Clinical Cancer Research最新文献

{"title":"Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.","authors":"Kris Ann P Schultz, Suzanne P MacFarland, Melissa R Perrino, Sarah G Mitchell, Junne Kamihara, Alexander T Nelson, Paige H R Mallinger, Jack J Brzezinski, Kara N Maxwell, Emma R Woodward, Bailey Gallinger, Sun Young Kim, Mary-Louise C Greer, Kami Wolfe Schneider, Sarah R Scollon, Anirban Das, Jonathan D Wasserman, Charis Eng, David Malkin, William D Foulkes, Orli Michaeli, Andrew J Bauer, Douglas R Stewart","doi":"10.1158/1078-0432.CCR-24-1947","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-24-1947","url":null,"abstract":"<p><p>PTEN hamartoma tumor syndrome (PHTS), DICER1-related tumor predisposition (DICER1) and tuberous sclerosis complex (TSC) are rare conditions which each increase risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection and multidisciplinary care. In this manuscript, we present updated surveillance recommendations and considerations for children and adolescents with PHTS, DICER1 and TSC and provide suggestions for further research in each of these conditions.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An AI-driven preoperative radiomic subtype for predicting the prognosis and treatment response of patients with papillary thyroid carcinoma","authors":"Qiang Li, Weituo Zhang, Tian Liao, Yi Gao, Yanzhi Zhang, Anqi Jin, Ben Ma, Ning Qu, Huan Zhang, Xiangqian Zheng, Dapeng Li, Xinwei Yun, Jingzhu Zhao, Herbert Yu, Ming Gao, Yu Wang, Biyun Qian","doi":"10.1158/1078-0432.ccr-24-2356","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2356","url":null,"abstract":"Purpose: 8-28% of Papillary thyroid carcinoma (PTC) experience recurrence, complicating risk stratification and treatment. We previously identified an inflammatory molecular subtype of PTC associated with poor prognosis. Based on this subtype, we aimed to develop and validate a noninvasive radiomic signature to predict prognosis and treatment response in PTC patients. Experimental Design: We collected preoperative ultrasound images from two large independent centers (n=2506) to develop and validate a Deep Learning Radiomics signature of Inflammation (DLRI) for predicting the inflammatory subtype of PTC, including its correlation with prognosis and anti-inflammatory traditional Chinese medicine (TCM) treatment. Training set 1 (n=64) and internal validation set 2 (n=1108) were from Tianjin Medical University Cancer Institute and Hospital. External validation set 1 (n=76) and 2 (n=1258) were from Fudan University Shanghai Cancer Center. Results: We developed DLRI to accurately predict PTC's inflammatory subtype (AUC=0.97 in the training set 1 and AUC=0.82 in the external validation set 1). High-risk DLRI was significantly associated with poor disease-free survival in the first cohort (HR=16.49, 95% CI: 7.92-34.35, P&amp;lt;0.001) and second cohort (HR=5.42, 95%: 3.67-8.02, P&amp;lt;0.001). DLRI independently predicted disease-free survival, irrespective of clinicopathological variables (P&amp;lt;0.001 for all). Furthermore, patients with high-risk DLRI were likely to benefit from anti-inflammatory TCM treatment (HR=0.19, 95% CI: 0.06-0.55, P=0.002), whereas those in low-risk DLRI did not. Conclusions: DLRI is a reliable noninvasive tool for evaluating prognosis and guiding anti-inflammatory TCM treatment in PTC patients. Prospective studies are needed to confirm these findings.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"11 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multi-center Cohort Study","authors":"Guopan Yu, Yu Zhang, Sijian Yu, Zhao Yin, Guangyang Weng, Na Xu, Xin Du, Dongjun Lin, Jie Xiao, Zhiqiang Sun, Hongyu Zhang, Xinquan Liang, Ziwen Guo, Weihua Zhao, Min Dai, Zhiping Fan, Li Xuan, Hui Liu, Dan Xu, Jieyu Ye, Xuejie Jiang, Pengcheng Shi, Hua Jin, Qifa Liu","doi":"10.1158/1078-0432.ccr-24-1332","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1332","url":null,"abstract":"Purpose: We investigated whether homoharringtonine (HHT) added to venetoclax (VEN) plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML). Experimental Design: A multi-center, retrospective, cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups. Results: A total of 321 patients (VAH, n=172; VA, n=149) were analyzed. Compared to VA, VAH significantly improved the rates of CRc (44.3% vs. 66.3%, P&amp;lt;0.001), MRD-negativity (34.8% vs. 59.3%, P=0.002), prolonged OS (median: 15.1 months vs. not reached, P &amp;lt;0.001), and EFS (median: 3.8 vs. 13.0 months, P&amp;lt;0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with non-adverse European LeukemiaNet (ELN) risk, with a trend towards improved response in those with adverse ELN risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups. Conclusions: Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"159 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma","authors":"Kevin J. Contrera, Renata Ferrarotto, Brandon Gunn, Shirley Y. Su, Merrill S. Kies, Bonnie S. Glisson, Adam S. Garden, Dianna Roberts, Curtis Hanba, Camilla O. Hoff, Adel El-Naggar, Michelle D. Williams, Shaan M. Raza, Franco DeMonte, Melissa M. Chen, Mark S. Chambers, Ehab Y. Hanna","doi":"10.1158/1078-0432.ccr-24-1416","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1416","url":null,"abstract":"Purpose: Outcomes after primary surgery for advanced sinonasal squamous cell carcinoma (SCC) are poor. We tested whether induction chemotherapy (IC) can improve disease control or organ preservation. Patients and Methods: A phase II trial evaluated previously untreated patients with stage II-IV, M0 sinonasal SCC. Patients received IC with docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy (CRT) for responders and surgery with adjuvant radiotherapy or CRT for non-responders. The primary endpoints were overall response rate (ORR) and locoregional control (LRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), organ preservation, and treatment toxicity. Results: Of the 31 patients enrolled between 2008 and 2020, 28 were evaluated for efficacy. Disease was T4a, T4b, and N+ in 57%, 21%, and 36% of patients, respectively. The ORR was 82.1%; 17.9% of patients had stable disease, and 0% had progressive disease. Grade 3 and 4 adverse events (AE) occurred in 54% and 18% of patients, respectively; there were no Grade 5 AEs. The 2-year LRC and PFS rates were 64.3% (95% CI 40.4-77.6) and 52.4% (95% CI 32.3-69.0), respectively. The median PFS was 25.8 months. The median OS was 47.4 months, with a 2-year OS rate of 69.4% (95% CI 44.9-80.4). No survival difference was observed between surgery versus CRT (hazard ratio 1.07, 95% CI 0.9-3.84). Of patients alive at 2 years, 63% achieved organ preservation, avoiding maxillectomy (38%), craniotomy (13%), or orbital exenteration (38%). Conclusions: IC and response-directed treatment achieved promising disease control and added organ preservation for patients with advanced sinonasal SCC.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"32 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase Ib clinical and pharmacodynamic study of the TIE2 kinase inhibitor rebastinib with paclitaxel or eribulin in HER2-negative metastatic breast cancer","authors":"Jesus D. Anampa, Daniel L. Flynn, Cynthia Leary, Sun Oh, Xiaonan Xue, Maja H. Oktay, John S. Condeelis, Joseph A. Sparano","doi":"10.1158/1078-0432.ccr-24-2464","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2464","url":null,"abstract":"Purpose: Breast cancer cells disseminate to distant sites via Tumor Microenvironment of Metastasis (TMEM) doorways. The TIE2 inhibitor rebastinib blocks TMEM doorway function in the PyMT mouse model of breast cancer. We aimed to assess the safety and pharmacodynamics of rebastinib plus paclitaxel or eribulin in patients with HER2-negative metastatic breast cancer (MBC). Patients and Methods: This phase Ib trial enrolled 27 patients with MBC who received 50 mg or 100 mg of rebastinib PO BID in combination with weekly paclitaxel 80 mg/m2 (if ≤ 2 prior non-taxane regimens) or eribulin 1.4 mg/m2 on days 1 &amp; 8 (if ≥ 1 prior regimen). Safety, tolerability and pharmacodynamic parameters indicating TIE2 kinase inhibition and TMEM doorway function were evaluated. Results: No dose-limiting toxicities in cycle 1 or 2 were observed among the first 12 patients at either rebastinib dose level. The most common treatment-emergent adverse events (AEs) were anemia (85%), fatigue (78%), anorexia (67%), leukopenia (67%), increased alanine aminotransferase (59%), hyperglycemia (56%), nausea (52%), and neutropenia (52%). AEs attributed to rebastinib include muscular weakness and myalgias. Intraocular pressure increased at the 100 mg rebastinib dose level, whereas angiopoietin-2 levels increased at both dose levels, providing pharmacodynamic evidence for TIE2 blockade. Circulating tumor cells decreased significantly with the combined treatment. Objective response occurred in 5/23 (22%) evaluable patients. Conclusions: In patients with MBC, the recommended phase 2 dose of rebastinib associated with pharmacodynamic evidence of TIE2 inhibition is either 50 or 100 mg PO BID in combination with paclitaxel or eribulin.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"63 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting T-cell costimulation to the surface of tumor cells","authors":"Iñaki Eguren-Santamaría, Miguel F. Sanmamed, Paula Molero-Glez, Jose Luis Perez-Gracia, Ignacio Melero","doi":"10.1158/1078-0432.ccr-24-3003","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3003","url":null,"abstract":"Bispecific agents targeting tumor-cell surface antigens and activating receptors on T lymphocytes are being developed for solid tumors. Effective and safe strategies depend on target specificity and at least relative tumor-tissue confinement of T-cell activation. Novel evidence suggests that constructs targeting HER2 on tumor cells with the aim of providing costimulation (signal-2) to T lymphocytes via CD137 (4-1BB) are safe and can meaningfully invigorate antitumor responses in a proportion of patients.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"6 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2 study of acimtamig (AFM13) in patients with CD30-positive, relapsed or refractory peripheral T-cell lymphomas","authors":"Won Seog. Kim, Jake Shortt, Pier Luigi Zinzani, Natalia Mikhailova, Dejan Radeski, Vincent Ribrag, Eva Domingo Domenech, Ahmed Sawas, Karenza Alexis, Michael Emig, Riham Elbadri, Pallavi Hajela, Paulien Ravenstijn, Sheena Pinto, Linta Garcia, Andre Overesch, Kerstin Pietzko, Steven Horwitz","doi":"10.1158/1078-0432.ccr-24-1913","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1913","url":null,"abstract":"Background: Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. Materials &amp; Methods: This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL. Patients included those with CD30 expression in ≥1% of tumor cells and who were R/R following ≥1 prior line of systemic therapy. Acimtamig (200 mg) was administered once weekly in 8-week cycles. The primary endpoint was overall response rate (ORR) by fluorodeoxyglucose-positron emission tomography per independent review committee; secondary and exploratory endpoints included duration of response (DoR), safety, progression-free survival, and overall survival. Results: The ORR in 108 patients was 32.4% (95% CI: 23.7, 42.1) with a complete response rate of 10.2% (95% CI: 5.2, 17.5); median DoR was 2.3 months (95% CI: 1.9, 6.5). Patients with R/R angioimmunoblastic T-cell lymphoma exhibited the greatest number of responses (53.3% [95% CI: 34.3, 71.7]). Responses were independent of CD30 expression level, prior brentuximab vedotin treatment, or steroid premedication. Acimtamig exhibited a tolerable safety profile; the most common treatment-related adverse events were infusion-related reactions in 27 patients (25.0%) and neutropenia in 11 patients (10.2%). No cases of cytokine release syndrome or acimtamig-related deaths were reported. Despite exhibiting promising clinical activity and tolerable safety in a heavily pretreated PTCL population, the study did not meet the criteria for the primary endpoint. Conclusions: The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic natural killer cells.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"15 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized MRD Assessment in Peri-surgical ctDNA for Prognostic Prediction in Hepatocellular Carcinoma","authors":"Jie Hu, Haoran Tang, Can-Can Jia, Xiang-Yu Zhang, Ying Xu, Jin-Peng Tan, Jia Fan, Shidong Jia, Jian Zhou","doi":"10.1158/1078-0432.ccr-24-1897","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1897","url":null,"abstract":"Objective: Detecting residual disease is a critical clinical requirement in the peri-surgical management of patients with resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions exhibiting limited sensitivity and failed to meet the minimal residual disease (MRD) testing threshold. We introduce a next-generation sequencing (NGS) based assay, informed by baseline samples, facilitating MRD detection in hepatectomized HCC patients and offering prognostic predictions. Experimental Design: This study involved 88 HCC patients who underwent surgical resections January 2016 to May 2016 in Zhongshan Hospital Fudan University. Tumor and normal tissue samples were collected during surgery, while plasma samples were obtained both before surgery and up to seven days post-surgery. Using an NGS-based personalized circulating tumor DNA assay, we analyzed MRD in both pre-surgical and post-surgical blood samples and the correlation with prognosis. Results: With a median follow-up period of 80.7 months, our findings demonstrated significant correlations between pre-surgical ctDNA tumor fractions, post-surgical plasma MRD status, and both recurrence-free survival (RFS) and overall survival (OS). Post-surgical MRD status emerged as the most significant risk factor for cancer recurrence (HR=2.17, 95% CI: 1.09-4.30, p=0.027) compared to other clinical characteristics in multivariate Cox regression analysis. Notably, MRD status showed potential as a prognostic indicator among clinically low-recurrent-risk patients, such as those with BCLC stage 0-A, CNLC stage I-II. Conclusion: Evaluating personalized MRD provided crucial prognostic insights into RFS and OS. It efficiently identified patients at high risk of recurrence, even among those initially perceived as low-risk cases.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"25 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tumor-naive ctDNA assay detects minimal residual disease in resected stage II or III colorectal cancer and predicts recurrence: subset analysis from the GALAXY study in CIRCULATE-Japan","authors":"Yoshiaki Nakamura, Kristiyana Kaneva, Christine Lo, Daniel Neems, Jonathan E. Freaney, Hala Boulos, Seung Won Hyun, Farahnaz Islam, Jason Yamada-Hanff, Terri M. Driessen, Anne Sonnenschein, Dana F. DeSantis, Daisuke Kotani, Jun Watanabe, Masahito Kotaka, Saori Mishima, Hideaki Bando, Kentaro Yamazaki, Hiroya Taniguchi, Ichiro Takemasa, Takeshi Kato, Chithra Sangli, Robert Tell, Richard Blidner, Takayuki Yoshino, Kate Sasser, Eiji Oki, Halla Nimeiri","doi":"10.1158/1078-0432.ccr-24-2396","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2396","url":null,"abstract":"Purpose: Analysis of circulating tumor DNA (ctDNA) may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for molecular residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance. Experimental Design: Plasma samples were obtained from 80 study participants with stage II or III colorectal cancer (CRC) selected from CIRCULATE-Japan GALAXY. MRD status was assessed using a tumor-naïve ctDNA assay (xM) that integrates methylation and genomic variant data, delivering a binary call. MRD was assessed at 4 weeks post-surgery (landmark timepoint (LMT)) using methylation and genomic variant data and longitudinally (median 22.1 months) using only methylation data. Results: At LMT, 69/80 study participants were evaluable (36 recurrent; 33 non-recurrent). Of recurrent study participants, 22/36 had detectable ctDNA (MRD+) at LMT and 29/33 non-recurrent study participants had undetectable ctDNA (MRD-), yielding clinical sensitivity of 61.1% and specificity of 87.9%. Additionally, 74 study participants were evaluable for longitudinal performance with a clinical sensitivity of 83.3% and specificity of 89.5%. Median lead time from first MRD+ result to recurrence was 4.77 months overall, and 5.30 months for study participants with no adjuvant treatment. At 12 weeks post-surgery, MRD status strongly correlated with disease-free survival (DFS) [adj. HR 9.69], outperforming carcinoembryonic antigen (CEA) correlation [HR 2.13]. Conclusions: This tumor-naïve MRD assay demonstrated clinically meaningful performance at LMT and longitudinally, accurately predicting clinical recurrence. MRD status was a stronger prognostic biomarker to DFS compared to standard of care CEA.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"196 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic, epigenomic and transcriptomic inter- and intra-tumor heterogeneity in desmoid tumors","authors":"Chelsea De Bellis, Sujay Vennam, Christopher Eeles, Pegah Rahimizadeh, Justin Cates, Thomas Stricker, Jenny Hoffman, Kristen Ganjoo, Gregory W. Charville, Benjamin Haibe-Kains, Matt van de Rijn, Joanna Przybyl","doi":"10.1158/1078-0432.ccr-24-1240","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-1240","url":null,"abstract":"Purpose: Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas but little is known about molecular variability within locally aggressive tumors such as desmoids. Experimental Design: We performed transcriptomic profiling of 31 specimens from 20 primary desmoid tumors to identify genes predictive of relapse. We also performed multi-omic analysis including DNA methylation, copy number alterations, point mutations and gene expression on 24 specimens from different regions of primary and recurrent desmoid tumors from 3 patients (7-9 specimens per patient). Results: We observed highly variable expression of transcriptomic prognostic signatures, both in patients who did or did not progress. Signatures associated with favorable and unfavorable outcome were detected in different regions within the same tumor. Further multi-omic studies showed remarkable intra- and inter-tumor heterogeneity of genomic, epigenomic and transcriptomic patterns. The transcriptomic profiles showed the highest degree of variability within tumors and between primary and recurrent tumors from the same patient. Conclusions: This study shows an unexpected degree of intra- and inter-tumor heterogeneity in desmoid tumors. Our analysis indicates that molecular analysis of a single tumor biopsy may underestimate the magnitude of molecular alterations in desmoid tumors. Our study also shows that recurrent desmoid tumors acquire multiple new molecular alterations. Thus, molecular heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for desmoid tumors.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"33 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}