J V Schou1, F O Larsen2, B S Sørensen3, R Abrantes3, A K Boysen4, J S Johansen5, B V Jensen2, D L Nielsen5, K L Spindler6. 1. Department of Oncology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: j.schou@dadlnet.dk. 2. Department of Oncology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. 3. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Oncology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
Background: Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery. Patients and methods: In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%). Results: Median follow-up was 55 months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95% CI: 1.3-4.8, P = 0.007). The same applied to disease-free survival (DFS) (HR = 2.43, 95% CI: 1.27-4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis. Conclusion: We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.
Background: Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery. Patients and methods: In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%). Results: Median follow-up was 55 months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95% CI: 1.3-4.8, P = 0.007). The same applied to disease-free survival (DFS) (HR = 2.43, 95% CI: 1.27-4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis. Conclusion: We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.
Authors: Anders Kindberg Boysen; Martin Jensen; Dennis Tønner Nielsen; Frank Viborg Mortensen; Brita Singers Sørensen; Anni Ravnsbæk Jensen; Karen-Lise Spindler Journal: Oncol Lett Date: 2018-06-07 Impact factor: 2.967
Authors: Hariti Saluja; Christos S Karapetis; Susanne K Pedersen; Graeme P Young; Erin L Symonds Journal: Front Oncol Date: 2018-07-24 Impact factor: 6.244
Authors: Arvind Dasari; Van K Morris; Carmen J Allegra; Chloe Atreya; Al B Benson; Patrick Boland; Ki Chung; Mehmet S Copur; Ryan B Corcoran; Dustin A Deming; Andrea Dwyer; Maximilian Diehn; Cathy Eng; Thomas J George; Marc J Gollub; Rachel A Goodwin; Stanley R Hamilton; Jaclyn F Hechtman; Howard Hochster; Theodore S Hong; Federico Innocenti; Atif Iqbal; Samuel A Jacobs; Hagen F Kennecke; James J Lee; Christopher H Lieu; Heinz-Josef Lenz; O Wolf Lindwasser; Clara Montagut; Bruno Odisio; Fang-Shu Ou; Laura Porter; Kanwal Raghav; Deborah Schrag; Aaron J Scott; Qian Shi; John H Strickler; Alan Venook; Rona Yaeger; Greg Yothers; Y Nancy You; Jason A Zell; Scott Kopetz Journal: Nat Rev Clin Oncol Date: 2020-07-06 Impact factor: 65.011