Clinical Cancer Research最新文献

{"title":"Neither small adults nor big children: Doing better for TYAs with brain tumors.","authors":"Timothy A Ritzmann, Rebecca Hodgkinson, Shaarna Shanmugavadivel","doi":"10.1158/1078-0432.CCR-25-1007","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-25-1007","url":null,"abstract":"<p><p>A recent article presents a molecular analysis of High-Grade Gliomas in teenagers and young adults (TYAs). To maximise the benefit of this advancing knowledge we must address the basics. Here, we highlight the challenge of lengthy diagnostic intervals for TYAs, arguing that these must reduce to reap the benefits of molecular insights.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198386","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 population-level real-world analysis and single-center validation of melanoma brain metastasis epidemiology following dual-agent immunotherapy","authors":"Debarati Bhanja, Junjia Zhu, Hannah Wilding, Jorge Benavides-Vasquez, Leonardo de Macedo Filho, Ahmad Ozair, Camille Moeckel, Aarav Badani, Jinpyo Hong, Jeffrey Sivik, Joseph J. Drabick, Colette R. Pameijer, Kim Margolin, Manmeet Ahluwalia, Alireza Mansouri","doi":"10.1158/1078-0432.ccr-24-2681","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-2681","url":null,"abstract":"Purpose: Melanoma brain metastases (MBM) are common in advanced melanoma and linked to poor prognosis. Preventing MBM can improve survival and reduce morbidity. While dual-agent immunotherapy (dIT) improves survival, its role in MBM prevention is unclear. We compared MBM incidence, overall survival (OS), and brain metastasis-free survival (BMFS) between dIT and single-agent immunotherapies (sIT). Experimental Design: A real-world multi-institutional database identified melanoma patients without MBM at immunotherapy (IT) initiation. Patients were stratified by anti-CTLA4, anti-PD1, and combo anti-CTLA4/anti-PD1 (dIT) treatment. MBM incidences were measured within 5 years post-IT initiation and compared with risk ratios (RR). In a complementary single-institution cohort, median OS and BMFS were compared between dIT, anti-CTLA4, and anti-PD1 via log-rank tests and multivariate Cox proportional-hazards models. Results: TriNetX identified 8,287 patients receiving anti-CTLA (3,205), anti-PD1 (3,218), and dIT (1,864). MBM incidence was significantly lower in dIT (8.6%) and anti-PD1 (7.8%) vs. anti-CTLA4 (12.2%) cohorts, (RR[95% CI], 0.72[0.61-0.86] and 0.63[0.57-0.70], respectively). There was no significant difference in MBM incidence between anti-PD1 (7.8%) and dIT (8.6%) (RR[95% CI], 1.13[0.93-1.36]). In the single-institution analysis (n=119), 2-year OS probabilities were 90%, 80%, and 95%, and 2-year BMFS probabilities were 72.7%, 80%, and 95.7%, in the dIT, anti-CTLA4, and anti-PD1 cohorts, respectively. DIT and anti-PD1 showed improved early-phase protection against MBM development. Number of metastatic sites was significantly associated with MBM development (HR 2.36; 95% CI [1.22-4.58]; p=0.01). Conclusions: These findings highlight dIT’s potential role in primary prophylaxis against MBM, with anti-PD1 as the likely work horse agent. Prospective studies are warranted.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"6 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201434","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":"One-Two Punch: Combining Chemotherapy and Immunotherapy to Decrease Radiation Dose and Related Toxicity in Children and Adolescents with Nasopharyngeal Carcinoma","authors":"Hetal Dholaria, Vera Tsetlina, Shae K. Simpson, Emily Gillies, Nithyashri Eswaran, Carlos Rodriguez-Galindo, Kris Ann P. Schultz, Kenneth S. Chen, Cheng-Chia Wu, Matthew J. Krasin, Tristan Roemer, Hans Christiansen, Jin Piao, Theodore W. Laetsch, Farzana Pashankar, Udo Kontny, Robyn D. Gartrell","doi":"10.1158/1078-0432.ccr-24-3546","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3546","url":null,"abstract":"Nasopharyngeal carcinoma (NPC) is rare in children and adolescents. Although radiation has been an essential component of treatment for this often-curable tumor, it can lead to severe side-effects in survivors. Therefore, the reduction of radiation-related long-term effects by limiting radiation dose is a key clinical priority. Previous pediatric clinical trials by the Children’s Oncology Group (COG) and the German Society of Pediatric Oncology and Hematology (GPOH) have treated patients with induction chemotherapy followed by radiation with concomitant chemotherapy and adjuvant immunotherapy with interferon (GPOH), leading to excellent survival. These groups now take us forward into a new age of clinical trials using chemoimmunotherapy induction with anti-PD-1 therapies followed by response-adapted, dose-reduced radiation with the goal of preserving outcomes while limiting late effects and morbidities.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"19 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183778","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":"\"PIK\"ing the right patients for adjuvant aspirin therapy for colorectal cancer.","authors":"David A Drew, Jonathan M Downie, Andrew T Chan","doi":"10.1158/1078-0432.CCR-25-0953","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-25-0953","url":null,"abstract":"<p><p>Observational studies demonstrate aspirin use after diagnosis of colorectal cancer, particularly tumors with mutated PIK3CA, improves outcomes. However, randomized controlled trial data are lacking. Here, we discuss the SAKK41/13 adjuvant aspirin randomized controlled trial results in context of other adjuvant aspirin trials and emerging data on potential mechanisms of action.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172984","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":"FDA Approval Summary: Abatacept for prophylaxis of acute graft versus host disease","authors":"Kelly J. Norsworthy, Donna R. Rivera, Joseph Wynne, Jian Zhao, Robyn Konicki, Aida Kuzucan, Jonathon Vallejo, Ruby Leong, Olanrewaju O. Okusanya, Brian Booth, Paul G. Kluetz, Richard Pazdur, R. Angelo de Claro","doi":"10.1158/1078-0432.ccr-25-0688","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0688","url":null,"abstract":"In December 2021, FDA approved abatacept (Orencia; Bristol Myers Squibb) in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX) as the first drug for prophylaxis of acute graft versus host disease (aGVHD) in adults and pediatric patients 2 years and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor (URD). Study IM101311 included a randomized (1:1), double-blind evaluation of abatacept (N=73) versus placebo (N=69) +CNI+MTX as aGVHD prophylaxis in patients ≥6 years undergoing an 8/8 HLA-matched URD HSCT. Overall survival (OS) and Grade II-IV aGVHD free survival at Day 180 post-transplantation for abatacept versus placebo showed hazard ratio (HR) 0.33 (95% CI 0.12-0.93) and 0.54 (0.35-0.83), respectively. A second study, IM101841, was conducted using real-world data from Center for International Blood and Marrow Transplant Research (CIBMTR) registry for abatacept +CNI+MTX (N=54) versus CNI+MTX (N=162) in patients who underwent 7/8 mismatched URD HSCT. Day 180 OS was 98% (95% CI: 78, 100) with abatacept +CNI+MTX versus 75% (95% CI: 67, 82) with CNI+MTX. Serious adverse reactions included cytomegalovirus and Epstein-Barr Virus reactivation. An additional study in patients 2 to &amp;lt; 6 years was required as a condition of the approval.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"7 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165413","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":"GANNET53 Part II: A European Phase I/II Trial of the HSP90 inhibitor Ganetespib in high-grade Platinum-Resistant Ovarian Cancer - A Study of the GANNET53 consortium","authors":"Nicole Concin, Ioana Braicu, Pierre Combe, Regina Berger, Isabelle Ray-Coquard, Florence Joly, Philipp Harter, Ulrich Canzler, Frederic Selle, Sven Mahner, Atanas Ignatov, Jalid Sehouli, Eric Pujade-Lauraine, Alain Gustave. Zeimet, Wolfgang D. Schmitt, Els Van Nieuwenhuysen, Adriaan Vanderstichele, Matthias Dobbelstein, Daniela Kramer, Hanno Ulmer, Robert Zeillinger, Eva Obermayr, Nicole Heinzl, Christian Marth, Ute M. Moll, Ignace Vergote","doi":"10.1158/1078-0432.ccr-24-3705","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3705","url":null,"abstract":"Purpose: Mutant TP53 stabilized by heat shock protein 90 (HSP90) is a novel target in oncology. The open-label randomized phase II GANNET53 trial is the first to evaluate the HSP90 inhibitor Ganetespib (G) with Paclitaxel (P) in platinum-resistant epithelial ovarian cancer (EUDRACT 2013-003868-31; EU FP7 #602602). Patients and Methods: Patients were randomized 2:1 to receive G+P or P alone until progression. Primary endpoints were progression-free survival (PFS) and PFS rate at six months. Exploratory endpoints were biomarkers based on p53 and HSP90. Results: A total of 133 patients were enrolled. Median PFS was 3.5 (G+P) and 5.3 months (P) (HR 1.3, 95% CI: 0.897-1.895, P = 0.16), PFS rates at six months were 22% (G+P) and 33% (P). No significant differences were found in overall survival, objective response rate and post progression PFS between arms. Most frequent adverse events (AEs) were diarrhea (79% vs. 26%), anemia (46% vs. 51%), nausea (41% vs. 40%), and peripheral neuropathy (36% vs. 47%). Serious AEs were more common in G+P (39.5% vs. 23.3%). Gastrointestinal perforation was a new safety finding. Despite of a high TP53 mutation frequency, HSP90-p53 complexes were detected in only 39.6% of the cases and were also detected stably during treatment. In-vitro, no synergistic effects of G+P were observed, and mutp53 depletion did not sensitize ovarian cancer cells to treatment. Conclusions: Although no major safety findings were observed, G+P did not lead to survival benefit. Our companion diagnostic programme confirmed that G+P do not favorably cooperate in killing ovarian cancer cells.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"5 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165260","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":"CINSARC AND SARCULATOR IN PATIENTS WITH PRIMARY RETROPERITONEAL SARCOMA: A COMBINED ANALYSIS OF SINGLE INSTITUTION DATA AND EORTC-STBSG-62092 TRIAL (STRASS).","authors":"Dario Callegaro,Gabriele Tinè,Felix Boakye Oppong,Axelle Nzokirantevye,Saskia Litière,Stefano Percio,Andrea Carenzo,Loris De Cecco,Frederic Chibon,Silvia Brich,Alessia Bertolotti,Paola Collini,Anna Maria Frezza,Paul Huang,Rick Haas,Sylvie Bonvalot,Winan J van Houdt,Rosalba Miceli,Sandro Pasquali,Alessandro Gronchi","doi":"10.1158/1078-0432.ccr-25-0099","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0099","url":null,"abstract":"PURPOSEThe Complexity Index in SARComas (CINSARC) predicts the metastatic risk in patients with soft tissue sarcoma. The aims of this study were to provide the first independent validation of CINSARC in patients with retroperitoneal sarcoma (RPS) and to evaluate whether CINSARC could enhance the performance of Sarculator.EXPERIMENTAL DESIGNA retrospective cohort included patients with primary localized RPS resected with curative intent (2011-2015) at a single institution. The STRASS cohort comprised patients from the surgery-only arm of the EORTC-STBSG-62092 (STRASS) trial who had undergone CINSARC categorization. Patients were classified as CINSARC low-risk (C1) vs high-risk (C2). Primary study endpoints were overall survival (OS) and disease-free survival (DFS). Sarculator performance was assessed in terms of discrimination (Harrell's C-index) and calibration (calibration plots, Brier score) before and after adding CINSARC.RESULTSThe study cohorts included 104 and 69 patients, respectively, with similar OS. In a pooled cohort, at multivariable analysis for OS considering Sarculator and CINSARC, only Sarculator was significantly associated with OS (HR 1.93, 95%CI 1.35, 2.74, p<0.001). In multivariable analysis for DFS, both Sarculator (HR 1.51, 95%CI 1.09, 2.09, p=0.013) and CINSARC (HR 2.01, 95%CI 1.26, 3.23, p=0.004) were significantly associated with DFS. However, the addition of CINSARC did not improve Sarculator's discrimination or calibration for either OS or DFS.CONCLUSIONThis study validates CINSARC as a prognostic predictor for OS and DFS in patients with primary RPS. CINSARC did not improve the performance of Sarculator, suggesting that its addition to the Sarculator may not provide added clinical benefit.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"132 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146147","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":"FDA Approval Summary: Afamitresgene Autoleucel for Adults With HLA-Restricted MAGE-A4 Positive Unresectable or Metastatic Synovial Sarcoma After Prior Chemotherapy.","authors":"Katherine K Barnett,Abigail R Johnson,Asha Das,Ching-Hsien J Lee,Cong Wang,Xiaofei Wang,Elin S Cho,Paul G Kluetz,Lola A Fashoyin-Aje","doi":"10.1158/1078-0432.ccr-25-0595","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0595","url":null,"abstract":"On August 1, 2024, the FDA granted accelerated approval to afamitresgene autoleucel, a melanoma-associated antigen-A4 (MAGE-A4)-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with unresectable or metastatic synovial sarcoma (SS) who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumors express MAGE-A4 as determined by FDA-approved or cleared companion diagnostic devices. Approval was based on results from the phase 2, single-arm, open-label, multicenter Study ADP-0044-002. Patients received a single dose of afamitresgene autoleucel following lymphodepleting chemotherapy. Of the 44 efficacy evaluable patients, the overall response rate was 43.2% (95% CI: 28.4, 59.0), with complete response in two patients (4.5%). The median duration of response was 6.0 months (95% CI: 4.6, not reached [NR]) with a median follow-up of 21.9 months. Among the 44 patients, cytokine release syndrome occurred in 75% (Grade ≥3, 2%) warranting a Boxed Warning. Grade ≥3 infections occurred in 14% of patients and prolonged severe cytopenias also occurred. One patient developed Grade 1 immune effector cell-associated neurotoxicity and one patient developed Epstein-Barr virus-positive lymphoproliferative disease. Notably, during review of this application, FDA identified issues with data quality and study conduct that prompted an independent re-review of imaging assessments. The results of the re-review were the basis for FDA's determination of substantial evidence of effectiveness. This represents the first FDA approval of a T-cell receptor gene therapy. It is also the first FDA approval specifically for SS, representing a new treatment modality for this rare population who lack effective therapies.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"239 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146163","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":"Identification and Targeting of POLQ-Associated Hereditary Colorectal Cancer.","authors":"Ning Xu,Deng-Feng Zhang,Xiao-Xiao Shi,Ke-Xin Yang,Bei-Bei Gan,Yu Fan,Feng-Chang Huang,Jun-Yu Ren,Rui Bi,Yu Li,Mao-Sen Ye,Min Xu,Yong-Chun Zhou,Wen-Hui Li,Yong-Gang Yao,Wen-Liang Li","doi":"10.1158/1078-0432.ccr-25-0379","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0379","url":null,"abstract":"PURPOSEHereditary colorectal cancer (CRC) syndromes remain incompletely understood, with many cases lacking defined genetic causes. This study aimed to identify pathogenic mutations associated with hereditary CRC and explore their potential for targeted therapies.EXPERIMENTAL DESIGNThis observational study was conducted in Yunnan Province, China. We analyzed 43 individuals from 12 hereditary CRC families using whole-exome sequencing, screened 84 polyposis families and 310 sporadic CRC cases, and an expanded cohort of 285 individuals with potential hereditary CRC. A series of in vivo and in vitro assays were conducted to evaluate the mutation's effects on tumorigenesis.RESULTSA germline heterozygous stop-gain mutation, p.Arg1953X in the POLQ (polymerase theta) gene, was identified in two CRC families, showing co-segregation with disease status. A third POLQ mutation-positive family was identified in the expanded validation cohort. Cells carrying the mutation showed potential of tumorigenesis. The mutation hyperactivates error-prone theta-mediated end-joining (TMEJ), leading to high tumor mutational burden (TMB) and resistance to DNA-damaging treatments. Indeed, the probands exhibited mismatch repair deficient/microsatellite instability-high status (dMMR/MSI-H) that indicates high TMB. Treatment with the POLQ inhibitor Novobiocin suppressed TMEJ activity and restored tumor sensitivity to DNA damage, providing a combined medication scheme for drug-resistant POLQ-type CRC.CONCLUSIONSThis study identifies POLQ as a pathogenic gene in hereditary CRC, unveiling a novel POLQ-type CRC driven by TMEJ hyperactivation. Screening for POLQ mutations in patients with hereditary adenomas or early-onset CRC would benefit early diagnosis and personalized therapy for POLQ-associated CRC, while further clinical validation is warranted.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"1 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146144","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":"Early dynamics of circulating tumor HPV-DNA with neoadjuvant chemotherapy and response-adapted de-escalation in human papillomavirus-associated oropharyngeal cancer.","authors":"Ari J Rosenberg,Evgeny Izumchenko,Aditya Juloori,Rohan Katipally,John Cursio,Noura Choudhury,Zhen Gooi,Elizabeth Blair,Jeffrey Chin,Rifat Hasina,Augustin Vannier,Anna Starus,Frederick S Jones,Emily L Gramiccioni,Yuxuan Miao,Daniel J Haraf,Everett E Vokes,Alexander T Pearson,Nishant Agrawal","doi":"10.1158/1078-0432.ccr-25-0152","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-25-0152","url":null,"abstract":"PURPOSEHuman papillomavirus-associated (HPV+) oropharyngeal carcinoma (OPC) is associated with excellent survival, yet treatment drives substantial toxicity. Improved biomarkers are needed to select patients for de-escalated treatment. Circulating tumor HPV-DNA (ctHPV-DNA) represents a promising non-invasive biomarker to gauge treatment response and surveil for disease recurrence.PATIENTS AND METHODSA prospective biomarker clinical trial of response-stratified de-escalation was conducted. Eligible patients with non-metastatic HPV+ OPC received neoadjuvant chemotherapy followed by risk/response-stratified de-escalation with transoral robotic surgery, de-escalated (chemo)radiation to 50Gy, or standard chemoradiation to 70Gy. Deep response (>=50% tumor shrinkage per RECIST v1.1) qualified patients for de-escalation. ctHPV-DNA was measured using HPV-SEQ in plasma at baseline, during neoadjuvant chemotherapy, radiation, and following treatment. Primary endpoint was correlation of ctHPV-DNA kinetics and radiographic response.RESULTSForty-six eligible patients were enrolled, and 488 ctHPV-DNA samples were analyzed (median 11 per patient). Median follow-up was 30 months, and five recurrences were observed (10.9%). Baseline ctHPV-DNA was detected in 96% of evaluable patients. Rapid early ctHPV-DNA clearance after one cycle of neoadjuvant therapy (>=95% reduction) predicted radiographic deep response (p=0.04). Detection of ctHPV-DNA 3 months or later after treatment was associated with worse progression free and overall survival; p<0.001. Sensitivity, specificity, positive and negative predictive value of longitudinal ctHPV-DNA was 100%. The longest lead-time from positive ctHPV-DNA to detection of recurrent disease was 25 months.CONCLUSIONSRapid early clearance of ctHPV-DNA during neoadjuvant therapy demonstrates utility in predicting response to treatment. Detectable ctHPV-DNA following treatment is predictive of both disease recurrence and worse survival.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"1 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146145","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}