Hui Jing Hoe MBBS, FRACP, Benjamin J. Solomon MBBS, PhD, FRACP
Aberrant activation of the RET oncogene by mutations or gene fusions drives various malignancies, including 1%–2% of all non–small cell lung cancers (NSCLCs) that harbor RET gene fusions. Initial attempts to target RET 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 RET 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 RET 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 RET-rearranged NSCLC and summarizes the evolution of treatment strategies, current understanding of mechanisms of resistance, and development of new-generation agents to overcome resistance.
{"title":"Treatment of non–small cell lung cancer with RET rearrangements","authors":"Hui Jing Hoe MBBS, FRACP, 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}
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 MET alterations has only recently changed. Genomic alterations in MET are found in 3%–5% of patients with NSCLC, and can include MET exon 14 (METex14) skipping, MET-activating mutations, and MET 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.
{"title":"From knowledge to action: The journey toward targeting the MET pathway via MET exon 14 skipping","authors":"Wiktoria Bogdanska PharmD, BCOP, 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}
Jinyong Kim MD, PhD, Sehhoon Park MD, PhD, Bo Mi Ku PhD, Myung-Ju Ahn MD, PhD
This review provides a comprehensive update on the evolving landscape of treatment for non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, particularly focusing on advances in precision medicine and overcoming acquired resistance. Initial success with first-generation EGFR tyrosine kinase inhibitors (TKIs) in EGFR-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 EGFR-mutated NSCLC treatment, emphasizing the need for personalized strategies to optimize patient outcomes.
{"title":"Updates on the treatment of epidermal growth factor receptor-mutant non–small cell lung cancer","authors":"Jinyong Kim MD, PhD, Sehhoon Park MD, PhD, Bo Mi Ku PhD, 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}
Nicholas Clarke PhD, Therese Mooney PhD, Pamela Gallagher PhD, Christian von Wagner PhD, Paul Hanly PhD, Deirdre McNamara MD, Hilary Coffey MBS, Patricia Fitzpatrick MD, Linda Sharp PhD
Background
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.
Methods
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.
Results
Uptake was significantly higher in the FITD groups (SRL: 48%; MRL: 50%; SRL + FITD: 54%; MRL + FITD: 54%; p < .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.
Conclusion
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.
{"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, Therese Mooney PhD, Pamela Gallagher PhD, Christian von Wagner PhD, Paul Hanly PhD, Deirdre McNamara MD, Hilary Coffey MBS, Patricia Fitzpatrick MD, 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> < .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}
Xiru Peng PhD, Xiaorui Jing MS, Ting Li MS, Juan Cheng PhD
Background
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.
Methods
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.
Results
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%.
Conclusion
IL-6 and PCT can serve as potential biomarkers to predict PHR after allo-HSCT.
{"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, Xiaorui Jing MS, Ting Li MS, 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}
Onur Sahin PhD, Serageldin Kamel MD, Kareem A. Wahid PhD, Cem Dede MD, Nicolette Taku MD, MPhil, MPH, Renjie He PhD, Mohamed A. Naser PhD, Christina S. Sharafi BS, Antti Mäkitie MD, PhD, Benjamin H. Kann MD, Kimmo Kaski PhD, Jaakko Sahlsten DSc, Joel Jaskari DSc, Moran Amit MD, PhD, Gregory M. Chronowski MD, Eduardo M. Diaz Jr. MD, Adam S. Garden MD, Ryan P. Goepfert MD, Jeffrey P. Guenette MD, MPH, G. Brandon Gunn MD, Jussi Hirvonen MD, PhD, Frank Hoebers MD, PhD, Katherine A. Hutcheson PhD, Nandita Guha-Thakurta MD, Jason Johnson MD, Diana Kaya MD, Shekhar D. Khanpara MD, Kristofer Nyman MD, Stephen Y. Lai MD, PhD, Miriam Lango MD, Kim O. Learned MD, Anna Lee MD, MPH, Carol M. Lewis MD, MPH, Anastasios Maniakas MD, PhD, Amy C. Moreno MD, MS, Jeffrey N. Myers MD, PhD, Jack Phan MD, PhD, Kristen B. Pytynia MD, MPH, David I. Rosenthal MD, Vlad C. Sandulache MD, PhD, Dawid Schellingerhout MBChB, MBA, Shalin J. Shah MD, Andrew G. Sikora MD, PhD, Abdallah S. R. Mohamed MD, PhD, Melissa M. Chen MD, Clifton D. Fuller MD, PhD, Multidisciplinary Oropharyngeal Cancer Extra-Nodal Extension (OPC ENE) Assessment Working Group
Background
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.
Methods
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.
Results
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, p < .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 < 0.6).
Conclusions
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.
{"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, Serageldin Kamel MD, Kareem A. Wahid PhD, Cem Dede MD, Nicolette Taku MD, MPhil, MPH, Renjie He PhD, Mohamed A. Naser PhD, Christina S. Sharafi BS, Antti Mäkitie MD, PhD, Benjamin H. Kann MD, Kimmo Kaski PhD, Jaakko Sahlsten DSc, Joel Jaskari DSc, Moran Amit MD, PhD, Gregory M. Chronowski MD, Eduardo M. Diaz Jr. MD, Adam S. Garden MD, Ryan P. Goepfert MD, Jeffrey P. Guenette MD, MPH, G. Brandon Gunn MD, Jussi Hirvonen MD, PhD, Frank Hoebers MD, PhD, Katherine A. Hutcheson PhD, Nandita Guha-Thakurta MD, Jason Johnson MD, Diana Kaya MD, Shekhar D. Khanpara MD, Kristofer Nyman MD, Stephen Y. Lai MD, PhD, Miriam Lango MD, Kim O. Learned MD, Anna Lee MD, MPH, Carol M. Lewis MD, MPH, Anastasios Maniakas MD, PhD, Amy C. Moreno MD, MS, Jeffrey N. Myers MD, PhD, Jack Phan MD, PhD, Kristen B. Pytynia MD, MPH, David I. Rosenthal MD, Vlad C. Sandulache MD, PhD, Dawid Schellingerhout MBChB, MBA, Shalin J. Shah MD, Andrew G. Sikora MD, PhD, Abdallah S. R. Mohamed MD, PhD, Melissa M. Chen MD, Clifton D. Fuller MD, PhD, 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> < .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 < 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}
Stephanie L. Graff MD, FACP, FASCO, Sara M. Tolaney MD, MPH, Lowell L. Hart MD, FACP, Pedram Razavi MD, PhD, Wolfgang Janni MD, PhD, Lee S. Schwartzberg MD, FACP, Andriy Danyliv PhD, Murat Akdere PharmD, Ilia Ferrusi PhD, Rishi Rajat Adhikary PhD, Joyce A. O’Shaughnessy MD
Background
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.
Methods
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.
Results
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 p < .0001). iDFS accounted for 82% of variation in OS (R2 = 0.82). Results of all subgroup analyses were consistent with overall population.
Conclusions
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.
{"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, Sara M. Tolaney MD, MPH, Lowell L. Hart MD, FACP, Pedram Razavi MD, PhD, Wolfgang Janni MD, PhD, Lee S. Schwartzberg MD, FACP, Andriy Danyliv PhD, Murat Akdere PharmD, Ilia Ferrusi PhD, Rishi Rajat Adhikary PhD, 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 R<sup>2</sup> (clinical relevance R<sup>2</sup> ≥ 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> < .0001). iDFS accounted for 82% of variation in OS (R<sup>2</sup> = 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}
Alexandre Bertucci MD, Ondine Dufour MD, Romain Appay MD, PhD, Vincent Harlay MD, François Ducray MD, PhD, Charlotte Bronnimann MD, Apolline Djelad MD, Elisabeth Cohen-Jonathan Moyal MD, PhD, Mario Campone MD, Olivier Langlois MD, Mathilde Ducloie MD, Elodie Vauleon MD, Nadia Younan MD, Christine Desenclos MD, Carole Ramirez MD, Mehdi Touat MD, PhD, Ahmed Idbaih MD, Céline Bequet, Dominique Figarella-Branger MD, PhD, Caroline Dehais MD, Olivier Chinot MD, Emeline Tabouret MD, PhD, for the POLA network
Background
Brain tumors represent one of the main causes of cancer-related mortality in young patients. Among them, oligodendrogliomas (OG) are adult-type diffuse gliomas with the best prognosis. Nevertheless, characterization of these tumors in the young population remains poorly documented. Our objective was to characterize the population of young adults under 40 years of age with grade 3 OG in the POLA cohort.
Methods
Clinical data prospectively collected for all patients registered with grade 3 OG between April 2009 and August 2021 were extracted from the national POLA database. This study compared the patient subgroup <40 years of age to the one >40 years of age.
Results
The authors included 111 patients <40 years old and 363 patients ≥40 years old. Treatment received did not differ significantly between the two subgroups. Temporal location was more frequent in older patients (p = .009). Patients <40 years old presented more often seizure as initial symptom (p = .003). They had less frequent chromosome 9p loss (p < .001) and less CDKN2A homozygous deletion (p = .024). Median progression-free survival (PFS) was 123 months (range, 86–not reached [NR]) versus 88 months (range, 67–117) (p = .082) and median overall survival (OS) was not reached (range, 147–NR) versus 163 months (range, 137–NR) (p < .001) in younger and older subgroups, respectively. In multivariate analysis, complete or subtotal resection (p = .014) and seizure at diagnosis (p = .032) were associated with better OS.
Conclusion
Young patients with grade 3 OG have distinct clinical presentation, molecular features, and outcomes compared to the older patients.
{"title":"Characteristics, outcome, and prognostic factors of young patients with central nervous system World Health Organization grade 3 oligodendrogliomas IDH-mutant and 1p/19q codeleted: A French POLA network study","authors":"Alexandre Bertucci MD, Ondine Dufour MD, Romain Appay MD, PhD, Vincent Harlay MD, François Ducray MD, PhD, Charlotte Bronnimann MD, Apolline Djelad MD, Elisabeth Cohen-Jonathan Moyal MD, PhD, Mario Campone MD, Olivier Langlois MD, Mathilde Ducloie MD, Elodie Vauleon MD, Nadia Younan MD, Christine Desenclos MD, Carole Ramirez MD, Mehdi Touat MD, PhD, Ahmed Idbaih MD, Céline Bequet, Dominique Figarella-Branger MD, PhD, Caroline Dehais MD, Olivier Chinot MD, Emeline Tabouret MD, PhD, for the POLA network","doi":"10.1002/cncr.35814","DOIUrl":"https://doi.org/10.1002/cncr.35814","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Brain tumors represent one of the main causes of cancer-related mortality in young patients. Among them, oligodendrogliomas (OG) are adult-type diffuse gliomas with the best prognosis. Nevertheless, characterization of these tumors in the young population remains poorly documented. Our objective was to characterize the population of young adults under 40 years of age with grade 3 OG in the POLA cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical data prospectively collected for all patients registered with grade 3 OG between April 2009 and August 2021 were extracted from the national POLA database. This study compared the patient subgroup <40 years of age to the one >40 years of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The authors included 111 patients <40 years old and 363 patients ≥40 years old. Treatment received did not differ significantly between the two subgroups. Temporal location was more frequent in older patients (<i>p</i> = .009). Patients <40 years old presented more often seizure as initial symptom (<i>p</i> = .003). They had less frequent chromosome 9p loss (<i>p</i> < .001) and less <i>CDKN2A</i> homozygous deletion (<i>p</i> = .024). Median progression-free survival (PFS) was 123 months (range, 86–not reached [NR]) versus 88 months (range, 67–117) (<i>p</i> = .082) and median overall survival (OS) was not reached (range, 147–NR) versus 163 months (range, 137–NR) (<i>p</i> < .001) in younger and older subgroups, respectively. In multivariate analysis, complete or subtotal resection (<i>p</i> = .014) and seizure at diagnosis (<i>p</i> = .032) were associated with better OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Young patients with grade 3 OG have distinct clinical presentation, molecular features, and outcomes compared to the older patients.</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.35814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735523","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}
Jacopo Nanni MD, Irene Azzali PhD, Cristina Papayannidis MD, PhD, Antonino Mulè MD, Ernesta Audisio MD, Maria Paola Martelli MD, PhD, Barbara Scappini MD, Patrizia Chiusolo MD, PhD, Benedetta Cambò MD, PhD, Anna Candoni MD, Monia Lunghi MD, Francesco Albano MD, PhD, Attilio Olivieri MD, Nicola Fracchiolla MD, Massimo Bernardi MD, Claudio Romani MD, Gian Matteo Rigolin MD, PhD, Maria Benedetta Giannini MD, Monica Bocchia MD, Elisabetta Todisco MD, Daniela Cilloni MD, PhD, Maria Teresa Bochicchio MSc, Emanuela Ottaviani MSc, Agnese Mattei MD, Federica Zamagni MSS, Irene Valli M.Sc. in PVRA, MPharm, Roberta Volpi MPharm, Giovanni Marconi MD, PhD, Elisabetta Petracci PhD, FLAM Collaborative Group, Giovanni Martinelli MD, PhD
Background
The addition of a FLT3 inhibitor (FLT3i) to standard chemotherapy to treat fit newly diagnosed (ND) patients with FLT3-mutated acute myeloid leukemia (AML) represents the standard of care resulting from clinical trial results. However, evidence regarding FLT3i adoption in routine clinical practice is still scarce.
Methods
Clinical data are reported from 394 ND patients with FLT3-mutated AML enrolled in the retrospective observational Italian Cohort Study on FLT3-mutated patients with AML and treated with an upfront intensive regimen with (FLT3i group, n = 92) or without (CT group, n = 302) the addition of a FLT3i.
Results
With a median follow-up time of 34.5 months, an effectiveness benefit obtained by FLT3i incorporation both in terms of overall survival (median, 34.9 in the FLT3i vs 12.7 months in the CT group, p < .01) and relapse-free survival (median, 18.9 in the FLT3i vs 7.6 months in the CT group, p = .01) was documented, with a higher composite complete remission rate (75.4% in the FLT3i vs 62.4% in the CT group, p = .052). FLT3i benefit seemed to be independent from the transplant rate.
Conclusions
In conclusion, the benefit of FLT3i addition to upfront intensive treatment in newly diagnosed FLT3-mutated AML patients was confirmed in a large, real-life cohort study.
{"title":"Upfront intensive treatment analysis of the Italian Cohort Study on FLT3-mutated AML patients (FLAM): The impact of a FLT3 inhibitor addition to standard chemotherapy in the real-life setting","authors":"Jacopo Nanni MD, Irene Azzali PhD, Cristina Papayannidis MD, PhD, Antonino Mulè MD, Ernesta Audisio MD, Maria Paola Martelli MD, PhD, Barbara Scappini MD, Patrizia Chiusolo MD, PhD, Benedetta Cambò MD, PhD, Anna Candoni MD, Monia Lunghi MD, Francesco Albano MD, PhD, Attilio Olivieri MD, Nicola Fracchiolla MD, Massimo Bernardi MD, Claudio Romani MD, Gian Matteo Rigolin MD, PhD, Maria Benedetta Giannini MD, Monica Bocchia MD, Elisabetta Todisco MD, Daniela Cilloni MD, PhD, Maria Teresa Bochicchio MSc, Emanuela Ottaviani MSc, Agnese Mattei MD, Federica Zamagni MSS, Irene Valli M.Sc. in PVRA, MPharm, Roberta Volpi MPharm, Giovanni Marconi MD, PhD, Elisabetta Petracci PhD, FLAM Collaborative Group, Giovanni Martinelli MD, PhD","doi":"10.1002/cncr.35824","DOIUrl":"https://doi.org/10.1002/cncr.35824","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The addition of a FLT3 inhibitor (FLT3i) to standard chemotherapy to treat fit newly diagnosed (ND) patients with <i>FLT3</i>-mutated acute myeloid leukemia (AML) represents the standard of care resulting from clinical trial results. However, evidence regarding FLT3i adoption in routine clinical practice is still scarce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical data are reported from 394 ND patients with <i>FLT3</i>-mutated AML enrolled in the retrospective observational Italian Cohort Study on <i>FLT3</i>-mutated patients with AML and treated with an upfront intensive regimen with (FLT3i group, <i>n</i> = 92) or without (CT group, <i>n</i> = 302) the addition of a FLT3i.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With a median follow-up time of 34.5 months, an effectiveness benefit obtained by FLT3i incorporation both in terms of overall survival (median, 34.9 in the FLT3i vs 12.7 months in the CT group, <i>p</i> < .01) and relapse-free survival (median, 18.9 in the FLT3i vs 7.6 months in the CT group, <i>p</i> = .01) was documented, with a higher composite complete remission rate (75.4% in the FLT3i vs 62.4% in the CT group, <i>p</i> = .052). FLT3i benefit seemed to be independent from the transplant rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, the benefit of FLT3i addition to upfront intensive treatment in newly diagnosed FLT3-mutated AML patients was confirmed in a large, real-life cohort study.</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.35824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735525","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}
Baike Liu MD, Chaoyong Shen MD, Xiaonan Yin MD, PhD, Tianxiang Jiang MD, Yihui Han MD, Ruiwan Yuan MD, Yuan Yin MD, Zhaolun Cai MD, Bo Zhang MD
Background
The efficacy of perioperative chemotherapy for deficient mismatch repair or microsatellite instability–high (dMMR/MSI-H) gastric cancer (GC) remains controversial.
Methods
This study was preregistered with the PROSPERO platform (CRD42023494276), and studies comparing perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC were included. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of survival outcomes were extracted. A random-effects model was used in the pooled analysis.
Results
Twenty-two studies, which encompassed approximately 1600 patients with dMMR/MSI-H GC, were included. The results indicated that perioperative chemotherapy does not significantly improve overall survival (OS) (HR, 0.85; 95% CI, 0.58–1.26) and disease-free survival (DFS) (HR, 0.77; 95% CI, 0.53–1.12) in dMMR/MSI-H GC. In the subgroup analysis, adjuvant chemotherapy was not associated with improved OS (HR, 0.83; 95% CI, 0.50–1.37) but was associated with improved DFS (HR, 0.64; 95% CI, 0.43–0.96). However, the benefit of adjuvant chemotherapy for DFS was not significant in the pooled analysis of multivariable-adjusted results. Similar results were observed for neoadjuvant chemotherapy (OS: HR, 0.84; 95% CI, 0.44–1.57; DFS: HR, 1.13; 95% CI, 0.50–2.53). Additionally, stage stratification analysis demonstrated no significant survival benefit of adjuvant chemotherapy for stage II (OS: HR, 0.77; 95% CI, 0.31–1.90) or stage III (OS: HR, 0.72; 95% CI, 0.36–1.46) dMMR/MSI-H GC.
Conclusions
Despite indications that adjuvant chemotherapy may improve DFS in the subgroup analysis, this benefit was not sustained in multivariate assessments. Overall, the pooled results indicate that perioperative chemotherapy does not significantly improve OS or DFS in patients with resectable dMMR/MSI-H GC, and therefore such treatment may be spared in these patients.
{"title":"Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: A systematic review and meta-analysis","authors":"Baike Liu MD, Chaoyong Shen MD, Xiaonan Yin MD, PhD, Tianxiang Jiang MD, Yihui Han MD, Ruiwan Yuan MD, Yuan Yin MD, Zhaolun Cai MD, Bo Zhang MD","doi":"10.1002/cncr.35831","DOIUrl":"https://doi.org/10.1002/cncr.35831","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The efficacy of perioperative chemotherapy for deficient mismatch repair or microsatellite instability–high (dMMR/MSI-H) gastric cancer (GC) remains controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was preregistered with the PROSPERO platform (CRD42023494276), and studies comparing perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC were included. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of survival outcomes were extracted. A random-effects model was used in the pooled analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-two studies, which encompassed approximately 1600 patients with dMMR/MSI-H GC, were included. The results indicated that perioperative chemotherapy does not significantly improve overall survival (OS) (HR, 0.85; 95% CI, 0.58–1.26) and disease-free survival (DFS) (HR, 0.77; 95% CI, 0.53–1.12) in dMMR/MSI-H GC. In the subgroup analysis, adjuvant chemotherapy was not associated with improved OS (HR, 0.83; 95% CI, 0.50–1.37) but was associated with improved DFS (HR, 0.64; 95% CI, 0.43–0.96). However, the benefit of adjuvant chemotherapy for DFS was not significant in the pooled analysis of multivariable-adjusted results. Similar results were observed for neoadjuvant chemotherapy (OS: HR, 0.84; 95% CI, 0.44–1.57; DFS: HR, 1.13; 95% CI, 0.50–2.53). Additionally, stage stratification analysis demonstrated no significant survival benefit of adjuvant chemotherapy for stage II (OS: HR, 0.77; 95% CI, 0.31–1.90) or stage III (OS: HR, 0.72; 95% CI, 0.36–1.46) dMMR/MSI-H GC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite indications that adjuvant chemotherapy may improve DFS in the subgroup analysis, this benefit was not sustained in multivariate assessments. Overall, the pooled results indicate that perioperative chemotherapy does not significantly improve OS or DFS in patients with resectable dMMR/MSI-H GC, and therefore such treatment may be spared in these patients.</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":"143735524","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号