Cancer最新文献

{"title":"Targeting HER2 in lung cancers: Evolving treatment landscape and drug development strategies","authors":"Daniel Reinhorn MD,&nbsp;Mor Moskovitz MD,&nbsp;William D. Tap MD,&nbsp;Bob T. Li MD, PHD, MPH","doi":"10.1002/cncr.35780","DOIUrl":"https://doi.org/10.1002/cncr.35780","url":null,"abstract":"<p>ERBB2 (HER2) alterations, including mutations, amplifications, and overexpression are emerging therapeutic targets in non–small cell lung cancer (NSCLC). Despite recent advancements, standard first-line therapy remains chemotherapy with or without immunotherapy. Several therapies targeting HER2 are under development and have been evaluated in clinical trials with inconsistent efficacy, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates. A major landmark was recently reached when trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate, became the first Food and Drug Administration (FDA)-approved therapy for pretreated HER2-mutant NSCLC, following the promising efficacy demonstrated in the DESTINY-Lung trials. Furthermore, T-DXd has shown efficacy across various tumor types harboring HER2 alterations in the DESTINY-PanTumor trials, leading to its recent pan-tumor FDA approval for HER2-positive solid tumors, highlighting the potential of tumor-agnostic drug development strategies. In this review, the authors describe the different HER2 alterations and their clinical consequences, including their impact on prognosis and response to standard therapies. They provide an up-to-date overview of the current treatment landscape and add a comprehensive review of pivotal and ongoing clinical trials of HER2-targeted therapies, including tumor-agnostic drug development strategies.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAF in non–small cell lung cancer: From molecular mechanisms to clinical practice","authors":"Claudia Parisi MD,&nbsp;David Planchard MD, PhD","doi":"10.1002/cncr.35781","DOIUrl":"https://doi.org/10.1002/cncr.35781","url":null,"abstract":"<p>V-Raf murine sarcoma viral oncogene homolog B (<i>BRAF</i>) mutations are found in up to 4% of patients with non–small cell lung cancer (NSCLC). Approximately 2% of advanced NSCLC cases harbor a <i>BRAF</i> V600E (class I) mutation. Because targeted therapies inhibiting <i>BRAF</i> (e.g., dabrafenib and encorafenib) and <i>MEK</i> (trametinib and binimetinib) are associated with improved outcomes as first- or second-line treatment for <i>BRAF</i> V600E–mutant NSCLC, both European Society for Medical Oncology and National Comprehensive Cancer Network guidelines recommend testing for the <i>BRAF</i> V600E oncogenic driver at the time of diagnosis. In recent years, the treatment landscape of this molecular subgroup has seen great development. Different therapeutic strategies including anti–programmed death ligand 1 antibodies and kinase inhibitors have been assessed thus far, with novel agents (e.g., pan-BRAF inhibitors) and therapeutic associations underway in preclinical and clinical trials. This review describes the current understanding of the <i>BRAF</i> clinicopathologic role in NSCLC, with a special focus on published trials assessing currently approved therapies. Mechanisms of drug resistance and future perspectives on the therapeutic approach of <i>BRAF</i>-deregulated NSCLC are also summarized.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ROS1 rearrangements in non–small cell lung cancer: Current insights and future directions","authors":"Antoine Desilets MD, MSc,&nbsp;Matteo Repetto MD,&nbsp;Soo-Ryum Yang MD,&nbsp;Alexander Drilon MD","doi":"10.1002/cncr.35784","DOIUrl":"https://doi.org/10.1002/cncr.35784","url":null,"abstract":"<p><i>ROS1</i> rearrangements define a molecular subset of non–small cell lung cancer (NSCLC) by accounting for 1%–2% of cases. Targeted therapy with ROS1 tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes for these patients. First-generation inhibitors, such as crizotinib and entrectinib, have demonstrated impressive efficacy, with objective response rates exceeding 60%–70%. However, the emergence of resistance mechanisms, including solvent-front mutations such as <i>ROS1</i> G2032R, and limited blood–brain barrier penetration have limited the long-term efficacy of early-generation agents. Next-generation TKIs, including lorlatinib, taletrectinib, and repotrectinib, have been developed to overcome these challenges. These agents show enhanced central nervous system (CNS) penetration and activity against on-target <i>ROS1</i> resistance mutations. Repotrectinib, a potent, CNS-penetrant ROS1 inhibitor, has demonstrated superior activity in both TKI-naive and -resistant tumors, including those harboring the G2032R mutation. Zidesamtinib, a highly selective next-generation ROS1 inhibitor, further addresses TRK-mediated off-target neurological toxicities seen with prior agents, and is poised to offer improved tolerability. Ongoing research is focused on optimizing sequencing strategies for ROS1 inhibitors and exploring combination approaches to prevent or overcome resistance. In addition, the development of novel diagnostic tools, including RNA-based next-generation sequencing, has enhanced the detection of functional <i>ROS1</i> fusions by ensuring that patients with actionable mutations receive appropriate targeted therapies. These advances highlight the evolving landscape of treatment for <i>ROS1</i>-positive NSCLC, with the aim of maximizing long-term survival and quality of life.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of non–small cell lung cancer with RET rearrangements","authors":"Hui Jing Hoe MBBS, FRACP,&nbsp;Benjamin J. Solomon MBBS, PhD, FRACP","doi":"10.1002/cncr.35779","DOIUrl":"https://doi.org/10.1002/cncr.35779","url":null,"abstract":"<p>Aberrant activation of the <i>RET</i> oncogene by mutations or gene fusions drives various malignancies, including 1%–2% of all non–small cell lung cancers (NSCLCs) that harbor <i>RET</i> gene fusions. Initial attempts to target <i>RET</i> fusion–positive NSCLC with poorly selective multikinase RET inhibitors were associated with significant toxicities and limited efficacy. Two highly potent and selective RET small-molecule inhibitors, selpercatinib and pralsetinib, were granted accelerated approval for advanced <i>RET</i> fusion–positive NSCLC by the US Food and Drug Administration, and have been shown to be highly effective both in treatment-naive and previously treated patients with NSCLC. Selpercatinib has shown superiority over chemotherapy in a phase 3 study (LIBRETTO-431) in previously untreated patients with <i>RET</i> fusion–positive NSCLC, which established its place as the standard of care in this patient population. This review discusses the biology and clinical characteristics of <i>RET</i>-rearranged NSCLC and summarizes the evolution of treatment strategies, current understanding of mechanisms of resistance, and development of new-generation agents to overcome resistance.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From knowledge to action: The journey toward targeting the MET pathway via MET exon 14 skipping","authors":"Wiktoria Bogdanska PharmD, BCOP,&nbsp;Paul K. Paik MD","doi":"10.1002/cncr.35782","DOIUrl":"https://doi.org/10.1002/cncr.35782","url":null,"abstract":"<p>Targeted therapies have radically altered the prognosis of patients with non–small cell lung cancer (NSCLC). Although the MET pathway was characterized in 1984, the treatment paradigm for patients with <i>MET</i> alterations has only recently changed. Genomic alterations in <i>MET</i> are found in 3%–5% of patients with NSCLC, and can include <i>MET</i> exon 14 (METex14) skipping, <i>MET</i>-activating mutations, and <i>MET</i> amplification. These alterations lead to the prolonged activation of the cellular MET receptor and downstream proliferation pathways that drive cell survival and migration. This review explores the history and pathophysiology of the MET pathway by focusing on METex14 skipping, and highlights insights gained since its discovery. Both unsuccessful and successful treatments that have emerged alongside the evolution of next-generation sequencing are examined, as well as current approved therapies and future options that target potential resistance mechanisms.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on the treatment of epidermal growth factor receptor-mutant non–small cell lung cancer","authors":"Jinyong Kim MD, PhD,&nbsp;Sehhoon Park MD, PhD,&nbsp;Bo Mi Ku PhD,&nbsp;Myung-Ju Ahn MD, PhD","doi":"10.1002/cncr.35778","DOIUrl":"https://doi.org/10.1002/cncr.35778","url":null,"abstract":"<p>This review provides a comprehensive update on the evolving landscape of treatment for non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (<i>EGFR</i>) mutations, particularly focusing on advances in precision medicine and overcoming acquired resistance. Initial success with first-generation EGFR tyrosine kinase inhibitors (TKIs) in <i>EGFR</i>-mutated NSCLC has paved the way for precision oncology and subsequent development of third-generation EGFR TKIs, the current standard of care as first-line therapy in advanced stage NSCLC. Furthermore, a combinational approach of third-generation EGFR TKI with chemotherapy or amivantamab was associated with prolonged progression-free survival. The role of EGFR TKIs also has been investigated in locally advanced and early stage NSCLC, including perioperative and neoadjuvant settings. However, most patients experience acquired resistance, and the resistance mechanism is quite complex and heterogeneous, highlighting the importance of tailored subsequent therapeutic approaches. Overall, this review underscores the dynamic landscape of <i>EGFR</i>-mutated NSCLC treatment, emphasizing the need for personalized strategies to optimize patient outcomes.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventions to increase uptake in a fecal-immunochemical test population-based colorectal cancer screening program: A quasi-experimental study of first-time invitees","authors":"Nicholas Clarke PhD,&nbsp;Therese Mooney PhD,&nbsp;Pamela Gallagher PhD,&nbsp;Christian von Wagner PhD,&nbsp;Paul Hanly PhD,&nbsp;Deirdre McNamara MD,&nbsp;Hilary Coffey MBS,&nbsp;Patricia Fitzpatrick MD,&nbsp;Linda Sharp PhD","doi":"10.1002/cncr.35760","DOIUrl":"https://doi.org/10.1002/cncr.35760","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Many countries have established organized colorectal cancer screening programs because they can reduce mortality and incidence from the disease; however, they rely on high participation rates, which are often suboptimal. This study examined the effectiveness of two reminder interventions on uptake rates in Ireland’s population-based BowelScreen program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing a quasi-experimental design, one intervention mailed the fecal-immunochemical test (FIT) directly to clients not responding to an initial invitation; the other mailed a reminder letter modified with behavioral insights. Interventions were tested separately and in combination and compared to the standard reminder letter (1: standard reminder letter [SRL]; 2: modified reminder letter [MRL]; 3: SRL + FIT direct [FITD]; and 4: MRL + FITD). Primary outcome: overall uptake rate (test completion at 5 months); Subgroup outcome: uptake rate among only those receiving reminders. Outcomes were modeled using multivariable logistic regression with group allocation as a fixed effect, adjusted for sex and deprivation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Uptake was significantly higher in the FITD groups (SRL: 48%; MRL: 50%; SRL + FITD: 54%; MRL + FITD: 54%; <i>p</i> &lt; .001). After adjustment, compared to the SRL group, FITD groups had significantly higher odds of uptake (MRL: odds ratio [OR], 1.09; 95% confidence interval [CI], 0.96–1.23; SRL + FITD: OR, 1.30; 95% CI, 1.14–1.48; MRL + FITD: OR, 1.26; 95% CI, 1.11–1.44). This was also the case for subgroup analysis. The MRL did not result in higher uptake compared to SRL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Mailing the FIT kit directly to nonresponders resulted in improved FIT uptake. Organized FIT-based screening programs not reaching uptake targets should consider implementing this strategy if not already in place.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 7","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum of interleukin-6 and procalcitonin as early diagnostic markers for the identification of poor hematopoietic reconstitution following allogeneic hematopoietic stem cell transplantation","authors":"Xiru Peng PhD,&nbsp;Xiaorui Jing MS,&nbsp;Ting Li MS,&nbsp;Juan Cheng PhD","doi":"10.1002/cncr.35835","DOIUrl":"https://doi.org/10.1002/cncr.35835","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for the treatment of various hematologic diseases. Poor hematopoietic reconstitution (PHR) is a common and serious complicating disease after allo-HSCT. The authors conducted a case-control study to determine the potential value of serum interleukin (IL)-6 and procalcitonin (PCT) levels during the peritransplantation period in predicting PHR after allo-HSCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The concentrations of IL-6 and PCT were compared, and a receiver operating characteristic (ROC) curve was constructed to determine the optimal cutoff values. Sensitivity and specificity were subsequently calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our study, the levels of IL-6 and PCT were significantly elevated in patients with PHR compared to those in good hematopoietic restitution (GHR). The logistic regression analysis revealed that IL-6 and PCT posttransplantation were significant predictors of PHR after allo-HSCT. The calculation of the area under the curve (AUC) of IL-6 and PCT in predicting PHR was 0.805 and 0.724, respectively. The optimal cutoff values for PHR were 41.8 pg/mL and 0.404 ng/mL, with a sensitivity of 73.7% and 52.6% and a specificity of 81% and 85.7%, respectively. The AUC-ROC of IL-6 combined with PCT for predicting the PHR was 0.801, with a sensitivity of 75.4% and a specificity of 77.8%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IL-6 and PCT can serve as potential biomarkers to predict PHR after allo-HSCT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 7","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International multispecialty expert physician preoperative identification of extranodal extension in patients with oropharyngeal cancer using computed tomography: Prospective blinded human inter-observer performance evaluation","authors":"Onur Sahin PhD,&nbsp;Serageldin Kamel MD,&nbsp;Kareem A. Wahid PhD,&nbsp;Cem Dede MD,&nbsp;Nicolette Taku MD, MPhil, MPH,&nbsp;Renjie He PhD,&nbsp;Mohamed A. Naser PhD,&nbsp;Christina S. Sharafi BS,&nbsp;Antti Mäkitie MD, PhD,&nbsp;Benjamin H. Kann MD,&nbsp;Kimmo Kaski PhD,&nbsp;Jaakko Sahlsten DSc,&nbsp;Joel Jaskari DSc,&nbsp;Moran Amit MD, PhD,&nbsp;Gregory M. Chronowski MD,&nbsp;Eduardo M. Diaz Jr. MD,&nbsp;Adam S. Garden MD,&nbsp;Ryan P. Goepfert MD,&nbsp;Jeffrey P. Guenette MD, MPH,&nbsp;G. Brandon Gunn MD,&nbsp;Jussi Hirvonen MD, PhD,&nbsp;Frank Hoebers MD, PhD,&nbsp;Katherine A. Hutcheson PhD,&nbsp;Nandita Guha-Thakurta MD,&nbsp;Jason Johnson MD,&nbsp;Diana Kaya MD,&nbsp;Shekhar D. Khanpara MD,&nbsp;Kristofer Nyman MD,&nbsp;Stephen Y. Lai MD, PhD,&nbsp;Miriam Lango MD,&nbsp;Kim O. Learned MD,&nbsp;Anna Lee MD, MPH,&nbsp;Carol M. Lewis MD, MPH,&nbsp;Anastasios Maniakas MD, PhD,&nbsp;Amy C. Moreno MD, MS,&nbsp;Jeffrey N. Myers MD, PhD,&nbsp;Jack Phan MD, PhD,&nbsp;Kristen B. Pytynia MD, MPH,&nbsp;David I. Rosenthal MD,&nbsp;Vlad C. Sandulache MD, PhD,&nbsp;Dawid Schellingerhout MBChB, MBA,&nbsp;Shalin J. Shah MD,&nbsp;Andrew G. Sikora MD, PhD,&nbsp;Abdallah S. R. Mohamed MD, PhD,&nbsp;Melissa M. Chen MD,&nbsp;Clifton D. Fuller MD, PhD,&nbsp;Multidisciplinary Oropharyngeal Cancer Extra-Nodal Extension (OPC ENE) Assessment Working Group","doi":"10.1002/cncr.35815","DOIUrl":"https://doi.org/10.1002/cncr.35815","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathologic extranodal extension (pENE) is a crucial prognostic factor in oropharyngeal cancer (OPC), but determining pENE from imaging has high inter-observer variability. The role of clinician specialty in the accuracy of imaging-detected extranodal extension (iENE) remains unclear. The purpose of this study is to assess the influence of clinician specialty on the accuracy of preoperative iENE detection in human papillomavirus (HPV)-positive OPC using computed tomography (CT) imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective observational study evaluated pretherapy CT images from 24 HPV-positive OPC patients (30 scans, including duplicates). Thirty-four expert observers (11 radiologists, 12 surgeons, 11 radiation oncologists) assessed iENE and reported radiologic criteria and confidence. Ground-truth pENE status was confirmed pathologically. Accuracy, sensitivity, specificity, area under the receiver operating characteristic curve, and Brier scores were compared across specialties. Logistic regression determined significant predictors of pENE, whereas Fleiss’ kappa measured interobserver agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median accuracy was 0.57 (95% CI, 0.39–0.73), with no specialty showing performance beyond chance (median area under the receiver operating characteristic curve, 0.64). Minor differences were noted: surgeons had lower Brier scores (0.26 vs. 0.33, <i>p</i> &lt; .01) and higher sensitivity (0.69 vs. 0.48) compared to radiologists and oncologists. Predictive signs included indistinct capsular contour and nodal necrosis. Interobserver agreement was weak (κ &lt; 0.6).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Diagnostic performance for iENE on CT in HPV-positive OPC remains poor across specialties, with high variability and low accuracy. These findings highlight the need for automated systems or improved imaging methods to enhance iENE assessments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 7","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2– early breast cancer","authors":"Stephanie L. Graff MD, FACP, FASCO,&nbsp;Sara M. Tolaney MD, MPH,&nbsp;Lowell L. Hart MD, FACP,&nbsp;Pedram Razavi MD, PhD,&nbsp;Wolfgang Janni MD, PhD,&nbsp;Lee S. Schwartzberg MD, FACP,&nbsp;Andriy Danyliv PhD,&nbsp;Murat Akdere PharmD,&nbsp;Ilia Ferrusi PhD,&nbsp;Rishi Rajat Adhikary PhD,&nbsp;Joyce A. O’Shaughnessy MD","doi":"10.1002/cncr.35817","DOIUrl":"https://doi.org/10.1002/cncr.35817","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Overall survival (OS) is the gold standard for assessing clinical benefit in oncology but requires extended follow-up to detect sufficient events. Invasive disease-free survival (iDFS) requires shorter follow-up times and is considered an objective and clinically meaningful end point in early breast cancer (EBC) trials. The authors assessed iDFS as a surrogate end point for OS in adjuvant HR+/HER2– EBC using real-world patient-level data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on patient data from the ConcertAI Patient360 database (January 1995–April 2021). Key inclusion criteria: age ≥18 years, stage II or III (AJCC 8th Edition) HR+/HER2– EBC, prior surgery, adjuvant endocrine therapy (ET). Spearman ρ, iterative multiple imputation ρ (IMI; 0.8–1 considered “very strong”), and R² (clinical relevance R² ≥ 0.70) were used to assess iDFS–OS relationship. Subgroup analyses included ET (nonsteroidal aromatase inhibitor or tamoxifen), stage, menopausal status, nodal status, prior (neo)adjuvant chemotherapy, and prior radiotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3133 patients were included (1103 [35.2%] iDFS events; 554 [17.7%] OS events); mean age was 58.4 years, 98.8% were female, 29.9% were premenopausal, and 80.9% had stage II disease. Median follow-up time was 55.1 months. iDFS and OS exhibited a positive, very strong, clinically relevant correlation (Spearman ρ: 0.88 [0.87–0.89]; IMI ρ: 0.83 [0.79–0.86]; both <i>p</i> &lt; .0001). iDFS accounted for 82% of variation in OS (R² = 0.82). Results of all subgroup analyses were consistent with overall population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This patient-level real-world analysis demonstrated very strong, positive correlations between iDFS and OS, supporting the use of iDFS as a reliable primary end point in adjuvant HR+/HER2– EBC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 7","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.35817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}