tbuckley/cabot-search huggingface dataset:
Validation of a whole-blood RNA prognostic signature in metastatic castration-resistant prostate cancer (mCRPC) patients.
Authors: William K. Oh, Uma Chippada Venkata, Li Wang, Emma Reese, Tiffany Yee, Teena Kochukoshy, Che-Kai Tsao, Matt D. Galsky, Jun Zhu, Yixuan Gong
Journal: Journal of Clinical Oncology (2014)

36 Background: We developed a whole-blood RNA transcript-based six gene signature (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, CDKN1A), which separates patients with metastatic castration-resistant prostate cancer (mCRPC) into high- and low-risk survival groups (Ross et al. Lancet Oncology, 2012). In this study, the prognostic utility of the signature is validated on two independent platforms: an updated qPCR platform and an RNA-sequence platform in a new cohort of patients. The dynamic changes in the gene expression are examined during disease progression in serial samples from individual patients. Methods: Whole blood RNA was extracted from PAXgene tubes drawn from 63 patients with prostate cancer representing a range of clinical disease states. Serial samples were collected from a subset of patients (n=34). Survival prediction scores were derived independently based on the RNA-transcript levels of the six genes as quantified by a new ViiA 7 qPCR platform and by Illumina RNA-sequence. Results: The six gene signature scores generated on both qPCR and RNA-sequence platforms remain highly prognostic, separating mCRPC patients into high- and low-risk survival groups (logrank test; p-value for qPCR &lt;0.001; p-value for RNA-seq &lt;0.001). In contrast, prostate-specific antigen (PSA) fails to predict survival in the same cohort. There is a weak correlation between PSA and the six gene score (p-value of spearman correlation=0.14), indicating that the six gene score provides unique information regarding disease status. Patients with serial blood draws demonstrated no relationship with PSA changes. Patients with localized and hormone sensitive prostate cancer had significantly lower six gene scores (p-value=0.036). Individual gene analysis revealed that two genes, ABL2 and ITGAL, as the major contributors to the prognostic score. Conclusions: Our results further validate the prognostic significance of a six gene whole blood RNA signature, using an independent cohort and independent platforms.
Adherence (adh) to and beliefs about oral anticancer medications (OAMs) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Daniel M. Geynisman, Fay J. Hlubocky, Masha Kocherginsky, Walter Michael Stadler, Christopher Daugherty
Journal: Journal of Clinical Oncology (2013)

25 Background: Suboptimal adh to drugs is a problem in chronic diseases. In mRCC, OAMs are the mainstay of treatment (tx). Adh and its determinants in exclusively mRCC pts has not been studied in the US. This study aimed to evaluate adh to OAMs in mRCC pts, and describe pts understanding and beliefs about OAMs and their disease. Methods: Cross-sectional study of pts on OAMs for at least 60 days. Standardized assessment instruments used: Adh—MMAS-8 questionnaire (Q); beliefs and expectations regarding OAMs—Beliefs about Medicines Q (BMQ) and Brief-Illness Perception Q (IPQ); Quality of Life (QOL)—BSI-18, FKSI. Semi-structured interviews assessed financial burden, barriers to adh, understanding of prognosis and goals of therapy. Results: 52 pts interviewed with median age 65 (range 36-90), 73% male, 71% Caucasian, 40% college graduates. OAMs used: 38% sunitinib, 31% pazopanib, 21% everolimus, 8% axitinib. 1 st line OAM tx: 46%; 2 nd line tx: 33%; 3 rd or beyond: 21%. MMAS-8: 10% low adheres, 25% intermediate, 65% high. Income: 35%&lt;40K, 24%=40-60K, 41%&gt;60K. Adh decreased as income increased across the 3 income levels from 82% to 67% to 45% (P=0.02). 13% reported financial difficulty paying for OAMs; 19% had ≥ $100/mo (0-500) out-of-pocket (OOP) cost. BMQ-N: 20 ± 4 (8-25); BMQ-C: 12 ± 4 (5-24). IPQ: 40 ± 12 (6-71). QOL: BSI 9 ± 8 (0-38); FKSI 43 ± 8 (21-60). No significant difference between adherers and non-adherers in regard to demographic, QOL, OOP costs or belief variables was noted. 29% reported not receiving counseling on taking OAMs. 59% believed mRCC is a chronic disease, 41% believed that their OAM can cure them and strongly agreed or agreed with “I expect to be free of cancer in the future.” 48% reported discussing prognosis with their MD. Conclusions: Self-reported adh to OAMs in mRCC is much better than in other chronic diseases, but not ideal. Surprisingly, adherence was negatively associated with income. Many pts felt mRCC was a chronic disease and over 40% believed they could be cured. Further research is needed addressing the development of an oncology-specific adh tool and defining an optimal adh benchmark for OAMs via prospective studies of self-reported adh, serum drug levels, and outcomes.
Ductal carcinoma in situ (DCIS) of the breast: Race- and treatment-adjusted specific disease-free probability.
Authors: A. Stark, X. \(. Yan, R. Stapp, A. Raghunathan, L. Kirchner, J. Griggs, L. A. Newman, A. W. Dick, D. Chitale
Journal: Journal of Clinical Oncology (2011)

186 Background: Findings of DCIS outcome between African-American (AA) and White-American (WA) women are inconclusive. Methods: We conducted a retrospective longitudinal study with the objective of comparing the risk of any second breast cancer after the first primary DCIS, adjusting for pathologic prognostic indicators, treatment, age, and the established epidemiologic risk factors. Women were diagnosed and treated in one institution between 1990-1999. Diagnostic slides were reviewed and prognostic indicators documented; demographic, clinical and method of detection, screening mammography vs. palpation, were collected from medical records. We applied Accelerated Failure Time Modeling (AFTM) to determine the variables that were best associated with the risk of a second cancer. Results: 335 women, 29.6% (n=100) AA with mean age of 60 (±13) and 70.4% (n=235) WA with mean age of 57 (±12.4), contributed to this study. Distributions of some of the prognostic indicators and final treatment are presented. (Table) During the 10 years of follow-up 12.0% (n=12) of AA and 3.0% (n=7) WA experienced second cancer in ipsilateral breasts; 5.0% (n=5) of AA and 3.8% (n=9) WA in their contralateral breasts and 2 women, 1 AA and 1 WA, in both breasts. Results from the AFTM yielded race as the only variable associated with the risk of a second cancer but only in ipsilateral breasts (HR= 4.11, 95% CI=1.6-10.5 p=0.003). Conclusions: No difference in the risk of a second cancer in contralateral breast between AA and WA women support the notion of equal access and equal treatment in comparable treatment outcome. Reasons for increased risk of a second cancer in ipsilateral breast in AA women are being evaluated. [Table: see text]
Willingness of older people with cancer to participate in cancer clinical trials is not a barrier to accrual
Authors: K. K. Chan, L. Siu, C. Townsley, G. Pond, C. Marquez, S. Straus
Journal: Journal of Clinical Oncology (2005)

8245 Background: While about two-thirds of all new cancer cases occur in people ≥65 years old, <25% of clinical trial participants in U.S. and Canada are ≥65 years. Reasons for this under-representation are multi-factorial. This study aimed to explore the willingness of older patients to participate in trials. Methods: Eligible subjects >70 years old were identified from outpatient clinic lists at Princess Margaret Hospital between 4/03 and 9/03. A one-time self-administered survey was mailed to subjects. The survey was developed using a modified Delphi method and examined demographics, cancer history, previous trial participation, willingness to participate in trials using clinical scenarios, and factors that may influence willingness to participate. Scenario 1 examined the willingness to participate in cancer screening or prevention trials; scenario 2 explored treatment trials comparing experimental with standard treatment, and scenario 3 included treatment trials in situations where no standard treatment exists. The survey was distributed to 4 older patients to ensure face and content validity. Results: The response rate was 21% (92/436). Fifty-one percent of respondents were <75 years old, 34% were in remission and 30% were receiving anti-cancer treatment. Only 24% respondents reported previous trial participation; in the remaining respondents, only 19% were ever invited to participate in a trial, and only 3% actively sought trial opportunities. The willingness to participate in trials in scenarios 1, 2 and 3 were 77%, 51% and 70%, respectively. Patients not in remission and the younger elderly (age 70–74) were more willing to participate. Factors that influenced willingness to participate included oncologists’ recommendations, hope of symptomatic improvement and prolonged survival. Conclusions: Volunteer bias notwithstanding, many older subjects with cancer are willing to participate in trials. More subjects would be willing to participate in trials if they were informed of available trials. Lack of willingness to participate does not appear to be a significant barrier to accrual. Physician’s reluctance to discuss trials likely contributes to the poor observed accrual. No significant financial relationships to disclose.
AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has significant activity in imatinib-resistant <i>bcr-abl</i> positive chronic myeloid leukemia (CML)
Authors: H. Kantarjian, O. Ottmann, J. Cortes, B. Wassmann, D. Jones, A. Hochhaus, L. Alland, M. Dugan, M. Albitar, F. Giles
Journal: Journal of Clinical Oncology (2005)

3014 Background: AMN107, a novel aminopyrimidine ATP-competitive inhibitor of Bcr-Abl, is 10 to 50 fold more potent than imatinib against Bcr-Abl expressing cell lines, including most imatinib-resistant Bcr-Abl mutants. The increased potency and broader activity of AMN107, relative to imatinib, may result in clinical benefit for patients (pts) with CML. Methods: In a Phase I/II study of AMN, 52 of 67 total pts (other 15 had lymphoid disease) had imatinib resistant CML in different phases. Results: Median age was 62 years (range 15–83). CML phase was: chronic (CP) 2 pts, accelerated (AP) 35 pts; myeloid blastic (BP) 15 pts. AMN daily doses were (mg/day): 50 - 6 pts, 100 - 5 pts, 200 - 7 pts, 400 - 9 pts, 600 - 1 pt, 800 - 14 pts, 1200 - 9 pts, 400 mg BID - 1 pt. Patients have been treated for 12 to 200 days. In the overall cohort, possible AMN-related Grade 3 or 4 hematologic adverse events were observed in 5/67 pts (3 responded) at doses 200 mg or more: G3 thrombocytopenia (1 pt), G4 thrombocytopenia (1 pt), G4 thrombocytopenia, G3 anemia, G4 neutropenia (1 pt), G4 neutropenia, G4 thrombocytopenia, (1 pt), and G3 neutropenia (1 pt). Possible AMN-related non-hematologic Grade 3/4 events observed: 600 mg, G3 skin rash (1 pt); ≥ 800 mg, G3 SGOT and/or SGPT elevations (2 pts), G3 indirect hyperbilirubinemia (2 pts); 1200 mg, G2 pancreatitis (1 pt). In AP, 19/30 evaluated pts (63%) responded: 11 CHR, 7 return to chronic phase (RTC) and 1 marrow CR (MR). 6/30 evaluated pts (20%) had cytogenetic (CG) responses: complete 2, partial (Ph 1–34%) 2, minor (Ph 35–90%) 2. In myeloid BP, 7/12 evaluated pts (58%) responded: 2 CHR, 5 RTC; and 1/12 (8%) had a CG response. 1 pt in CP had CHR and a CGPR. Mutational data available in 36 pts showed 9 mutations in 15 pts: G250E(4); M351T (4); E355G (2); E459Q, Y253F, F317L, F359V, T315I, M244V (1 each). 12/15 pts with mutations responded to AMN. PK studies showed steady-states reached by day 8. Both Cmax and AUC were dose proportional from 50 to 400 mg with a median Tmax of 3 hours but were not increased with 800 - 1200 mg/daily. To increase exposure, a BID schedule is being explored. The half-life was 16 hours. Conclusions: AMN107 has significant activity in imatinib-resistant CML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera
Authors: Federico Lussana, Alessandra Carobbio, Silvia Salmoiraghi, Paola Guglielmelli, Alessandro Maria Vannucchi, Barbara Bottazzi, Roberto Leone, Alberto Mantovani, Tiziano Barbui, Alessandro Rambaldi
Journal: Journal of Hematology & Oncology (2017)

The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations. PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels. These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed.
Epidemiology and survival of metastatic gastrointestional stromal tumor: A Surveillance, Epidemiology, and End Results (SEER) database review.
Authors: Srinath Sundararajan, Abhijeet Kumar, Mohammed Nawaf Kanaan, Haiyan Cui, Emad Elquza, Hitendra Patel
Journal: Journal of Clinical Oncology (2016)

86 Background: Metastatic gastrointestinal stromal tumor (MGIST) is a rare disease with limited data available on its epidemiology and survival. We aimed to study the epidemiology and survival pattern of M-GIST by reviewing the Survival, Epidemiology and End Result (SEER) database. Methods: SEER database was reviewed for patients (pts) with histologically confirmed GIST between 2002 and 2007. Variables included were age, race, gender, date of diagnosis (DOD), stage, location of primary tumor, and disease specific survival (DSS). The association between survival and race, gender, and site of disease for metastatic GIST patients was investigated. Primary outcome was 3-year DSS. Survival rate was estimated using the Kaplan–Meier method and the difference in 3-years survival was tested by log-rank test. Cox proportional hazard regression model was employed to test the association between survival and age. Results: A total of 653 patients with MGIST pts were identified and 602 were included for analyses. The distribution of MGIST according to primary site was as follows: gastric (42%), small intestine (26.2%), colorectal (4.6%), peritoneal (4.5%), NOS (17%) and other sites (5.9%). The mean age of diagnosis was 61 years. Caucasians to African-American (AA) ratio was 3.5:1 and male to female ratio was 1.3:1. Three-year DSS was 56.5% for Caucasians compared to 62.9% in AA (p = 0.25). Three-year DSS was 57.8% for males compared to 58.6% in females (p = 0.88). Small intestine MGIST had the best 3-Year DSS of 73.8% compared to gastric MGIST, which had a 3-year DSS of 50.7%(p &lt; 0.0001). Peritoneal MGIST had the worst prognosis with 3-year DSS of 34.4%. Conclusions: MGIST had significant difference in survival based on the location of primary tumor. In contrary to the findings of previous studies, small intestine MGIST had superior 3-year DSS compared gastric primary M-GIST. There was no statistically significant difference in survival based on gender or race. [Table: see text]
Efficacy and safety of a combined treatment schedule with fulvestrant (F) and capecitabine (C) in elderly advanced breast cancer patients
Authors: I. Carreca, F. Bellomo, M. Brizzi, G. Bronte, S. Burgio, D. Piazza, S. Rizzo, S. Russo, L. Balducci
Journal: Journal of Clinical Oncology (2008)

12003 Background: Fulvestrant is the first of a new class of pure estrogen receptor antagonists. It was studied in comparison to anastrozole and tamoxifen in the 1st and 2nd line of hormonal treatment in women with advanced breast cancer. Since elderly patients develop rapid and often fatal toxicity during treatment with citotoxic drugs, we tried to design a new schedule for combined chemo-endocrine therapy to identify an effective and safe regimen for elderly pre-treated patients with positive comorbidity Charlson’s score. Methods: 20 elderly breast cancer patients with visceral metastases (mean age 70; range 65–86) previously treated with adjuvant endocrine therapy (tamoxifen or aromatase inhibitors). Comprehensive Geriatric Assessment (CGA) was previously performed to assess eligibility for chemotherapy. The dose of C was adjusted according to Kintzel-Dorr formula. Primary endpoint: clinical response rates (RR) according to WHO criteria. Secondary endpoints: toxicity profile using NCI-CTC v2.0 and quality of life (QoL) score measured through EORTC QLQ-C30 questionnaires. Results: 20 pts were treated with C 1000 mg/m2 b.i.d p.o. on days 1 to 14 every 21 days and F 250 mg as a single 5 mL i.m. injection once-monthly until disease progression. Based on CGA all patients were included into groups I-II, according to Balducci’s classification of frailty. None of the pts needed any delay in drugs delivery. We observed 7 (35%) objective responses (2 complete, 5 partial responses). Stable disease was acquired in 8 (40%) pts. Clinical benefit in 15 (75%) pts. Median time to progression was 3,2 months. No grade-4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Conclusions: First results show that this schedule is effective and safe for breast cancer elderly pts with comorbidity and frailty. All pts are till now monitored for long- term toxicity and QoL. In order to confirm these preliminary outcomes, the authors are encouraged to enlarge the study. No significant financial relationships to disclose.
Incidence of thrombosis in gastro-esophageal cancer; a cohort study of 761 patients
Authors: M. Tesselaar, N. Steeghs, F. Rosendaal, S. Osanto
Journal: Journal of Clinical Oncology (2004)

8218 Background: The incidence of venous thrombosis (VT) is increased in cancer patients compared to the general population. Patients with adenocarcinoma are believed to have the highest risk of developing VT, but limited data are available on the incidence of VT in different histological types of malignancy. To study the incidence of VT with an emphasis on the comparison between different histological types of cancer in the same organ site, we conducted a retrospective analysis in patients with upper gastro-intestinal cancer. Methods: Between 1980 and 2000, a total of 530 patients (213 adeno- and 317 squamous cell carcinoma) with esophageal cancer and between 1990 and 2000, 231 patients with gastric adenocarcinoma were included in the study. Patients and tumor characteristics were recorded from the medical records, whereas information about the VT was collected from medical records, oncology database and the regional anticoagulation clinics. All VT 1 year before, during or after the diagnosis of cancer were used for analysis. Results: Twenty-nine (5 %) of the 530 esophageal cancer patients and 23 (10 %) of the 231 gastric cancer patients developed VT. Five (10 %) of 52 VT occurred within 1 year before the diagnosis of cancer was made, 38 (73 %) coinciding with the time of diagnosis, whereas 9 (17 %) VT occurred after cancer was diagnosed (all 9 VT occurred at the time of recurrence of their cancer). The risk for VT in patients with adenocarcinoma was more than 2-fold increased as compared to those patients with a squamous cell carcinoma in all patients with upper gastro-intestinal tract cancer; i.e. 9.0 % respectively 3.8 % (OR= 2.51; 95% CI 1.30–4.88). In the patients with esophageal cancer the risk for VT was also 2-fold increased in adenocarcinoma as compared to squamous cell carcinoma; i.e. 3.8 % respectively 8.0 % (OR= 2.20; 95% CI 1.03–4.72). Conclusions: The risk of VT in patients with carcinoma arising in the upper gastro-intestinal tract is more than two-fold increased in adenocarcinoma as compared to squamous cell carcinoma. Our data on upper gastro-intestinal carcinoma confirm the notion that particular adenocarcinoma are associated with coagulopathy. No significant financial relationships to disclose.
The requirement of fentanyl patch in terminally ill patients with cancer.
Authors: Naoki Shimada, Aya Watanabe, Hiroto Ishiki, Tsukuru Chiba, Junya Kinkawa, Chie Watanabe, Keisuke Ariyoshi, Masanori Nojima, Satoru Iwase, Arinobu Tojo
Journal: Journal of Clinical Oncology (2016)

202 Background: Cancer pain is the most important problem to overcome in terminally ill cancer patients (TICPs). Recently, the fentanyl patch (FP) has been widely used for the treatment of cancer pain. However, the FP requirement largely varies in patients. The purpose of this study was to identify the determinants of the FP requirement in TICPs and propose effective pain relief using a FP. Methods: In a retrospective chart review, we investigated cancer patients who were admitted in our hospital from April 2012 to July 2015 and used FP until their deaths. We examined the time course of FP use in TICPs until death. We used descriptive statistics and a mixed effect model. The primary endpoint of this study was the final dose of FP use (FDFP). Results: Eighty patients were included the analysis. The clinical characteristics were as follows: age (median, range): 64.5 (29-88) years; male/female ratio: 40/40; primary tumor sites: pancreas (n = 33), digestive tract (n = 12), liver and bile duct (n = 7), ovary and uterus (n = 6), hematologic (n = 5), lung (n = 4), head and neck (n = 4), breast (n = 3), and other (n = 6). FDFP was inversely correlated with age (R = -0.272, P &lt; 0.05; Spearman test). The FDFP (mean ± SD) administered in the patients was 3.06 ± 3.20 mg/day (Male/Female: 3.83 ± 4.06/2.29 ± 1.81 mg/day). The FDFP was 4.36 ± 4.32/2.15 ± 1.64 mg/day in patients with/without pancreatic cancer. FDFP was significantly higher in male than in female patients (P &lt; 0.05; student’s t test), and also significantly higher in patients with pancreatic cancer than in patients without pancreatic cancer (P &lt; 0.005; student’s t test). In pancreatic cancer patients, the FP adjustments were more frequent in the last 60 days of life than in patients with other malignancies (P for interaction &lt; 0.001; mixed effect model). Conclusions: We found that younger age, male sex, and pancreatic cancer were risk factors for higher requirement of FP in TICPs. TICPs with pancreatic cancer in particular required more frequent adjustment of FP near death. We should consider quick titration of fentanyl in patients with pancreatic cancer because the pain-relieving action of FP requires time.