Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma

2015 ◽  
Vol 33 (22) ◽  
pp. 2457-2463 ◽  
Author(s):  
Steffen Böhm ◽  
Asma Faruqi ◽  
Ian Said ◽  
Michelle Lockley ◽  
Elly Brockbank ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Scoring System ◽  
Validation Cohort ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
High Grade ◽  
Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Response Score ◽  
Response To Neoadjuvant Chemotherapy

Purpose 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. Patients and 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. Conclusion 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.

scholarly journals The Added Value of CA125 Normalization Before Interval Debulking Surgery to the Chemotherapy Response Score for the Prognostication of Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy for Advanced Disease

2020 ◽  
Author(s):  
Wei-feng Liang ◽  
Li-juan Wang ◽  
Jie-ying Wu ◽  
Chang-hao Liu ◽  
Miao-fang Wu ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Risk Group ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
Debulking Surgery ◽  
Cox Regression Analysis ◽  
Stratification Method ◽  
Interval Debulking Surgery ◽  
Two Factors

Abstract Objective: To investigate whether CA125 normalization following neoadjuvant chemotherapy (NACT) can complement the chemotherapy response system (CRS) in the prognostication of patients with tubo-ovarian high-grade serous carcinoma (HGSC).Methods: In total, 106 HGSC patients who received NACT followed by interval debulking surgery (IDS) for FIGO stage IIIC-IV disease were included, and their clinical data were retrospectively reviewed. The primary endpoint was progression-free survival (PFS). Cox regression analysis was performed to identify predictors of PFS.Results: Following NACT, CRS3 was noted in 24 patients (22.6%), and CA125 normalization (≤ 35 U/ml) was noted in 54 patients (50.9%). Both CRS3 and CA125 normalization were identified as independent prognosticators of PFS. Combining these two factors, we stratified the 106 patients into three groups with different risks of recurrence: low-risk group (CRS3 + post-NACT CA125≤ 35 U/ml; n = 17, 16.0%), intermediate-risk group (CRS3 + post-NACT CA125 > 35 U/ml; n = 7, 6.6%) and high-risk group (CRS1-2; n= 82, 77.4%). The differences in PFS between the three groups were significant (log-rank test, P < 0.0001). In Cox regression analyses, the new stratification method was found to have an independent prognostic effect.Conclusion: Both the CRS system and the normalization of CA125 following NACT could reliably predict the risk of recurrence following primary treatment. The combination of the two factors refined the prognostic stratification of HGSC patients who were treated with NACT and IDS.

scholarly journals A Modified 2 Tier Chemotherapy Response Score (CRS) and Other Histopathologic Features for Predicting Outcomes of Patients with Advanced Extrauterine High-Grade Serous Carcinoma after Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 704
Author(s):  
Yanping Zhong ◽  
Jinsong Liu ◽  
Xiaoran Li ◽  
Shannon N. Westin ◽  
Anais Malpica ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Clinical Information ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
High Grade ◽  
Entire Cohort ◽  
The Impact ◽  
Response Score

Background: The impact of chemotherapy response score (CRS) on prognosis has varied among studies. We addressed the prognostic significance of CRS and the prognostic value of previously undescribed histologic features using a cohort of 245 patients. Methods: Retrospective study in patients with advanced extrauterine high-grade serous carcinomas treated with neoadjuvant chemotherapy followed by interval tumor reductive surgery from 1990 to 2018 in our hospital. Gynecologic pathologists assessed tumor CRS and other histologic features. Clinical information was collected, and multivariate analyses were conducted. Results: A modified 2 tier CRS (CRS 1/2 versus CRS 3) was significantly associated, independent of scoring site (omental versus adnexal), with overall survival (OS) (omentum, p = 0.018; adnexa, p = 0.042; entire cohort, p = 0.002) and progression-free survival (PFS) (p = 0.021, p = 0.035, and p = 0.001, respectively). On multivariate survival analysis, 2 tier CRS, oncocytic change, inflammation, and desmoplasia were significant for OS (p = 0.034, p = 0.020, p = 0.007, and p = 0.010, respectively). Likewise, 2 tier CRS, inflammation, and desmoplasia were significant for PFS (p = 0.012, p = 0.003, p = 0.011, respectively). Conclusions: The modified 2 tier CRS was significantly associated with survival, independent of scoring site. Additional histologic features including oncocytic change, inflammation, and desmoplasia can also predict patient outcomes.

Measuring response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma: an analysis of the correlation between CT imaging and chemotherapy response score

2019 ◽  
Vol 29 (5) ◽  
pp. 929-934 ◽  
Author(s):  
Meabh McNulty ◽  
Adarsh Das ◽  
Paul A Cohen ◽  
Andrew Dean
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Stable Disease ◽  
Progression Free Survival ◽  
Chemotherapy Response ◽  
High Grade ◽  
Free Survival ◽  
Radiological Response ◽  
Response Score

IntroductionResponse to neoadjuvant chemotherapy is measured by CT and the decision to proceed with interval surgery is made on the radiological response after two or three cycles of therapy. The Chemotherapy Response Score grades histological tumor regression in omental metastases resected at interval surgery and is associated with progression-free survival and overall survival. It is uncertain whether radiological response is associated with prognosis and whether radiological response predicts Chemotherapy Response Score.To assess if radiological response is associated with progression-free survival and overall survival. Additionally, to investigate whether radiological response predicts the Chemotherapy Response Score.MethodsRetrospective cohort study of patients with high-grade serous ovarian cancer treated with neoadjuvant chemotherapy. Radiological response was assessed by comparing CT imaging at baseline and after neoadjuvant chemotherapy using RECIST (Response Evaluation Criteria In Solid Tumors) and classified as stable disease, partial response, complete response, or progressive disease. Survival analysis was performed using Cox proportional-hazard models and the log-rank test.ResultsA total of 71 patients met the inclusion criteria. Of these, 51 had pre- and post-neoadjuvant chemotherapy CT scans available for analysis. Radiological response was not associated with progression-free survival or overall survival on univariate analysis (stable disease vs partial response; HR for progression-free survival 1.15; 95% CI 0.57 to 2.32; p = 0.690; HR for overall survival 1.19; 95% CI 0.57 to 2.46; p = 0.645). In a multivariate model, radiological response was not associated with either progression-free survival (stable disease vs partial response; HR=1.19; 95% CI 0.498 to 2.85; p = 0.694) or overall survival (stable disease vs partial response; HR=0.954; 95% CI 0.38 to 2.40; p = 0.920). There was a significant association between the Chemotherapy Response Score and radiological response (p = 0.005).DiscussionA partial response and stable disease on radiological assessment after neoadjuvant chemotherapy in women with advanced high-grade serous ovarian cancer were not associated with survival, despite having a correlation with the Chemotherapy Response Score.

Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer

2010 ◽  
Vol 28 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Carsten Denkert ◽  
Sibylle Loibl ◽  
Aurelia Noske ◽  
Marc Roller ◽  
Berit Maria Müller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Validation Cohort ◽  
Independent Predictor ◽  
Pathologic Complete Response ◽  
Marker Genes ◽  
Cancer Tissue ◽  
Chemotherapy Response ◽  
Training Cohort ◽  
Response To Neoadjuvant Chemotherapy

Purpose Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. Methods We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell–related markers CD3D and CXCL9 with pCR. Conclusion The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.

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