Clinical Research Papers:
The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation
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Paola Carpinetti1,2,3, Elisa Donnard1,2,3, Fabiana Bettoni2, Paula Asprino2, Fernanda Koyama1, Andrei Rozanski2, Jorge Sabbaga4, Angelita Habr-Gama5,6, Raphael B. Parmigiani2, Pedro A.F. Galante2, Rodrigo O. Perez1,5,6, Anamaria A. Camargo1,2
1Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
2Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil
3Programa de Pós Graduação em Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil
4Centro de Oncologia Clínica, Hospital Sírio Libanês, São Paulo, SP, Brazil
5Angelita & Joaquim Gama Institute, São Paulo, SP, Brazil
6University of São Paulo, School of Medicine, São Paulo, SP, Brazil
Anamaria A. Camargo, e-mail: [email protected]
Keywords: rectal cancer, liquid biopsies, ctDNA, personalized biomarkers, neoadjuvant therapy
Received: June 19, 2015 Accepted: September 24, 2015 Published: October 06, 2015
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.
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