Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC)

Abstract

A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS system. We retrospectively identified advanced stage HGSC patients who received neoadjuvant chemotherapy and underwent interval debulking. If available, a hemotoxylin and eosin slide from the omentum and the adnexa was selected for the study. Slides were independently scored by 13 pathologists using the 3-tiered CRS system. Reviewers then received web-based training and rescored the slides. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the log-rank test. A total of 68 patients with omental (n=65) and/or adnexal (n=59) slides were included in the study. Interobserver reproducibility was moderate for omentum (κ, 0.48) and poor for adnexa (κ, 0.40), which improved for omentum (κ, 0.62) but not for adnexa (κ, 0.38) after online training. For omental slides, a consensus CRS of 1/2 was associated with a shorter median progression-free survival (10.9 mo; 95% confidence interval, 9-14) than a CRS of 3 (18.9 mo; 95% CI, 18-24; P=0.020). In summary, a 3-tiered CRS system of hemotoxylin and eosin-stained omental deposits can yield prognostic information for HGSC patients receiving neoadjuvant chemotherapy, and web-based training improved reproducibility but did not alter determination of clinical outcomes. The CRS system may allow oncologists to identify potential nonresponders and triage HGSC patients for heightened observation and/or clinical trials.

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

“…We retrieved 6 published papers and 5 met the inclusion criteria [7,[10][11][12][13]. 1 duplicate was removed ( Fig.…”

“…The International Collaboration on Cancer Reporting (ICCR) subsequently recommended the use of the CRS to assess histological NACT effect in HGSC to enable standardized and objective reporting [9]. Single institution retrospective studies have since reported an association between CRS and progression-free survival (PFS) but not OS [10][11][12][13]. These studies are limited by small sample sizes, lack of power to detect associations between CRS and OS, heterogeneity in participants, and the number of NACT cycles and regimens used.…”

Prognostic impact of intraoperative peritoneal cytology in interval debulking surgery for pelvic high‐grade serous carcinoma

“…For improving inter‐observer reproducibility of CRS, the training web site has been launched; furthermore, various external validation studies have confirmed the prognostic impact of CRS . However, assessment of CRS requires an appropriate number of sampling from the omentum and training of the scoring practice . In contrast, PWC has been already utilized in the daily practice of gynecologic surgery and needs no additional training or sampling.…”

Role of the pathologist in assessing response to treatment of ovarian and endometrial cancers

“…Reproducibility of CRS assignment between pathologists from different centres and with different levels of experience has been noted . In their study, Ditzel and colleagues noted that the interobserver agreement of the three‐tiered CRS scoring system was moderate, with a K ‐value of 0.48 at the first instance . After using the using the online tool available at Genetic Pathology Evaluation Centre (CRS: training website for the CRS system), the interobserver agreement improved to substantial with a K ‐value of 0.76.…”

“…17 In their study, Ditzel and colleagues noted that the interobserver agreement of the three-tiered CRS scoring system was moderate, with a K-value of 0.48 at the first instance. 11 After using the using the online tool available at Genetic Pathology Evaluation Centre (CRS: training website for the CRS system), 18 the interobserver agreement improved to substantial with a K-value of 0.76. The CRS2 category increased after the online training, drawing both from CRS1 and CRS3 categories.…”