and cost-effectiveness threshold values of gemcitabine plus nab-paclitaxel versus gemcitabine alone in metastatic pancreatic cancer in the French setting.","authors":"Carlo Lazzaro","doi":"10.1177/17588359241276812","DOIUrl":"10.1177/17588359241276812","url":null,"abstract":"","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241276812"},"PeriodicalIF":4.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of esogastric cancer in older patients.","authors":"Thomas Aparicio, Anna Carteaux-Taieb, Amélie Arégui, Janina Estrada, Geoffroy Beraud-Chaulet, Virginie Fossey-Diaz, Pascal Hammel, Pierre Cattan","doi":"10.1177/17588359241272941","DOIUrl":"10.1177/17588359241272941","url":null,"abstract":"<p><p>Although esogastric cancers often affect patients over 75, there are no specific age-related guidelines for the care of these patients. Esogastric cancers have a poor prognosis and require multimodal treatment to obtain a cure. The morbidity and mortality of these multimodal treatments can be limited if care is optimized by selecting patients for neoadjuvant treatment and surgery. This can include a geriatric assessment, prehabilitation, renutrition, and more extensive use of minimally invasive surgery. Denutrition is frequent in these patients and is particularly harmful in older patients. While older patients may be provided with neoadjuvant chemotherapy or radiotherapy, it must be adapted to the patient's status. A reduction in the initial dose of palliative chemotherapy should be considered in patients with metastases. These patients tolerate immunotherapy better than systemic chemotherapy, and a strategy to replace chemotherapy with immunotherapy whenever possible should be evaluated. Finally, better supportive care is needed in patients with a poor performance status. Prospective studies are needed to improve the care and prognosis of elderly patients.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241272941"},"PeriodicalIF":4.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies.","authors":"Ah-Reum Jeong, Aaron H Trando, Sean D Thomas, Paul Riviere, Patrick J Sakowski, Ethan S Sokol, Aaron M Goodman, Razelle Kurzrock","doi":"10.1177/17588359241273053","DOIUrl":"10.1177/17588359241273053","url":null,"abstract":"<p><strong>Background: </strong>The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.</p><p><strong>Objectives: </strong>This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.</p><p><strong>Design: </strong>This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).</p><p><strong>Methods: </strong>TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records.</p><p><strong>Results: </strong>In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range, 0-46.83). Forty-eight patients (12%) had TMB ⩾10 mutations/Mb, 90% of which were B-cell or T-cell NHL. In 85 samples with available PD-L1 scores, 11 were high; 26, low; and 48, no tumor cell expression. PD-L1 TPS positive (⩾1%) was most common in T-cell NHL (7/9 (77%) cases) followed by B-cell NHL (21/51 (41%) cases). TMB ⩾4 mutations/Mb and PD-L1 score ⩾1% were significantly associated with shorter overall survival (OS) from diagnosis, with hazard ratio (HR) = 1.46 (<i>p</i> = 0.02, 95% confidence interval (CI) 1.05-2.03) and HR = 2.11 (<i>p</i> = 0.04, 95% CI 1.04-4.30), respectively; the relationship was more pronounced when PD-L1 ⩾50% versus <50% was used (HR = 2.80, <i>p</i> = 0.02, 95% CI 1.19-6.59). Higher TMB and higher PD-L1 positivity correlation were significant but weak (Pearson correlation coefficient <i>R</i> ² = 0.04, <i>p</i> = 0.04).</p><p><strong>Conclusion: </strong>TMB ⩾4 mutations/Mb and positive PD-L1 TPS are poor prognostic factors, correlating with shorter OS across hematologic malignancies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02478931.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241273053"},"PeriodicalIF":4.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}