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

{"title":"Outcome Predictors of Hardware Complications in Head and Neck Free Flap Reconstruction.","authors":"Abhinav Talwar, Shravan Asthana, Jennifer Silva-Nash, Laila A Gharzai, Sandeep Samant, Urjeet Patel, Katelyn Stepan","doi":"10.1097/COC.0000000000001180","DOIUrl":"10.1097/COC.0000000000001180","url":null,"abstract":"<p><strong>Objectives: </strong>Osteocutaneous free flap reconstruction can be complicated by hardware failure. The present study investigates the frequency and predictors of hardware failure in head and neck osteocutaneous reconstruction.</p><p><strong>Methods: </strong>Patients who underwent osteocutaneous head and neck free flap reconstruction between the years of 2014 and 2022 were identified at our institution. Hardware failure was defined as hardware infection, screw plate loosening, exposed hardware, migration, deformation, or fracture.</p><p><strong>Results: </strong>We identified 47 patients who met the inclusion criteria for this study. Common indications for intervention included squamous cell carcinoma (35, 74%) and osteoradionecrosis (8, 17%). Most operations used fibular flaps (31, 66%) or osteocutaneous radial forearm flaps (12, 26%). The median age at the time of reconstruction was 66 years (IQR: 59 to 72). In total, 17 (36%) patients experienced hardware failure in the postoperative period. On univariable analysis, estimated blood loss ( P =0.01) and early postoperative infectious complication ( P =0.03) were the only significant predictors of hardware failure. On multivariable analysis, these factors retained significance. Estimated blood loss had an OR of 1.004 (95% CI: 1.001-1.008; P =0.01), and infectious complication had an OR of 5.22 (95% CI: 1.28-24.84; P =0.03).</p><p><strong>Conclusion: </strong>The incidence of hardware failure among patients who undergo head and neck osteocutaenous free flap reconstruction is high (36%). Patients with infectious complications and high estimated blood loss may be more likely to develop hardware failure.</p><p><strong>Level of evidence: </strong>Level III.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"319-324"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450882","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":"Unlocking the Mysteries of Breast Cancer: The Role of Epigenetics in Diagnosis, Treatment, and Beyond.","authors":"Zaheer Qureshi, Faryal Altaf, Abdur Jamil, Rimsha Siddique","doi":"10.1097/COC.0000000000001177","DOIUrl":"10.1097/COC.0000000000001177","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer is an intricate and varied disease exhibiting a range of molecular subgroups and clinical consequences. Epigenetic alterations have become essential players in the pathophysiology of breast cancer because they control gene expression without changing the DNA sequence. This review provides a comprehensive overview of epigenetics' diagnostic, prognostic, and therapeutic implications in breast cancer. This review aims to present a comprehensive study of the function of epigenetics in breast cancer, emphasizing current developments and potential avenues for future research.</p><p><strong>Methods: </strong>A narrative review methodology involved an extensive literature search and selection to gather relevant studies and trial data. PubMed, Embase, and Web of Science databases were searched using relevant keywords such as \"epigenetics,\" \"breast cancer,\" \"DNA methylation,\" \"histone modification,\" \"noncoding RNA,\" and \"linical trials.\" Relevant studies and clinical trial data were selected and synthesized to summarize the topic comprehensively.</p><p><strong>Results: </strong>The review synthesizes critical findings from current research, underscoring the pivotal role of epigenetic mechanisms in breast cancer initiation, progression, and therapeutic response. It highlights the potential of epigenetic biomarkers for diagnosis and prognosis and the promise of epigenetic-targeted therapies in breast cancer management. Furthermore, the review outlines future directions for research, emphasizing the importance of elucidating the dynamic interplay between epigenetic alterations and tumor microenvironments in shaping breast cancer phenotypes.</p><p><strong>Conclusions: </strong>Epigenetic modifications influence breast cancer progression, diagnosis, and therapy. Emerging biomarkers and targeted treatments hold promise, but further research is essential to refine their clinical application and improve personalized cancer management strategies.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"276-282"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538058","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":"Statewide Social Vulnerability Index (SVI) in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.","authors":"Asher C Park, Shravan Asthana, Abhinav Talwar, Kirsten Burdett, Laila Gharzai, Urjeet Patel, Sandeep Samant, Katelyn O Stepan","doi":"10.1097/COC.0000000000001216","DOIUrl":"https://doi.org/10.1097/COC.0000000000001216","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association between social determinants of health, as measured by the social vulnerability index (SVI), with outcomes in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).</p><p><strong>Methods: </strong>This study included patients from Illinois with HPV-OPSCC from 2007 to 2022. State-level SVI measured neighborhood-level disadvantage and associations between SVI and clinicodemographic factors, clinical presentation, and outcomes were analyzed using logistic regression for advanced preliminary staging, while survival and recurrence were assessed within the framework of a Cox proportional hazards model.</p><p><strong>Results: </strong>Higher overall (high vulnerability) and racial-ethnicity SVI scores were significantly associated with increased odds of advanced clinical staging (OR=1.12, P=0.041; OR=1.16, P=0.026) on univariable analysis. Multivariable analysis showed that minority race was significantly associated with advanced clinical staging (OR=5.50, P<0.001). Overall survival was significantly associated with insurance payer type and age, where Medicaid/uninsured status had higher mortality compared with Medicare in both the univariable and multivariable setting (HR=4.47, P=0.006; HR=7.93, P=0.019). The same held for age, where increased age at diagnosis was significantly associated with higher mortality (HR=1.07, P<0.001; HR=1.10, P<0.001). Recurrence-free survival was significantly associated with age (HR=1.04, P=0.004) and payer type, with Medicaid/uninsured patients having 4 times the hazard of patients with Medicare (HR=4.16, P=0.009).</p><p><strong>Conclusions: </strong>Higher overall and racial ethnicity SVI may be associated with advanced clinical staging upon presentation. Individual factors such as race, age, and insurance status are significantly associated with patient prognosis.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121456","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":"A Multicenter Real-Life Evaluation of Safety and Effectiveness of the Antibody-Drug Conjugate Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.","authors":"Federica Martorana, Maria V Sanò, Alessandra Fabi, Ida Paris, Vita Leonardi, Gabriella Bini, Oriana Maiorana, Paolo Vigneri, Vittorio Gebbia, Giuseppina Scandurra, Francesco Giotta, Annabella Curaba, Maria R Valerio","doi":"10.1097/COC.0000000000001201","DOIUrl":"https://doi.org/10.1097/COC.0000000000001201","url":null,"abstract":"<p><strong>Objectives: </strong>Randomized trials showed that the third-generation antibody-drug conjugate, sacituzumab govitecan (SG), is active against metastatic triple-negative breast cancer (mTNBC). Real-world data are relatively limited. This retrospective study reports the efficacy and safety of SG in a series of women with mTNBC in clinical practice.</p><p><strong>Methods: </strong>Eighty-four patients with widely pretreated, de novo, or metachronous mTNBC were treated with SG at the recommended dose of 10 mg/kg on days 1 and 8 every 3 weeks over a 3-hour intravenous infusion at 6 medical oncology units.</p><p><strong>Results: </strong>No complete response was observed. Overall, 29 patients (34%; 95% CI: 24.4%-44.7%) achieved a partial response with a median duration of 6 months (range: 5 to 14 mo). Twenty patients 24 (29%; 95% CI: 18.9%-38.2%) had stabilization of disease with a median duration of 7 months (4 to 13 mo), while 31 (37%; 95% CI: 26.6%-47.2%) progressed. The median progression-free survival was 5 months (range: 1 to 14 mo) and the median overall survival as 10 months (range: 1 to 18 mo). Twelve patients (22%) had metastatic deposits in CNS and had received radiotherapy.</p><p><strong>Conclusions: </strong>The real-life data reported in this paper confirm the randomized trial results regarding efficacy and tolerability. The authors stressed the importance of the early identification of severe side effects in managing these patients.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095779","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":"Global Trends in Childhood Acute Lymphoblastic Leukemia Burden and Quality of Care Inequalities Across Regions, 1990 to 2021: A Systematic Analysis Using Global Burden of Disease Study 2021 Data.","authors":"Ying Huang, Xiaoxia Chen, Cailing Gao","doi":"10.1097/COC.0000000000001210","DOIUrl":"https://doi.org/10.1097/COC.0000000000001210","url":null,"abstract":"<p><strong>Objective: </strong>To reveal the global trends in the burden and quality of care for childhood ALL from 1990 to 2021, along with inequalities in quality of care across regions, thus identifying regions requiring targeted interventions for optimizing health care resource allocation.</p><p><strong>Methods: </strong>Utilizing Global Burden of Disease Study 2021 data, this research analyzed the temporal trends in the global burden of childhood ALL from 1990 to 2021. The quality of care index (QCI) was used to quantify care quality, and the gender disparity ratio (GDR) was used to assess gender disparities. Trend analyses were conducted using the estimated annual percentage change (EAPC), and the associations between QCI, GDR, and the sociodemographic index (SDI) were explored. Inequalities in QCI and GDR across regions were evaluated using the slope index of inequality (SII) and health inequality concentration index.</p><p><strong>Results: </strong>From 1990 to 2021, the incidence and death rates, as well as disability-adjusted life years (DALYs) and years of life lost (YLLs) due to childhood ALL, significantly decreased. However, the number of prevalence and prevalence crude rate increased by 66.818% and 37.923%, respectively. Global care quality continued to improve, with an EAPC of 2.566 (95% CI: 2.488-2.645). In 2021, regions with high QCI were concentrated in high-income areas like Western Europe, while low QCI regions were primarily in low-income areas like sub-Saharan Africa and Oceania. Although the health inequality concentration index of global quality of care decreased from 0.550 in 1990 to 0.395 in 2021, the SII increased from 35.396 to 87.141. Care quality was consistently higher in females than in males, particularly in low and low-middle SDI regions, while the disparities in high and middle SDI regions were gradually narrowing.</p><p><strong>Conclusion: </strong>Despite the gradual decrease in the burden of childhood ALL globally and the steady improvement in quality of care, absolute inequalities remain a significant challenge. Future efforts should focus on increasing health care resource allocation in low SDI regions, enhancing international cooperation, improving the quality and accessibility of care in priority regions, and promoting global health equity.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095780","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":"Metabolic Plasticity in Prostate Cancer: The Warburg Effect and Its Clinical Relevance.","authors":"Arielle Sabbah, Guila Delouya, Mikhael Laskine, Daniel Taussky","doi":"10.1097/COC.0000000000001215","DOIUrl":"https://doi.org/10.1097/COC.0000000000001215","url":null,"abstract":"<p><strong>Objectives: </strong>This paper examines the life and research of Otto Warburg (1883 to 1970), who identified the so-called Warburg effect. Warburg personal life and scientific career were notable.</p><p><strong>Methods: </strong>This study summarizes the key aspects of his life, the Warburg effect, and its significance in prostate cancer.</p><p><strong>Results: </strong>Despite being classified as non-Aryan, Warburg continued his research as the director of the Kaiser Wilhelm Institute for Cell Physiology during World War II. He also cohabited openly with a male partner. The Warburg effect is a metabolic hallmark of cancer, where cells preferentially utilize glycolysis over oxidative phosphorylation, even in the presence of oxygen. This metabolic shift confers key advantages to tumor survival, including rapid ATP production, biosynthetic support for proliferation, and resistance to apoptosis. In prostate cancer, the metabolism undergoes a unique transformation. Normal prostate cells are characterized by citrate secretion; however, as malignancy develops, the cells adapt to oxidative metabolism. At the metastatic stage, the Warburg effect becomes more pronounced and is influenced by the tumor microenvironment and interactions with cancer-associated fibroblasts and bone marrow adipocytes. These metabolic changes have significant clinical implications. While FDG-PET scans serve as a diagnostic tool in many cancers, their utility in early-stage prostate cancer is limited owing to its delayed metabolic shift. Metabolic-targeted therapies, such as dichloroacetate (DCA) and glycolysis inhibitors, are emerging as promising strategies to enhance the efficacy of chemotherapy and radiotherapy.</p><p><strong>Conclusions: </strong>Elucidating the role of metabolic reprogramming in prostate cancer could reveal new avenues for treatment, particularly for castration-resistant and metastatic diseases.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081854","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":"Research Progress of SBRT Combined With Immunotherapy in Locally Advanced Head and Neck Cancer.","authors":"Yumei Feng, Ping Zhou, Xirui Duan, Qin Ye, Ke Xie","doi":"10.1097/COC.0000000000001204","DOIUrl":"https://doi.org/10.1097/COC.0000000000001204","url":null,"abstract":"<p><p>The incidence of head and neck cancer ranks sixth among malignant tumors in the world. According to the GLOBOCAN 2020 database, there are about 930,000 new cases and 467,000 deaths per year. Among malignant head and neck tumors, head and neck squamous cell carcinoma (HNSCC) comprises approximately 90% of cases. Between 70% and 80% of HNSCC patients are diagnosed at an advanced stage (III or IV). Following comprehensive treatment, the recurrence rate within 2 years ranges from 40% to 60%. In cases of recurrent or metastatic HNSCC, the median survival period after traditional chemotherapy or targeted therapy is about 1 year, with a 5-year survival rate below 10%. However, several current trials are examining new tactics, such as better prediction biomarkers and combination strategies with chemotherapy, targeted therapy, additional immunotherapy, or radiotherapy, given the relatively poor response rate of immune checkpoint inhibitor monotherapy. Consequently, the research on stereotactic body radiation therapy (SBRT) in conjunction with immunotherapy for locally advanced head and neck tumors is reviewed in this article.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038733","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 Balance and Imbalance of Microbial Communities: Oral-Gut Microbiota and Colorectal Cancer.","authors":"Zihui Zhao, Zhikun Yuan, Yanhui Li, Xiaochun Huang","doi":"10.1097/COC.0000000000001213","DOIUrl":"https://doi.org/10.1097/COC.0000000000001213","url":null,"abstract":"<p><p>The microbiome is a significant multimicrobial community that coexists with the human body in a symbiotic relationship. These microbial communities participate in mechanisms, such as defense against infections, absorption of nutrients, and maintenance of internal homeostasis. Although the microbiome is involved in physiological processes that are beneficial to host health, it can also lead to serious problems. Despite being far apart, the oral cavity and colon are both highly colonized by different microbial communities. Studies have shown that oral bacteria can migrate to and colonize the colon, which is most evident in diseases such as periodontitis. These oral pathogenic bacteria, which contain a large number of carcinogenic factors such as Fusobacterium nucleatum and Porphyromonas gingivalis, can penetrate the large intestine and cause intestinal microbial imbalance and dysfunction, thereby stimulating carcinogenesis. Increasing evidence suggests that oral microbiota, especially certain periodontal pathogens, may be used as biomarkers for colorectal cancer (CRC). Understanding the exact mechanisms of microbiome interactions and their impact on CRC will provide future opportunities for the prevention and treatment of colorectal cancer, and is an important prerequisite for its use as a precise noninvasive biomarker, which is crucial for the early detection of CRC. This review aims to summarize the current research status of oral microbiota, gut microbiota, and their association with CRC, and to evaluate the effectiveness of oral microbiome-derived biomarkers.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039164","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":"Prevalence and Development of Cachexia Before and After Diagnosis of Non-small Cell Lung Cancer.","authors":"L Anne Gilmore, Jonas Willmann, Santiago Olaechea, Brian W Gilmore, Edward Christopher Dee, Mihir Rao, Bhavani S Gannavarapu, Shivaek Venkateswaran, Christian M Alvarez, Chul Ahn, Dirk K M de Ruysscher, Urvi A Shah, Neil M Iyengar, Daniel R Gomez, Rodney Infante, Puneeth Iyengar","doi":"10.1097/COC.0000000000001211","DOIUrl":"https://doi.org/10.1097/COC.0000000000001211","url":null,"abstract":"<p><strong>Objective: </strong>Cachexia is commonly defined based on weight loss at the time of cancer diagnosis. However, regular weight measurements before cancer diagnosis are often lacking and may be subject to recall bias if retrospectively self-reported by patients. To analyze the development and progression of cachexia, we employ body weight trajectories from 1 year before and after diagnosis of non-small cell lung cancer (NSCLC). We hypothesized that cachexia could be detected as early as 1 year before NSCLC diagnosis and that cachexia prevalence would increase in the year following diagnosis.</p><p><strong>Methods: </strong>This retrospective study included consecutive patients with NSCLC treated at UTSW between 2005 and 2019 who had body weight measurements before and after NSCLC diagnosis recorded in their electronic health records. Weights were binned in 3-month intervals. Cachexia was defined per the International Consensus Definition of cachexia, that is, loss of >5% body weight 12 months preceding cancer diagnosis for patients with BMI ≥20 kg/m2 or weight loss of >2% for patients with a BMI <20 kg/m2. The association of disease stage and primary treatment with weight changes was investigated.</p><p><strong>Results: </strong>Among 4294 patients screened, 661 patients were included in the final analysis. Patients had a mean age of 69.3 (SD: 10.6) years, and a majority were current/former smokers (83%), identified as white (76%), and were diagnosed with either stage I (47%) or stage IV (28%) nonsquamous NSCLC (78%). At cancer diagnosis, 28% (n=183) presented with cachexia, having incurred a mean loss of 8.6 (SEM: 0.4%) (P<0.0001) of body weight within the year before cancer diagnosis. Weight loss after cancer diagnosis was comparable in patients with and without cachexia at cancer diagnosis (P=0.05). By 12 months postcancer diagnosis, 58% of patients (n=383) met the criteria for cachexia based on weight loss. Weight loss consistent with cachexia occurred over a median period of 220 (IQR: 265) days.</p><p><strong>Conclusion: </strong>Weight loss in patients with cachexia at NSCLC diagnosis may commence as early as 12 months before cancer diagnosis. Within a year after a cancer diagnosis, more than half of patients develop cachexia, particularly those with advanced disease. These findings support the integration of early nutritional and pharmacological interventions in patients with NSCLC.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062893","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":"MOSAIC: A Multi-Feature Genomic Instability Score Independently Predicts Sarcoma Survival in 2138 Patients.","authors":"Daniel Schneider, Jacob Gluski, Ethan D L Brown, Akash Mishra, Daniel M Sciubba, Sheng-Fu L Lo","doi":"10.1097/COC.0000000000001207","DOIUrl":"https://doi.org/10.1097/COC.0000000000001207","url":null,"abstract":"<p><strong>Objectives: </strong>While genomic profiling has identified prognostic markers in sarcoma, clinical risk stratification remains largely histology-based. The combined impact of multiple genomic instability features on survival remains poorly understood. This study evaluated the prognostic utility of a novel Measure Of Sarcoma Aggregate Instability Complex (MOSAIC) Score.</p><p><strong>Methods: </strong>We conducted a secondary analysis of 2138 sarcoma patients from the Sarcoma (MSK, Nat Commun. 2022) data set in cBioPortal. The MOSAIC score integrated 6 genomic instability markers: mutation burden, whole-genome doubling, copy number alterations, ploidy, microsatellite instability, and a fraction of genome altered. Cox proportional hazards models adjusted for clinical covariates assessed survival associations.</p><p><strong>Results: </strong>Higher MOSAIC scores correlated with worse survival (HR=1.11 per unit, 95% CI: 1.07-1.15, P=4.67 × 10-8). The first principal component explained 47.6% of the total variance. A threshold effect emerged between quartiles, with higher quartiles showing nearly doubled mortality risk (adjusted HRs: Q2=1.89, Q3=1.88, Q4=1.96; all P<0.001). Chromosomal instability markers (copy number alterations: 0.51, whole-genome doubling: 0.49) contributed more than point mutations (mutation burden: 0.15). MOSAIC's prognostic impact varied by anatomic site, with strong effects in thoracic (HR=1.66, P=4.74 × 10-4) and trunk (HR=1.50, P=0.018) sarcomas.</p><p><strong>Conclusions: </strong>MOSAIC provides independent prognostic value across sarcoma subtypes, surpassing conventional clinical factors. Its integration of routine genomic features broadens applicability and may inform immunotherapy response prediction. The observed threshold effect and dominance of chromosomal instability markers offer novel insights into sarcoma biology and therapeutic targeting. Prospective validation is warranted for clinical implementation.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006856","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}