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

{"title":"Beyond the Clinic: A Social Media Network Analysis of 5466 Posts Reveals the Interconnected Challenges Facing Sarcoma Patients.","authors":"Daniel Schneider, Ethan D L Brown, Jacob Gluski, Akash Mishra, Daniel M Sciubba, Sheng-Fu L Lo","doi":"10.1097/COC.0000000000001191","DOIUrl":"https://doi.org/10.1097/COC.0000000000001191","url":null,"abstract":"<p><strong>Objectives: </strong>Social media platforms have increasingly been investigated as a source of patient perspectives that may not emerge in clinical settings. This study aimed to explore how disease status, treatment, and the patient experience interconnect for sarcoma patients posting on a major social media platform.</p><p><strong>Methods: </strong>We conducted a systematic thematic analysis of 5466 posts across 7 health-related subreddits using a framework of 6 major categories: physical symptoms, disease status, treatments, psychosocial impact, support systems, and daily life impact. Theme detection utilized regular expression matching across 27 subthemes, while VADER sentiment analysis assessed emotional valence. The statistical analysis examined theme co-occurrences using Fisher exact tests and sentiment patterns using Mann-Whitney U tests.</p><p><strong>Results: </strong>Treatment-related discussions dominated the discourse, with chemotherapy (65.6%) and radiation therapy (60.2%) strongly associated with work-related impacts (OR=2.85 and 2.47, respectively; all OR P<0.001). Financial discussions and work-related posts demonstrated the highest user engagement. Disease progression was a critical transition point, demonstrating robust relationships with treatment modalities (chemotherapy: OR=3.12; radiation: OR=4.09), anxiety (OR=2.23), and uncertainty (OR=2.13). Support-seeking behavior (34.9%) was positively associated with medical team interactions (OR=2.16). Physical symptoms exhibited negative sentiment (-0.331±0.154), particularly discussions of weakness (-0.589) and breathing difficulties (-0.308). Hope-related discussions showed more positive sentiment than other psychosocial themes (Cohen d=-0.595, P<0.001).</p><p><strong>Conclusions: </strong>This network analysis reveals critical intersections between treatment decisions, financial concerns, and work impact within sarcoma care. Integrated support interventions that address both clinical and practical challenges-particularly treatment transitions and financial toxicity-may improve patient care.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797012","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":"Death From Infection Among Patients Living With Cancer.","authors":"Mckenzee Chiam, Kyle Mani, Xi Wang, Ming Wang, Daniel M Trifiletti, Leslie J Parent, Daniel E Spratt, Leila Tchelebi, Nicholas G Zaorsky","doi":"10.1097/COC.0000000000001182","DOIUrl":"https://doi.org/10.1097/COC.0000000000001182","url":null,"abstract":"<p><strong>Objectives: </strong>Early identification of patients living with cancer at higher risk of death from an infection is critical in infection mortality prevention. We characterize patients living with cancer at the highest risk of dying from an infection.</p><p><strong>Methods: </strong>7,529,481 US cancer survivors (1992 to 2015) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) and 95% CIs were calculated. Fine-gray survival analysis was performed to calculate hazard ratios by adjusting for the effects of competing risks (eg, deaths due to causes other than infection).</p><p><strong>Results: </strong>Among 7,529,481 patients living with cancer (1992 to 2015), 101,167 (1.3%) died of infection. The rate of infection-specific mortality was 27.19/10,000 person-years, with an SMR of 3.29 (95% CI: 3.26-3.32, P<0.001). Patients who were older, male, black, and unmarried were at a greater risk of fatal infection. Overall, the risk of infection-specific mortality for patients living with cancer is greatest 1 year after diagnosis compared with the general population (SMR: 8.68, 95% CI: 8.53-8.84; P<0.0001), and this risk decreases with follow-up time (SMR at >10 y after diagnosis: 2.93, 95% CI: 2.87-3.00; P<0.0001). Among patients with Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Kaposi Sarcoma, 9.2%, 11.5%, and 82.2% of all deaths within the first year after cancer diagnosis occurred due to acute infectious disease. In contrast, for patients with liver cancer, the relative percentage of infection-specific mortality increases with follow-up time from 3.5% at <1 year after cancer diagnosis and 10.4% at 10+ years of follow-up.</p><p><strong>Conclusion: </strong>The results of this study characterize infection mortality in patients living with cancer, which can guide more targeted research and interventions in this population.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781353","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 Tolerability of Concurrent Radiotherapy and Sacituzumab Govitecan in Metastatic Breast Cancer.","authors":"Pierre Loap, Salma Chabli, Paul Cottu, Youlia Kirova","doi":"10.1097/COC.0000000000001195","DOIUrl":"https://doi.org/10.1097/COC.0000000000001195","url":null,"abstract":"<p><strong>Objectives: </strong>Sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, is approved for metastatic triple-negative breast cancer (TNBC) from the second-line setting and for hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer from the third line. Radiotherapy is frequently required in metastatic settings for symptom control, but its combination with sacituzumab govitecan has not been formally evaluated. This study aims to assess the safety and tolerability of concurrent sacituzumab govitecan and radiotherapy in metastatic breast cancer patients.</p><p><strong>Methods: </strong>This retrospective, single-center study included all metastatic breast cancer patients who received sacituzumab govitecan and underwent external beam radiotherapy (EBRT) at Institut Curie. Clinical and pathologic data, treatment details, toxicities graded per CTCAE v5.0, and survival outcomes were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method.</p><p><strong>Results: </strong>Thirteen patients were included, with a mean age of 54 years. The majority (61.5%) had TNBC. A total of 19 metastatic sites were irradiated, including 10 brain and 9 bone metastases. No radiation-induced toxicity was observed, and no patients required treatment interruption. Grade 3 to 4 toxicities were limited to neutropenia (15.4%). The median OS from radiotherapy completion was 6 months, with a 6-month OS rate of 45.1% and a 12-month OS rate of 16.9%.</p><p><strong>Conclusions: </strong>The concurrent administration of sacituzumab govitecan and radiotherapy appears well tolerated, with no increased toxicity. This combination may be feasible in metastatic breast cancer patients when clinically indicated. Further studies with larger cohorts are necessary to confirm these findings.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774841","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":"Geospatial Mapping of Head and Neck Cancer Research: Assessing Access, Disparities, and Characteristics of Head and Neck Cancer Clinical Trials Across the United States.","authors":"Alexander Glehan, Talitha Kumaresan, Tam Ramsey, Jonathan Kumaresan, Neil Gildener-Leapman","doi":"10.1097/COC.0000000000001160","DOIUrl":"10.1097/COC.0000000000001160","url":null,"abstract":"<p><strong>Objective: </strong>To report geographic distribution and characteristics of head and neck cancer (HNC) clinical trials in the United States.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of U.S. HNC clinical trials searching ClinicalTrials.gov from January 1, 2017 to December 31, 2021 using the terms \"head and neck cancer\" or \"head and neck neoplasms.\"</p><p><strong>Results: </strong>A total of 381 clinical trials met inclusion criteria with 2181 trial opportunities, which were correlated with population density. Of the U.S. population, 72% live within a 25-mile radius of trials. California, Pennsylvania, and New York had the greatest number of clinical trial entries. The majority of patients living more than 25 miles from an HNC clinical trial site are located in rural areas. One hundred sixty-five (43.3%) trials were about systemic therapy, of which 138 (83.6%) involved targeted immunotherapy. There were 286 unique principal investigators. One hundred six (37.1%) were females and 180 (62.9%) were males.</p><p><strong>Conclusions: </strong>We demonstrate disparity in the geographic distribution of HNC trials favoring densely populated urban areas, which may limit patient access due to travel burden. Studies are skewed towards immunotherapy drug trials, with fewer radiation and surgery investigations.</p><p><strong>Level of evidence: </strong>Level III.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"180-184"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752212","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":"Separation Surgery Followed by Conformal Postoperative Spine Stereotactic Body Radiation Therapy Does Not Increase Risk of Adjacent Spine Level Progression in the Management of Spine Metastases.","authors":"Michael J Strong, Joseph R Linzey, Peyton Goethe, Varun Kathawate, Lila Tudrick, Johan Lee, Oludotun Ogunsola, Mark M Zaki, Ayobami L Ward, Noah Willett, Rushikesh S Joshi, Whitney Muhlestein, Yamaan S Saadeh, Robert Y North, Joseph R Evans, Nicholas J Szerlip, William C Jackson","doi":"10.1097/COC.0000000000001164","DOIUrl":"10.1097/COC.0000000000001164","url":null,"abstract":"<p><strong>Objective: </strong>To determine if piecemeal separation surgery, in conjunction with smaller treatment volumes utilized with spine stereotactic radiation therapy (S-SBRT), increased the risk of adjacent level progression (ALP).</p><p><strong>Methods: </strong>We performed a retrospective analysis of a prospectively maintained database of adult spine oncologic patients who underwent SBRT to the spine at University of Michigan from 2010 to 2021. We compared ALP in patients undergoing SBRT who had pretreatment surgery with those who did not.</p><p><strong>Results: </strong>Four hundred and ninety-eight treatment sites were identified in 417 patients. Of these, 366 (73.5%) were treated with SBRT alone and 132 (26.5%) were treated with surgery followed by S-SBRT. Patients treated with SBRT alone were significantly older (63.3 y) compared with the surgery plus SBRT group (60.2 y; P =0.02). More radiosensitive histologies were treated with SBRT alone (34%) compared with 11% for the surgery plus SBRT group ( P <0.001). Lesions treated in the surgery plus SBRT group had significantly more severe metastatic epidural spinal cord compression (65%) compared with the SBRT only group (8%) ( P <0.001). Both infield progression (9.3% vs. 7.6%; P =0.43) and ALP (21.3% vs. 18.9%; P =0.37) were not significantly different between groups.</p><p><strong>Conclusions: </strong>Spine oncology patients treated with surgery followed by conformal postoperative S-SBRT had similar infield and ALP compared with patients receiving SBRT alone, suggesting that piecemeal separation surgery does not locally spread tumor cells, leading to an increased risk of ALP failure, and supporting the use of conformal postoperative S-SBRT.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"200-205"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015685","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":"Talazoparib for the Treatment of Metastatic Castration-resistant Prostate Cancer: A Narrative Review.","authors":"Zaheer Qureshi, Eeshal Fatima, Adnan Safi, Mikail Khanzada, Faryal Altaf","doi":"10.1097/COC.0000000000001159","DOIUrl":"https://doi.org/10.1097/COC.0000000000001159","url":null,"abstract":"<p><p>Breast and prostate cancer are among the most commonly diagnosed cancers worldwide. Recent advances in tumor sequencing and gene studies have led to a paradigm shift from treatment centered on the type of tumor to therapy more focused on specific immune phenotype markers and molecular alterations. In this review, we discuss the utility and function of talazoparib concerning prostate cancer treatment and summarize recent and planned clinical trials on talazoparib. We searched medical databases for articles relating to the use of talazoparib in prostate cancer from inception. Poly ADP ribose polymerase (PARP) is a family of 17 necessary DNA repair enzymes responsible for base excision repair, single-strand break repair, and double-strand break repair. PARP inhibitors are a class of oral targeted therapies that compete for the NAD + binding site on PARP molecules. Talazoparib, a potent PARP inhibitor, has emerged as a significant therapeutic option in the treatment of metastatic castration-resistant prostate cancer (mCRPC), particularly for patients with specific genetic alterations. Its role as a PARP inhibitor makes it a targeted therapy, focusing on cancer cells with DNA repair deficiencies. Talazoparib's role as a biomarker-directed therapy in advanced prostate cancer has been increasingly recognized. The TALAPRO-1 demonstrated durable antitumor activity in mCRPC patients. TALAPRO-2 is a notable clinical trial, specifically examining the effectiveness of Talazoparib when used in combination therapies. Current investigations demonstrate a significant improvement in survival outcomes for the patients of mCRPC, making Talazoparib a promising intervention.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":"48 4","pages":"206-214"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702133","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":"Treatment of Cutaneous Adnexal Carcinoma With Radiotherapy: A 20-Year, Single-Institution Experience in 49 Patients.","authors":"Nader Mohamed, Sarah Mattessich, Daphna Y Gelblum, Nancy Y Lee, Christopher A Barker","doi":"10.1097/COC.0000000000001163","DOIUrl":"10.1097/COC.0000000000001163","url":null,"abstract":"<p><strong>Objectives: </strong>Cutaneous adnexal carcinomas (CACs) are rare skin cancers with no established treatment guidelines. Given the limited data, this study aims to explore the characteristics and outcomes of patients with CAC treated with radiation therapy (RT).</p><p><strong>Methods: </strong>Patients diagnosed with CAC between 2000 and 2020 who received RT were included. Kaplan-Meier methods measured time to local recurrence (LR), regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), and progression-free survival (PFS). Fisher exact test compared frequency distributions.</p><p><strong>Results: </strong>Forty-nine patients with an average age of 65 years were studied. Most were White males with head and neck tumors. Common subtypes were adnexal adenocarcinoma, sebaceous carcinoma, and microcystic adnexal carcinoma. Patients received RT diagnosis or recurrence. The median overall survival was 44 months, with a median follow-up of 41 months for surviving patients. For patients with de novo cancer treated with surgery and adjuvant RT (n=22), 2-year PFS, LR, RR, LRR, DM, and OS were 77%, 5%, 0%, 5%, 10%, and 95%, respectively, with all LRR occurring outside the irradiated area. Patients with de novo cancer who received definitive RT (n=9) experienced 2-year PFS, LR, RR, LRR, DM, and OS of 30%, 46%, 13%, 55%, 40%, and 67%, respectively, with all LRR events occurring within the irradiated area. LR within the irradiated volume was associated with immunosuppression (95% CI: 19-99). Patients treated at recurrence had inferior outcomes.</p><p><strong>Conclusions: </strong>Surgical resection and adjuvant RT effectively control CAC, while definitive RT shows lower disease control. Novel strategies are needed to improve outcomes in patients receiving definitive RT.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"193-199"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061058","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":"Executive Summary of the American Radium Society Appropriate Use Criteria for Management of Squamous Cell Carcinoma of the Cervical Esophagus: Systematic Review and Guidelines.","authors":"Vonetta M Williams, Christopher L Hallemeier, Krishan R Jethwa, J Eva Selfridge, Pari Shah, Christopher J Anker, Gerard Abood, Dmitriy Akselrod, Jordan Berlin, Ed Kim, Timothy Kennedy, Percy Lee, Navesh Sharma, Small William, Leila Tchelebi, Suzanne Russo","doi":"10.1097/COC.0000000000001165","DOIUrl":"10.1097/COC.0000000000001165","url":null,"abstract":"<p><strong>Objectives: </strong>Cervical esophageal cancer (CEC) is an uncommon malignancy accounting for <5% of all esophageal carcinomas. Treatment of CEC varies and is adapted from established regimens used for squamous cell carcinoma (SCC) or the lower esophageal and head and neck. The present systematic review and guidelines are intended to assist treatment decision making for patients with CEC based on the available evidence.</p><p><strong>Methods: </strong>Using the Population, Intervention, Comparator, Outcome, Timing, and Study Design (PICOTS) framework, the evidence regarding treatment outcomes was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective Phase II to III trials and retrospective analyses published between January 1, 2013 and February 23, 2024 in the Ovid Medline database. These references were assessed through the American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. A systematic review PRISMA 2020 checklist confirmed the completion of essential elements. RAND-UCLA consensus methodology was used by the expert panel to rate the appropriateness of the treatment options.</p><p><strong>Results: </strong>ARS AUC recommendations include (1) larynx preservation using endoscopic resection (EMR or ESD) alone for the typical case with pT1a cN0 cM0 CEC, (2) definitive CRT for the typical case with cT1bN0M0 in patients who cannot undergo endoscopic resection, (3) larynx-preserving using definitive CRT (with or without induction chemotherapy) for the typical case with nonmetastatic locally advanced CEC (advanced T-stage tumors or involved lymph nodes), with surgery reserved for those patients with incomplete response or locoregional recurrence.</p><p><strong>Conclusions: </strong>This ARS AUC summary provides guidelines for the management of SCC of the cervical esophagus provides based on available evidence. Topics that warrant further investigation include optimization of (1) patient selection; (2) multimodality therapies including chemotherapy, immunotherapy, and targeted agents; (3) radiation dose, schedule, and treatment volume; and (4) supportive care for patients with CEC. Ongoing trials continue to improve outcomes for patients with CEC.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"163-179"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257264","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":"KRAS Mutations in Cancer: From Molecular Insights to Therapeutic Strategies.","authors":"Yuanzhu Zhang, Yujie Ma, Kexin Zhang, Yuqun Wang, Xiaodong Sun, Chengxia Kan, Fang Han","doi":"10.1097/COC.0000000000001192","DOIUrl":"https://doi.org/10.1097/COC.0000000000001192","url":null,"abstract":"<p><p>The global burden of cancer remains a major public health challenge, with Kirsten rat sarcoma viral oncogene homolog (KRAS) emerging as the most common mutated oncogene across diverse malignancies. Once considered \"undruggable\" due to its unique structure, KRAS has garnered intense research focus, resulting in significant advancements. This paper aims to review recent developments in our understanding of KRAS biology, including its structural and functional aspects, and to explore the latest insights into its mutations across various cancer types. Emphasis is placed on prognosis, predictive roles, and emerging therapeutic strategies targeting KRAS. This review aspires to deepen our comprehension of KRAS and potentially enhance treatment outcomes for cancer patients harboring KRAS mutations in the future.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755679","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":"Subtype-Specific Patterns of Tumor Purity and Mutation Load Suggest Treatment Implications: A Cross-Sectional Analysis of 7494 Soft Tissue and Bone Sarcomas (MSK Cohort).","authors":"Daniel Schneider, Ethan D L Brown, Jacob Gluski, Akash Mishra, Harshal A Shah, Daniel M Sciubba, Sheng-Fu Larry Lo","doi":"10.1097/COC.0000000000001161","DOIUrl":"10.1097/COC.0000000000001161","url":null,"abstract":"<p><strong>Objectives: </strong>Sarcomas are complex mesenchymal malignancies whose molecular characteristics can significantly influence treatment strategies. This study aimed to investigate the relationship between tumor purity, mutation load, and clinical characteristics across sarcoma subtypes, focusing on potential implications for therapeutic stratification.</p><p><strong>Methods: </strong>This study analyzed the molecular characteristics of 7494 sarcoma cases from the Soft Tissue and Bone Sarcoma (MSK, Nat Commun 2022) data set using available case analysis. Correlations between tumor purity, mutation load, age, and sex were analyzed using nonparametric methods, with subtype-specific analyses conducted using Kruskal-Wallis tests and Bonferroni-corrected post hoc comparisons. A comprehensive analysis of mutation patterns was performed using microsatellite instability (MSI) status.</p><p><strong>Results: </strong>Significant correlations between mutation load and tumor purity (ρ=0.320, P <0.001) were identified, with marked heterogeneity across subtypes. Tumor purity ranged from 20.0% in brain sarcomas to 78.5% in dermatofibrosarcoma protuberans. Age-related molecular changes were observed in brain (ρ=0.711, P =0.006) and skin sarcomas (ρ=0.450, P =0.006), suggesting distinct evolutionary patterns. A subset of hypermutated, microsatellite stable cases (0.15%) with mutation loads exceeding 100 mutations/mb were identified, suggesting alternative mechanisms of genomic instability. MSI-high status was rare (0.24%) but associated with higher mutation loads (median: 25.84 vs. 2.42, P <0.001), particularly in uterine sarcomas (0.7% prevalence).</p><p><strong>Conclusions: </strong>The identification of distinct molecular patterns across sarcoma subtypes challenge existing morphology-based classification systems and may hold implications for therapeutic stratification. These findings may help inform future immunotherapeutic and molecular-guided approaches to treatment in sarcoma patients, particularly for elderly patients with brain sarcomas or females with uterine sarcomas.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"185-192"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631033","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}