Basile M. Njei MD, MPH, PhD, Yazan A. Al-Ajlouni MD, MPhil
{"title":"Interpreting projected gastrointestinal cancer burden in Africa: The case of liver cancer","authors":"Basile M. Njei MD, MPH, PhD, Yazan A. Al-Ajlouni MD, MPhil","doi":"10.1002/cncr.70296","DOIUrl":"10.1002/cncr.70296","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103208","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}
Yiwen Ma PhD, Xiaorui Li MM, Yujun Jiang MM, Liping Xiao MM, Tao Sun MD
Background
Although trastuzumab deruxtecan (T-DXd) demonstrated unprecedented intracranial efficacy in HER2-positive breast cancer brain metastases (BCBM), its association with interstitial lung disease (ILD)/pneumonitis posed a critical safety concern in this high-risk population. Previous safety assessments lacked BCBM-specific analysis of ILD.
Methods
This systematic review and meta-analysis (PROSPERO identifier CRD420251130832) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The authors searched the PubMed, Embase, Web of Science, and Cochrane databases and major oncology conferences through July 2025 for studies that reported T-DXd-related, treatment-emergent adverse events (TEAEs) in patients with HER2-positive BCBM, focusing on ILD/pneumonitis incidence and severity. Pooled rates were calculated using random effects models.
Results
In total, nine studies involving 684 patients with BCBM were included. The pooled incidence rates for all-grade and grade ≥3 ILD/pneumonitis were 10% (95% confidence interval [CI], 5%–16%) and 2% (95% CI, 1%–4%), respectively. ILD/pneumonitis led to discontinuation in 11% (95% CI, 0%–24%) of patients with BCBM. No fatal ILD events were reported. Overall, any-grade TEAEs occurred in 97% of patients, with grade ≥3 TEAEs occurring in 48%. Fatigue and nausea were the most prevalent all-grade TEAEs, with incidences of 67% and 60%, respectively.
Conclusions
In patients with BCBM, T-DXd–associated ILD/pneumonitis occurred in 10% of patient and frequently necessitated treatment modification. Although no fatal ILD was observed, the high discontinuation rate underscored the imperative for vigilant monitoring and protocol-guided management to mitigate pulmonary toxicity while preserving intracranial efficacy.
{"title":"The safety of trastuzumab deruxtecan (T-DXd) in breast cancer brain metastases with a focus on interstitial lung disease/pneumonitis: A systematic review and meta-analysis","authors":"Yiwen Ma PhD, Xiaorui Li MM, Yujun Jiang MM, Liping Xiao MM, Tao Sun MD","doi":"10.1002/cncr.70268","DOIUrl":"10.1002/cncr.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although trastuzumab deruxtecan (T-DXd) demonstrated unprecedented intracranial efficacy in HER2-positive breast cancer brain metastases (BCBM), its association with interstitial lung disease (ILD)/pneumonitis posed a critical safety concern in this high-risk population. Previous safety assessments lacked BCBM-specific analysis of ILD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review and meta-analysis (PROSPERO identifier CRD420251130832) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The authors searched the PubMed, Embase, Web of Science, and Cochrane databases and major oncology conferences through July 2025 for studies that reported T-DXd-related, treatment-emergent adverse events (TEAEs) in patients with HER2-positive BCBM, focusing on ILD/pneumonitis incidence and severity. Pooled rates were calculated using random effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, nine studies involving 684 patients with BCBM were included. The pooled incidence rates for all-grade and grade ≥3 ILD/pneumonitis were 10% (95% confidence interval [CI], 5%–16%) and 2% (95% CI, 1%–4%), respectively. ILD/pneumonitis led to discontinuation in 11% (95% CI, 0%–24%) of patients with BCBM. No fatal ILD events were reported. Overall, any-grade TEAEs occurred in 97% of patients, with grade ≥3 TEAEs occurring in 48%. Fatigue and nausea were the most prevalent all-grade TEAEs, with incidences of 67% and 60%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with BCBM, T-DXd–associated ILD/pneumonitis occurred in 10% of patient and frequently necessitated treatment modification. Although no fatal ILD was observed, the high discontinuation rate underscored the imperative for vigilant monitoring and protocol-guided management to mitigate pulmonary toxicity while preserving intracranial efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100013","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}
Jiefeng Luo PhD, Zhengxiong Li MSc, Jun Ge PhD, Sizhen Cai MSc, Xinyi Mo MSc, Wensheng Liu PhD, Chengxia Gui MSc, Qiong Du PhD, Jiyong Liu PhD
Background
Nivolumab plus ipilimumab has shown survival benefits as first-line treatment for unresectable hepatocellular carcinoma (HCC) but their high cost raises concerns about value. This study assessed the cost-effectiveness of nivolumab plus ipilimumab compared with lenvatinib or sorafenib from a United States (US) health care payer perspective.
Methods
A partitioned survival model was developed using data from the CheckMate 9DW trial with a 10-year horizon. Costs and outcomes were discounted by 3% annually. Clinical inputs were derived from CheckMate 9DW trial, and cost inputs were obtained from public databases and published studies. Primary outcomes were quality-adjusted life years (QALYs), total costs, life years (LYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and scenario analyses were conducted to test uncertainties.
Results
Nivolumab plus ipilimumab produced an incremental gain of 0.66 QALYs at an additional cost of $132,652, yielding an ICER of $200,409/QALY, above US willingness-to-pay thresholds ($100,000/QALY and $150,000/QALY). Probabilistic sensitivity analysis indicated a low probability of cost-effectiveness at current prices (4.6%–20%). Scenario analyses showed that extending maintenance nivolumab dosing from every 4 weeks to every 8 weeks reduced the ICER to $82,202/QALY, making the regimen cost-effective. Moderate price reductions also substantially increased the likelihood of cost-effectiveness.
Conclusions
Nivolumab plus ipilimumab is unlikely to be cost-effective as first-line therapy for unresectable HCC from US health care payer perspective. However, extended dosing interval or price reductions may render the regimen economically viable, with important implications for clinical practice, payers, and policy.
{"title":"Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma: A cost-effectiveness analysis","authors":"Jiefeng Luo PhD, Zhengxiong Li MSc, Jun Ge PhD, Sizhen Cai MSc, Xinyi Mo MSc, Wensheng Liu PhD, Chengxia Gui MSc, Qiong Du PhD, Jiyong Liu PhD","doi":"10.1002/cncr.70259","DOIUrl":"10.1002/cncr.70259","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nivolumab plus ipilimumab has shown survival benefits as first-line treatment for unresectable hepatocellular carcinoma (HCC) but their high cost raises concerns about value. This study assessed the cost-effectiveness of nivolumab plus ipilimumab compared with lenvatinib or sorafenib from a United States (US) health care payer perspective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A partitioned survival model was developed using data from the CheckMate 9DW trial with a 10-year horizon. Costs and outcomes were discounted by 3% annually. Clinical inputs were derived from CheckMate 9DW trial, and cost inputs were obtained from public databases and published studies. Primary outcomes were quality-adjusted life years (QALYs), total costs, life years (LYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and scenario analyses were conducted to test uncertainties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nivolumab plus ipilimumab produced an incremental gain of 0.66 QALYs at an additional cost of $132,652, yielding an ICER of $200,409/QALY, above US willingness-to-pay thresholds ($100,000/QALY and $150,000/QALY). Probabilistic sensitivity analysis indicated a low probability of cost-effectiveness at current prices (4.6%–20%). Scenario analyses showed that extending maintenance nivolumab dosing from every 4 weeks to every 8 weeks reduced the ICER to $82,202/QALY, making the regimen cost-effective. Moderate price reductions also substantially increased the likelihood of cost-effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Nivolumab plus ipilimumab is unlikely to be cost-effective as first-line therapy for unresectable HCC from US health care payer perspective. However, extended dosing interval or price reductions may render the regimen economically viable, with important implications for clinical practice, payers, and policy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096698","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}
Bruce Montgomery MD, Julie A. Lynch MBA, RN, PhD, Jessica Brown BA, Kara N. Maxwell MD, PhD, Craig C. Teerlink PhD, Nismeta Kabilovic BS, Katie Stoll MS, Julie Simon MS, Maria Kogan BA, Sajida Hassan PhD, Stacey B. Whitbourne PhD, Sumitra Muralidhar PhD, Martin W. Schoen MD, MPH, Rachel Ramoni DMD, J. Michael Gaziano MD, Alexandra O. Sokolova MD, Heather H. Cheng MD, PhD, Ruth Etzioni PhD, Colin C. Pritchard MD, PhD
Background
Germline pathogenic variants can inform targeted therapy for metastatic prostate cancer (mPC), and improve cancer early detection and risk reduction for family members. Guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing is only 10%–12%.
Methods
This prospective study enrolled veterans participating in the VA Million Veteran Program (MVP) with a diagnosis of mPC. Veterans were contacted by mail with option to opt-out of future contact. Eligible veterans who did not opt-out were mailed study information and received a follow-up phone call to establish interest in germline testing. Participants provided verbal consent and were mailed a saliva collection kit for a CLIA-level multigene cancer predisposition gene panel test. Results were disclosed to the patient and oncology provider. All steps were performed with genetic counseling support.
Results
Of 2104 eligible patients, 1952 veterans with mPC did not opt out. Of these, 681 (35%) provided consent and 459 (24%) completed testing. Of those who were approached 63% were White and 25% were Black. Fifty-nine (13%) of those completing testing carried a germline pathogenic variant in a cancer risk gene. Of the 37 eligible for targeted therapy, 14 received targeted therapy, 18 did not yet have an indication for that therapy, and five were deceased without having received targeted therapy.
Conclusions
Participant completion of remote germline testing was facilitated at rates higher than the 10% previously reported. Remote genetic testing can augment uptake of testing in large, integrated health care systems.
{"title":"Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program pilot study","authors":"Bruce Montgomery MD, Julie A. Lynch MBA, RN, PhD, Jessica Brown BA, Kara N. Maxwell MD, PhD, Craig C. Teerlink PhD, Nismeta Kabilovic BS, Katie Stoll MS, Julie Simon MS, Maria Kogan BA, Sajida Hassan PhD, Stacey B. Whitbourne PhD, Sumitra Muralidhar PhD, Martin W. Schoen MD, MPH, Rachel Ramoni DMD, J. Michael Gaziano MD, Alexandra O. Sokolova MD, Heather H. Cheng MD, PhD, Ruth Etzioni PhD, Colin C. Pritchard MD, PhD","doi":"10.1002/cncr.70283","DOIUrl":"10.1002/cncr.70283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Germline pathogenic variants can inform targeted therapy for metastatic prostate cancer (mPC), and improve cancer early detection and risk reduction for family members. Guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing is only 10%–12%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective study enrolled veterans participating in the VA Million Veteran Program (MVP) with a diagnosis of mPC. Veterans were contacted by mail with option to opt-out of future contact. Eligible veterans who did not opt-out were mailed study information and received a follow-up phone call to establish interest in germline testing. Participants provided verbal consent and were mailed a saliva collection kit for a CLIA-level multigene cancer predisposition gene panel test. Results were disclosed to the patient and oncology provider. All steps were performed with genetic counseling support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 2104 eligible patients, 1952 veterans with mPC did not opt out. Of these, 681 (35%) provided consent and 459 (24%) completed testing. Of those who were approached 63% were White and 25% were Black. Fifty-nine (13%) of those completing testing carried a germline pathogenic variant in a cancer risk gene. Of the 37 eligible for targeted therapy, 14 received targeted therapy, 18 did not yet have an indication for that therapy, and five were deceased without having received targeted therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Participant completion of remote germline testing was facilitated at rates higher than the 10% previously reported. Remote genetic testing can augment uptake of testing in large, integrated health care systems.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12857595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083760","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}
Christian J. Nelson PhD, Kathleen Flaherty MA, Elizabeth Schofield DrPH, Thomas M. Atkinson PhD, Hayley Pessin PhD, Addison Kitrel BA, Barry Rosenfeld PhD, Rebecca M. Saracino PhD
Background
Depression in older adults with cancer (OACs) is poorly captured by patient-reported outcomes (PROs) because traditional criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) may overlook unique symptoms in OACs. By using US Food and Drug Administration Guidance for Industry on PRO development, the authors conceptualized depression in OACs and created the Older Adults with Cancer-Depression Scale (OAC-D). This study evaluates the psychometric properties of this novel measure.
Methods
Based on a refined conceptual model informed by literature reviews and qualitative work with patients and experts in geriatric oncology, a 35-item draft PRO was developed. The draft was administered, alongside legacy measures, to OACs aged >70 years and older at a comprehensive cancer center and across the United States. Exploratory graph analysis was used to identify items and factors.
Results
The mean ± standard deviation age of the 155 participants was 76 ± 5 years, and 56% were women. Exploratory graph analysis yielded an 18-item measure with five domains: (1) interest and enjoyment, (2) purpose and meaning, (3) loneliness, (4) social withdrawal, and (5) regret and guilt. Internal consistency (Cronbach alpha, .85–.95) and test-retest reliability (intraclass correlation coefficient = 0.61–0.80) were strong. Convergent validity was supported by correlations with the Patient Health Questionnaire-9 (r = 0.75), the Patient-Reported Outcomes Measurement Information System anxiety score (r = 0.69), and the Patient-Reported Outcomes Measurement Information System physical score (r = −0.39). Known groups analysis demonstrated higher OAC-D scores for those with a history of depression (p < .001).
Conclusions
The OAC-D identified five unique domains of depression, only one of which overlapped with DSM criteria. It demonstrated robust psychometric properties, providing a nuanced alternative to DSM-based measures and addressing the distinctive psychological challenges of cancer and aging.
{"title":"Advancing depression assessment in older adults with cancer: Development and validation of the Older Adults with Cancer-Depression Scale (OAC-D), a novel, patient-reported outcome","authors":"Christian J. Nelson PhD, Kathleen Flaherty MA, Elizabeth Schofield DrPH, Thomas M. Atkinson PhD, Hayley Pessin PhD, Addison Kitrel BA, Barry Rosenfeld PhD, Rebecca M. Saracino PhD","doi":"10.1002/cncr.70255","DOIUrl":"10.1002/cncr.70255","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Depression in older adults with cancer (OACs) is poorly captured by patient-reported outcomes (PROs) because traditional criteria from the <i>Diagnostic and Statistical Manual of Mental Disorders</i> (DSM) may overlook unique symptoms in OACs. By using US Food and Drug Administration Guidance for Industry on PRO development, the authors conceptualized depression in OACs and created the Older Adults with Cancer-Depression Scale (OAC-D). This study evaluates the psychometric properties of this novel measure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on a refined conceptual model informed by literature reviews and qualitative work with patients and experts in geriatric oncology, a 35-item draft PRO was developed. The draft was administered, alongside legacy measures, to OACs aged >70 years and older at a comprehensive cancer center and across the United States. Exploratory graph analysis was used to identify items and factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean ± standard deviation age of the 155 participants was 76 ± 5 years, and 56% were women. Exploratory graph analysis yielded an 18-item measure with five domains: (1) interest and enjoyment, (2) purpose and meaning, (3) loneliness, (4) social withdrawal, and (5) regret and guilt. Internal consistency (Cronbach alpha, .85–.95) and test-retest reliability (intraclass correlation coefficient = 0.61–0.80) were strong. Convergent validity was supported by correlations with the Patient Health Questionnaire-9 (<i>r</i> = 0.75), the Patient-Reported Outcomes Measurement Information System anxiety score (r = 0.69), and the Patient-Reported Outcomes Measurement Information System physical score (<i>r</i> = −0.39). Known groups analysis demonstrated higher OAC-D scores for those with a history of depression (<i>p</i> < .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The OAC-D identified five unique domains of depression, only one of which overlapped with DSM criteria. It demonstrated robust psychometric properties, providing a nuanced alternative to DSM-based measures and addressing the distinctive psychological challenges of cancer and aging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083699","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}
Konopleva M, Pemmaraju N, Sweet KL, et al. Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm. Cancer. 2026;e70243. doi:10.1002/cncr.70243
Michael Zuurman’s degree was incorrect in the originally published version of this article. The correct degree is as follows: Michael Zuurman PhD
{"title":"Correction to “Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm”","authors":"","doi":"10.1002/cncr.70288","DOIUrl":"10.1002/cncr.70288","url":null,"abstract":"<p>Konopleva M, Pemmaraju N, Sweet KL, et al. Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm. <i>Cancer</i>. 2026;e70243. doi:10.1002/cncr.70243</p><p>Michael Zuurman’s degree was incorrect in the originally published version of this article. The correct degree is as follows: Michael Zuurman PhD</p><p>We apologize for this error.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058391","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}
Theresa Abdo MD, Ahmad Alhalabi MD, Sacha Yaghi BS, Mohammad Aloran MD, You Li MD, María Herrán MD, Rami Tfayli MD, Thomas A. Samuel MD, Zeina Nahleh MD, FACP
Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utility of ctDNA MRD in gastrointestinal, lung, breast, and other malignancies, with positive postoperative or post-treatment MRD status correlating with higher recurrence risk and inferior survival outcomes. However, integration into clinical practice remains limited by challenges, including tumor heterogeneity, variable ctDNA shedding across tumor stage, location and timing, lack of standardized assay interpretation, and cost-effectiveness concerns. Emerging technologies such as methylation-based sequencing, ultra-deep next-generation sequencing, and machine learning–driven risk models hold promise for improving detection accuracy and clinical applicability. Ongoing clinical trials are expected to determine the impact of earlier MRD detection and intervention on patient outcomes, potentially supporting the broader adoption of ctDNA MRD. In this article, the authors reviewed the recent clinical applications, limitations and future directions of MRD in solid tumors.
{"title":"Minimal residual disease in solid tumors: Clinical applications and future directions","authors":"Theresa Abdo MD, Ahmad Alhalabi MD, Sacha Yaghi BS, Mohammad Aloran MD, You Li MD, María Herrán MD, Rami Tfayli MD, Thomas A. Samuel MD, Zeina Nahleh MD, FACP","doi":"10.1002/cncr.70286","DOIUrl":"10.1002/cncr.70286","url":null,"abstract":"<p>Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utility of ctDNA MRD in gastrointestinal, lung, breast, and other malignancies, with positive postoperative or post-treatment MRD status correlating with higher recurrence risk and inferior survival outcomes. However, integration into clinical practice remains limited by challenges, including tumor heterogeneity, variable ctDNA shedding across tumor stage, location and timing, lack of standardized assay interpretation, and cost-effectiveness concerns. Emerging technologies such as methylation-based sequencing, ultra-deep next-generation sequencing, and machine learning–driven risk models hold promise for improving detection accuracy and clinical applicability. Ongoing clinical trials are expected to determine the impact of earlier MRD detection and intervention on patient outcomes, potentially supporting the broader adoption of ctDNA MRD. In this article, the authors reviewed the recent clinical applications, limitations and future directions of MRD in solid tumors.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091584","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}
Caitlin P. O’Connell MPH, Sonja I. Berndt PharmD, PhD, Kenechukwu Chudy-Onwugaje MBBS, MPH, MS, Andrew Kunzmann PhD, Wen-Yi Huang PhD, MSPH, Kathryn Hughes Barry PhD, MPH, Erikka Loftfield PhD, MPH
Background
Alcohol drinking is associated with higher colorectal cancer (CRC) risk, but research on lifetime alcohol drinking is limited. The objective of the current study was to estimate the association of lifetime alcohol drinking with incident colorectal adenoma and cancer.
Methods
US adults enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial reported alcohol intake during four age periods. Average lifetime alcohol intake was calculated as average drinks per week from age 18 years until study baseline. Alcohol intake patterns were defined by past and current drinking frequency. Among 12,327 participants with a negative baseline screen, 812 had an adenoma on the second screen. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident adenoma. During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 participants. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for CRC.
Results
Current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, compared with one drink or less per week, had a higher risk of CRC (HR, 1.25; 95% CI, 1.01–1.53), especially rectal cancer (HR, 1.95; 95% CI, 1.17–3.28). Consistent heavy drinking versus light drinking was positively associated with CRC risk (HR, 1.91; 95% CI, 1.17–3.12). Compared with current drinkers averaging less than one drink per week, former drinkers had lower odds of nonadvanced adenoma (OR, 0.58; 95% CI, 0.39–0.84). Current drinkers averaging from seven to less than 14 drinks compared with less than one drink per week had a lower risk of CRC (HR, 0.79; 95% CI, 0.64–0.97), especially distal colon cancer (HR, 0.64; 95% CI, 0.42–1.00).
Conclusions
Consistent heavy alcohol intake and higher average lifetime alcohol drinking may increase CRC risk, whereas cessation may lower adenoma risk. Associations may differ by tumor site.
{"title":"Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial","authors":"Caitlin P. O’Connell MPH, Sonja I. Berndt PharmD, PhD, Kenechukwu Chudy-Onwugaje MBBS, MPH, MS, Andrew Kunzmann PhD, Wen-Yi Huang PhD, MSPH, Kathryn Hughes Barry PhD, MPH, Erikka Loftfield PhD, MPH","doi":"10.1002/cncr.70201","DOIUrl":"10.1002/cncr.70201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol drinking is associated with higher colorectal cancer (CRC) risk, but research on lifetime alcohol drinking is limited. The objective of the current study was to estimate the association of lifetime alcohol drinking with incident colorectal adenoma and cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>US adults enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial reported alcohol intake during four age periods. Average lifetime alcohol intake was calculated as average drinks per week from age 18 years until study baseline. Alcohol intake patterns were defined by past and current drinking frequency. Among 12,327 participants with a negative baseline screen, 812 had an adenoma on the second screen. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident adenoma. During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 participants. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, compared with one drink or less per week, had a higher risk of CRC (HR, 1.25; 95% CI, 1.01–1.53), especially rectal cancer (HR, 1.95; 95% CI, 1.17–3.28). Consistent heavy drinking versus light drinking was positively associated with CRC risk (HR, 1.91; 95% CI, 1.17–3.12). Compared with current drinkers averaging less than one drink per week, former drinkers had lower odds of nonadvanced adenoma (OR, 0.58; 95% CI, 0.39–0.84). Current drinkers averaging from seven to less than 14 drinks compared with less than one drink per week had a lower risk of CRC (HR, 0.79; 95% CI, 0.64–0.97), especially distal colon cancer (HR, 0.64; 95% CI, 0.42–1.00).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Consistent heavy alcohol intake and higher average lifetime alcohol drinking may increase CRC risk, whereas cessation may lower adenoma risk. Associations may differ by tumor site.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045745","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}
Rituparna Bhattacharya PhD, Kalé Kponee-Shovein ScD, MS, MPH, Yipeng Gao PhD, Yan Song PhD, Jingyi Liu MBI, Katherine Wei BA, Ekta Kapadia MD, Haojie Li PhD, Ashish M. Kamat MD, MBBS, FACS
Background
Event-free survival (EFS) and complete response rate (CRR) are recommended as primary endpoints in bladder cancer trials to enable timely assessment of therapeutic benefit. However, their surrogacy relationship with overall survival (OS) in high-risk non–muscle-invasive bladder cancer (HR NMIBC) remains unclear. This meta-analysis evaluated EFS and CRR as surrogate endpoints for OS in bacillus Calmette-Guérin (BCG)–naive or –remote HR NMIBC.
Methods
A systematic literature review identified trials enrolling BCG-naive or -remote HR NMIBC patients and reporting EFS, CRR, and OS. Weighted linear regression models estimated trial-level associations between the hazard ratio (HR) for EFS and HR for OS, odds ratio for CRR and HR for OS, and arm-level association between median EFS and median OS. Strength of association was quantified using the correlation coefficient (R) and coefficient of determination (R2). Sensitivity analyses evaluated consistency across EFS definitions, publication year, and BCG treatment history.
Results
Ten eligible trials were identified for surrogacy analyses of EFS and CRR. Strong correlations were observed between EFS and OS at the trial level (R = 0.85; R2 = 0.72) and arm level (R = 0.90; R2 = 0.82). Trial-level associations between CRR and OS were weaker (R2 = 0.36 for 3-month CRR; R2 = 0.30 for 6-month CRR). Sensitivity analyses confirmed robustness of the primary results.
Conclusion
In BCG-naive or -remote HR NMIBC, EFS shows strong correlation with OS at the trial and arm levels, supporting its potential as a surrogate endpoint. Further validation incorporating additional trials across varied therapeutic modalities is warranted.
{"title":"Event-free survival and complete response rate as surrogate endpoints for overall survival in high-risk non–muscle-invasive bladder cancer: A meta-analysis of bacillus Calmette-Guérin—naive or —remote cases","authors":"Rituparna Bhattacharya PhD, Kalé Kponee-Shovein ScD, MS, MPH, Yipeng Gao PhD, Yan Song PhD, Jingyi Liu MBI, Katherine Wei BA, Ekta Kapadia MD, Haojie Li PhD, Ashish M. Kamat MD, MBBS, FACS","doi":"10.1002/cncr.70220","DOIUrl":"10.1002/cncr.70220","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Event-free survival (EFS) and complete response rate (CRR) are recommended as primary endpoints in bladder cancer trials to enable timely assessment of therapeutic benefit. However, their surrogacy relationship with overall survival (OS) in high-risk non–muscle-invasive bladder cancer (HR NMIBC) remains unclear. This meta-analysis evaluated EFS and CRR as surrogate endpoints for OS in bacillus Calmette-Guérin (BCG)–naive or –remote HR NMIBC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature review identified trials enrolling BCG-naive or -remote HR NMIBC patients and reporting EFS, CRR, and OS. Weighted linear regression models estimated trial-level associations between the hazard ratio (HR) for EFS and HR for OS, odds ratio for CRR and HR for OS, and arm-level association between median EFS and median OS. Strength of association was quantified using the correlation coefficient (<i>R</i>) and coefficient of determination (<i>R</i><sup><i>2</i></sup>). Sensitivity analyses evaluated consistency across EFS definitions, publication year, and BCG treatment history.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten eligible trials were identified for surrogacy analyses of EFS and CRR. Strong correlations were observed between EFS and OS at the trial level (<i>R</i> = 0.85; <i>R</i><sup><i>2</i></sup> = 0.72) and arm level (<i>R</i> = 0.90; <i>R</i><sup>2</sup> = 0.82). Trial-level associations between CRR and OS were weaker (<i>R</i><sup><i>2</i></sup> = 0.36 for 3-month CRR; <i>R</i><sup><i>2</i></sup> = 0.30 for 6-month CRR). Sensitivity analyses confirmed robustness of the primary results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In BCG-naive or -remote HR NMIBC, EFS shows strong correlation with OS at the trial and arm levels, supporting its potential as a surrogate endpoint. Further validation incorporating additional trials across varied therapeutic modalities is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040034","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}
Yiyang Shan MD, Bo Ding MD, Feng Ji PhD, Hao Lin PhD, Weiwei Shi PhD, Enxiu Wang PhD, Chen Wang PhD, Yang Shen PhD
Background
Ovarian cancer remains a formidable therapeutic challenge due to late diagnosis, high recurrence rates, and limited treatment options. Mesothelin (MSLN) is highly expressed in ovarian cancer, making it a promising target for immunotherapy. Given this target profile, the authors developed a novel T-cell receptor (TCR)-like chimeric antigen receptor (CAR) T-cell therapy targeting MSLN, designated KT127.
Methods
A first-in-human, dose-escalation trial of KT127 was conducted following preclinical evaluation in vitro and in vivo. A combination of rapid titration and a standard “3 + 3” dose-escalation design was implemented. Eleven patients received KT127 at doses ranging from 1 × 106 to 2 × 107 cells/kg following lymphodepletion. The primary objectives were to assess the safety and tolerability of KT127. Secondary objectives included overall survival, disease control rate (DCR), and progression-free survival as efficacy measures. Quality of life (QOL) was assessed using the European Organisation for Research and Treatment of Cancer QLQ-OV28 questionnaire.
Results
No dose-limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome were observed. The DCR was 80% (95% confidence interval, 44.4%–97.5%). QOL assessments indicated improvement in abdominal/gastrointestinal symptoms post-treatment (p = .037), with no significant deterioration in other domains. Proteomic analysis identified differential expression of kallikrein-related peptidases (KLK13, KLK14) and chemokine CXCL17 at baseline, potentially linked to treatment outcomes.
Conclusions
This study highlights that KT127 has a manageable safety profile and shows preliminary biological activity in patients with advanced ovarian cancer, particularly those who have failed multiple lines of therapies.
{"title":"T-cell receptor–like chimeric antigen receptor T cells targeting mesothelin: A first-in-human dose-escalation trial for platinum-resistant advanced ovarian cancer","authors":"Yiyang Shan MD, Bo Ding MD, Feng Ji PhD, Hao Lin PhD, Weiwei Shi PhD, Enxiu Wang PhD, Chen Wang PhD, Yang Shen PhD","doi":"10.1002/cncr.70279","DOIUrl":"10.1002/cncr.70279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ovarian cancer remains a formidable therapeutic challenge due to late diagnosis, high recurrence rates, and limited treatment options. Mesothelin (MSLN) is highly expressed in ovarian cancer, making it a promising target for immunotherapy. Given this target profile, the authors developed a novel T-cell receptor (TCR)-like chimeric antigen receptor (CAR) T-cell therapy targeting MSLN, designated KT127.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A first-in-human, dose-escalation trial of KT127 was conducted following preclinical evaluation in vitro and in vivo. A combination of rapid titration and a standard “3 + 3” dose-escalation design was implemented. Eleven patients received KT127 at doses ranging from 1 × 10<sup>6</sup> to 2 × 10<sup>7</sup> cells/kg following lymphodepletion. The primary objectives were to assess the safety and tolerability of KT127. Secondary objectives included overall survival, disease control rate (DCR), and progression-free survival as efficacy measures. Quality of life (QOL) was assessed using the European Organisation for Research and Treatment of Cancer QLQ-OV28 questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No dose-limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome were observed. The DCR was 80% (95% confidence interval, 44.4%–97.5%). QOL assessments indicated improvement in abdominal/gastrointestinal symptoms post-treatment (<i>p</i> = .037), with no significant deterioration in other domains. Proteomic analysis identified differential expression of kallikrein-related peptidases (KLK13, KLK14) and chemokine CXCL17 at baseline, potentially linked to treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights that KT127 has a manageable safety profile and shows preliminary biological activity in patients with advanced ovarian cancer, particularly those who have failed multiple lines of therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040079","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}
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