title: Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma.
abstract: OBJECTIVE
  To develop and validate a histopathologic scoring system for measuring response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIC to IV tubo-ovarian high-grade serous carcinoma.
  
  
  METHODS
  A six-tier histopathologic scoring system was proposed and applied to a test cohort (TC) of 62 patients treated with neoadjuvant chemotherapy and interval debulking surgery. Adnexal and omental sections were independently scored by three pathologists. On the basis of TC results, a three-tier chemotherapy response score (CRS) system was developed and applied to an independent validation cohort of 71 patients.
  
  
  RESULTS
  The initial system showed moderate interobserver reproducibility and prognostic stratification of TC patients when applied to the omentum but not to the adnexa. Condensed to a three-tier score, the system was highly reproducible (kappa, 0.75). When adjusted for age, stage, and debulking status, the score predicted progression-free survival (PFS; score 2 v 3; median PFS, 11.3 v 32.1 months; adjusted hazard ratio, 6.13; 95% CI, 2.13 to 17.68; P < .001). The three-tier CRS system applied to omental samples from the validation cohort showed high reproducibility (kappa, 0.67) and predicted PFS (CRS 1 and 2 v 3: median, 12 v 18 months; adjusted hazard ratio, 3.60; 95% CI, 1.69 to 7.66; P < .001). CRS 3 also predicted sensitivity to first-line platinum therapy (94.3% negative predictive value for progression < 6 months). A Web site was established to train pathologists to use the CRS system.
  
  
  CONCLUSIONS
  The CRS system is reproducible and shows prognostic significance for high-grade serous carcinoma. Implementation in international pathology reporting has been proposed by the International Collaboration on Cancer Reporting, and the system could potentially have an impact on patient care and research.
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM. steffen.boehm@bartshealth.nhs.uk.
authors.forename: Steffen
authors.initials: S
authors.lastname: Böhm
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Asma
authors.initials: A
authors.lastname: Faruqi
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Ian
authors.initials: I
authors.lastname: Said
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lockley
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Elly
authors.initials: E
authors.lastname: Brockbank
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Arjun
authors.initials: A
authors.lastname: Jeyarajah
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Amanda
authors.initials: A
authors.lastname: Fitzpatrick
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Darren
authors.initials: D
authors.lastname: Ennis
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dowe
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Santos
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cook
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Tinker
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Nhu D
authors.initials: ND
authors.lastname: Le
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, and Naveena Singh, Barts Health National Health Service Trust; Steffen Böhm, Michelle Lockley, Darren Ennis, and Thomas Dowe, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Jennifer L. Santos, Anna V. Tinker, and Nhu D. Le, British Columbia Cancer Agency; C. Blake Gilks, University of British Columbia, Vancouver, BC, Canada; and Linda S. Cook, University of New Mexico, Albuquerque, NM.
authors.forename: Naveena
authors.initials: N
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D065426:Cytoreduction Surgical Procedures; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007044:Hysterectomy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009852:Omentum / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D058994:Salpingectomy; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel