tbuckley/cabot-search huggingface dataset:
A cost benefit analysis of the 21-gene breast cancer assay within a Canadian health care system.
Authors: S. Hassan, N. Mittmann
Journal: Journal of Clinical Oncology (2011)

6111 Background: The 21-gene breast cancer assay (21BCA; Oncotype DX) is a predictor of 10-year risk of distant recurrence and anticipated chemotherapy benefit for node-negative, early-stage, estrogen-receptor positive, HER2-negative breast cancer (BC). 21BCA represents a new cost to a health system. There may be some cost offsets. The budget impact relative to the addition of 21BCA to a Canadian provincial framework was estimated. Methods: An Ontario population-based cohort was evaluated in 2010 Canadian dollars. A population-specific BC cohort was multiplied by the unit cost of 21BCA for the budget impact. Chemotherapy utilization, unit cost of chemotherapy, and proportion of recurrence score (RS) were used to determine potential cost offsets. For the base case eligible patients who received the assay, drug utilization was allocated equally between one of two treatments: docetaxel + cyclophosphamide (TC) or fluorouracil + epirubicin + cyclophosphamide or docetaxel (FEC-D). RS results were based on Canadian clinical experience and patients with low RS+50% of patients with intermediate RS were estimated to not receive chemotherapy. Sensitivity analyses included RS ranges, reduction in granulocyte-colony stimulating factor (G-CSF) use and chemotherapy costs. A three year time horizon for the analysis was used. The cost of adverse events was not considered in the analysis. Results: The cost of introducing 21BCA to the system in the first year would be $15.8 million (m), which would rise to $16.5m by year three. For cost offset, there would be a $27.0m cost savings associated with a reduction in chemotherapy administration in the first year; $28.2m by year three. Total system savings would represent $34.5m over three years. The results of the sensitivity analysis were robust indicating a three-year cost savings to the system ranging from $15m for low risk patients to $100m for G-CSF reduction. Conclusions: The budget impact of the cost of 21BCA would be offset by a reduction in costs associated with treatment. The use of 21BCA in BC patients resulted in more than $11m per year in savings to the health care system. This conservative analysis may show even greater costs savings if adverse event costs were considered.
Early abiraterone treatment after surgical castration in in vivo castration resistant prostate cancer (CRPC) tumors in nude mice.
Authors: Paul Thelen, Verena Reupke, Felix Bremmer, Hubertus Jarry
Journal: Journal of Clinical Oncology (2016)

263 Background: ADT is the initial therapy for advanced prostate cancer, and androgen biosynthesis inhibitors (abiraterone-acetate, AA) reveal clinical survival benefit for CRPC. On CRPC progression, therapy sequencing towards androgen receptor (AR) antagonism is applied and AA withdrawal / re-challenge strategies (+AA-AA+AA) succeeded in several case reports. Here we established a VCaP-tumor mouse model for a +AA-AA+AA-sequence and external testosterone-boosts (+AA[-AA+T]+AA). Methods: 20 tumor bearing mice (from 10 6 VCaP in Matrigel) received surgical ADT and then +AA-AA+AA, (AA intraperitoneal 70mg/kg, daily [Janssen-Cilag]), or +AA[-AA+T]+AA (+0.6 µl/kg Nebido [250mg testosterone-undecaonate/ml, Jenapharm]). Tumor growth was monitored with calipers. When tumors grew &gt; 200 mm 3 , animals were castrated and treatment-sequences began when CRPC growth became evident (n = 15) or early one week after castration (n = 5). Expression analyses were performed with Experion, CSX-96 and ChemiDoc, chemicals, software (BioRad). Steroids were quantified by Dept. Clin. Chemistry. Results: 20 tumor-bearing mice received ADT. To interfere with ADT failure for 15 mice +AA-AA+AA (n = 7) or +AA[-AA+T]+AA (n = 8) commenced when tumors doubled within two weeks. Animals benefited a reduction of up to 210 mm 3 receiving +AA-AA+AA, whereas a T-Boost in +AA[-AA+T]+AA revealed a loss of solid tumor mass as mean 42% (+/-21%) liquid effusion. No complete remission was observed, tumors &gt; 1 cm 3 were considered dead-of-disease (DOD). Another group (n = 5) was AA-treated one week after castration. There +AA-AA+AA and +AA[-AA+T]+AA resulted for one animal in DOD, however tumors of up to 990 mm 3 underwent complete remissions (n = 4) and tumor-free untreated survival. AA-withdrawal is associated with progesterone decrease and DHEA increase. AR (+ AR-Vs) decreases to 95% expression immediately after -AA and to 39% (no AR-Vs) upon +T. Conclusions: Therapy sequences with AA-withdrawal/rechallenge may lead to tumor regression and complete tumor-free survival. Concomitant with tumor regression upon AA-withdrawal, AR overexpression is reduced, which may be boosted with testosterone supplementation.
Influence of hormone receptor status on survival in male breast cancer: A SEER database analysis.
Authors: Orimisan Samuel Adekolujo, Shams Aziz Mistry, Nishkarsh Saxena, Marcello Schmidt, Perla Subbaiah, Rukevwe Ehwarieme, Madan L. Arora, Radhika Kakarala
Journal: Journal of Clinical Oncology (2014)

158 Background: In female breast cancer, estrogen receptor (ER) and/or progesterone receptor (PR) positivity confers a favorable prognosis; however, the effect of these hormone receptors (HR) on survival in male breast cancer (MBC) is controversial. The aim of this study isto determine if there is a difference in the 5 year cancer specific survival (CSS) rate of patients in different HR subgroups of MBC using the SEER database. Methods: We included patients with MBC ≥ 18 years of age in the SEER database from 1990 to 2011. Patients with unknown or borderline ER or PR status were excluded. Patients were divided into four subgroups based on HR status: ER+/PR+, ER+/PR-, ER-/PR+, ER-/PR-. Univariate analysis was done using t-test and chi-square. Multivariate Cox regression analysis was used to evaluate hazard ratios and determine the significance of covariates. Kaplan -Meier method was used to estimate survival. Results: We included 3,341 patients. The mean age was 64.9 years (SD 12.7) and most (2736, 81.9%) were Caucasians. The majority (2770, 82.9%) had ER+/PR+ tumors, 377 (11.3%) had ER+/PR- , 33 (1.0 %) had ER-/PR+ and 161(4.8%) had ER-/PR- tumors. Caucasians were more likely to have MBC positive for both ER and PR compared to African-Americans (84.1% versus 74.3%, P&lt; 0.001). ER-/PR- tumors were more likely to be poorly differentiated compared to ER+/PR+ , ER+/PR- and ER-/PR+ (62.7%, 32.2%, 44.8%, 36.4% respectively , P&lt;0.001). There was a significant difference in 5 year CSS of HR subgroups only in stage III and IV, with subgroups positive for ER consistently showing improved survival compared to ER-/PR- (Table). On multivariate analysis, positive ER or PR status was independently associated with decreased hazard of death (Hazard Ratio: 0.68 (p = 0.03); 0.78 (p = 0.04) respectively). Conclusions: Our study showed a significant difference in the 5 year CSS rate of patients in different HR subgroups of advanced stages (III and IV) of MBC. Positive HR status was associated with a better prognosis. [Table: see text]
Sorafenib in hepatocellular carcinoma (HCC): Is there a role for starting patients on a total daily dose of 400mg daily?
Authors: Olugbenga Olanrele Olowokure, Brian Singeltary, Abhimanyu Ghose,, Michelle Lynn Mierzwa, Tahir Latif, Shimul Shah, Ross Ristagno, Alok kumar Dwivedi
Journal: Journal of Clinical Oncology (2014)

364 Background: S at a starting daily dose of 400mg twice daily (800mg) is considered the standard systemic therapy for HCC, in pts with well preserved liver function and advanced stage HCC, based largely on data reported by the SHARP and Asia-pacific trials. Due to complaints regarding SE and reluctance to start at full dose, we decide to retrospectively look at our HCC data base. This single institution retrospective review, evaluated the impact of starting S at a 400mg daily (200mg twice daily). Methods: From 06/01/09-09/01/13, using ICD code 155, newly registered advanced HCC pts, ECOG PS 2, Childs Pugh (CP) class A or B who were started on S 400mg daily were identified : CT scans and AFP levels were followed. PFS was estimated from the date of commencing therapy to date of progression or death if this occurred first and OS was estimated from date of commencing therapy until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% (CI). Log rank test was used to compare the PFS according to CP class. Results: 33 pts (M:F, 21:12), mean age of 59.8y (SD: 12.40) met inclusion criteria, the median duration (MD) of follow up was 8.7 m ( 1.07-27.43). 23(69.7%) pts were CP-A. 70% had abnormal AFP and this decreased &gt; 50% from baseline in 8 (35%). 96% of the pts received prior locoregional therapy in CP-A and 50% in CP-B. Initial dose tolerance was observed in 23 (69.7%) pts. 16 pts (48.5%) needed dose reduction (CP-A: 56.5%, CP-B: 30%) while 19 (57.6%) pts were able to escalate their dose at some point (CP-A: 60.9%, CP-B: 50%). MD of (400mg/d) was 3m prior to any adjustment (CP-A: 3, CP-B: 2). Mean duration of S use was 8.88m (A-10.04, B-6.2). During follow up, 26 pts had POD and 24 pts died. There was no difference in PFS between CP-A and B and following POD 10/19 evaluable pts continued S. OS was 79 % (95%CI: 61-89%) at 3m, 67% (95%CI: 48-80%) at 6m, 50% (95%CI: 32-66%) at 9m, and 40% (95%CI: 23-57%) at 12m. The most common reported toxicities were fatigue 87.5%, diarrhea 53.1% and HFS/rash 43.8% Conclusions: In this cohort of pts S started at 400mg/d did not seem to result in worse outcomes compared to historic controls possibly due to the ability to tolerate therapy for a longer period of time.
TG-0054, a Novel and Potent Stem Cell Mobilizer, Displays Excellent PK/PD and Safety Profile in Phase I Trial.
Authors: David T. Chung, Li-Wen Chang, Ying-Huey Huang, Cheng-Yuan Tsai, Ching-Hung Hsu, Chi-Hsin R. King, Judy H. Yuan, Chi-Feng Yen, Yu-Mai Chen, Yi Chin Lu, Ming-Chu Hsu
Journal: Blood (2009)
Using adjuvant radiotherapy to improve cancer-specific survival in patients with highly aggressive prostate cancer: Examining recently released criteria.
Authors: Firas Abdollah, Giorgio Gandaglia, Alberto Briganti, Quoc-Dien Trinh, Paul Linh Nguyen, Jim C. Hu, Francesco Montorsi, Paul Perrotte, Pierre I. Karakiewicz, Maxine Sun
Journal: Journal of Clinical Oncology (2014)

30 Background: Although adjuvant radiotherapy (aRT) after radical prostatectomy (RP) improves biochemical recurrence (BCR)-free survival rates, its effect on cancer-specific mortality (CSM) in patients with prostate cancer (PCa) is still controversial. The aim of our study was to test the effect of aRT on CSM according to a risk score based on the number and nature of adverse pathological characteristics (Gleason score 8-10; pT3b/4, lymph node invasion [LNI]). Methods: Overall, 7,616 patients with pT3/4 N0/1 PCa treated with RP between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included in the study. Patients were stratified according to the risk score (less than 2 vs. 2 or more adverse characteristics), and the impact of aRT on CSM was examined in each sub-group. Additionally, to evaluate the effectiveness of aRT, we calculated the number needed to treat (NNT), defined as the average number of patients who must be treated to prevent one detrimental outcome. Subsequently, competing-risks regression models were used to test the effect of aRT on CSM rates in the overall population and after stratifying patients according to their risk score (less than 2 vs. 2 or more). Results: The risk score was associated with increasing 10-year CSM rates (P&lt;0.001). When focusing on patients with a risk score 2 or more, 10-year CSM rates were significantly lower for individuals undergoing aRT compared to their counterpart not receiving aRT (6.9 vs. 16.2%, respectively; P=0.002). The corresponding NNT to prevent one death from PCa was 10. Adjuvant RT was not associated with lower CSM rates overall and in patients with a risk score less than 2. This was confirmed in multivariable analyses, where aRT decreased the risk of CSM only in patients with a risk score 2 or more (P≤0.02). Conclusions: Our findings confirm the validity of the previously reported risk score in selecting the most optimal candidates for aRT after surgery in a large contemporary population-based cohort of patients with pT3/4 N0/1 PCa. Patients with two or more adverse pathological characteristics at RP might benefit the most from aRT in terms of reduced CSM.
Disparities in baseline magnetic resonance imaging (MRI) utilization and imaging characteristics for prostate cancer (PCa) patients.
Authors: Ayobami Ajayi, Mark Alan Rosen, Neha Vapiwala, Stefan Both, Atu Agawu, John Paul Christodouleas, Justin E. Bekelman, Zelig Tochner, Curtiland Deville
Journal: Journal of Clinical Oncology (2015)

119 Background: Blacks with low risk PCa more likely to have adverse pathologic features at prostatectomy and larger dominant intraprostatic lesions (DIPL) with high anterior foci prevalence. Whether pretreatment MRI identifies these differences is unknown. The aim of this study was to determine whether disparities exist in MRI utilization and imaging characteristics for PCa patients. Methods: An institutional database of 617 PCa patients treated with proton and/or intensity modulated radiotherapy from 2005-2013 identified patients with pelvic MRI (T2 weighted, diffusion weighted, and/or dynamic contrast-enhanced sequences, 91% with endorectal coil). DIPL presence, size, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were reviewed. Whites vs. Blacks overall and stratified by risk group were compared using Fishers exact test for categorical and student’s t-test for continuous variables (P&lt;0.05 significant). Results: Race was 367 White (59%), 208 Black (34%), and 42 Asian/Other (7%). Age (mean 67±8), Gleason score, and risk group did not differ significantly for Whites vs Blacks; clinical stage and mean PSA (ng/mL) did (White 8±11 vs Black 14±22, P&lt;0.001). Overall, 472 (77%) patients underwent baseline MRI, with Blacks (67%) less likely than Whites (81%), P&lt;0.001. The disparity was greatest for low-risk Blacks (47% vs 90%, P&lt;0.001), not significant in the intermediate-risk group (70% vs 78%, P=0.205), and reversed in high-risk (94% vs 75%, P=0.007). There were no significant differences in DIPL presence, diameter, area, ECE, or SVI overall or within low- and intermediate-risk groups. For high-risk, Blacks demonstrated smaller DIPL in maximum diameter 17 ± 8 mm (vs 21 ± 10; P=0.042) and area 185 ± 156 mm 2 (vs 295 ± 285; P=0.042), with no differences in DIPL presence, additional IPLs, ECE, or SVI. Conclusions: In this urban, academic center cohort, Black PCa patients were significantly less likely to undergo staging MRI. No differences were found in DIPL presence, area, ECE, or SVI, except in the high-risk group. Further investigation is required to better understand how pretreatment MRI utilization and imaging characteristics differ by race.
Association of long-term regular aspirin use with reduction of gastric cancer risk: A nationwide cohort study.
Authors: Young-Il Kim, So Young Kim, Jong-Hyock Park, Soo-Jeong Cho, Jun Ho Lee, Young Woo Kim, Il Ju Choi
Journal: Journal of Clinical Oncology (2014)

24 Background: Aspirin use has been associated with a decreased incidence and mortality of various gastrointestinal malignancies. In this study, we evaluated the association between aspirin use and gastric cancer risk. Methods: We randomly selected 200,000 patients with hypertension or type 2 diabetes from the Korean National Health Insurance claim database at 2004. Of these, 3,907 patients who used aspirin regularly (aspirin users) and 7,808 patients who did not use aspirin (aspirin non-users) were selected by 1:2 frequency matching (age, sex, co-morbid illnesses, and starting time of follow-up), and assessed gastric cancer incidence during the followed-up periods from January 2004 to December 2010. Results: In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) in aspirin users and 1.1% (86/7,808) in aspirin non-users, but the cumulative incidence rates were not significantly different between aspirin users and non-users (P=0.11, log-rank test). Although there was no statistical significance, a multivariate analysis showed that aspirin use was associated with reduced gastric cancer risk (adjusted hazard ratio [AHR], 0.71; 95% confidential interval [CI], 0.47–1.08; P=0.11). However, duration of aspirin use was significantly associated with the reduction of gastric cancer risk (overall AHR, 0.85; 95% CI 0.73–1.00, P=0.04), especially in patients that used aspirin for more than 3 years (AHR, 0.40; 95% CI, 0.16–0.98; P=0.04). Conclusions: Long-term regular aspiri n use is significantly associated with reduced gastric cancer risk.
Impact of polymorphisms on docetaxel-induced neutropenia in Japanese patients with gynecologic cancer.
Authors: K. Ishitani, H. Kanno, T. Uchiyama, J. Oka, T. Hamada, K. Saito, H. Matsui
Journal: Journal of Clinical Oncology (2011)

e13015 Background: Docetaxel is a key drug for the treatment of patients with gynecologic cancer. However, docetaxel-induced neutropenia, which may occur as a result of individual genetic variation, is a significant side effect of this therapy. In this study, we examined the correlation between previously reported single nucleotide polymorphisms (SNPs), rs12762549 in ABCC2 and rs11045585 in SLCO1B3, rs2740574 in CYP3A4, rs776746 in CYP3A5 and severe docetaxel-induced neutropenia in a population comprising gynecologic cancer patients who were treated with a docetaxel-contained combination therapy. Methods: Fifty-one gynecologic cancer patients treated with docetaxel were genotyped. Of these, 46 patients were treated with a combination of docetaxel and carboplatin and 5 with a combination of docetaxel and gemcitabine. We performed the TaqMan SNP genotyping assay to evaluate SNPs in ABCC2 and SLCO1B3. The DMET Plus genotyping platform (DMET) was used to evaluate other SNPs. Results: The reported scoring system using ABCC2 and SLCO1B3 did not show any significant correlation with severe neutropenia due to docetaxel. When we focused on the 42 patients treated with DC combination therapy, the homozygotes either rs12762549 in ABCC2 or rs776746 in CYP3A5 are significantly predominant in the 19 patients having grade 4 neutropenia. Conclusions: Our results suggest that the risk of severe neutropenia among Japanese gynecologic cancer patients treated with DC might be predicted by genotyping SNPs of ABCC2 and CYP3A5.
An interdisciplinary model for predicting patients at high risk for readmission amongst solid tumor oncology patients in a comprehensive cancer center.
Authors: Arvind Shinde, Ruth Nolen, Marjorie Jen Hein, Eduardo Siccion, Laura E. Crocitto, Tricia Kassab, Denise Morse, Lucille A. Leong
Journal: Journal of Clinical Oncology (2013)

190 Background: Increasing emphasis is being placed on reducing hospital readmission (readm) rates. Reduction of hospital readm remains a challenge, especially among the oncology population. Identifying patients (pts) at increased risk can assist with developing targeted interventions. Methods: From 1/1/11 to 12/31/12, an interdisciplinary team consisting of medical oncologists, hospitalist physician and NP, QI specialist, and case manager prospectively reviewed the medical oncology inpatient census on a biweekly basis to identify pts at risk for readm. Pts with any of the following conditions were considered at high risk for readm: significant pain, wounds, intestinal obstruction, refractory neutropenia despite GCSF, elderly/frail, unstable housing, patient/family non-compliance, rapid cancer progression, refusal of appropriate hospice care, and stalled care plans. These criteria were based upon previous years’ anecdotal experience. Interdisciplinary interventions to address these conditions were identified and initiated. Results: 272 pts were assessed during these sessions. Each session took on average 60 minutes. 69 pts (25%) were deemed to have at least one high risk factor. Chart review revealed that 6 died in the hospital and 13 were discharged to hospice. No pts on hospice were readmitted. Of the remaining 50 high risk pts, 14 (28%) and 25 (50%) pts were readmitted within 14 days and 30 days, respectively. Conclusions: This interdisciplinary team model seems to have a fair predictive value in identifying pts at higher risk for readmission. However, it is time and labor intensive. Enrollment of appropriate high risk pts in hospice mitigates this risk. Given the current emphasis on decreasing readm and the increased cost/penalties associated with readm, the next step will be to pilot cost-effective interventions for pts with these high risk factors. Potential interventions which we have instituted include follow-up calls, social service referrals, intensive family/pt education, clinic appointments within 3 days of discharge, greater coordination with primary care physicians, and more effective hospice discussions. Supported by CA 62505.
A phase II trial of capecitabine and docetaxel followed by 5-FU/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with breast cancer
Authors: H. Jinno, T. Ikeda, M. Mukai, Y. Kitagawa
Journal: Journal of Clinical Oncology (2008)

11536 Background: Capecitabine (X) and docetaxel (T) have demonstrated synergistic effect in preclinical models and survival benefit in metastatic breast cancer. Sequential combination of anthracycline and taxane is a care of standard as perioperative setting as well as adjuvant setting. Our purpose is to determine the efficacy of capecitabine and docetaxel followed by 5-FU/epirubicin/cyclophosphamide (FEC) in the perioperative setting. Methods: Pts with stage II-III BC received 4 cycles of XT (X 1,650 mg/m2 bid d1–14 + T 60 mg/m2 d7 q21 days) followed by 4 cycles of FEC (500, 90, 500 mg/m2 d1 q21 days). Primary endpoints were pCR rate and adverse drug reaction. A pCR was defined as the disappearance of all tumors either on macroscopic or microscopic assessment. Secondary endpoints were clinical response rate, breast conservation rate, and postoperative disease-free survival. Results: From August 2004 to June 2007, a total of 41 pts were enrolled. Median age was 50 yrs (range 27–65). Median tumor size was 3.7 cm (range 3–18). Twenty-seven (84.4%) pts were clinically node-positive. ER+, PgR+, and HER2 3+ pts were 24 (58.5%), 13 (31.7%), and 7 (17.1%), respectively. Overall response rate was 92.7%, including 22 CRs and 16 PRs. Overall pCR rate was 9.8% (4/41). Twenty-nine pts (70.7%) underwent breast conserving surgery. HER2-positive and ER-negative status was significantly correlated with a high pCR rate (p<0.01). Because of grade 3/4 neutropenia seen in 85.4% of pts, 4 pts needed dose reduction and no pts withdrew consent. Conclusions: These data indicate that XT followed by FEC90 is a well-tolerated, effective neoadjuvant treatment with a 9.8% pCR rate, 92.7% response rate, and 70.7% breast conserving rate. No significant financial relationships to disclose.