title: The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.|Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.|Programa de Pós Graduação em Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil.
authors.forename: Paola
authors.initials: P
authors.lastname: Carpinetti
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.|Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.|Programa de Pós Graduação em Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Donnard
authors.affiliation: Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bettoni
authors.affiliation: Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Asprino
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Koyama
authors.affiliation: Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Andrei
authors.initials: A
authors.lastname: Rozanski
authors.affiliation: Centro de Oncologia Clínica, Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sabbaga
authors.affiliation: Angelita & Joaquim Gama Institute, São Paulo, SP, Brazil.|University of São Paulo, School of Medicine, São Paulo, SP, Brazil.
authors.forename: Angelita
authors.initials: A
authors.lastname: Habr-Gama
authors.affiliation: Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Raphael B
authors.initials: RB
authors.lastname: Parmigiani
authors.affiliation: Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Pedro A F
authors.initials: PA
authors.lastname: Galante
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.|Angelita & Joaquim Gama Institute, São Paulo, SP, Brazil.|University of São Paulo, School of Medicine, São Paulo, SP, Brazil.
authors.forename: Rodrigo O
authors.initials: RO
authors.lastname: Perez
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.|Centro de Oncologia Molecular Hospital Sírio Libanês, São Paulo, SP, Brazil.
authors.forename: Anamaria A
authors.initials: AA
authors.lastname: Camargo
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001706:Biopsy / Q000379:methods*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000556:secondary; D008297:Male; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: ctDNA; liquid biopsies; neoadjuvant therapy; personalized biomarkers; rectal cancer