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Avram MF, Lupa N, Koukoulas D, Lazăr DC, Mariș MI, Murariu MS, Olariu S. Random forests algorithm using basic medical data for predicting the presence of colonic polyps. Front Surg 2025; 12:1523684. [PMID: 40099225 PMCID: PMC11911476 DOI: 10.3389/fsurg.2025.1523684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Background Colorectal cancer is considered to be triggered by the malignant transformation of colorectal polyps. Early diagnosis and excision of colorectal polyps has been found to lower the mortality and morbidity associated with colorectal cancer. Objective The aim of this study is to offer a predictive model for the presence of colorectal polyps based on Random Forests machine learning algorithm, using basic patient information and common laboratory test results. Materials and methods 164 patients were included in the study. The following data was collected: sex, residence, age, diabetes mellitus, body mass index, fasting blood glucose levels, hemoglobin, platelets, total, LDL and HLD cholesterol, triglycerides, serum glutamic-oxaloacetic transaminase, chronic gastritis, presence of colonic polyps at colonoscopy. 80% of patients were included in the training set for creating a Random forests algorithm, 20% were in the test set. External validation was performed on data from 42 patients. The performance of the Random Forests was compared with the performance of a generalized linear model (GLM) and support vector machine (SVM) built and tested on the same datasets. Results The Random Forest prediction model gave an AUC of 0.820 on the test set. The top five variables in order of importance were: body mass index, platelets, hemoglobin, triglycerides, glutamic-oxaloacetic transaminase. For external validation, the AUC was 0.79. GLM performance in internal validation was an AUC of 0.788, while for external validation AUC-0.65. For SVN, the AUC - 0.785 for internal validation and 0.685 for the external validation dataset. Conclusions A random forest prediction model was developed using patient's demographic data, medical history and common blood tests results. This algorithm can foresee, with good predictive power, the presence of colonic polyps.
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Affiliation(s)
- Mihaela-Flavia Avram
- Department of Surgery X, 1st Surgery Discipline, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Timisoara, Romania
- Abdominal Surgery and Phlebology Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Nicolae Lupa
- Department of Mathematics, "Politehnica" University of Timişoara, Timisoara, Romania
| | - Dimitrios Koukoulas
- Department of Gastroenterology, Municipal Hospital "Dr. Teodor Andrei", Lugoj, Romania
| | - Daniela-Cornelia Lazăr
- Department V of Internal Medicine I, Discipline of Internal Medicine IV, "Victor Babeș" University of Medicine and Pharmacy, Timisoara, Romania
| | - Mihaela-Ioana Mariș
- Department of Functional Sciences, Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
- Center for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Marius-Sorin Murariu
- Department of Surgery X, 1st Surgery Discipline, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Timisoara, Romania
- Abdominal Surgery and Phlebology Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Sorin Olariu
- Department of Surgery X, 1st Surgery Discipline, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Timisoara, Romania
- Abdominal Surgery and Phlebology Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
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Sergeev D, Heisser T, Hoffmeister M, Brenner H. Potential for enhancing efficacy of screening colonoscopy by lowering starting ages and extending screening intervals: A modelling study for Germany. Int J Cancer 2025. [PMID: 39751766 DOI: 10.1002/ijc.35322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/05/2024] [Accepted: 12/16/2024] [Indexed: 01/04/2025]
Abstract
Studies aimed to evaluate the expected impact of alternative screening strategies are essential for optimizing colorectal cancer (CRC) screening offers, but such studies are lacking in Germany, where two screening colonoscopies (CS) 10 years apart are offered for men from age 50 and women from age 55. Our aim was to explore whether and to what extent the efficacy of utilizing two CS could be enhanced by alternative starting ages and screening intervals. We modeled the expected numbers of CRC cases, CRC deaths, years of potential life lost (YPLL), and disability-adjusted life years (DALYs) due to CRC in hypothetical cohorts of 100,000 men and women aged 45-85 using COSIMO, a validated Markov-based multi-state simulation model. Modeled strategies included combinations of starting ages (45/50/55/60) and CS (10/15/20 years). For men, CRC deaths could be slightly reduced by extending the interval to 15 years, with a second CS at 65. YPLL and DALYs would be reduced by decreasing starting age to 45 when combined with a 15-year screening interval. For women, use of two CS at ages 50 and 65 would reduce all CRC burden parameters compared to the current earliest-use offer at 55 and 65 years. Our results suggest that lowering the starting age of screening colonoscopy to 45 for men and 50 for women, combined with extending the CS screening interval to 15 years would have the potential to enable significant reductions in years of potential life lost, and disability-adjusted life years compared to current screening offers in Germany.
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Affiliation(s)
- Dmitry Sergeev
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Heisser T, Sergeev D, Hoffmeister M, Brenner H. Contributions of early detection and cancer prevention to colorectal cancer mortality reduction by screening colonoscopy: a validated modeling study. Gastrointest Endosc 2024; 100:710-717.e9. [PMID: 38462054 DOI: 10.1016/j.gie.2024.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/17/2024] [Accepted: 03/04/2024] [Indexed: 03/12/2024]
Abstract
BACKGROUND AND AIMS Screening colonoscopy, recommended every 10 years, reduces mortality from colorectal cancer (CRC) by early detection of prevalent but undiagnosed CRC, as well as by removal of precursor lesions. The aim of this study was to assess the relative contribution of both components to total CRC mortality reduction over time. METHODS Using a validated multistate Markov model, we simulated hypothetical cohorts of 100,000 individuals aged 55 to 64 years with and without screening at baseline. Main outcomes included proportions of prevented CRC deaths arising from (asymptomatic) CRC already present at baseline and from newly developed CRC during 15 years of follow-up, and mortality rate ratios of screened versus nonscreened groups over time. RESULTS Early detection of prevalent cases accounted for 52%, 30%, and 18% of deaths prevented by screening colonoscopy within 5, 10, and 15 years, respectively. Relative reduction of mortality was estimated to be much larger for mortality from incident cancers than for mortality from cancers that were already present and detected early at screening endoscopy and for total CRC mortality (ie, 88% versus 67% and 79%, respectively, within 10 years from screening). CONCLUSIONS Reduction of CRC mortality mainly arises from early detection of prevalent cancers during the early years after screening colonoscopy, but prevention of incident cases accounts for the majority of prevented deaths in the longer run. Prevention of incident cases leads to sustained strong reduction of CRC mortality, possibly warranting an extension of screening intervals.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Dmitry Sergeev
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany
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Fu M, Sheng B, Liu R, Li Y, Chen G, Chen H, Chen X, Duan G, Huang H, Chen J, Chen Y. Impact of different doses of esketamine on the incidence of hypotension in propofol-based sedation for colonoscopy: a randomized controlled trial. Ther Adv Drug Saf 2024; 15:20420986241278499. [PMID: 39314988 PMCID: PMC11418320 DOI: 10.1177/20420986241278499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 08/08/2024] [Indexed: 09/25/2024] Open
Abstract
Background Hypovolemia is common in colonoscopy due to fasting and bowel preparation, and propofol itself can reduce systemic vascular resistance, resulting in relative hypovolemia. Therefore, hypotension is not a rare event during propofol-based sedation for colonoscopy. Objectives Our objective was to explore the efficacy of esketamine as a sedative adjuvant in reducing the incidence of hypotension during colonoscopy. Design This was a prospective randomized trial. The trial was registered with the Chinese Clinical Trial Registry (ID: ChiCTR 2100047032). Methods We included 100 eligible patients who planned to receive a colonoscopy and randomly divided them into 4 groups with 25 patients in each group, which were propofol 2 mg/kg (Group P), propofol 1 mg/kg with esketamine 0.2 mg/kg (Group E1), propofol 1 mg/kg with esketamine 0.3 mg/kg (Group E2), and propofol 1 mg/kg with esketamine 0.4 mg/kg (Group E3). The hemodynamic and respiratory parameters were documented at various times during the procedure, including the patient's entry into the endoscopic room (T0), the induction of sedation (T1), the insertion of the colonoscope (T2), the removal of the colonoscope (T3), and the awakening of the patient (T4). The primary outcome was the incidence of hypotension. Secondary outcomes were cardiovascular side effects other than hypotension, incidence of hypoxia, cumulative changes in cardiovascular and respiratory parameters, total propofol dosage, anesthesia recovery time, and satisfactory levels of both patients and endoscopists. Results The incidence of hypotension in Group E1 (16%), Group E2 (16%), and Group E3 (12%) was significantly lower than in Group P (60%), with p values 0.003, 0.003, and <0.001 respectively. The cumulative changes in diastolic blood pressure and mean arterial pressure in Groups E1, E2, and E3 were significantly higher than in Group P (p = 0.024, p < 0.001, p = 0.006, respectively). Cumulative changes in systolic blood pressure in Group E3 were significantly higher than those in Group P (p = 0.012). The respiratory-related parameters were not statistically significant. Conclusions This study showed that the application of 0.4 mg/kg esketamine in propofol-based sedation reduced the incidence of hypotension during colonoscopy while providing satisfactory sedation.
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Affiliation(s)
- Mengyue Fu
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Bo Sheng
- Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Rui Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yongjie Li
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Guizhen Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hai Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xuehan Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Guangyou Duan
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - He Huang
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
| | - Yuanjing Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
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Brenner H, Heisser T, Cardoso R, Hoffmeister M. Reduction in colorectal cancer incidence by screening endoscopy. Nat Rev Gastroenterol Hepatol 2024; 21:125-133. [PMID: 37794234 DOI: 10.1038/s41575-023-00847-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2023] [Indexed: 10/06/2023]
Abstract
Colorectal cancer (CRC) incidence rates decreased by up to 50% in older age groups in the USA in the era of the widespread uptake of screening colonoscopy, despite adverse trends in CRC risk factors and increasing CRC incidence at younger ages. However, reported first results from a randomized trial, the NordICC study, suggested rather modest effects of screening colonoscopy. As outlined in this Perspective, the apparent discrepancy between real-world and trial evidence could be explained by strong attenuation of effect estimates from screening endoscopy trials by several factors, including limited screening adherence, widespread uptake of colonoscopy outside the screening offers and the inclusion of prevalent, non-preventable CRC cases in reported numbers of incident cases. Alternative interpretations of screening endoscopy trial results accounting for prevalence bias are in line with trends in CRC incidence reduction in countries offering CRC screening, and should encourage more widespread implementation and uptake of effective CRC screening.
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Affiliation(s)
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumour Diseases (NCT), Heidelberg, Germany.
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rafael Cardoso
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Sroczynski G, Hallsson LR, Mühlberger N, Jahn B, Rehms R, Hoffmann S, Crispin A, Lindoerfer D, Mansmann U, Siebert U. Long-term benefits and harms of early colorectal cancer screening in German individuals with familial cancer risk. Int J Cancer 2024; 154:516-529. [PMID: 37795630 DOI: 10.1002/ijc.34747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 08/04/2023] [Accepted: 08/21/2023] [Indexed: 10/06/2023]
Abstract
Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit-harm trade-offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10-yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov-state-transition model was developed and used to estimate health benefits (CRC-related deaths avoided, life-years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm-benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32-36 CRC-related deaths per 1000 persons were avoided with colonoscopy and 29-34 with iFOBT screening, compared to 29-31 (colonoscopy) and 28-30 (iFOBT) CRC-related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45-65 vs no screening), four (biennial, age 35-65), six (biennial, age 30-70) and 34 (annual, age 30-54; biennial, age 55-75). Corresponding IHBRs for 10-yearly colonoscopy were four (age 55-65), 10 (age 45-65), 15 (age 35-65) and 29 (age 30-70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group.
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Affiliation(s)
- Gaby Sroczynski
- Department of Public Health, Health Services Research, and Health Technology Assessment, UMIT TIROL-University for Health Sciences and Technology, Hall in Tirol, Austria
| | - Lára R Hallsson
- Department of Public Health, Health Services Research, and Health Technology Assessment, UMIT TIROL-University for Health Sciences and Technology, Hall in Tirol, Austria
| | - Nikolai Mühlberger
- Department of Public Health, Health Services Research, and Health Technology Assessment, UMIT TIROL-University for Health Sciences and Technology, Hall in Tirol, Austria
| | - Beate Jahn
- Department of Public Health, Health Services Research, and Health Technology Assessment, UMIT TIROL-University for Health Sciences and Technology, Hall in Tirol, Austria
- Division of Health Technology Assessment, ONCOTYROL-Center for Personalized Cancer Medicine, Innsbruck, Austria
| | - Raphael Rehms
- Department of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany
| | - Sabine Hoffmann
- Department of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany
| | - Alexander Crispin
- Department of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany
| | - Doris Lindoerfer
- Department of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany
- Chronobiology and Health, Department of Sport and Health Sciences, Technical University of Munich, Munich, Germany
| | - Ulrich Mansmann
- Department of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany
| | - Uwe Siebert
- Department of Public Health, Health Services Research, and Health Technology Assessment, UMIT TIROL-University for Health Sciences and Technology, Hall in Tirol, Austria
- Division of Health Technology Assessment, ONCOTYROL-Center for Personalized Cancer Medicine, Innsbruck, Austria
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Health Policy & Management, Center for Health Decision Science, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Radiology, Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Zheng S, Schrijvers JJA, Greuter MJW, Kats-Ugurlu G, Lu W, de Bock GH. Effectiveness of Colorectal Cancer (CRC) Screening on All-Cause and CRC-Specific Mortality Reduction: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:cancers15071948. [PMID: 37046609 PMCID: PMC10093633 DOI: 10.3390/cancers15071948] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/14/2023] [Accepted: 03/22/2023] [Indexed: 04/14/2023] Open
Abstract
(1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62-1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.
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Affiliation(s)
- Senshuang Zheng
- Medical Center Groningen, Department of Epidemiology, University of Groningen, 9700 RB Groningen, The Netherlands
| | - Jelle J A Schrijvers
- Medical Center Groningen, Department of Epidemiology, University of Groningen, 9700 RB Groningen, The Netherlands
| | - Marcel J W Greuter
- Medical Center Groningen, Department of Radiology, University of Groningen, 9700 RB Groningen, The Netherlands
- Robotics and Mechatronics (RaM) Group, Technical Medical Centre, Faculty of Electrical Engineering Mathematics and Computer Science, University of Twente, 7522 NH Enschede, The Netherlands
| | - Gürsah Kats-Ugurlu
- Medical Center Groningen, Department of Pathology, University of Groningen, 9700 RB Groningen, The Netherlands
| | - Wenli Lu
- Department of Epidemiology and Health Statistics, Tianjin Medical University, Tianjin 300070, China
| | - Geertruida H de Bock
- Medical Center Groningen, Department of Epidemiology, University of Groningen, 9700 RB Groningen, The Netherlands
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Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppälä TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kühn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Møller P, Monahan KJ, Möslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YQN, Yurgelun MB, Zuppardo RA, Stoffel EM. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol 2023; 21:581-603.e33. [PMID: 36549470 PMCID: PMC11207185 DOI: 10.1016/j.cgh.2022.12.006] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/01/2022] [Accepted: 12/01/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
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Affiliation(s)
- Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesc Balaguer
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Heather Hampel
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California
| | - Sonia S Kupfer
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, Illinois
| | - Alessandro Repici
- Gastrointestinal Endoscopy Unit, Humanitas University, Humanitas Research Hospital, Rozzano, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Toni T Seppälä
- Faculty of Medicine and Medical Technology, University of Tampere and TAYS Cancer Centre, Arvo Ylpön katu, Tampere, Finland; Unit of Gastroenterological Surgery, Tampere University Hospital, Elämänaukio, Tampere, Finland; Applied Tumor Genomics Research Program and Department of Surgery, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Vincenzo Valentini
- Department of Radiology, Radiation Oncology and Hematology, Università Cattolica del Sacro Cuore di Roma, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
| | - Clement Richard Boland
- Department of Medicine, Division of Gastroenterology, University of California San Diego, San Diego, California
| | - Randall E Brand
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Tineke E Buffart
- Department of Medical Oncology. Amsterdam UMC, Location de Boelelaan, Amsterdam, The Netherlands
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Renato Cannizzaro
- SOC Gastroenterologia Oncologica e Sperimentale Centro di Riferimento Oncologico di Aviano (CRO) IRCCS 33081, Aviano, Italy
| | - Stefano Cascinu
- Oncology Department, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emma J Crosbie
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom; Division of Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Silvio Danese
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Maria Daca-Alvarez
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Francesco Deni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Mev Dominguez-Valentin
- Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
| | - Cathy Eng
- Department of Medicine, Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | - Ajay Goel
- Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, California
| | - Josè G Guillem
- Department of Surgery and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Britt B S L Houwen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Charles Kahi
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Matthew F Kalady
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Fay Kastrinos
- Division of Digestive and Liver Diseases, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center and the Vagelos College of Physicians and Surgeons, New York, New York
| | - Florian Kühn
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Luigi Laghi
- Department of Medicine and Surgery, University of Parma, Parma, and Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Andrew Latchford
- Lynch Syndrome Clinic, Centre for Familial Intestinal Cancer, St Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, United Kingdom
| | - David Liska
- Department of Colorectal Surgery and Edward J. DeBartolo Jr Family Center for Young-Onset Colorectal Cancer, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Patrick Lynch
- Department of Gastroenterology, M. D. Anderson Cancer Center, Houston, Texas
| | - Alberto Malesci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gianluca Mauri
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy
| | - Elisa Meldolesi
- Department of Radiology, Radiation Oncology and Hematology, Università Cattolica del Sacro Cuore di Roma, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
| | - Pål Møller
- Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
| | - Kevin J Monahan
- Lynch Syndrome Clinic, Centre for Familial Intestinal Cancer, St Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, United Kingdom; Faculty of Medicine, Department of Surgery & Cancer, Imperial College, London, United Kingdom
| | - Gabriela Möslein
- Surgical Center for Hereditary Tumors, Ev. BETHESDA Khs. Duisburg, Academic Hospital University of Düsseldorf, Düsseldorf, Germany
| | - Caitlin C Murphy
- School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas
| | - Karlijn Nass
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Kimmie Ng
- Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Cristina Oliani
- Medical Oncology, AULSS 5 Polesana, Santa Maria Della Misericordia Hospital, Rovigo, Italy
| | - Enrico Papaleo
- Centro Scienze della Natalità, Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Swati G Patel
- University of Colorado Anschutz Medical Center and Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Marta Puzzono
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Remo
- Pathology Unit, Mater Salutis Hospital, ULSS9, Legnago, Verona, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, Universita degli Studi di Bologna, Bologna, Italy
| | - Carla Ida Ripamonti
- Department of Onco-Haematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
| | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Satish K Singh
- Department of Medicine, Section of Gastroenterology, VA Boston Healthcare System and Boston University, Boston, Massachusetts
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter P Stanich
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sapna Syngal
- Brigham and Women's Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Stefano Turi
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuele Damiano Urso
- Chirurgia Generale 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University Hospital of Padova, Padova, Italy
| | - Laura Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Center (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Madrid, Spain
| | - Valeria Stella Vanni
- Centro Scienze della Natalità, Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Eduardo Vilar
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Yi-Qian Nancy You
- Department of Colon & Rectal Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew B Yurgelun
- Brigham and Women's Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Raffaella Alessia Zuppardo
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elena M Stoffel
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan
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9
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Heisser T, Cardoso R, Niedermaier T, Hoffmeister M, Brenner H. Making colonoscopy-based screening more efficient: A "gateopener" approach. Int J Cancer 2023; 152:952-961. [PMID: 36214791 DOI: 10.1002/ijc.34317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 09/07/2022] [Accepted: 09/22/2022] [Indexed: 01/06/2023]
Abstract
Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a "gateopener" for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single ("gateopener") FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such "gateopener screening" (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a "gateopener" low-threshold FIT would substantially enhance efficiency of colonoscopy screening.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Rafael Cardoso
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Tobias Niedermaier
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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10
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Hornschuch M, Schwarz S, Haug U. 10-year prevalence of diagnostic and screening colonoscopy use in Germany: a claims data analysis. Eur J Cancer Prev 2022; 31:497-504. [PMID: 34983895 PMCID: PMC9928559 DOI: 10.1097/cej.0000000000000736] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/29/2021] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Studies providing detailed information on colonoscopy use are important for the interpretation of patterns and trends in colorectal cancer incidence and mortality, but there is a lack of such studies from Germany. To fill this gap, we aimed to describe the 10-year prevalence of colonoscopy use based on German health claims data. METHODS Using the German Pharmacoepidemiological Research Database (short GePaRD; claims data from ~20% of the German population), we determined the 10-year prevalence of colonoscopy use for the year 2017. We determined this prevalence for any colonoscopy, screening (reimbursable from age 55) and diagnostic colonoscopy, stratified by sex, age, educational level and regional factors (e.g. federal state, physicians density in the district of residence). RESULTS In men, the 10-year prevalence of colonoscopy use was as follows (not all age groups reported): 30-34 years: 8%, 40-44 years: 12%, 50-54 years: 21%, 55-59 years: 33% (screening: 10%), 60-64 years: 44% (screening: 23%), 70-74 years: 53% (screening: 23%), 80-84 years: 52% (screening: 15%). In women, the prevalences were similar, with differences mostly less than or equal to 3 percentage points. Also, in analyses stratified by educational level or regional factors, prevalences were mostly similar or varied by less than or equal to 4 percentage points. CONCLUSION In 2017, about 45-50% of men and women in Germany aged 60-84 years had any colonoscopy in the previous 10 years, and about 11-26% had a screening colonoscopy. Our findings suggest no relevant social or regional disparities in the utilization of colonoscopy in Germany.
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Affiliation(s)
- Michel Hornschuch
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen
| | - Sarina Schwarz
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen
| | - Ulrike Haug
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen
- Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
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11
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Patel G, Patil P. Worrisome Trends in Young-Onset Colorectal Cancer: Now Is the Time for Action. Indian J Surg Oncol 2022; 13:446-452. [PMID: 36187542 PMCID: PMC9515296 DOI: 10.1007/s13193-022-01496-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/11/2022] [Indexed: 11/30/2022] Open
Abstract
Colorectal cancer (CRC) in the young adult population is of increasing incidence and concern. Since 1994, CRC incidence in individuals younger than 50 years has been increasing by 2% per year. The surge of CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Young-onset CRCs are characterized by more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left-colon sided location of the primary tumor. Genetic predisposition and heritable syndromes contribute to this trend, but perhaps more concerning is the majority of new diagnoses that involve no traceable genetic risk factors are sporadic. This review provides a summary of key aspects related to colorectal cancer in young adults, including epidemiology, etiology, genetics, clinical difficulties, early diagnosis, and prevention with emphasis on screening age.
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Affiliation(s)
- Gaurav Patel
- Department of Surgical Oncology, Bombay Hospital and Medical Research Centre, Marine lines, Mumbai, 400020 India
| | - Prakash Patil
- Department of Surgical Oncology, Bombay Hospital and Medical Research Centre, Marine lines, Mumbai, 400020 India
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12
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial. Lancet Gastroenterol Hepatol 2022; 7:513-521. [DOI: 10.1016/s2468-1253(21)00473-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 12/21/2022]
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13
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Dean J, Goldberg E, Michor F. Designing optimal allocations for cancer screening using queuing network models. PLoS Comput Biol 2022; 18:e1010179. [PMID: 35622852 PMCID: PMC9182689 DOI: 10.1371/journal.pcbi.1010179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 06/09/2022] [Accepted: 05/07/2022] [Indexed: 11/19/2022] Open
Abstract
Cancer is one of the leading causes of death, but mortality can be reduced by detecting tumors earlier so that treatment is initiated at a less aggressive stage. The tradeoff between costs associated with screening and its benefit makes the decision of whom to screen and when a challenge. To enable comparisons across screening strategies for any cancer type, we demonstrate a mathematical modeling platform based on the theory of queuing networks designed for quantifying the benefits of screening strategies. Our methodology can be used to design optimal screening protocols and to estimate their benefits for specific patient populations. Our method is amenable to exact analysis, thus circumventing the need for simulations, and is capable of exactly quantifying outcomes given variability in the age of diagnosis, rate of progression, and screening sensitivity and intervention outcomes. We demonstrate the power of this methodology by applying it to data from the Surveillance, Epidemiology and End Results (SEER) program. Our approach estimates the benefits that various novel screening programs would confer to different patient populations, thus enabling us to formulate an optimal screening allocation and quantify its potential effects for any cancer type and intervention. We describe a mathematical modeling methodology that offers quantitative insights into the potential benefits of screening and other interventions on cancer mortality. Our queuing-theoretic approach represents a potentially useful alternative to more traditional modeling approaches, in that it can provide more detailed results and entirely circumvents the need for simulations. Our methodology can be widely applied to estimate costs and benefits of screening strategies. By providing a detailed example of our method applied to epidemiological data, we hope to encourage greater uptake of this methodology in the community.
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Affiliation(s)
- Justin Dean
- Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America
| | - Evan Goldberg
- Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - Franziska Michor
- Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America
- Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
- The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
- The Ludwig Center at Harvard, Boston, Massachusetts, United States of America
- * E-mail:
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14
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Jotanovic J, Milin-Lazovic J, Alafuzoff I. Gastrointestinal Biopsy Obtained During Cancer Screening, a Biological Marker for α-Synucleinopathy? J Neuropathol Exp Neurol 2022; 81:356-362. [PMID: 35388426 PMCID: PMC9041339 DOI: 10.1093/jnen/nlac023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The hallmark alteration in α-synucleinopathies, α-synuclein, is observed not only in the brain but also in the peripheral tissues, particularly in the intestine. This suggests that endoscopic biopsies performed for colon cancer screening could facilitate the assessment of α-synuclein in the gastrointestinal (GI) tract. Using immunohistochemistry for α-synuclein, we assessed whether GI biopsies could be used to confirm an ongoing α-synucleinopathy. Seventy-four subjects with cerebral α-synucleinopathy in various Braak stages with concomitant GI biopsies were available for study. In 81% of the subjects, α-synuclein was seen in the mucosal/submucosal GI biopsies. Two subjects with severe cerebral α-synucleinopathy and a long delay between biopsy and death displayed no α-synuclein pathology in the gut, and 11 subjects with sparse cerebral α-synucleinopathy displayed GI α-synuclein up to 36 years prior to death. The finding that there was no GI α-synuclein in 19% of the subjects with cerebral α-synucleinopathy, and α-synuclein was observed in the gut of 11 subjects (15%) with sparse cerebral α-synucleinopathy even many years prior to death is unexpected and jeopardizes the use of assessment of α-synuclein in the peripheral tissue for confirmation of an ongoing cerebral α-synucleinopathy.
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Affiliation(s)
- Jelena Jotanovic
- Department of Pathology, Uppsala University Hospital, Uppsala, Sweden
| | - Jelena Milin-Lazovic
- Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Irina Alafuzoff
- Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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15
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Lu B, Wang L, Lu M, Zhang Y, Cai J, Luo C, Chen H, Dai M. Microsimulation Model for Prevention and Intervention of Coloretal Cancer in China (MIMIC-CRC): Development, Calibration, Validation, and Application. Front Oncol 2022; 12:883401. [PMID: 35530306 PMCID: PMC9072786 DOI: 10.3389/fonc.2022.883401] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 03/24/2022] [Indexed: 11/23/2022] Open
Abstract
Introduction A microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. Methods We comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model’s external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. Results We found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. Conclusions The well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention.
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Affiliation(s)
- Bin Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Le Wang
- Department of Cancer Prevention, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
| | - Ming Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuhan Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Cai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenyu Luo
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongda Chen
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Min Dai, ; Hongda Chen,
| | - Min Dai
- Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Min Dai, ; Hongda Chen,
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16
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Heisser T, Hoffmeister M, Brenner H. Model based evaluation of long-term efficacy of existing and alternative colorectal cancer screening offers: A case study for Germany. Int J Cancer 2021; 150:1471-1480. [PMID: 34888862 DOI: 10.1002/ijc.33894] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/30/2021] [Accepted: 12/02/2021] [Indexed: 12/17/2022]
Abstract
For individuals willing to minimize their lifetime risk of colorectal cancer (CRC), the most effective screening approach remains unclear. Here, we sought to compare the long-term performance of existing and alternative CRC screening offers in a case study for Germany. Applying the perspective of a perfectly adhering man or woman at average risk, we used COSIMO, a validated Markov-based multistate model, to simulate the effects of current CRC screening offers in Germany. These include age- and sex-dependent offers for fecal immunochemical testing (FIT) or screening colonoscopy, which may be used twice starting at age 50 in men and age 55 in women. For comparison, we modeled screening colonoscopies at ages 50, 60 and 70, screening colonoscopies at ages 50 and 60, followed by biennial FITs and conventional FIT-based strategies at varying intervals. We found that the highest reductions in lifetime risks of developing (76%-84%) and dying from CRC (82%-90%) were achieved by three colonoscopies, followed by annual FIT screening and strategies combining both modalities. In men, additional screening from age 70 onwards reduced the risk of dying from CRC by another 9% units and resulted in 32 to 39 additional life-years-gained per 1000 individuals. Among women, three colonoscopies outperformed current screening offers in all outcomes, at little risk of screening-related complications. In summary, several FIT- and colonoscopy-based offers yield comparably high CRC risk reductions, including approaches combining both modalities. German screening offers may be optimized by lowering the eligibility age for screening colonoscopy for women, along with additional offers for the elderly.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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17
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Heisser T, Cardoso R, Guo F, Moellers T, Hoffmeister M, Brenner H. Strongly Divergent Impact of Adherence Patterns on Efficacy of Colorectal Cancer Screening: The Need to Refine Adherence Statistics. Clin Transl Gastroenterol 2021; 12:e00399. [PMID: 34506306 PMCID: PMC8437219 DOI: 10.14309/ctg.0000000000000399] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 07/13/2021] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION The performance of colorectal cancer (CRC) screening programs depends on the adherence to screening offers. However, identical adherence levels may result from varying patterns of the population's screening behavior. We quantified the effects of different adherence patterns on the long-term performance of CRC screening for annual fecal immunochemical testing and screening colonoscopy at 10-year intervals. METHODS Using a multistate Markov model, we simulated scenarios where, while at the same overall adherence level, a certain proportion of the population adheres to all screening offers (selective adherence) or the entire population uses the screening offers at some point(s) of time, albeit not in the recommended frequency (sporadic adherence). Key outcomes for comparison were the numbers of prevented CRC cases and prevented CRC deaths after 50 simulated years. RESULTS For screening with annual fecal immunochemical testing at adherence levels of 10%-50%, ratios of prevented CRC cases (CRC deaths) resulting from a sporadic vs a selective pattern ranged from 1.8 to 4.4 (1.9-5.3) for men and from 1.7 to 3.6 (1.8-4.4) for women, i.e., up to 4-5 times more CRC cases and deaths were prevented when the population followed a sporadic instead of a selective adherence pattern. Comparisons of simulated scenarios for screening colonoscopy revealed similar patterns. DISCUSSION Over a lifelong time frame, large numbers of irregular screening attendees go along with much larger preventive effects than small numbers of perfectly adhering individuals. In clinical practice, efforts to reach as many people as possible at least sporadically should be prioritized over efforts to maximize adherence to repeat screening offers.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Rafael Cardoso
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Feng Guo
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Tobias Moellers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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18
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Brenner H, Cross AJ. Merits, Challenges, and Limitations of Randomized Trials on Colorectal Cancer Screening Effectiveness. Gastroenterology 2021; 160:1009-1011. [PMID: 33359088 DOI: 10.1053/j.gastro.2020.12.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 12/17/2020] [Indexed: 12/23/2022]
Affiliation(s)
- Hermann Brenner
- Clinical Epidemiology and Aging Research Division, German Cancer Research Center, Heidelberg, Germany.
| | - Amanda J Cross
- Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK
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19
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Curtius K, Dewanji A, Hazelton WD, Rubenstein JH, Luebeck GE. Optimal Timing for Cancer Screening and Adaptive Surveillance Using Mathematical Modeling. Cancer Res 2020; 81:1123-1134. [PMID: 33293425 DOI: 10.1158/0008-5472.can-20-0335] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 09/08/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023]
Abstract
Cancer screening and early detection efforts have been partially successful in reducing incidence and mortality, but many improvements are needed. Although current medical practice is informed by epidemiologic studies and experts, the decisions for guidelines are ultimately ad hoc. We propose here that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain "window of opportunity" for intervention when early cancer development may be observable. Alternative to a strictly empirical approach or microsimulations of a multitude of possible scenarios, biologically based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett's esophagus, these methods were applied for a model of esophageal adenocarcinoma that was previously calibrated to U.S. cancer registry data. Optimal screening ages for patients with symptomatic gastroesophageal reflux disease were older (58 for men and 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Collectively, our framework captures critical aspects of cancer evolution within patients with Barrett's esophagus for a more personalized screening design. SIGNIFICANCE: This study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes, with the added potential to improve surveillance regimes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/4/1123/F1.large.jpg.
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Affiliation(s)
- Kit Curtius
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. .,Division of Biomedical Informatics, Department of Medicine, University of California, San Diego, San Diego, California
| | - Anup Dewanji
- Applied Statistics Unit, Indian Statistical Institute, Kolkata, India
| | - William D Hazelton
- Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Joel H Rubenstein
- Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan.,Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan
| | - Georg E Luebeck
- Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington
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20
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Jiang TJ, Wang F, Wang YN, Hu JJ, Ding PR, Lin JZ, Pan ZZ, Chen G, Shao JY, Xu RH, Zhao Q, Wang F. Germline mutational profile of Chinese patients under 70 years old with colorectal cancer. Cancer Commun (Lond) 2020; 40:620-632. [PMID: 32914570 PMCID: PMC7668457 DOI: 10.1002/cac2.12093] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. METHODS We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. RESULTS We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild-type APC (75.0% vs. 17.4%). CONCLUSION These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.
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Affiliation(s)
- Teng-Jia Jiang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Fang Wang
- Department of Molecular Diagnosis, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Ying-Nan Wang
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jia-Jia Hu
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jun-Zhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Jian-Yong Shao
- Department of Molecular Diagnosis, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Rui-Hua Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Qi Zhao
- Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
| | - Feng Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China
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21
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Soffer S, Klang E, Tau N, Zemet R, Ben-Horin S, Barash Y, Kopylov U. Evolution of colorectal cancer screening research in the past 25 years: text-mining analysis of publication trends and topics. Therap Adv Gastroenterol 2020; 13:1756284820941153. [PMID: 32733602 PMCID: PMC7372615 DOI: 10.1177/1756284820941153] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 06/15/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND There is a growing research effort in the field of colorectal cancer (CRC) screening, with varying topics and shifting research foci over the years. The aim of this study was to apply a text-mining technique to evaluate trends in publications for CRC screening in the last 25 years. METHODS We retrieved MEDLINE/PubMed datasets from 1992-2017. We selected keywords from Medical Subject Headings to include CRC screening related publications. For each article, we extracted the following data: title, journal, publication date, abstract, article type, citation frequency, and country of origin. Articles were categorized into topics using word combination and title match technique. RESULTS In 1992-2017, 14,119 CRC screening related papers were published. The US had the highest number of papers (n = 4824) and China had the highest growth rate in publications. Overall, the most researched topic was "screening and surveillance programs" (38%). The topics of "quality assurance" (r = 0.87) and "racial disparities" (r = 0.91) have gained increased research attention over the years. In total, 11 of the 20 most cited articles in the field were published in The New England Journal of Medicine. CONCLUSION The number of publications devoted to CRC screening has grown, with high-quality research reaching top-tier journals. A surge in the number of publications has been increasing in countries previously less involved in research in the field. Screening programs remain the most researched topic, and quality indicators is attracting a growing attention. Text-mining analysis of CRC screening research contributes to an understanding of publication trends and topics and can point to the need for potential future investigations.
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Affiliation(s)
- Shelly Soffer
- Shelly Soffer Department of Diagnostic Imaging,
Sheba Medical Center, Tel Hashomer, Israel
- Sackler Medical School, Tel Aviv University, Tel
Aviv, Israel DeepVision Lab, Sheba Medical Center, Tel Hashomer,
Israel
| | - Eyal Klang
- Department of Diagnostic Imaging, Sheba Medical
Center, Tel Hashomer, Israel
- Sackler Medical School, Tel Aviv University, Tel
Aviv, Israel DeepVision Lab, Sheba Medical Center, Tel Hashomer,
Israel
| | - Noam Tau
- Department of Diagnostic Imaging, Sheba Medical
Center, Tel Hashomer, Israel, and Sackler Medical School, Tel Aviv
University, Tel Aviv, Israel
| | - Roni Zemet
- Department of Obstetrics and Gynecology, Sheba
Medical Center, Tel Hashomer, Israel, and Sackler Medical School, Tel Aviv
University, Tel Aviv, Israel
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical
Center, Tel Hashomer, Israel
- Sackler Medical School, Tel Aviv University, Tel
Aviv, Israel
| | - Yiftach Barash
- Department of Diagnostic Imaging, Sheba Medical
Center, Tel Hashomer, Israel
- Sackler Medical School, Tel Aviv University,
Tel Aviv, Israel DeepVision Lab, Sheba Medical Center, Tel Hashomer,
Israel
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical
Center, Tel Hashomer, Israel
- Sackler Medical School, Tel Aviv University,
Tel Aviv, Israel
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22
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Heisser T, Weigl K, Hoffmeister M, Brenner H. Age-specific sequence of colorectal cancer screening options in Germany: A model-based critical evaluation. PLoS Med 2020; 17:e1003194. [PMID: 32678831 PMCID: PMC7367446 DOI: 10.1371/journal.pmed.1003194] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 06/26/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The current organized screening program for colorectal cancer in Germany offers both sexes 5 annual fecal immunochemical tests (FITs) between ages 50 and 54 years, followed by a first screening colonoscopy at age 55 years if all of these FITs were negative. We sought to assess the implications of this approach for key parameters of diagnostic performance. METHODS AND FINDINGS Using a multistate Markov model, we estimated the expected detection rates of advanced neoplasms (advanced adenomas and cancers) and number needed to scope (NNS) to detect 1 advanced neoplasm at a first screening colonoscopy conducted at age 55 after 5 preceding negative FITs and compared them with the corresponding estimates for a first screening colonoscopy at age 55 with no preceding FIT testing. In individuals with 5 consecutive negative FITs undergoing screening colonoscopy at age 55, expected colonoscopy detection rate (NNS) was 3.7% (27) and 0.10% (1,021) for any advanced neoplasm and cancer, respectively, in men, and 2.1% (47) and 0.05% (1,880) for any advanced neoplasm and cancer, respectively, in women. These NNS values for detecting 1 advanced neoplasm are approximately 3-fold higher, and the NNS values for detecting 1 cancer are approximately 8-fold higher, than those for a first screening colonoscopy at age 55 without prior FITs. This study is limited by model simplifying assumptions and uncertainties related to input parameters. CONCLUSIONS Screening colonoscopy at age 55 after 5 consecutive negative FITs at ages 50-54, as currently offered in the German cancer early detection program, is expected to have very low positive predictive value. Our results may inform efforts to enhance the design of screening programs.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
- * E-mail:
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
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23
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Mannucci A, Zuppardo RA, Rosati R, Leo MD, Perea J, Cavestro GM. Colorectal cancer screening from 45 years of age: Thesis, antithesis and synthesis. World J Gastroenterol 2019; 25:2565-2580. [PMID: 31210710 PMCID: PMC6558439 DOI: 10.3748/wjg.v25.i21.2565] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/15/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer incidence and mortality in patients younger than 50 years are increasing, but screening before the age of 50 is not offered in Europe. Advanced-stage diagnosis and mortality from colorectal cancer before 50 years of age are increasing. This is not a detection-bias effect; it is a real issue affecting the entire population. Three independent computational models indicate that screening from 45 years of age would yield a better balance of benefits and risks than the current start at 50 years of age. Experimental data support these predictions in a sex- and race-independent manner. Earlier screening is seemingly affordable, with minimal impediments to providing younger adults with colonoscopy. Indeed, the American Cancer Society has already started to recommend screening from 45 years of age in the United States. Implementing early screening is a societal and public health problem. The three independent computational models that suggested earlier screening were criticized for assuming perfect compliance. Guidelines and recommendations should be derived from well-collected and reproducible data, and not from mathematical predictions. In the era of personalized medicine, screening decisions might not be based solely on age, and sophisticated prediction software may better guide screening. Moreover, early screening might divert resources away from older individuals with greater biological risks. Finally, it is still unknown whether early colorectal cancer is part of a continuum of disease or a biologically distinct disease and, as such, it might not benefit from screening at all. The increase in early-onset colorectal cancer incidence and mortality demonstrates an obligation to take actions. Earlier screening would save lives, and starting at the age of 45 years may be a robust screening option.
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Affiliation(s)
- Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Raffaella Alessia Zuppardo
- Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Riccardo Rosati
- Department of Surgery, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
| | - Milena Di Leo
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Department of Biomedical Science, Humanitas University, Milan 20090, Italy
| | - José Perea
- Surgery Department, “Fundación Jiménez Díaz” University Hospital, Madrid 28040, Spain
- Health Research Institute-Fundación Jiménez Díaz University Hospital, Madrid 28040, Spain
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy
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