JNCI Cancer Spectrum最新文献

{"title":"Antibiotic treatment and survival in patients with resected, early-stage pancreatic ductal adenocarcinoma receiving chemotherapy.","authors":"Emma Gong, Daniel J Fulop, Joyce Serebrenik, Arielle J Labiner, Deirdre J Cohen, Keith M Sigel, Aimee L Lucas","doi":"10.1093/jncics/pkaf024","DOIUrl":"https://doi.org/10.1093/jncics/pkaf024","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging malignancy, largely due to chemoresistance. Bacteria within the PDAC microbiome may mediate chemoresistance, suggesting that alteration of the microbiome with antibiotics could improve chemotherapy response.</p><p><strong>Methods: </strong>We utilized the SEER-Medicare database to select patients with resected, early-stage PDAC diagnosed between 2007 and 2017. The primary outcome of this study was overall survival (OS). Receipt of antibiotic treatment within one month after adjuvant chemotherapy initiation was determined from Medicare claims data. Propensity scores (PSs) were used to match patients who received antibiotics with patients who did not receive antibiotics. The Kaplan-Meier method was used to calculate 5-year OS rates, and cox regression analysis was used to assess association between receiving antibiotics and OS. All hypotheses were 2-sided.</p><p><strong>Results: </strong>Of the 712 patients with resected, early-stage PDAC, 629 (88.3%) were treated with adjuvant gemcitabine and 177 (24.9%) received antibiotics in the one month following chemotherapy initiation. The mean (SD) age at diagnosis was 73.7 (5.1) years and patients were mostly women, White, and from metropolitan areas in the northeastern or western US. A total of 143 PS-matched pairs were evaluated. Among patients treated with gemcitabine, antibiotic treatment was associated with a 37% improvement in OS and a 30% improvement in cancer-specific survival.</p><p><strong>Conclusions: </strong>Antibiotic treatment in the one month following adjuvant gemcitabine initiation was associated with improved survival. These findings provide additional support for the hypothesis that antibiotic treatment may alter the pancreatic microbiome in a manner that reduces chemoresistance, potentially improving PDAC outcomes.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do trial benefits predict real-world gains in metastatic castration resistant prostate cancer.","authors":"Sarah Axeen, Alice J Chen, Darius N Lakdawalla, Neal Masia, Alexander Niyazov, Bhakti Arondekar, Stephen J Freedland","doi":"10.1093/jncics/pkaf018","DOIUrl":"https://doi.org/10.1093/jncics/pkaf018","url":null,"abstract":"<p><strong>Background: </strong>It is important to understand the relationship between drug efficacy measured in randomized clinical trials (RCTs) and real-world drug effectiveness. We estimate how RCT overall survival (OS) and RCT radiographic progression-free survival (rPFS) benefits predict the association between treatments and real-world OS gains for metastatic castration-resistant prostate cancer (mCRPC) drugs.</p><p><strong>Methods: </strong>Using the National Cancer Institute list of approved cancer drugs and the National Comprehensive Cancer Network Treatment Guidelines, we identified all pharmaceutical therapies for mCRPC approved between 2010 to 2019. We obtained RCT OS and rPFS hazard ratios from the pivotal trials used for Food and Drug Administration (FDA) approval, and we estimated real-world OS hazard ratios using the Optum Clinformatics Extended DataMart Databases. We modeled real-world OS hazard ratios as a function of both RCT OS and RCT rPFS hazard ratios using Cox proportional hazard regressions, adjusted for year of diagnosis, age, race, and Elixhauser Comorbidity Index.</p><p><strong>Results: </strong>When we did not account for non-random real-world selection of patients into receiving a newly approved therapy (ie, \"treatment selection bias\"), real-world OS gains were 15% lower than associated RCT OS and RCT rPFS benefits. However, after accounting for treatment selection bias in real-world settings, real-world OS gains were almost 28% greater than RCT OS and RCT rPFS benefits. Association between treatment and OS gains increased the longer a new therapy was on the market.</p><p><strong>Conclusions: </strong>After adjusting for treatment selection bias, RCT OS and RCT rPFS estimates serve as useful, or even conservative, predictors of RW OS gains.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of large language models to enhance cancer clinical trial educational materials.","authors":"Mingye Gao, Aman Varshney, Shan Chen, Vikram Goddla, Jack Gallifant, Patrick Doyle, Claire Novack, Maeve Dillon-Martin, Teresia Perkins, Xinrong Correia, Erik Duhaime, Howard Isenstein, Elad Sharon, Lisa Soleymani Lehmann, David Kozono, Brian Anthony, Dmitriy Dligach, Danielle S Bitterman","doi":"10.1093/jncics/pkaf021","DOIUrl":"https://doi.org/10.1093/jncics/pkaf021","url":null,"abstract":"<p><strong>Background: </strong>Adequate patient awareness and understanding of cancer clinical trials is essential for trial recruitment, informed decision-making, and protocol adherence. While Large Language Models (LLMs) have shown promise for patient education, their role in enhancing patient awareness of clinical trials remains unexplored. This study explored the performance and risks of LLMs in generating trial-specific educational content for potential participants.</p><p><strong>Methods: </strong>GPT4 was prompted to generate short clinical trial summaries and multiple-choice question-answer pairs from informed consent forms (ICFs) from ClinicalTrials.gov. Zero-shot learning was used for summaries, using a direct summarization, sequential extraction, and summarization approach. One-shot learning was used for question-answer pairs development. We evaluated performance through patient surveys of summary effectiveness and crowdsourced annotation of question-answer pair accuracy, using held-out cancer trial ICFs not used in prompt development.</p><p><strong>Results: </strong>For summaries, both prompting approaches achieved comparable results for readability and core content. Patients found summaries to be understandable, and to improve clinical trial comprehension and interest in learning more about trials. The generated multiple-choice questions achieved high accuracy and agreement with crowdsourced annotators. For both summaries and multiple-choice questions, GPT4 was most likely to include inaccurate information when prompted to provide information that was not adequately described in the ICFs.</p><p><strong>Conclusions: </strong>LLMs such as GPT4 show promise in generating patient-friendly educational content for clinical trials with minimal trial-specific engineering. The findings serve as a proof-of-concept for the role of LLMs in improving patient education and engagement in clinical trials, as well as the need for ongoing human oversight.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional outcomes after primary versus delayed robot-assisted radical prostatectomy following active surveillance.","authors":"Christian Corsini, Pietro Scilipoti, Andri Wilberg Orrason, Rolf Gedeborg, Marcus Westerberg, Pär Stattin","doi":"10.1093/jncics/pkaf020","DOIUrl":"https://doi.org/10.1093/jncics/pkaf020","url":null,"abstract":"<p><strong>Background: </strong>It is unknown if a period of active surveillance before prostatectomy for prostate cancer (PCa) worsens functional outcomes. The aim of this study was to compare functional outcomes after primary vs delayed robot-assisted radical prostatectomy.</p><p><strong>Methods: </strong>We included men registered in the National Prostate Cancer Register of Sweden with low and favorable intermediate-risk PCa who underwent robot-assisted prostatectomy in 2018-2020 and had filled a questionnaire on patient-reported outcome measures. Multivariable logistic regression analysis was used to compare the functional outcomes of primary and delayed prostatectomy.</p><p><strong>Results: </strong>2571 men underwent primary, and 921 men underwent delayed prostatectomy. Delayed prostatectomy was not associated with reduced overall quality of life [adjusted Odds Ratio (OR) 1.04; 95% confidence interval (CI) 0.71-1.55] or erectile dysfunction (adjusted OR 0.90, 95% CI 0.69-1.22). Urinary incontinence was slightly more common after delayed prostatectomy (15% vs 11%; adjusted OR 1.38, 95% CI 0.91-2.01). There were weak associations between time to prostatectomy and urinary symptoms and bother, with a 3% annual increase in the risk for urinary incontinence (adjusted OR 1.03; 95% CI 0.94 - 1.13).</p><p><strong>Conclusion: </strong>These results suggest that a period on active surveillance before robot-assisted radical prostatectomy has little detrimental effect on functional outcomes. Since only around half of men on active surveillance will transit to prostatectomy, these outcomes represent a worst-case scenario for men who start active surveillance. These results support the use of active surveillance for men with low-risk and favourable intermediate-risk PCa.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol consumption, polygenic risk score and the risk of colorectal neoplasia.","authors":"Ruojin Fu, Xuechen Chen, Teresa Seum, Michael Hoffmeister, Hermann Brenner","doi":"10.1093/jncics/pkaf017","DOIUrl":"https://doi.org/10.1093/jncics/pkaf017","url":null,"abstract":"<p><strong>Introduction: </strong>Excess alcohol consumption is associated with increased risk of colorectal cancer (CRC), but the evidence on the individual and joint effects of alcohol consumption and genetic risk on the occurrence of various stages of colorectal carcinogenesis is limited.</p><p><strong>Methods: </strong>We evaluated the associations of alcohol consumption and a polygenic risk score (PRS) based on 140 CRC-related loci with findings of colorectal neoplasia among 4,662 participants in the German screening colonoscopy program. Analyses were conducted by multiple logistic regression. We determined genetic risk equivalents (GREs) to quantify the effect of alcohol consumption in terms of the difference in PRS conveying equivalent risk.</p><p><strong>Results: </strong>Moderate and high (12-<25 and ≥25 g/day) alcohol consumption was associated with increased risk of advanced colorectal neoplasia (aOR [95% CI]: 1.28 [1.03-1.58] and 1.44 [1.14-1.81], respectively), while associations with any colorectal neoplasia were weaker. No significant interactions between alcohol consumption and PRS were observed. Participants with high alcohol consumption in the highest PRS tertile had a 3.4-fold increased risk of advanced neoplasia compared to those with low or no alcohol consumption in the lowest PRS tertile. The estimated impact of high alcohol consumption on the risk of advanced neoplasia was equivalent to the risk increase by a 26 percentiles higher PRS (GRE 26, 95% CI 9-44).</p><p><strong>Conclusion: </strong>High alcohol consumption and PRS both have a major impact on the risk of advanced colorectal neoplasia. The estimated preventive impact of avoiding high alcohol consumption is as strong as the impact of having a substantially lower polygenic risk.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel machine learning-based cancer-specific CVD risk score among patients with breast, colorectal, or lung cancer.","authors":"Nickolas Stabellini, Omar M Makram, Harikrishnan Hyma Kunhiraman, Hisham Daoud, John Shanahan, Alberto J Montero, Roger S Blumenthal, Charu Aggarwal, Umang Swami, Salim S Virani, Vanita Noronha, Neeraj Agarwal, Susan Dent, Avirup Guha","doi":"10.1093/jncics/pkaf016","DOIUrl":"https://doi.org/10.1093/jncics/pkaf016","url":null,"abstract":"<p><strong>Background: </strong>Cancer patients have up to a 3-fold higher risk for cardiovascular disease (CVD) than the general population. Traditional CVD risk scores may be less accurate for them. We aimed to develop cancer-specific CVD risk scores and compare them with conventional scores in predicting 10-year CVD risk for patients with breast cancer (BC), colorectal cancer (CRC), or lung cancer (LC).</p><p><strong>Methods: </strong>We analyzed adults diagnosed with BC, CRC, or LC between 2005-2012. An ML Extreme Gradient Boosting (XGBoost) algorithm ranked 40-50 covariates for predicting CVD for each cancer type using SHapley Additive exPlanations (SHAP) values. The top 10 ML-predictors were used to create predictive equations using logistic regression and compared to ACC/AHA Pooled Cohort Equations (PCE), Predicting Risk of cardiovascular disease EVENTs (PREVENT), and Systematic COronary Risk Evaluation-2 (SCORE2) using the area under the curve (AUC).</p><p><strong>Results: </strong>We included 10,339 patients: 55.5% had BC, 15.6% had CRC, and 29.7% had LC. The actual 10-year CVD rates were: BC 21%, CRC 10%, and LC 28%. The predictors derived from the ML algorithm included cancer-specific and socioeconomic factors. The cancer-specific predictive scores achieved AUCs of 0.84, 0.76, and 0.83 for BC, CRC, and LC, respectively, and outperformed PCE, PREVENT and SCORE2, increasing the absolute AUC values by up to 0.31 points (with AUC ranging from 0 to 1). Similar results were found when excluding patients with cardiac history or advanced cancer from the analysis.</p><p><strong>Conclusion(s): </strong>Cancer-specific CVD predictive scores outperform conventional scores and emphasize the importance of integrating cancer-related covariates for precise prediction.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for comprehensive social needs in patients with cancer: a narrative review.","authors":"Isabel Arana, Raymond Liu, Lawrence Kushi, Erin Hahn, Meera Ragavan","doi":"10.1093/jncics/pkaf012","DOIUrl":"https://doi.org/10.1093/jncics/pkaf012","url":null,"abstract":"<p><strong>Background: </strong>Patients with cancer who report social needs have worse quality of life, lower healthcare access, and suboptimal health outcomes. However, screening for social needs does not happen systematically and successful screening tools, strategies, and workflows have seldom been described. The downstream effects of screening including resource navigation have also not been well characterized. This objective of this narrative review was to fill these gaps.</p><p><strong>Methods: </strong>Two investigators searched Pubmed and Embase for studies that implemented a patient-facing social screening tool among patients with cancer between 2008-2023 using search terms including \"social screening,\" \"social needs,\" and \"cancer.\"</p><p><strong>Results: </strong>We identified 19 articles that met study inclusion criteria. The most common tool used was the validated Health Leads Social Toolkit. Most often, screening tools were administered electronically, sent directly to patients, and captured needs at a single time point during a patient's diagnosis. Screening response rates ranged between 10-60%. Less than half of the studies described downstream resource navigation for patients who screened positive for social needs Only one study evaluated the impact of screening on clinical outcomes and quality of life. Screening for patients who do not speak English or who belong to historically racial, ethnic, and gender minority groups was limited.</p><p><strong>Conclusions: </strong>Screening for social needs has been shown to be feasible across delivery systems with numerous validated tools available. However, gaps remain in generalizability to diverse patient populations. Future work must identify how screening workflows can be successfully incorporated into routine clinical workflows.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration of aromatase inhibitor use and long-term cardiovascular risk in breast cancer survivors.","authors":"Yuhan Huang, Marilyn L Kwan, Susan R Heckbert, Nicholas L Smith, Megan Othus, Cecile A Laurent, Janise M Roh, Eileen Rillamas-Sun, Valerie S Lee, Tatjana Kolevska, Richard K Cheng, Carlos Irribarren, Mai Nguyen-Huynh, Dawn L Hershman, Lawrence H Kushi, Heather Greenlee","doi":"10.1093/jncics/pkaf009","DOIUrl":"10.1093/jncics/pkaf009","url":null,"abstract":"<p><strong>Background: </strong>There are limited data on duration of aromatase inhibitor (AI) and cardiovascular disease (CVD) risk in breast cancer (BC) survivors. We examined risk of CVD and mortality associated with duration of AI use in postmenopausal women with early-stage hormone receptor-positive BC.</p><p><strong>Methods: </strong>Postmenopausal women diagnosed with hormone receptor-positive BC (n = 5,853) who used an AI were included. Cause-specific hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between AI use duration (short-term: >0 and <2 years; intermediate-term: ≥2 and <5 years; long-term: ≥5 years) and CVD and mortality outcomes. The landmark method was used to avoid immortal time bias; the selected landmark was 6 years after BC diagnosis.</p><p><strong>Results: </strong>Anastrozole was the AI predominantly prescribed (95.4%). Over a median follow-up of 3 years for women who survived 6 years after BC diagnosis, a lower risk of stroke was observed in intermediate-term AI users (HR = 0.60, 95% CI: 0.37-0.96) and long-term AI users (HR = 0.51, 95% CI: 0.30-0.85), than in short-term AI users. The longer duration of AI use was also associated with lower risk of all-cause mortality and non-CVD-related mortality. In addition, long-term AI users were at 37% lower risk of CVD-related mortality than short-term AI users. No significant differences were observed in risks of major adverse cardiovascular events, ischemic heart disease, and heart failure across the three groups.</p><p><strong>Conclusion: </strong>Among postmenopausal women with early-stage hormone receptor-positive BC who survived to 6 years after BC diagnosis, longer duration of AI use was not associated with elevated CVD risk.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer risk in carriers of TP53 germline variants grouped into different functional categories.","authors":"Lucas John Müntnich, Christina M Dutzmann, Anika Großhennig, Valentina Härter, Myriam Keymling, Angela Mastronuzzi, Emilie Montellier, Juliane Nees, Natalie E Palmaers, Judith Penkert, Stefan M Pfister, Tim Ripperger, Sarah Schott, Farina Silchmüller, Pierre Hainaut, Christian P Kratz","doi":"10.1093/jncics/pkaf008","DOIUrl":"https://doi.org/10.1093/jncics/pkaf008","url":null,"abstract":"<p><p>Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups. Partially-functional and cluster B or C variants were enriched in patients not meeting clinical testing criteria. Time to first malignancy was longer in carriers of partially-functional variants (Hazard Ratio [HR] = 0.38; 95% CI, 0.22 to 0.66). Variants grouped within clusters B (HR = 0.45; 95% CI, 0.28 to 0.71) or C (HR = 0.34; 95% CI, 0.19 to 0.62) were associated with later cancer onset than NULL variants. These findings can be used to risk-stratify patients and inform care.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor localization strategies of multi-cancer early detection tests: a quantitative assessment.","authors":"Christopher Tyson, Kevin H Li, Xiting Cao, James M O'Brien, Elliot K Fishman, Elizabeth K O'Donnell, Carlos Duran, Vijay Parthasarathy, Seema P Rego, Omair A Choudhry, Tomasz M Beer","doi":"10.1093/jncics/pkaf011","DOIUrl":"https://doi.org/10.1093/jncics/pkaf011","url":null,"abstract":"<p><strong>Background: </strong>Multi-cancer early detection (MCED) tests may expand cancer screening. Characterizing diagnostic resolution approaches following positive MCED tests is critical. Two trials employed distinct resolution approaches: a molecular signal to predict tissue of origin (TOO) and an imaging-based diagnostic strategy. This modeling study characterizes diagnostic journeys and impact in a hypothetical population of average risk MCED eligible patients.</p><p><strong>Methods: </strong>A mathematical expression for diagnostic burden was derived using positive predictive value (PPV), molecular TOO localization accuracy, and numbers of procedures associated with each diagnostic outcome. Imaging-based and molecular TOO-informed strategies were compared. Excess lifetime cancer risk due to futile radiation exposure was estimated using organ-specific diagnostic imaging radiation doses.</p><p><strong>Results: </strong>Across all PPVs and localization performances, a molecular TOO strategy resulted in a higher diagnostic burden: 3.6 procedures [SD 0.445] vs 2.6 procedures [SD 0.100] for the imaging strategy. Estimated diagnostic burden was higher for molecular TOO in 95.5% of all PPV and TOO accuracy combinations; ≥79% PPV and 90% accuracy would be required for a molecular TOO-informed strategy to be less burdensome than imaging. The maximum rate of excess cancer incidence from radiation exposure for MCED false positive results (individuals aged 50-84) was 64.6/100,000 (annual testing, 99% specificity), 48.5/100,000 (biennial testing, 98.5% specificity), and 64.6/100,000 (biennial testing, 98% specificity).</p><p><strong>Conclusions: </strong>An imaging-based diagnostic strategy is more efficient than a molecular TOO-informed approach across almost all PPV and TOO accuracy combinations. The use of an imaging-based approach for cancer localization can be efficient and low-risk compared to a molecular-informed approach.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}