6 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. The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening:a nationwide cross-sectional study
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Simon Ladefoged Rasmussen, Christian Torp-Pedersen, Kåre Andersson Gotschalck, and Ole Thorlacius-Ussing
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Feces ,Cross-Sectional Studies ,Anticoagulants/therapeutic use ,Mass Screening/methods ,Fibrinolytic Agents/therapeutic use ,Occult Blood ,Gastroenterology ,Administration, Oral ,Humans ,Colonoscopy ,Colorectal Neoplasms/diagnosis ,Early Detection of Cancer/methods - Abstract
Background Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. Methods This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. Results Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56–1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48–2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %–6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %–6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51–0.66]). Conclusion Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.
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- 2023
4. 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
5. Fear of cancer recurrence and quality of life in a ctDNA based surveillance program following curative intended treatment of colorectal cancer – a substudy of IMPROVE-IT2
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Jesper Berg Nors, Therese Juul, Kåre Andersson Gotschalck, Claus Lindbjerg Andersen, and Lene Hjerrild Iversen
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- 2021
6. Serial circulating tumor DNA analysis to assess recurrence risk, benefit of adjuvant therapy, growth rate and early relapse detection in stage III colorectal cancer patients
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J.A. Carbonell-Asins, Marisol Huerta, Susana Roselló, Lene Hjerrild Iversen, Claus L. Andersen, Ole Thorlacius-Ussing, Tenna V Henriksen, Alexey Aleshin, Andrés Cervantes, Uffe S. Løve, Kåre Andersson Gotschalck, Noelia Tarazona, Thomas Reinert, Shruti Sharma, Amanda Frydendahl, Derrick Renner, Himanshu Sethi, and Desamparados Roda
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Adjuvant chemotherapy ,Early Relapse ,Postoperative management ,Recurrence risk ,Circulating tumor DNA ,Internal medicine ,Stage III colorectal cancer ,Adjuvant therapy ,Medicine ,business ,Selection (genetic algorithm) - Abstract
3540 Background: Challenges in the postoperative management of stage III colorectal cancer include: 1) selection of high-risk patients for adjuvant chemotherapy (ACT), 2) lack of markers to assess ACT efficacy, 3) assessment of recurrence risk after ACT, and 4) lack of markers to guide treatment decisions for high-risk patients e.g. additional therapy or intensified surveillance. Circulating tumor DNA (ctDNA) is a promising marker with potential to mitigate the challenges. Here we used serial ctDNA measurements to assess the correlation between recurrence and ctDNA detection: postoperative, during and after ACT, and during surveillance; and to assess growth rates of metachronous metastases. Uniquely, we also used concurrent CT scans and ctDNA measurements to compare the sensitivity for detecting recurrence. Methods: Stage III CRC patients treated with curative intent at Danish and Spanish hospitals in 2014-2019 were recruited (n = 166). Blood samples (n = 1227) were collected prior to and immediately after surgery, and every third month for up to 36 months. Per patient 16 personal mutations were used to quantify plasma ctDNA (Signatera, bespoke mPCR NGS assay). Results: Detection of ctDNA was a strong recurrence predictor, both postoperatively (HR 7.2, 95% CI 3.8-13.8, P< 0.001), directly after ACT (HR = 18.2, 95% CI 7.1-46, P < 0.001), and when measured serially after end of treatment (HR = 41, 95% CI 16-100, P < 0.001). The recurrence rate of postoperative ctDNA positive patients treated with ACT was 80% (16/20). Patients who stayed ctDNA positive during ACT all recurred. Serial post-treatment ctDNA measurements revealed exponential growth for all recurrence patients following either a SLOW (26%-increase/month) or a FAST (126%-increase/month) pattern (P < 0.001). From ctDNA detection to radiologic recurrence, ctDNA levels of FAST patients increased by a median 117-fold, and up to 554-fold. The 3-year overall survival was 43% for FAST patients and 100% for SLOW and non-recurrence patients (HR = 41.3, 95% CI 7.5-228, P < 0.001). Coinciding CT scans and ctDNA measurements (n = 113 patients, 235 coinciding events, median 2 per patient) showed a high agreement (92%) and ctDNA either detected residual disease before the CT scan (n = 7 patients) or at the same time (n = 14 patients). The median lead-time was 7.5 months. Conclusions: The study confirmed the prognostic power of serial postoperative ctDNA analysis. Moreover, it provided novel analyses demonstrating that ctDNA is more sensitive for recurrence detection than CT scans and can be used for tumor growth rate assessments. The difference between FAST and SLOW growing tumors suggest that growth rates could guide whom to start on systemic therapy rapidly and whom to send for diagnostic imaging. Altogether, the study highlights many potential utilities of ctDNA in guiding clinical decision-making.
- Published
- 2021
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