10 results on '"Kåre Andersson Gotschalck"'
Search Results
2. Comparing single‐target and multitarget approaches for postoperative circulating tumour DNA detection in stage II–III colorectal cancer patients
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Tenna Vesterman Henriksen, Thomas Reinert, Mads Heilskov Rasmussen, Christina Demuth, Uffe Schou Løve, Anders Husted Madsen, Kåre Andersson Gotschalck, Lene Hjerrild Iversen, and Claus Lindbjerg Andersen
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circulating tumour DNA ,colorectal cancer ,liquid biopsy ,residual disease ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single‐target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II–III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient‐specific variants. The strategies exhibited good concordance (90%, Cohen's Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard‐of‐care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection.
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- 2022
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3. Identifying Recurrences Among Non-Metastatic Colorectal Cancer Patients Using National Health Data Registries: Validation and Optimization of a Registry-Based Algorithm in a Modern Danish Cohort
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Jesper Nors, Trine Block Mattesen, Deirdre Cronin-Fenton, Aurélie Mailhac, Jesper Bertram Bramsen, Kåre Andersson Gotschalck, Rune Erichsen, and Claus Lindbjerg Andersen
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Epidemiology ,oncology ,surveillance ,time to recurrence ,Clinical Epidemiology ,chemotherapy - Abstract
Jesper Nors,1,2,* Trine Block Mattesen,1,* Deirdre Cronin-Fenton,3 Aurélie Mailhac,3 Jesper Bertram Bramsen,1,2 KÃ¥re Andersson Gotschalck,2,4 Rune Erichsen,2,3,5 Claus Lindbjerg Andersen1,2 1Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Surgery, Horsens Regional Hospital, Horsens, Denmark; 5Department of Surgery, Randers Regional Hospital, Horsens, Denmark*These authors contributed equally to this workCorrespondence: Claus Lindbjerg Andersen, Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark, Tel +45 78455319, Email cla@clin.au.dkPurpose: Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR).Patients and Methods: We ascertained data on 1129 patients operated for UICC TNM stage IâIII CRC during 2012â 2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark. Individual-level data were linked with data from the Danish Colorectal Cancer Group database, Danish Cancer Registry, Danish National Registry of Patients, and Danish Pathology Registry. The algorithm identified recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence more than 180 days after CRC surgery. A subgroup was selected for validation of the algorithm using medical record reviews as a reference standard.Results: We found a 3-year cumulative recurrence rate of 20% (95% CI: 17â 22%). Manual medical record review identified 80 recurrences in the validation cohort of 522 patients. The algorithm detected recurrence with 94% sensitivity (75/80; 95% CI: 86â 98%) and 98% specificity (431/442; 95% CI: 96â 99%). The positive and negative predictive values of the algorithm were 87% (95% CI: 78â 93%) and 99% (95% CI: 97â 100%), respectively. The median difference in TTR (TTRMedical_chart-TTRalgorithm) was â 8 days (IQR: â 21 to +3 days). Restricting the algorithm to chemotherapy codes from oncology departments increased the positive predictive value from 87% to 94% without changing the negative predictive value (99%).Conclusion: The algorithm detected recurrence and TTR with high precision in this contemporary cohort. Restriction to chemotherapy codes from oncology departments using department classifications improves the algorithm. The algorithm is suitable for use in future observational studies.Keywords: time to recurrence, surveillance, chemotherapy, oncology
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- 2023
4. Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
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Claus Lindbjerg Andersen, Andres Cervantes, Alexey Aleshin, Himanshu Sethi, Kåre Andersson Gotschalck, Lene Hjerrild Iversen, Ole Thorlacius-Ussing, Per Vadgaard Andersen, Uffe S. Løve, Anders Husted Madsen, Susana Roselló, Marisol Huerta, Desamparados Roda, Dina Hafez, Derrick Renner, Shruti Sharma, Juan Antonio Carbonell-Asins, Francisco Gimeno-Valiente, Thomas Reinert, Amanda Frydendahl, Noelia Tarazona, and Tenna Vesterman Henriksen
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Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
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- 2023
5. Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
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Claus Lindbjerg Andersen, Andres Cervantes, Alexey Aleshin, Himanshu Sethi, Kåre Andersson Gotschalck, Lene Hjerrild Iversen, Ole Thorlacius-Ussing, Per Vadgaard Andersen, Uffe S. Løve, Anders Husted Madsen, Susana Roselló, Marisol Huerta, Desamparados Roda, Dina Hafez, Derrick Renner, Shruti Sharma, Juan Antonio Carbonell-Asins, Francisco Gimeno-Valiente, Thomas Reinert, Amanda Frydendahl, Noelia Tarazona, and Tenna Vesterman Henriksen
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Purpose:Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates.Experimental Design:We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing.Results:Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7–13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4–167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9–172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1–6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography.Conclusions:Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making.See related commentary by Morris and George, p. 438
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- 2023
6. Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer
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Jonas Kabel, Tenna Vesterman Henriksen, Christina Demuth, Amanda Frydendahl, Mads Heilskov Rasmussen, Jesper Nors, Nicolai J. Birkbak, Anders Husted Madsen, Uffe S. Løve, Per Vadgaard Andersen, Thomas Kolbro, Alessio Monti, Ole Thorlacius-Ussing, Mikail Gögenur, Jeppe Kildsig, Nis Hallundbæk Schlesinger, Peter Bondeven, Lene Hjerrild Iversen, Kåre Andersson Gotschalck, and Claus Lindbjerg Andersen
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circulating tumor DNA ,Cancer Research ,Oncology ,whole genome doubling ,cancer diagnostics ,colorectal cancer - Abstract
Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients.Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients.Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients.Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell. Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. Methods: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. Results: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12–2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22–5.03) and Stage II (OR = 1.76, 95%CI: 1.11–2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44–1.53) patients. Conclusion: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.
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- 2023
- Full Text
- View/download PDF
7. Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences
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Lene Hjerrild Iversen, Claus L. Andersen, Derrick Renner, Thomas Reinert, Ole Thorlacius-Ussing, Desamparados Roda, Tenna V Henriksen, Alexey Aleshin, Andrés Cervantes, Noelia Tarazona, Per Vadgaard Andersen, Shruti Sharma, Susana Roselló, J.A. Carbonell-Asins, Dina Hafez, Anders Husted Madsen, Uffe S. Løve, Kåre Andersson Gotschalck, Amanda Frydendahl, Marisol Huerta, F. Gimeno-Valiente, and Himanshu Sethi
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,Adjuvant chemotherapy ,Clinical Decision-Making ,Circulating Tumor DNA ,Text mining ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,Stage III colorectal cancer ,medicine ,Adjuvant therapy ,Humans ,Tumor growth ,Aged ,Neoplasm Staging ,business.industry ,Prognosis ,Minimal residual disease ,Confidence interval ,Circulating tumor DNA ,Female ,Drug Monitoring ,Neoplasm Recurrence, Local ,Colorectal Neoplasms ,business - Abstract
Purpose: Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates. Experimental Design: We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing. Results: Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7–13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4–167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9–172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1–6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography. Conclusions: Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making. See related commentary by Morris and George, p. 438
- Published
- 2021
8. Abstract 1959: Sensitive detection of circulating tumor DNA by whole genome sequencing: Validation of MRDetect using serial blood samples from stage III colorectal cancer patients
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Amanda Frydendahl, Thomas Reinert, Jesper Nors, Sunil Deochand, Dillon Maloney, Noah Friedman, Tomer Lauterman, Danielle Afterman, Imane Bourzgui, Nidhi Ramaraj, Zohar Donenhirsh, Ronel Veksler, Ravi Kandasamy, Iman Tavassoly, Jonathan Rosenfeld, Anders Husted Andersen, Uffe S. Løve, Per V. Andersen, Ole Thorlacius-Ussing, Lene Hjerrild Iversen, Kåre Andersson Gotschalck, Boris Oklander, Asaf Zviran, and Claus Lindbjerg Andersen
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Cancer Research ,Oncology - Abstract
Background: While detection of circulating tumor DNA (ctDNA) is associated with poor cancer prognosis, the clinical utility for guiding treatment decisions is unresolved. Patients with minimal residual disease (MRD) often have less than one genome equivalent of ctDNA per 10 mL blood. Consequently, it is stochastic whether a 10 mL sample contains ctDNA from a particular genomic locus. Consequently, the sensitivity of ctDNA detection methods targeting a limited number of tumor loci is heavily affected by sampling bias. To overcome this challenge, we developed MRDetect; a whole genome sequencing (WGS) approach, which detects ctDNA using the patient-specific cumulative signal from tens of thousands of mutations throughout the genome. Recently, we showed how MRDetect found ctDNA fractions down to 10-4. Here, we performed a validation study to confirm the prognostic impact of MRDetect. Aim: Validation of MRDetect for sensitive ctDNA detection to monitor residual disease in stage III colorectal cancer (CRC) patients treated with curative intent. Methods: From a large, uniform cohort of stage III CRC patients n = 146), we had plasma samples collected every third month (n = 938, median = 9 per patient) and a median follow-up of 34 months. For each patient, a genome-wide mutational signature was established by WGS of tumor and matched normal DNA. Enhanced by an AI-based error suppression model, this signature was used to detect ctDNA in 1-2 mL plasma samples using WGS (20x coverage). We used de-novo point mutation and copy number variation analysis to investigate cancer evolution after treatment. To evaluate the reproducibility of MRDetect, aliquot samples (n = 2x190 samples) from 5 recurrence and 10 non-recurrence patients were processed and sequenced at two independent laboratories. Outcome measures: ctDNA status, tumor fraction, false positive rate, Time To ctDNA Recurrence (TTcR), and Time To radiological Recurrence (TTrR). Results: Analysis of paired samples showed great reproducibility with high agreement between both ctDNA status calls (Cohens Kappa = 0.81) and the estimated tumor fractions (r2 = 0.99). MRDetect revealed post-operative ctDNA in all recurrence patients (5/5) with detected tumor fractions down to 2 x 10-4. Median TTcR was 0.9 month (range 0.5 - 7.3 months) while median TTrR was 12.8 months (range 11.3 - 31.1 months). The false positive rate was 1% (1/100), assessed in longitudinal samples from the 10 non-relapsing patients. Tumor evolution dynamics in plasma samples revealed novel amplification and deletions, which were absent in the primary tissue but confirmed in metachronous metastases. We will present results from the full cohort at AACR 2022. Conclusion: MRDetect detects ctDNA with high sensitivity and specificity and enables effective postoperative assessment of MRD, cancer evolution dynamics and early relapse detection. Citation Format: Amanda Frydendahl, Thomas Reinert, Jesper Nors, Sunil Deochand, Dillon Maloney, Noah Friedman, Tomer Lauterman, Danielle Afterman, Imane Bourzgui, Nidhi Ramaraj, Zohar Donenhirsh, Ronel Veksler, Ravi Kandasamy, Iman Tavassoly, Jonathan Rosenfeld, Anders Husted Andersen, Uffe S. Løve, Per V. Andersen, Ole Thorlacius-Ussing, Lene Hjerrild Iversen, Kåre Andersson Gotschalck, Boris Oklander, Asaf Zviran, Claus Lindbjerg Andersen. Sensitive detection of circulating tumor DNA by whole genome sequencing: Validation of MRDetect using serial blood samples from stage III colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1959.
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- 2022
9. 420P Minimal residual disease detection and tracking tumour evolution using ctDNA in stage I-III colorectal cancer patients
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Lene Hjerrild Iversen, Shruti Sharma, N. Tarazona, Svetlana Shchegrova, Thomas Reinert, Andrés Cervantes, Anders Husted Madsen, Antony Tin, J.A. Carbonell-Asins, M. Huerta, Alexey Aleshin, Tenna V Henriksen, Claus L. Andersen, Susana Roselló, Kåre Andersson Gotschalck, Bernhard Zimmermann, Himanshu Sethi, H.-T. Wu, and Desamparados Roda
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Internal medicine ,medicine ,Hematology ,medicine.disease ,business ,Minimal residual disease - Published
- 2020
10. IMPROVE-IT2: Implementing non-invasive circulating tumor DNA analysis to optimize the operative and postoperative treatment for patients with colorectal cancer – Intervention Trial 2. Study protocol
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Claus L. Andersen, Lene Hjerrild Iversen, Tenna V Henriksen, Jes Søgaard, Kåre Andersson Gotschalck, Jesper Nors, and Therese Juul
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medicine.medical_specialty ,RESECTION ,Colorectal cancer ,MEDLINE ,GUIDELINES ,Circulating Tumor DNA ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Postoperative treatment ,law ,Internal medicine ,SURVEILLANCE ,medicine ,MANAGEMENT ,Humans ,EPIDEMIOLOGY ,Radiology, Nuclear Medicine and imaging ,Postoperative Period ,Intervention trial ,METACHRONOUS METASTASES ,RECURRENCE ,Protocol (science) ,business.industry ,COLON-CANCER ,Follow up studies ,Hematology ,General Medicine ,Prognosis ,medicine.disease ,Oncology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,CURATIVE TREATMENT ,Colorectal Neoplasms ,business ,FOLLOW-UP ,Colorectal Surgery ,Follow-Up Studies - Abstract
Death of colorectal cancer (CRC) is primarily associated to distant metastases, present at the time of diagnosis or appearing later following a cancer-free period. At time of diagnosis, 75% of pati...
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