tbuckley/cabot-search huggingface dataset:
Suberoylanilide hydroxamic acid (vorinostat) post chemotherapy in hormone refractory prostate cancer (HRPC) patients (pts): A phase II trial by the Prostate Cancer Clinical Trials Consortium (NCI 6862)
Authors: M. Hussain, R. Dunn, D. Rathkopf, W. Stadler, G. Wilding, D. C. Smith, D. Bradley, K. A. Cooney, J. Zweibel, H. Scher
Journal: Journal of Clinical Oncology (2007)

5132 Background: Histone deacetylases (HDACs) are key regulators of histone acetylation status, which is critical to expression of genes implicated in the regulation of cell survival, proliferation, differentiation and apoptosis. Vorinostat is a potent oral HDAC inhibitor with anti-tumor activity in PC models and in phase I clinical trials. A phase II trial is assessing vorinostat in HRPC pts. Methods: Eligible pts had disease progression on 1 prior chemotherapy for HRPC, a PSA of ≥ 5ng/ml, and adequate organ function. Vorinostat was administered orally at 400 mg daily in 21-day cycles. Response was assessed every 12 weeks. The primary endpoint is proportion of pts without progression at 6 months by objective and biochemical measures. This study is designed to accrue 29 pts (80% power at the 5% significance level to distinguish between a rate of 10% vs 30%). If ≥ 7/29 pts are progression-free at 6 months, the drug will be recommended for further study. Secondary endpoints include safety, rate of PSA decline, objective response rate and overall survival. Correlative studies assessing the effect of vorinostat on serum levels of IL-6, soluble IL-6 receptor and gp130 levels were conducted. Results: To date 23/29 pts have been accrued. Median age is 68 years (range 54–77), 70% had performance status 1 and 78% are white. At registration disease progression was defined by: PSA in 83%, bone in 74% and soft tissue in 43%. Median number of cycles is 2 (range 1–6), 57% of pts required at least 1 dose reduction. At time of this report 39% of pts remain on therapy. 19 pts are toxicity evaluable. Most common treatment related adverse events (AEs) were: fatigue (74%), anorexia (63%), nausea (58%), diarrhea (32%), dehydration, taste alteration and vomiting (26% each). There was 1 grade (G) 4 thrombosis and 11 pts had G 3 AEs, the most common were: fatigue (32%) and nausea and anorexia (11% each). 3/9 response evaluable pts achieved stable disease. Conclusions: Vorinostat is feasible post chemotherapy in pts with HRPC, however it is associated with significant toxicities requiring dose reductions. Final efficacy, safety and correlative studies will be reported. Support: CTEP, N01-CM-62201, PC051375, PC 051382 No significant financial relationships to disclose.
CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA
Authors: Shuli Kang, Qingjiao Li, Quan Chen, Yonggang Zhou, Stacy Park, Gina Lee, Brandon Grimes, Kostyantyn Krysan, Min Yu, Wei Wang, Frank Alber, Fengzhu Sun, Steven M. Dubinett, Wenyuan Li, Xianghong Jasmine Zhou
Journal: Genome biology (2017)

We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios. CancerLocator also achieves promising results on patient plasma samples with low DNA methylation sequencing coverage.
Knowledge, attitudes, and beliefs of parents toward whole-genome sequencing in pediatric cancer.
Authors: Jenny Ruiz, Julia Lynne Glade Bender, Jennifer Oberg, Elizabeth Cohn, Jennifer Levine
Journal: Journal of Clinical Oncology (2014)

10090 Background: Introducing whole genome sequencing (WGS) in pediatric cancer patients at diagnosis poses a unique set of issues. We investigated parental knowledge, attitudes and beliefs about the role of genetics and WGS in the care of children with cancer and towards the return of secondary findings. Methods: Focus groups with parents/caretakers of children with cancer and semi-structured interviews with parents of healthy children were conducted. Participants were recruited from the outpatient pediatric oncology clinic and in-patient units, respectively, at Columbia University Medical Center. The topic guides included questions on genetic research, WGS, secondary findings, and timing of the consent process. All focus groups and interviews were audio recorded, transcribed and analyzed using thematic analysis. Results: 4 focus groups (16 participants (11 females, 5 males; 4 Hispanic, 4 African American, 1 Asian, 10 White)), and 8 semi structured interviews (7 females, 2 males; 4 Hispanic, 3 African American, and 3 White) ranging from high school to graduate school education were conducted. A wide range of knowledge about genetic testing existed among participants; few participants had prior knowledge about WGS. Participants expected that WGS research was more likely to benefit future children rather than their own child. Most participants said they would participate in WGS if there were no additional immediate risks to their child; they wanted to be told about secondary findings but worried about the potential psychosocial burden of those results. There was close to universal opinion that they would not be offering informed consent if asked to participate in WGS at diagnosis and preferred the idea of a two-step consent process. Conclusions: At baseline, parents have very limited knowledge about WGS, regardless of gender, ethnicity or attained education. Parents felt their current level of understanding and perceived level of stress at the time of a cancer diagnosis in their child would hamper the ability to give informed consent. Additional research is required to optimize patient education and timing of the informed consent discussion for WGS.
Baseline serum predictors of clinical response to CTLA4 inhibitor therapy in melanoma patients.
Authors: Krisztian Homicsko, Natacha Bordry, David Gfeller, Daniel E Speiser, Olivier Michielin
Journal: Journal of Clinical Oncology (2015)

3025 Background: A CTLA4 specific antibody (Ipilimumab, Yervoy) has been approved as first line therapy for metastatic melanoma. Despite long-term benefit for a subpopulation (~20%) of patients, the majority will unfortunately not benefit. To date, only VEGFA levels have been suggested as a potential predictive marker in serum. In the current study we set out to identify serum protein marker/s that could identify patients benefiting from ipilimumab. Methods: We performed a retrospective discovery analysis of serum samples obtained before melanoma patients started Ipilimumab treatment. We selected 5 responder and 5 non-responder patients. Response was evaluated based on the first CT scan (W12) after the first course of Ipilimumab therapy. The protocol was approved by the local IRB. Samples were analyzed for 440 proteins using the RayBio Quantibody Multiplex ELISA platform. Results are being verified in a validation cohort of 12 patients. Results: Out of 440 proteins, 29 showed a statistically significant difference (p < 0.05, two-tailed Student t-test), with 7 proteins upregulated and 22 downregulated in responders. VEGFA levels were not predictive (p = 0.4246). One particular protein showed the most significant difference and was undetectable in 5 out of 5 responders, while 4 out of 5 non-responders in the discovery cohort had the protein expressed. In this cohort, this protein showed a positive predictive value (PPV) of 83% and also a negative predictive value of 100%. We will also present the ongoing analyzes of 12 additional pretreatment samples as a validation cohort. We generated a 10-protein signature, which we are comparing with the single protein predictor. Multivariate analyzes of markers and clinical parameters are ongoing to confirm that protein B alone or the 10-protein signature is a better predictor of response and survival. Recruitment of additional patients in this translational protocol is ongoing. Conclusions: The finding that a serum protein or a protein signature predicts clinical response to ipilimumab warrants further validation in larger prospective studies. (The use of protein B and/or the 10-protein signature as predictors of response to anti-CTLA4 therapy is pending patent application).
Impact of salvage therapy with APC8015F on the overall survival (OS) benefit achieved with sipuleucel-T in three phase III studies of metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Leonard G. Gomella, Chadi Nabhan, Todd DeVries, James Boyd Whitmore, Mark Walter Frohlich, Daniel J. George
Journal: Journal of Clinical Oncology (2012)

e15120 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. Three phase III sipuleucel-T trials (D9901, D9902A and D9902B [IMPACT]) allowed control patients (pts) to receive salvage treatment with an autologous product derived from previously frozen cells (APC8015F). We previously reported that salvage therapy with APC8015F demonstrated no deleterious effect and may have improved outcomes in control pts, potentially reducing the observed survival benefit seen with sipuleucel-T. Thus, we performed an exploratory analysis of pooled data from phase III studies to estimate the impact of APC8015F treatment on the OS benefit conferred by sipuleucel-T. Methods: We analyzed the effect of salvage APC8015F therapy on OS, and used a rank-preserving structural failure time (RPSFT) model to estimate control arm OS if treatment with APC8015F had not occurred. This allows estimation of the effect of sipuleucel-T treatment on OS, adjusting for salvage effect. Results: Median OS from randomization in the three pooled trials was 25.4 months with sipuleucel-T (n=488) and 21.5 months with control (n=249). Of the control arm pts, 165 (66.3%) subsequently received APC8015F. Median OS from randomization in the control population was 23.6 months for pts receiving APC8015F and 12.7 months for those who did not. Using the RPSFT model, and assuming APC8015F was as effective as sipuleucel-T, the estimate of median OS for control pts was 17.3 months, representing an 8.1 month median increase in OS with sipuleucel-T. Results from extensions of the RPSFT model, where APC8015F is assumed to have less treatment effect than sipuleucel-T, will be presented. Conclusions: These analyses estimated a median OS benefit for sipuleucel-T between 3.9 and 8.1 months, assuming that APC8015F had either no efficacy or comparable efficacy to sipuleucel-T, respectively. The results suggest a possible greater treatment effect of sipuleucel-T than was reported in the three phase III studies. Future studies should account for potential crossover treatment bias as this may diminish estimates of OS benefit.
Correlation between the DCIS Score and traditional clinicopathologic features in the prospectively-designed Ontario population-based validation study.
Authors: Eileen Rakovitch, Sharon Nofech-Mozes, Wedad Hanna, Frederick L. Baehner, Refik Saskin, Steven M. Butler, Alan Tuck, Sandip Sengupta, Leela Elavathil, Prashant A Jani, Michel Bonin, Martin Chang, Susan Robertson, Elzbieta Slodkowska, Cindy H Fong, Joseph Michael Anderson, Farid Jamshidian, Diana B. Cherbavaz, Steven Shak, Lawrence Frank Paszat
Journal: Journal of Clinical Oncology (2015)

581 Background: In the Ontario population based study, the DCIS Score was significantly associated with 10 year risk of an ipsilateral local recurrence (LR - in situ or invasive carcinoma) in women treated with breast conserving surgery (BCS) without radiation (RT) (P < 0.001). Here we evaluate correlation between DCIS Score and clinicopathologic (CP) features in the same cohort, and whether DCIS Score provides independent recurrence risk information. Methods: The study population included 571 women diagnosed with DCIS in the province of Ontario from 1994 – 2003 prospectively selected for treatment with BCS without RT. CP variables examined included age at diagnosis, DCIS tumor size, DCIS nuclear grade, comedo necrosis (absent, focal, or extensive), histologic type, multifocality, and surgical margin width. The association between DCIS Score and CP variables was examined by spearman rank correlation, and proportional hazards regression models were used to determine variables significantly associated with LR. Results: Tumor size (p = 0.002), multifocality (p < 0.001), histologic type (p = 0.005), and nuclear grade (p = 0.04) were significantly associated with LR. In a multivariable analysis, including significant CP covariates, the DCIS Score was statistically significantly associated with LR (p = 0.02). DCIS Score was moderately correlated with grade (rs= 0.47; 95% CI 0.41,0.54), comedo necrosis (rs= 0.43; CI 0.36,0.50), tumor size (rs= 0.24; CI 0.13,0.35), and multifocality (rs= 0.11; CI 0.03,0.19) but not other features. All CP subgroups showed a wide range of DCIS Scores in each subgroup. Conclusions: DCIS Score is only moderately correlated with grade, comedo necrosis, tumor size, and multifocality. DCIS Score provides recurrence risk information independent of CP features, and quantifies risk of local recurrence in individuals treated by BCS alone, validating previous findings from the E5194 clinical trial
Normative data and clinically significant effect sizes for single-item numerical linear analogue self-assessment (LASA) scales.
Authors: Jasvinder A Singh, Dona E Locke, Daniel Satele, Suneetha Puttabasavaiah, Jan C. Buckner, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2014)

e17619 Background: To provide normative data for the single-item numerical linear analogue self-assessment (LASA) scale for overall quality of life (QOL). Methods: We analyzed baseline data from 36 clinical trials and 6 observational studies from various populations, including healthy volunteers, cancer trial patients (patients with advanced incurable cancer and patients receiving treatment with curative intent), and hospice patients. The QOL LASA was rated 0 (as bad as it can be) to 10 (as good as it can be). We calculated the summary statistics and the proportion of patients reporting a clinically meaningful deficit (CSD) of a score equal to 5 or less on the 0-10 scale. Results: For the collective sample of 9,295 individuals, the average overall QOL reported was 7.39 (SD=2.11) with a markedly skewed distribution. Roughly 17% reported a score of 5 or below indicating a clinically significant deficit in overall QOL. Hospice patients report a much lower average score of 5.7 upon entry to hospice; hospice caregivers average 7.4. Cancer patients vary within these two extremes with most patient scores averaging in the 7s on the 0-10 scale (range, 0 to 10). Men and women’s QOL distributions were virtually identical (average of 7.6 and 7.5, respectively). Overall baseline QOL was weakly related to performance status with a Spearman correlation coefficient of -0.29. Overall QOL varied across tumor type and was not related to tumor response, i.e. patients with a full or partial response reported a CSD in 11.4% of cases compared to 14.4% among those with stable disease and 18.5% among those with disease progression. Conclusions: This study provides normative data for cancer patients and healthy volunteers for overall QOL using the LASA, indicating that overall QOL is independent of performance status and tumor response.These data can serve as benchmarks for future studies.
Place matters: Identifying communities with unequal risk for prostate cancer.
Authors: Anne-Marie Meyer, Tzy-Mey Kuo, Angela Smith, Matthew Edward Nielsen
Journal: Journal of Clinical Oncology (2015)

e17519 Background: The epidemiology of prostate cancer (CaP) in the US is influenced by patient demographics, community, and provider characteristics which vary geographically. We explore this variation using incidence rates (IR) to identify areas of highest risk and deconstruct the relative influence of community and provider characteristics in the state of North Carolina (NC). Methods: We examine age-adjusted IR data from the NC cancer registry and county-level data (number of primary care and urology physicians per capita, race, education/insurance/employment) from the Area Resource File to describe disease risk in NC. Spatial clustering analysis methods were applied to evaluate spatial autocorrelation and identify clusters with significant high (HH) and low (LL) incidence relative to the surrounding area. Analyses were used to compare defining characteristics between clusters. Results: The geographic distribution of CaP Incidence in NC is not random (p<.001). Local Indicator of Spatial Association (LISA) analysis identified 12 HH clusters and 11 LL clusters. The HH clusters had a significantly larger proportion of black residents, fewer urologists and primary care physicians per capita, and lower SES than LL clusters. Conclusions: This study suggests that county-level socioeconomic and racial variables, as well as access to primary and specialty care, are associated with geographic disparities in prostate cancer. These observations support additional work with spatial regression to further characterize factors affecting disparities in incidence and outcomes to better identify targets for intervention. Community characteristics (mean and standard deviation) by HH and LL clusters. Characteristics HH Clusters (N=12) LL Clusters (N=11) P-value from t-test Urologists per 100,000 (2005) 1.3 (1.8) 4.9 (4.3) 0.0239 Primary care doctors per 100,000 (2010) 43.0 (38.1) 61.4 (33.0) 0.2287 Percent people in poverty (2006) 20.7 (4.3) 16.0 (3.0) 0.0072 Percent black (2006) 45.5 (13.1) 8.2 (9.6) < 0.0001 Percent males without insurance (2006) 18.4 (2.5) 23.9 (2.2) < 0.0001 Percent of people with less than high school education (2005-2009) 23.7 (4.5) 18.7 (4.1) 0.0121 Unemployment rate (2006) 5.9 (0.9) 4.7 (0.9) 0.0036
Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): The prostate cancer registry.
Authors: Simon Chowdhury, Alison J. Birtle, Anders Bjartell, Luis Costa, Susan Feyerabend, Luca Galli, Ewa Kalinka-Warzocha, Gero Kramer, Nicolaas Lumen, Pablo Maroto, Vsevolod B. Matveev, Thomas Paiss, Salvatore Pisconti, Dominique Spaeth, Laurent Antoni, Edwin Klumper, Robert Wapenaar, Erik Van Den Berg, Emma Lee
Journal: Journal of Clinical Oncology (2017)

212 Background: The Prostate Cancer Registry is the first prospective, international observational study in mCRPC documenting characteristics and management in routine clinical practice, independent of treatment used. The study began in June 2013 enrolling &gt; 3000 mCRPC patients (pts) followed for ≤ 3 years. Methods: Source-verified data were collected from men with documented mCRPC initiating a new mCRPC treatment or in surveillance. A history of disease progression despite surgical or chemical ADT was confirmed in all pts. This interim analysis reports baseline characteristics, treatments and outcomes in pts with no prior mCRPC treatment. To evaluate comparative effectiveness between treatments, propensity scoring (PS) methods were used to reduce effects of confounding. Results: Of 1906 evaluable pts with ≥ 12-month follow-up, the most commonly initiated first-line mCPRC treatments (n ≥ 50) were abiraterone acetate + prednisone (AA, n = 472), enzalutamide (ENZ, n = 98) or docetaxel (DOC, n = 382). Baseline characteristics, time to progression (TTP) and prostate-specific antigen (PSA) response ( ≥ 50% decrease within 6 months) are shown in the table below. Conclusions: In this real-world study, pts receiving DOC as their first mCRPC treatment had more severe disease at entry and a trend for shorter TTP vs androgen inhibitors. TTP results are consistent with those in randomised clinical trials for AA and ENZ. Clinical trial information: NCT02236637. [Table: see text]
Retrospective analysis of CA19-9 decrease in patients with metastatic pancreatic carcinoma (MPC) treated with FOLFIRINOX or gemcitabine (gem) in a randomized phase III study (ACCORD11/PRODIGE4).
Authors: Marie Robert, Marta Jarlier, Thierry Conroy, Sophie Gourgou, Françoise Desseigne, Marc Ychou, Olivier Bouche, Beata Juzyna, Jaafar Bennouna
Journal: Journal of Clinical Oncology (2014)

4115 Background: RECIST criteria remain the reference for tumor response evaluation. Carbohydrate antigen 19-9 (CA19-9) is known to be a sensitive and specific serum marker in pancreatic cancer. Its determination could be helpful to assess early therapeutic efficacy (MPACT trial, ASCO 2013, abstract 4058). Our retrospective analysis aims to evaluate CA19-9 decrease in patients included in the randomized phase III study ACCORD11/PRODIGE4 comparing FOLFIRINOX and gem in MPC. Methods: 342 patients were treated in the ACCORD11/PRODIGE4 study. CA19-9 levels were available at inclusion for all patients and 283 had abnormal values. CA19-9 measures were performed at 8 weeks ± 2 for 160 patients (gem arm, 75 patients and FOLFIRINOX arm, 85 patients). In this retrospective study, best CA19-9 decrease, or 8-week CA19-9 decrease ≥ 20 % were analysed. According to these CA19-9 rates, efficacy parameters, progression free survival (PFS) and overall survival (OS) were estimated. Results: FOLFIRINOX superiority compared with gem is confirmed in this population subgroup with a better PFS (6.7 vs 3.9 months; HR 0.52, IC95%: 0.36-0.73, p<0.001) and OS (12.0 vs 7.6 months; HR 0.55; IC95%: 0.38-0.79, p=0.001). 8-week CA19.9 decrease ≥20% was correlated with a better OS [10.3 vs 7.8 months; HR 0.57, (IC95%: 0.40-0.81); p=0.002] and PFS [6.1 vs 3.0 months, HR=0.58 (IC95%: 0.42-0.81), p=0.001]. A higher proportion of patients in the FOLFIRINOX arm had an 8-week CA19-9 and a best CA 19-9 decreases ≥20%. Median OS, PFS and ORR for those patients were improved (Table). Conclusions: CA19-9 response was increased in patients treated with FOLFIRINOX regimen and correlated with OS, PFS and ORR. CA19-9 could be considered as a potential early surrogate marker and therefore help to evaluate the efficacy of FOLFIRINOX and gem regimen. FOLFIRINOX n=85 Gem n=75 Best CA19-9 decrease, n (%) 60 (70,6) 42 (56,0) ORR, % 45,0 21,4 Median OS, mo 13,7 8,6 1-year OS, % 59,6 31,5 HR (95%CI) 0,49 [0,31-0,79] p value 0,003 8-week CA19-9 decrease ≥20%, n (%) 50 (58,8) 39 (52,0) ORR, % 44,0 23,1 median OS, mo 13,5 8,6 1-year OS, % 54,4 30,0 HR (95%CI) 0,55 [0,33-0,91] p value 0,021