An estimation model for Oncotype Dx score using routine clinical and pathological parameters.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 548-548
Author(s):  
Rossana Esther Ruiz Mendoza ◽  
Fernando Namuche ◽  
Claudio J. Flores ◽  
Alfredo Aguilar ◽  
Henry Leonidas Gomez

548 Background: Oncotype Dx(ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, its cost makes it prohibitive for many health care systems. Our objective is to develop a model using routine clinical and pathological parameters to estimate ODX high risk category to guide adjuvant chemotherapy decisions. Methods: We retrospectively reviewed ODX and pathology reports from 190 early BC patients (2014 to 2016) in a specialized cancer center. Variables were selected through a multiple linear regression model. Coefficients of statistically significant variables were used to build an equation. Its results were divided into 2 estimated risk categories. ODX RS was also divided into 2 categories; above or below 25 (cut-off in TAILORx and RxPONDER). The final locked model was independently validated in 57 patients. Results: Among the tested variables, tumor size (pT), progesterone receptor (PR), Ki67 and Elston-Ellis grade were significantly associated with ODX RS (Table 1). The linear predictor is: (0.2544 x pT) – (0.0739 x PR) + (0.0861 x Ki67) + (5.4232 x Elston grade). The threshold score for this equation was set on 13 (median value) to discriminate low and high estimated risks. The correct classification rate (CCR) for the training and validation sets was 60% and 56%, respectively. CCR for high risk was 72% and 87% in the training and validation sets, respectively. Conclusions: An equation based on readily available variables correctly classified more than half of cases. Although the overall CCR is modest, our equation is remarkably useful for high risk cases requiring chemotherapy. With further validation, our model could provide a clinically useful estimation of high risk at lower cost. [Table: see text]

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6098-6098
Author(s):  
Winston Wong ◽  
Joseph Cooper ◽  
Steve Richardson ◽  
Bruce A. Feinberg

6098 Background: CareFirst BlueCross BlueShield (CFBCBS) insurance network partnered with Cardinal Health Specialty Solutions (CHSS) to develop a cancer care pathway for network physicians in 2008. The program included a recommendation for molecular diagnostic testing with the Oncotype DX assay for pts with early-stage estrogen receptor-positive breast cancer. Based on NCCN guidelines, the pathway suggested adjuvant chemotherapy for all pts with Oncotype DX Recurrence Scores (RS) in the high-risk category. We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using data from CFBCBS, CHSS proprietary claims software, and Genomic Health, we retrospectively identified a cohort of women with breast cancer who were treated on the CFBCBS clinical care pathways program from 8/2008 to 6/2011 and received Oncotype DX testing. We determined the number of pts with a RS value in the low- (RS <18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of 1174 women who received Oncotype DX testing, 53% of pts were in the low-, 35% in intermediate-, and 12% in the high-risk groups. Five percent of low-, 41% of intermediate-, and 74% percent of pts in the high-risk category were treated with chemotherapy. Twenty-six percent of pts in the high-risk group did not receive chemotherapy. Conclusions: The proportionate use of chemotherapy in the low and intermediate risk groups was as expected based on adjuvant chemotherapy guidelines; however, the underuse of chemotherapy in 26% of high-risk pts was an unexpected finding. Further study is needed to determine: (1) why physicians avoided chemotherapy in 26% of high-risk pts; (2) the overall number of appropriate pts who underwent Oncotype DX testing; and, (3) the tumor characteristics that may have driven the underutilization of chemotherapy in the high-risk population.


2020 ◽  
Author(s):  
Jiaman Lin ◽  
Zihe Guo ◽  
Shuo Wang ◽  
Xinyu Zheng

Abstract Background: Previous randomized studies have assessed the possibility of omission of chemotherapy in some hormone receptor (HR)-positive and HER2-negative (HR+/HER2-) breast cancers (BC) based on gene profiling test, e.g., Oncotype DX. The goal of this study was to evaluate if combination of six proliferation related biomarkers by immunohistochemistry (6-IHC) could be a cost-effective option in determining the necessity of adjuvant chemotherapy in HR+/HER2- BC.Methods: A retrospective analysis of HR+/HER2- BC patients was conducted in the First Affiliated Hospital of China Medical University from 2010 to 2016. The expression of 6 BC-related proliferation and invasion genes (Cathepsin L2, MMP11, CyclinB1, Aurora A, Survivin and Ki67) from Oncotype DX were analyzed through IHC (designated as 6-IHC). All the included patients were divided randomly at a 7:3 ratio into training and testing cohorts. The cutoff prognosis index (PI) of 6-IHC was determined by multivariate Cox risk regression analysis after calculating the PI of each patient in training cohort and confirmed in testing cohort. The patients were classified into “Low” and “High” risk groups based on the PI value. Kaplan-Meier (KM) method was used to analyze Disease-free survival (DFS) and overall survival (OS). 6-IHC score and other factors associated with survival benefit of adjuvant chemotherapy were compared with Ki67 index.Results: A total of 330 patients were included and divided into training cohort (n = 231) and validation cohort (n = 99). The receiver operating characteristic (ROC) curve analysis showed that the patients can be divided into 6-IHC score “High” and “Low” risk groups using the cut-off PI of 2.16. The 8-year DFS and OS were 54.6% and 69.2%, respectively in the 6-IHC score “High” risk group; 85.5% and 92.5%, respectively in the 6-IHC score “Low” risk group. The 8-year DFS and OS were 70.8% and 80.9%, respectively in the Ki67 “High” risk group, 77.7% and 87.6%, respectively in the Ki67 “Low” risk group. The KM curves showed that chemotherapy did not significantly improve the DFS in the 6-IHC score “Low” risk group (p = 0.830), but significantly improved the DFS in the 6-IHC score “High” risk group (P = 0.012).Conclusions: Combined 6-IHC score could be a reliable tool in predicting cancer-specific recurrences and survival in HR+/HER2- BC patients and identifying patients who could benefit from adjuvant chemotherapy regardless of the involvement of axillary lymph node (ALN).


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 557-557
Author(s):  
Catherine Pesce ◽  
Michelle Stempel ◽  
Anne Eaton ◽  
Sujata Patil ◽  
Edi Brogi ◽  
...  

557 Background: Oncotype DX Recurrence Score [RS] is used to predict the benefits of chemotherapy added to adjuvant hormone therapy in ER positive early stage breast cancer. It is also prognostic. However, its expense may be a concern in some health care systems and communities. In addition, it is labor intensive, requiring shipment of tissue samples to a single laboratory with an average 10-14 day turnaround time (in the US). A reliable and inexpensive estimator of the Oncotype DX risk score using readily available pathologic variables from tumor specimens could be useful. Methods: We reviewed our prospective database of patients with Oncotype DX results obtained over 2.5 years (1155 specimens with Oncotype DX scores, September 2008 – March 2011) and identified 766 invasive ductal carcinomas with known ER status, PR status, histologic grade, and nuclear grade. Through linear regression analysis, we predicted recurrence score for each tumor using these four parameters. After categorizing according to the same risk classification as in Oncotype DX (low risk: RS<18, intermediate risk: RS 18-30, or high risk: RS>30) we compared our predicted recurrence score to actual Oncotype DX recurrence score. Results: Overall 69.7% of specimens were assigned the same risk category as with the Oncotype DX level. In the predicted low risk group, 1.7% of patients were actually high risk. None of the predicted high risk patients had a low score. Conclusions: We found a strong correlation between scores estimated using our model and actual reported Recurrence Scores. If validated, our model could provide a clinically useful estimation of risk at lower cost. [Table: see text]


2018 ◽  
pp. 1-8 ◽  
Author(s):  
Renata Rodrigues da Cunha Colombo Bonadio ◽  
Renata Gondim Meira Velame Azevedo ◽  
Guilherme Harada ◽  
Samantha Cabral Severino da Costa ◽  
Vanessa Costa Miranda ◽  
...  

Purpose The best adjuvant treatment in high-risk endometrial cancer remains unclear. Although adjuvant chemotherapy seems to improve overall survival (OS) in locally advanced disease, the role of adding radiotherapy is not certain. We evaluated the outcomes of patients with high-risk endometrial cancer treated with adjuvant chemotherapy followed by radiotherapy. Patients and Methods We performed a retrospective analysis of patients with high-risk endometrial cancer (endometrioid histology stages III to IVA or carcinosarcoma, clear cell, or serous histology stages I to IVA) treated with adjuvant carboplatin and paclitaxel, followed by radiotherapy, from 2010 to 2017 at a Brazilian cancer center. The Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed using the Cox proportional hazards model. Results One hundred forty-six consecutive patients were evaluated. The OS rates were 86.2% at 3 years and 75.4% at 5 years. OS was significantly affected by pelvic lymphadenectomy ( P = .001) and positive peritoneal cytology ( P < .001). Three- and 5-year disease-free survival (DFS) rates were 78.3% and 69.5%, respectively. The initial site of recurrence was limited to the pelvis in 4.1% of patients, within the abdomen in 1.3%, and extra-abdominal in 11.6%. Patients with grade 1 or 2 endometrioid carcinoma had better prognosis than patients with endometrioid carcinoma grade 3 or nonendometrioid histology (3-year DFS, 93.67% v 68.5%, respectively; P = .0017). Conclusion Adjuvant carboplatin and paclitaxel, followed by radiotherapy, is effective in high-risk endometrial cancer and associated with low rates of pelvic recurrence, which might be explained by the addition of radiotherapy. The high-risk group is heterogeneous, and the benefit of adjuvant treatment in patients with grade 1 or 2 endometrioid carcinoma is less clear.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 229-229
Author(s):  
Komal Akhtar ◽  
Margaret K Formica ◽  
Bhaskara Madhira ◽  
Alina Basnet

229 Background: RTOG0521 and STAMPEDE showed improved Overall survival (OS) and progression free survival (PFS) respectively, of ACT (adjuvant chemotherapy) to ADT (androgen deprivation therapy) and RT (adjuvant radiotherapy) in HrPC (High Risk localized Prostate Cancer). The median age of males in these trials is in 60’s. We present an observational study reporting OS on addition of ACT to ADT and RT in male age > 65 with HrPC. Methods: A retrospective national cancer center database (NCDB) (2004-2015) analysis was done. Patients aged >65 years with non-metastatic HrPC who underwent ADT and RT with or without ACT were included. Group1 included RT+ ADT+ ACT, Group2 included RT+ ADT. OS was estimated using Kaplan Meier analysis, reported for sub groups based on age. An adjusted hazard ratio (aHR) was calculated utilizing a Cox proportional hazard regression model. Results: 1,380,357 patients with HrPC were identified. 11734 met our inclusion criteria; 128 in Group1 and 11606 in Group2. Median Age, Gleason and PSA were: Group1- 72, 9, 14.6, Group2- 74, 9 and 14. Patients who received ACT were more likely to be younger and treated in an academic setting. OS stratified by age is depicted in table. Among patients ≥ 75, OS was uniformly worse with ACT with non-significant p value (p=0.08). The aHR, group 1 vs group 2 is 1.22, 95% CI = 0.96-1.57, p=0.11, when adjusted for Age, Facility Type, Insurance, and Charlson-Deyo Score (CDS). Conclusions: Very elderly patients ≥75 years were not likely to get ACT. OS was not improved by addition of chemotherapy, at age ≥ 65yrs and more prominent at age ≥ 75. Limitations of observational database study are lack of randomizations, missing information, physician bias on choices of ACT, RT and ADT. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12562-e12562
Author(s):  
Fernando Namuche ◽  
Rossana Ruiz ◽  
Zaida Morante ◽  
Claudio J. Flores ◽  
Henry Leonidas Gomez

e12562 Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, it puts aside important clinical features. Our objective is to develop a model that uses routine clinical parameters associated with Oncotype Dx score to estimate the recurrence rate in our population. Methods: We retrospectively reviewed ODX and pathology reports from 371 early BC patients diagnosticated between 2014 and 2016 in a specialized cancer center, with a 5 year follow up. Variables were selected first with a univariate cox regression, then the statistically significant variables underwent a multivariate cox regression. The β coefficients from selected variables were used to create the prediction formula. Results: Among the tested variables, ki67, estrogen receptor (ER) and ODx score were significantly associated with Recurrence. The linear predictor is: (0.1331 x Ki67) + (0.4232 x ER)+(0.2112xODx score). The threshold score for this equation was set on 33 (median value) to discriminate low and high estimated risks for recurrence. The correct classification rate (CCR) for the training and validation sets was 76% and 68%, respectively. Conclusions: It is possible to optimize the Oncotype Dx to better determine a recurrence score with selected pathological features.


2020 ◽  
Author(s):  
Soo Youn Cho ◽  
Jeong Hoon Lee ◽  
Jai Min Ryu ◽  
Jeong Eon Lee ◽  
Eun Yoon Cho ◽  
...  

Abstract Background: The predictive value of adjuvant chemotherapy for early-stage hormone receptor-positive breast cancer has been only validated by a 21-gene expression assay. We hypothesized that deep-learning prediction from HE images, called Lunit-SCOPE, is a potential prognostic and predictive biomarker of adjuvant chemotherapy.Methods: We retrospectively collected HE slides from 1153 de-identified breast cancer patients at the Samsung Medical Center (SMC) in order to develop a deep-learning algorithm called Lunit-SCOPE. The histological parameters from 255 patients, deciphered by Lunit-SCOPE, were trained to predict the recurrence score (RS) using the 21-gene assay from Oncotype DX. We validated the model’s performance using the recurrence survival of 898 patients and The Cancer Genome Atlas (TCGA) cohort, and examined related biological functions through RNA sequence data.Results: The histologic parameter-based RS prediction model predicted the oncotype DX score (R2=0.96) and the recurrence survival analysis on the validation (p<0.01) and TCGA cohort (p<0.01), where the most important variables were the nuclear grade and the mitotic cells in the cancer epithelium. Of the 85 patients classified as the high-risk group, 72 patients who received adjuvant therapy had a significantly better survival (p<0.01). The functions of the top 300 highly correlated genes with a predicted RS were enriched for cell cycle, nuclear division and cell division. Of the 21-genes from the Oncotype DX, the predicted RS had positive correlations with the proliferation category genes and was negatively correlated with the prognostic genes in the estrogen category.Conclusion: An integrative analysis using Lunit-SCOPE predicts a high risk of recurrence and those who would benefit from adjuvant chemotherapy for early-stage hormone-positive breast cancer.


2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 32-32
Author(s):  
Michaela Ann Dinan ◽  
Xiaojuan Mi ◽  
Shelby D. Reed ◽  
Gary H. Lyman ◽  
Lesley H Curtis

32 Background: The Oncotype DX (ODX) multigene assay has been previously suggested to result in an overall reduction in the use of adjuvant chemotherapy and associated costs for women with early stage, estrogen receptor (ER)-positive breast cancer. However, the association between adoption of ODX and chemotherapy costs has only previously been considered in theoretical models and has not been examined using actual patient outcomes in real world clinical practice. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) -Medicare data of the association between overall and chemotherapy-specific costs associated with adoption of ODX testing in patients diagnosed with invasive, non-metastatic, ER-positive breast cancer between 2005 and 2009. We limited our primary analysis to women ages 66 to75 to include women in which adjuvant chemotherapy would be most likely to be considered. Total Medicare payments were used to calculate direct costs in the year following diagnosis. NCCN guidelines were used to stratify patients on the basis of clinical and pathologic features into low ( < 1.0 cm), intermediate, and high risk (node positive) disease. Results: A total of 21,272 women met study criteria. Average costs in the year following diagnosis were $31,532 in the overall cohort, and was highest for women with NCCN high risk ($45,192) vs. intermediate ($28,642) or low ($23,662) risk disease. Chemotherapy costs followed similar trends ($4,819, $1,157, and $226 respectively). In multivariable analyses, ODX was associated with a relative decrease in chemotherapy costs among high risk women (RR 0.54, 0.37-0.77), but increased costs among low and intermediate risk women (RR1.36, 1.13-1.26 and RR 3.73, 2.13-56.54). Women with high risk disease had significantly lower absolute chemotherapy costs associated with receipt of ODX (-$2,298, -$3,049 to -$1,547; All P < 0.001). Conclusions: Receipt of ODX testing was associated with relative and absolute decreases in chemotherapy costs, but only in women with high NCCN risk disease. Further research is needed to disentangle correlative vs. causative association of ODX testing with patient outcomes and costs.


Author(s):  
Nazanin K Majd ◽  
Maximilan Mastall ◽  
Heather Lin ◽  
Seyede Shiva Dibaj ◽  
Kenneth R Hess ◽  
...  

Abstract Background Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments. Methods 200 adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4y (7.1, 10.3). Results Patient’s median age at diagnosis was 29y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy . Median overall survival (OS) was 8.8y (7.2, 12.2) and median progression-free survival (PFS) was 6.6y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR]=2.5 [1.5, 4.2], p=0.0006) and PFS (HR=2.3 [1.3, 3.9], p=0.002) compared to standard-risk patients. Age, sex, and metastatic disease were not associated with survival. After adjusting for risk status, those who received RT plus adjuvant chemotherapy had superior PFS compared to RT plus neoadjuvant chemotherapy [HR=0.46 (0.22, 0.95), p=0.0357]. Within a subgroup for whom detailed clinical data were available, those who received RT plus adjuvant chemotherapy had improved PFS compared to RT only [HR = 0.24 (0.074-0.76), p = 0.016]. The substitution of cisplatin for carboplatin and the elimination of vincristine did not negatively affect outcomes. Conclusion This is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes.


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