tbuckley/cabot-search huggingface dataset:
Relationship between response and progression free survival in 8965 patients with advanced renal cell carcinoma treated with first-line antiangiogenic therapy in 39 trials.
Authors: Emilie Boissier, Johanna Wassermann, Emmanuelle Kempf, Jean-Philippe Spano, Christophe Tournigand, Benoit Rousseau
Journal: Journal of Clinical Oncology (2015)

e15581 Background: Association between objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS) remains controversial in renal cell carcinoma treated with first line antiangiogenics for advance disease. Methods: Following PRISMA guidelines, as of July,1, 2014, two independent reviewers systematically searched in MEDLINE and collected data from all published trials evaluating at least one antiangiogenic drug for advanced RCC (1st line or after cytokine only). Trials were included if it contains data about ORR, DCR and median PFS (mPFS). The association between ORR, DCR and mPFS was investigated by linear regression analysis weighted by sample size. Results: After screening 1,608 reports, we identified 33 eligible trials (19 randomised trials): 9 phase III, 21 phase II, 2 phase I-II and 1 phase I, involving 8965 pts and 57 treatment arms (35 monotherapy, 22 combination treatment). The median ORR and DCR were 27% (range 0-59) and 77% (22-93), respectively. mPFS and median overall survival (mOS) were 8.9 mo (2.8-16.8) and 23.5 mo (15.2-36.5), respectively. ORR and DCR significantly correlated with mPFS (p<001 and 0.004 respectively) with a better explicative power for the model including ORR (Adjusted R²: 47% for ORR and 16% for DCR). The regression coefficient was 0.15 for ORR, meaning that for or each 10% increase in ORR, PFS improved by 1.5 months. Conclusions: Our model suggests that ORR and DCR correlate with PFS in 1stline antiangiogenic trials in advanced RCC. ORR could be an interesting surrogate marker of PFS in future trials with antiangiogenics in RCC. Study characteristics. Total Total nb of trials 33 Total nb of treatment arms 57 Total nb. of pts 8965 Median nb. of pts per trial (range) 91 (18-557) Total nb of randomly arms 40 Total nb of randomized trials 19 Phase (III/II/I-II/I) 9/21/2/1 Nb of monotherapy / combination regimen 35 / 22 Pts with good MSKC, median % (range) 34 (6-55) Pts with intermediate MSKC, median % (range) 56 (39-92) Pts with poor MSKC, median % (range) 7 (0-26) Male pts, median % (range) 71,5 (44-85) Median age (range) 61 (18-89) % no antiangiogenics pretreated pts 84 % prior nephrectomy 87
Racial disparities in breast cancer survival.
Authors: Jeffrey H. Silber, Paul R. Rosenbaum, Amy Sanders Clark, Min Wang, Yun Teng, Richard N. Ross, Justin Ludwig, Bijan Niknam, Orit Even-Shoshan, Bruce J. Giantonio, Kevin R. Fox
Journal: Journal of Clinical Oncology (2012)

6000 Background: Reducing racial disparities in breast cancer survival has been a federal priority since the early 1990’s. We present a new method to assess disparities using sequential multivariate matching. We ask if racial disparities have increased or decreased over time and if so, what were potential reasons for such changes. Methods: We studied all women over 65 years of age in the Medicare fee for service system diagnosed with breast cancer between 1991 and 2005 who were treated in one of 12 SEER sites (the sites in SEER since 1991). There were 5,251 black patients (74% early stage (I-III), 9% late stage (IV) and 17% missing stage) and 72,695 white patients (81% early stage, 5% late stage and 14% missing stage). All black cases represented the focal group for all matches. Using multivariate matching and the propensity score, white controls were matched to blacks in steps: (1) White controls matched to black cases on age and year of diagnosis; (2) Age, year of diagnosis, and stage; (3): Age, year, stage, estrogen receptor status, grade, and 30 comorbidities. We then compare 5-year survival in the Pre and Post-Taxane periods (1991-1998, 1999-2005). Results: When whites were matched to blacks on age and diagnosis year, 5-year Kaplan-Meier survival was 69.2% vs. 56.7%, P &lt; 0.0001. Matching additionally on stage, differences = 64.1% vs. 56.7%, P &lt; 0.0001; Matching further on tumor characteristics and 30 comorbidities, the disparity reduced to 61.6% vs. 56.7%, P &lt; 0.0001. Comparing trends over time, white-black differences in survival matched for age and year were 67.6% vs. 55.2% (P &lt; 0.0001) in the pre-Taxane era (difference = 12.4%) and 71.2% vs. 58.7% (P &lt; 0.0001) in the post Taxane era (difference = 12.5%); age and year matched paired racial differences were not different across eras (P = 0.389). Conclusions: While there may have been some improvements in overall survival, racial disparities in breast cancer survival have not improved, despite important policy initiatives and treatment advances. Adjusting for presentation at diagnosis does reduce differences in survival, but even these differences remain large and significant, suggesting that differences in both presentation and treatment given presentation are contributing to this disparity.
Integration of survivorship care plans into standard care: A quality improvement project.
Authors: Patricia Deslauriers, Shanmuga Subbiah, Jane M. Fall-Dickson
Journal: Journal of Clinical Oncology (2017)

70 Background: American College of Surgeons’ Commission on Cancer accredited programs are required to provide Survivorship Care Plans (SCPs) to cancer survivors after initial cancer treatment. A critical need exists to evaluate SCP patient outcomes. The primary purpose of this quality improvement project was to integrate SCP into standard care for adult stage I, II, and III breast and colon cancer patients. Secondary aims were to examine the hypothesis that the SCP will improve participants’ knowledge base regarding their cancer, health promotion and disease prevention, satisfaction with delivery of health care, quality of life, and adherence to follow-up and surveillance testing. Methods: The IRB approved study was conducted at a hospital-based Medical Oncology Clinic (MOC) in the Western US. A pre/post design was used. Sociodemographic, Medical Outcomes Study Form-36 (MOS-SF-36), Patient Satisfaction Questionnaire Short Form-PSQ-18 (PSQ-SF-18), and Patient Knowledge of Disease Questionnaire (PKDQ) data were collected pre/post SCP. At the follow-up visit, MOS-SF-36, PSQ-SF-18, PKDQ, and open-ended evaluative questionnaire (OEEQ) data were collected. Results: Forty-two subjects were enrolled. The sample is primarily female (n = 36; 86%), Caucasian (n = 41; 97.6%), Hispanic (n = 36; 85.7%), non-high school graduates (n = 26; 61%), and unemployed/retired (n = 32; 78%). Annual incomes were primarily less than $20K (n = 32; 78%). Paticipants were post-treatment for breast cancer (n = 36) or colon cancer (n = 6). 100% of the participants returned for follow-up visits with only 2 (4.8%) delayed. There were significant increases in knowledge (p &lt; 0.001). There were no statistically significant changes in the MOS-SF-36 ant the PSQ-SF-18. Themes in the OEEQ captured satisfaction with the provision of the SCP, changes in health promotion and disease prevention habits. Conclusions: This pilot study supports the hypothesis that SCPs improve adherence to follow-up and patient knowledge, especially in a unique setting of a low socio-economic, ethnically diverse population. A larger study is needed to show statistically significant improvements in health-related quality of life and satisfaction with delivery of health care.
Histone demethylase KDM7a to control androgen receptor activity in hormone-sensitive prostate cancer.
Authors: Minyong Kang, Chang Wook Jeong, Kyoung-Hwa Lee, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak
Journal: Journal of Clinical Oncology (2017)

262 Background: Prostate cancer can be controlled by androgen-hormone treatment until the cancer becomes refractory. It is believed that hormone sensitivity is largely dependent on androgen receptor (AR) activity. Here, we investigated the molecular mechanism whereby androgen receptor activity is regulated by histone demethylase KDM7a, which demethylates histone H3K9 and H3K27. Methods: The LNCaP, PC3, and DU145 cell lines were cultured at 37 °C in 5% CO 2 in Minimum Essential Medium alpha, which was supplemented with 10% fetal bovine serum. We engineered AR-positive LNCaP cells to stably express a short-hairpin RNA against KDM7a mRNA from a lentiviral vector. To examine the mechanisms of AR regulation by KDM7a, we used various techniques of molecular biology, such as real-time PCR, western blot, and chromatin immunoprecipitation assay. Also, we performed immunohistochemical staining by using prostate cancer tissue microarray. Results: By measuring AR downstream gene expression following androgen stimulation, we found that a KDM7a-deficient cell line showed lower AR downstream gene expression compared to a control cells. KDM7a knock-down in LNCaP cell line caused decreased cell proliferation, compared to control cell line. Silencing KMD7a in AR insensitive cell lines did not cause differences in cell proliferation. Western blot analysis with modified-histone antibody revealed that the KDM7a-knock-down LNCaP cell line had increased H3K27 dimethylation. We confirmed KDM7a binding on AR target-gene promoters after hormone stimulation in chromatin-immunoprecipitation experiments. And increased H3K27 di-methylation was observed in KDM7a knock-down LNCaP stable cell. Finally, we observed that the KDM7a protein was significantly upregulated in prostate cancer tissue (compared to control tissue), and that this difference correlated with the Gleason score. Conclusions: These data suggested that KDM7a is potentially a good therapeutic target for prostate cancer drugs and can be used as potentially a good prognostic indicator for prostate cancer and related treatment strategies.
Retrospective analysis of the use of GCSF and its impact on dose-response effect for anthracycline plus taxane-based schedules in early breast cancer.
Authors: Begona Bermejo, Jose Alejandro Perez-Fidalgo, Isabel Chirivella, Isabel Catoira, Patricia Martinez, Estela Contel, Ana Lluch
Journal: Journal of Clinical Oncology (2012)

e11523 Background: Previous studies have confirmed that prophylactic GCSF significantly reduced the incidence of febrile neutropenia. Less is known about its impact on the dose-density administered in taxane-based schedules. The objective of this observational, retrospective database analysis was to evaluate the relative dose-intensity (RDI) achieved in a non-selected population in whom GCSF was administered under clinician criteria according to guidelines. Methods: Early breast cancer (stage I-IIIA) patients diagnosed from January 1999 through December 2006 and considered candidates for adjuvant anthracyclines and taxanes were included. RDI administered was measured by the number of delayed cycles as well as by the number of delayed days. GCSF was considered to have been administered even if it was given in only 1 cycle, as primary or secondary prophylaxis, or to treat neutropenia. Results: 231 breast cancer patients were included. Patients had a median age of 59 years (26-80) of whom 52% had stage III cancer. Most patients had tumors positive for hormonal receptors (83%) and 7% of tumors were considered triple negative. Adjuvant schedules administered included docetaxel (68%) or paclitaxel (32%) plus anthracyclines. GCSF was given to 40% of patients, as primary (60%) or secondary prophylaxis (31%), as well as to treat neutropenia (9%). Prophylactic GCSF was mostly given in schedules with docetaxel and anthracyclines such as TAC (85% of patients). Overall, 5 patients (2%) received &lt;85% of the RDI, 23 (10%) delayed 1 cycle and 15 (7%) delayed ≥2 cycles, and 5 (2%) showed a delay of ≥15 days. 5 and 10-year DFS rates were 0.88 (95% CI: 0.84-0.92) and 0.80 (95% CI: 0.72-0.87), respectively. No differences in terms of DFS between patients with &lt;85% vs. ≥85% of RDI were found (p=0.695). Conclusions: With adequate use of GCSF in patients treated with taxane-based schedules, 98% of patients achieved a RDI ≥85%. Schedules with docetaxel or given concurrently with anthracyclines were more likely to receive GCSF. This study was partially funded by Amgen SA.
Treatment patterns after the use of the 17-gene Genomic Prostate Score assay in Veterans newly diagnosed with clinically low-risk prostate cancer.
Authors: Julie Ann Lynch, Megan Rothney, Raoul Salup, Cesar Emilio Ercole, Sharad Mathur, David Duchene, Joseph W. Basler, Javier Hernandez, Michael Andre Liss, Michael P Porter, Jonathan L. Wright, Michael Christopher Risk, Olga Efimova, Bela Stephen Denes, Phillip G. Febbo, Atreya Dash
Journal: Journal of Clinical Oncology (2017)

54 Background: Active surveillance (AS) is a recommended management approach for low risk prostate cancer (PCa). Studies have shown high rates of AS in the Veterans Administration (VA), but concerns about missing aggressive disease lead to variation between centers. The 17-gene Genomic Prostate Score (GPS) has been validated to predict likelihood of favorable pathology (LFP) in men with clinically low risk PCa. This study compared treatment patterns before and after introduction of the GPS to determine if the assay influenced treatment patterns. Methods: Men newly diagnosed with PCa who met NCCN criteria for very low (VL), low (L), or intermediate (INT) risk PCa were eligible. Chart review of men across 6 VA medical centers (VAMCs) established treatment in untested patients in 2013-2014. In 2015, Veterans at the same VAMCs were offered the assay in a prospective study measuring treatment recommendations before and after the assay and treatment implemented based on chart review. Results: There were 200 men in the untested cohort. Characteristics: age (median = 66, range:43-83), Gleason Score (GS) (3+3:64%, 3+4:37%), PSA (mean = 6.6, range:0.7-20), NCCN risk (VL:18%, L:37%, INT:46%). There were 190 men in the prospective study with complete data. NCCN risk group: age (median = 66, range:50-85), GS (3+3:74%, 3+4:26%), PSA (mean = 6.4, range:0.4-18.1), VL:22%, L:43%, INT:35%. GPS ranged from 0-61 and LFP ranged from 38%-91%. GPS identified 24 patients who had more favorable pathology and 13 patients who had less favorable pathology than would be expected using NCCN alone. 62% of untested Veterans pursued AS compared to 74% of tested Veterans. AS increases between untested and tested cohorts were 1% in VL, 16% in L, and 3% in INT. Conclusions: Both untested and tested patients had clinical characteristics representative of low risk PCa in the VA. Use of AS increased in tested Veterans compared to untested, with the largest increases observed in NCCN low risk patients. The 17-gene assay used biological information to provide refined risk estimates in tested Veterans, assisting physicians in appropriately identifying candidates for AS or immediate treatment.
Use of Axl, a therapeutic target in AML, to mediate stroma-induced chemoresistance.
Authors: Isabel Ben Batalla, Alexander Schultze, Mark Wroblewski, Robert Erdmann, Michael Heuser, Kristoffer Riecken, Mascha Binder, Miguel Cubas-Cordova, Janning Melanie, Jasmin Wellbrock, Boris Fehse, Christian Hagel, Jürgen Krauter, James B. Lorens, Arnold Ganser, Walter M. Fiedler, Peter Carmeliet, Klaus Pantel, Carsten Bokemeyer, Sonja Loges
Journal: Journal of Clinical Oncology (2013)

7027 Background: Axl, the receptor for Growth Arrest-specific protein 6 (Gas6) plays a role in AML pathobiology (Blood Suppl. Nov 2011; 118: 940). Here, we investigated whether Axl represents a therapeutic target in AML. Methods: Gas6 levels were measured by ELISA and immunohistochemistry. Axl expression was detected by flow cytometry. Co-cultures of (murine) BM stroma cells (primary, OP9, S17) with Mv4-11 and OCI-AML5 cell lines were performed. Results: We found (i) higher expression of Axl in AML BM compared to healthy BM donors (66.20 ± 10.87 vs. 0.65 ± 0.10 %; n=8/6; p&lt;0.05); (ii) Axl expression by 68 ± 31% of AML blasts and (iv) higher expression of Axl by CD34 + CD38 - AML stem cells compared to healthy CD34 + CD38 - BM stem cells (58.43 ± 4.63 % vs. 6.00 ± 2.01 %; n=7/6; p&lt;0.05). The Axl inhibitor BGB324 dose-dependently inhibited proliferation of primary AML cells with a mean IC50 of 1.8 µM. Sensitivity to BGB324 (i.e. a lower IC50) correlated with Axl expression on leukemia cells (Pearson’s r = -0.9656, p&lt;0.05). Combination therapy with BGB324 and cytarabine exerted an additive therapeutic effect and BGB324 could chemosensitize cytarabine-resistant AML cells. Analyses of BM sections revealed that Gas6 expression was low in AML cells, similar to healthy hematopoietic cells while it was abundantly expressed in AML BM stromal cells with fibroblastic/mesenchymal morphology (BMDSCs). Gas6 expression was considerably lower in control BMDSCs (86 ± 14 % vs. 20 ± 20 %; n=5/7; p&lt;0.05) thus suggesting a possible paracrine interaction between AML cells and BMDSCs leading to Gas6 upregulation in the stroma compartment. Co-culture experiments indicated specific upregulation of murine (m)Gas6 in BMDSCs via leukemia-cell derived IL-10 and M-CSF. This stroma-derived Gas6 could mediate chemoresistance of AML cells in co-culture, which was abrogated by sAxl or by BGB324. Thus, interaction between stroma-derived Gas6 and Axl + leukemia cells forms a chemoprotective niche for leukemia cells. In line with these findings Axl blockade chemosensitizes Mv4-11 cells for treatment with doxorubicine in vivo. Conclusions: Axl represents a therapeutic target in AML and Axl inhibition by BGB324 holds potential to treat chemosensitive and chemoresistant AML.
Circulating tumor cell (CTC) enumeration in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide post-chemotherapy (phase 3 AFFIRM study).
Authors: Martin Fleisher, Daniel Costin Danila, Karim Fizazi, Mohammad Hirmand, Brian Selby, De Phung, Johann Sebastian De Bono, Howard I. Scher
Journal: Journal of Clinical Oncology (2015)

5035 Background: CTC enumeration is a biomarker associated with clinical outcomes in patients (pts) with mCRPC. CTC count at baseline (BL) and post-treatment is prognostic for survival. Enzalutamide (ENZA) was approved for post-chemotherapy CRPC based on the overall survival (OS) benefit (AFFIRM trial). In this trial, CTC enumeration was embedded as a biomarker endpoint. Methods: AFFIRM was a phase 3 study (N = 1199; NCT00974311) randomizing men who received ≤ 2 docetaxel-based chemotherapy regimens to ENZA 160 mg/day or placebo (PBO) (2:1). CTC samples were collected at sites selected for logistics and investigator interest. Conversion rate was defined as a decline from ≥ 5 (unfavorable) to < 5 (favorable) CTCs/7.5 mL of blood from BL to best post-BL result. Results: BL CTCs were obtained from 447 of 1199 pts at 89 of 156 study sites; BL demographics and disease history were similar to pts in whom samples were not collected. 382 pts had both BL and post-BL counts; OS, rPFS and select disease characteristics for pts with CTC data are shown in the table. Conversion from unfavorable to favorable CTC counts was observed in 61 of 127 pts (48%; 95% CI 39%-57%) treated with ENZA compared to 6 of 62 pts (9.7%; 95% CI 3.6%-20%) with PBO (p < 0.0001). Progression from favorable to unfavorable counts occurred in 18% of ENZA pts compared to 44% with PBO. Conclusions: Unfavourable baseline CTC counts were associated with higher PSA and greater disease burden. The higher rate of conversion from unfavorable to favorable and lower conversion from favorable to unfavorable for ENZA relative to placebo was consistent with observed OS benefit. Clinical trial information: NCT00974311. Baseline CTC < 5 ENZA n = 131 CTC < 5 PBO n = 62 CTC ≥ 5 ENZA n = 127 CTC ≥ 5 PBO n = 62 Median Age 69 70 70 70 ECOG = 0 71 (54%) 29 (47%) 36 (28%) 20 (32%) Brief Fatigue Inventory = 0 62 (52%) 19 (34%) 38 (33%) 21 (36%) Median PSA (ng/mL) 68 55 241 211 Median Hemoglobin (g/L) 124 126 114 115 Median Alk Phosphatase (U/L) 85 87 178 147 Median LDH (U/L) 185 190 236 242 Bone Mets >20 22 (17%) 11 (18%) 74 (58%) 36 (58%) OS Not reached 19.5 m 13.6 m 10.7 m HR (95% CI) 0.52 (0.28-0.98) 0.78 (0.51-1.17) rPFS 11.0 m 2.8 m 5.8 m 2.8 m HR (95% CI) 0.23 (0.16-0.35) 0.38 (0.26-0.54)
Effect of heparin bridged transrectal prostate biopsy on the risk of hemorrhage in patients requiring temporary discontinuation of warfarin.
Authors: Itsuto Hamano, Shingo Hatakeyama, Tohru Yoneyama, Yuki Tobisawa, Osamu Soma, Teppei Matsumoto, Hayato Yamamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2017)

125 Background: Safety of heparin bridging therapy for transrectal ultrasound-guided prostate (TRUS) biopsy in patients requiring temporary discontinuation of antithrombotic therapy is unknown. This study aimed to assess the relationship between heparin bridging therapy and the incidence of complications after TRUS biopsy. Methods: From January 2005 to November 2015, we performed 1307 consecutive TRUS biopsies on 1134 patients in our hospital. The patients were assigned to two groups: those without heparin bridging (the control group) and those with temporary discontinuation of antithrombotic agents with heparin bridging therapy (the bridging group). A 10–12-core TRUS biopsy was performed; the patients were evaluated for bleeding-related complications. Results: Of 1134 patients, 1109 (1281 biopsies) and 25 (26 biopsies) were assigned to the control and bridging group, respectively. Patient background did not significantly differ between the control and bridging groups, except for age, history of diabetes, cardiovascular diseases, and CHADS2 scores. Compared with the control group, the bridging group showed a significantly higher rate of complication for any complication (35% vs. 8.3%, P &lt; 0.001), bleeding-related complications (27% vs. 4.4%), and urinary tract infection (7.7% vs. 1.2%). No thromboembolic event was observed in the present study. Multivariate logistic analysis showed that heparin bridging therapy was a significant risk factor for the incidence of any complication and bleeding-related complications. Conclusions: Heparin bridging therapy with temporal discontinuation of antithrombotic agents may increase the risk of complications after TRUS biopsy. Further, large-scale studies are required to clarify the safety of heparin bridging therapy.