tbuckley/cabot-search huggingface dataset:
Outcome of BRCA 1/2-mutated (BRCA+) and triple-negative, BRCA wild type (BRCA-wt) breast cancer patients in a phase I study of single-agent veliparib (V).
Authors: Shalu Pahuja, Jan Hendrik Beumer, Leonard Joseph Appleman, Hussein Abdul-Hassan Tawbi, Ronald G. Stoller, James J. Lee, Yan Lin, Brian Kiesel, Jing Yu, Antoinette R. Tan, Chandra Prakash Belani, Helen K. Chew, Agustin A. Garcia, Robert Morgan, Alice P. Chen, Vincent L. Giranda, Stacie Peacock Shepherd, Edward Chu, Shannon Puhalla
Journal: Journal of Clinical Oncology (2014)

135 Background: Veliparib (V) (ABT-888) is an oral, potent inhibitor of PARP 1/2. PARP inhibitors have preclinical and clinical efficacy in BRCA+ malignancies. There are genotypic and phenotypic similarities between BRCA+ cancers, serous ovarian cancer and basal-like breast cancer and we postulated that these tumors types may be similarly sensitive to single-agent PARP inhibition. This study sought to establish the maximum tolerated dose (MTD), dose -limiting toxicities (DLT), pharmacokinetic and pharmocodynamic properties, and preliminary efficacy of chronically-dosed V in 2 cohorts of patients, BRCA+ and BRCA-wt (consisting of serous ovarian cancer and triple-negative breast cancer (TNBC). Methods: A 3+3 dose escalation phase I trial was performed. Nine dose levels (DL) were planned, and dose escalation started at 50 mg BID to a maximum of 500 mg BID to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). V was administered orally continuously on a 28 day cycle. BRCA+ and BRCA-wt patients were enrolled in 2 separate cohorts with 2 separate escalations. Results: 98 (70 BRCA+ and 28 BRCA-wt) pts have been enrolled. The maximum administered dose (MAD) was 500mg BID and the MTD/RP2D is 400mg BID for both cohorts. 59 BRCA+ pts and 24 BRCA-wt pts (21 TNBC and 3 ovary) were evaluable for response. ORR was defined as CR+PR and clinical benefit rate (CBR) as CR+PR+SD &gt; 6 months. Results are summarized in the table. Conclusions: There is evidence of anti-tumor activity with V comparable to that of other PARP inhibitors in the BRCA+ population. There was indication of dose responsiveness with greater activity in this population at higher doses. There is less activity in the mostly TNBC, BRCA-wt population, although there was evidence of benefit in a small number of patients. Ongoing tissue correlative studies will help to identify potential mechanisms of sensitivity and resistance. Clinical trial information: NCT00892736. [Table: see text]
Geographic patterns of gynecologic cancer incidence and mortality
Authors: S. L. Stewart, T. D. Thompson, R. R. German, C. J. Cardinez, C. Friedman, P. A. Wingo
Journal: Journal of Clinical Oncology (2005)

5094 Background: In 2004, it is estimated that 82,550 women will be diagnosed with, and 28,720 women will die from gynecologic cancer. Uterine, cervical, and ovarian cancers account for most of gynecologic cancer diagnoses and deaths. To monitor cancer burden and define targeted interventions, CDC supports cancer incidence registration in 46 states through the National Program of Cancer Registries (NPCR), and vital stats offices in all U.S. states. Methods: The most recent incidence data from 92% and mortality data from 100% of the U.S. population were used to calculate rates. Age-adjusted aggregate incidence rates were calculated for Northeast (NE), West (W), and Midwest (MW) (but not South) regions; aggregate death rates were calculated for all U.S. census regions. Incidence and mortality comparisons were made among NE, W, and MW regions. Results: Uterine cancer (UtCa) incidence rates varied by state, ranging from 16.0 to 31.6 per 100,000 women; death rates varied and ranged from 2.5 to 6.4 per 100,000 women. Cervical cancer (CeCa) incidence rates ranged from 6.0 to 12.2; death rates ranged from 1.3 to 5.2. Ovarian cancer (OvCa) incidence rates ranged from 7.9 to 16.4; death rates ranged from 7.0 to 10.9. UtCa and OvCa incidence rates were higher among women in the NE(p<0.0001). Interestingly, although OvCa incidence was lower in the MW and W, OvCa mortality was the same in these regions compared to NE(p=0.11 NE vs. MW);(p=0.26 NE vs. W). UtCa incidence was significantly lower in the MW; whereas UtCa mortality was similar compared to NE(p=0.06). CeCa incidence and mortality was similar among the three U.S. census regions compared. Conclusions: Geographically-comprehensive cancer incidence and mortality statistics, along with tumor characteristic data, are collected and reported by NPCR and CDC. These data are an invaluable resource for clinicians for assessment of quality and access to health care. No significant financial relationships to disclose.
Capecitabine and ABI-007 chemotherapy as neoadjuvant treatment of locally advanced breast cancer
Authors: A. Veerapaneni, M. Boisvert, A. Choi, A. Aggarwal
Journal: Journal of Clinical Oncology (2008)

11535 Background: Neoadjuvant chemotherapy is used for the management of locally advanced breast cancer. Capecitabine (X) and paclitaxel have proven efficacy in the neoadjuvant setting with different dose-limiting toxicities. ABI-007 (A) is an albumin-bound form of paclitaxel that is free of solvents and is well tolerated. The primary objective of this study was to evaluate pathologic complete response (pCR) to combination XA. Methods: This phase II study was conducted at a single center with a two-stage design. Twenty-nine patients were planned for treatment, with 10 patients enrolled in the first stage. The study continued to the second stage if 1 patient experienced a pCR (no residual invasive carcinoma). Patients with untreated infiltrating carcinoma of the breast, stage II-IIIB disease, of any hormonal, HER2, or menopausal status (pre- or post-), received 4 cycles of X 825 mg/m2 orally twice daily for 14 days, and A 260 mg/m2 IV on day 1 of a 21-day treatment cycle. Clinical tumor response was assessed by ultrasound or MRI after the second and fourth cycles. pCR was assessed at the time of definitive breast surgery. Results: Between 9/2006 and 10/2007 14 patients were enrolled. Median age was 59 years (range, 45–73), 12/14 (87%) patients had Elston grade 3 tumors, 6/14 (43%) ER+/PR+/HER2-, 1/14 (7%) ER+/PR-/HER2-, 6/14 (43%) ER-/PR-/HER2-, and 1/14 (7%) HER2+. Forty-three percent of patients received the full dose of X for 4 cycles, while 64% of patients received the full dose of A for 4 cycles. Four patients (29%) received full doses of XA for 4 cycles. One of fourteen patients (7%) had a pCR, 10/14 (71%) had PR, 3/14 (21%) had SD, and 1/14 (7%) had PD. Among 6 “triple-negative” patients, there were 4 PR, 1 SD and 1 PD. The study was stopped early secondary to concerns about toxicity and low pCR. Most toxicities were grade1–2: pain (10), hyperpigmentation (10), sensory neuropathy (9), nausea/vomiting (9), diarrhea (5). Grade 3–4 toxicities leading to treatment discontinuation were hand-foot syndrome (2), neutropenia/neutropenic fever (2), syncope (2) and hypertension (1). Four patients had lumpectomy, ten patients had mastectomy. Conclusions: Combination XA has limited activity in the neoadjuvant setting with a toxicity profile that prevents administration of full-dose chemotherapy. No significant financial relationships to disclose.
Elderly patients with metastatic esophageal/gastric cancer: A pooled analysis of age-based outcomes from 8 consecutive North Central Cancer Treatment Group (NCCTG) therapeutic trials
Authors: A. Jatoi, N. R. Foster, J. Egner, P. Burch, P. J. Stella, J. Rubin, S. R. Dakhil, D. J. Sargent, B. Murphy, S. R. Alberts
Journal: Journal of Clinical Oncology (2008)

9507 Background: Do elderly patients with metastatic esophageal/gastric cancer do as well as their younger counterparts with chemotherapy? To our knowledge, this question remains unaddressed in patients with these malignancies. Methods: This study focused on 367 patients who had participated in 8 consecutive NCCTG first-line trials for incurable gastric/esophageal adenocarcinoma from 1987 through 2006. These trials tested 1) etoposide + cisplatin; 2) 5-fluorourucil + leucovorin; 3) 5-fluorouracil + levamisole; 4) irinotecan; 5) docetaxel + irinotecan; 6) docetaxel + capecitabine; 7) oxaliplatin + capecitabine; and 8) bortezomib + paclitaxel + carboplatin. The primary goal of the present study was to compare outcomes in patients ≥65 years of age versus younger. Results: 154 (42%) patients were ≥65 years old (range: 65, 86), and 213 were younger (range: 20, 64). Elderly and younger patients were comparable based on gender, cancer site (gastric versus esophagus versus gastroesophageal junction), and body mass index. Elderly patients had worse performance scores (2–3): 19% versus 8% (p<0.0001). The median survival of elderly and younger patients was 6 and 6.7 months, respectively (p=0.45); progression-free survival was 3.3 months for both groups (p=0.46). Duration of first-line therapy was also comparable in both groups. However, rates of severe hematologic and non-hematologic adverse events were higher among elderly patients: grade 3+ leukopenia occurred in 28% versus 18% (p=0.02); grade 3+ stomatitis: 6% versus 1% (p=0.01); grade 3+ fatigue: 15% versus 5% (p=0.0006); and grade 4+ vomiting: 7% versus 2% (p=0.03). Elderly patients had overall higher rates of grade 4+ events: 40% versus 28% (p=0.02). Findings were similar with an age cutoff of ≥70 years. Conclusions: Elderly patients who participated in the above trials manifested survival outcomes comparable to their younger counterparts. Although age should not preclude trial entry, the high rates of severe adverse events in the elderly suggest a need to develop more tolerable regimens. No significant financial relationships to disclose.
Tolerance of hemodialysis
Authors: D M Collins, M B Lambert, J S Tannenbaum, M Oliverio, S J Schwab
Journal: Journal of the American Society of Nephrology (1993)

Hemodialysis is frequently complicated by hypotension and associated symptoms. It has been suggested that these symptoms may be related to the biochemical changes caused by cellulosic dialysis membranes. In this study, a prospective randomized crossover trial was conducted comparing the incidence of hypotension and acute symptoms during dialysis with large-surface-area (1.6 m2) cellulosic (cuprophane [CUP]) and noncellulosic (polyacrylonitrile [PAN], AN69) membranes. Dialyzers were used for a single use only. There was no difference in predialysis BUN, predialysis blood pressure, intradialytic weight gain, blood flow, dialysis efficiency (urea reduction), dialysis duration, hematocrit, or erythropoietin dose between the two study phases. When these clinical characteristics were matched, there was no difference in the number of episodes of hypotension (CUP, 19 +/- 3; PAN, 22 +/- 3; P = not significant [NS]). The incidence of symptomatic hypotension, as reflected by the number of episodes of hypotension requiring more than 100 mL of saline for correction, was also not different between study phases (CUP, 10 +/- 1; AN69, 11 +/- 2; P = NS). The incidence of intradialytic symptoms, including emesis, cramping, headache, angina, pruritus, and bronchospasm, was similar during the two study phases (CUP, 11 +/- 2; AN69, 10 +/- 1; P = NS). It was concluded that noncellulosic membranes do not offer any significant advantage over cellulosic membranes in reducing the acute complications of hemodialysis.
An interoperable HL7 document standard to improve the quality of cancer care across multiple locations.
Authors: Jeremy Warner, Kevin S. Hughes, John C. Krauss, Suzanne Maddux, Peter Paul Yu, Edward P. Ambinder
Journal: Journal of Clinical Oncology (2013)

12 Background: Cancer care is by nature interdisciplinary and increasingly depends on seamless electronic transmission of clinical data. Health information exchange and semantic understanding are critical for improved outcomes, personalized medicine, comparative effectiveness research, and cost control. While there is a growing focus on this, sharing patient information remains difficult due to a lack of standardization and general incompatibility between electronic health record products. There is a need for well-designed, oncology-specific interoperability standards. Thus ASCO is developing standards to improve the quality and insight of cancer care. Methods: ASCO volunteers formed a Standards Work Group (Standards WG) in 2012, and ASCO engaged an independent consulting firm to perform the technical work. The Standards WG first developed an interoperable standard with broad application that would also be a foundation for future standards work. They adapted ASCO’s Breast Cancer Adjuvant Treatment Plan and Summary (Breast TPS), which was originally developed as a paper-based form. This adaptation required extensive work involving input from medical and surgical oncologists, ASCO staff, and the consultants. This preparatory work was vital to define and disambiguate clinical concepts. Some value sets in the original Breast TPS were replaced with National Cancer Institute value sets. Multiple oncology and standards stakeholders reviewed the draft to ensure accurate representation of the data and harmonization with related standards. Results: The standard was developed using the Health Level Seven International (HL7) Clinical Document Architecture, a widely used XML-based markup standard with national and international recognition. The draft Breast Cancer Adjuvant Treatment Plan and Summary Standard was successfully balloted through HL7 in May 2013 and will subsequently be published for trial use in late 2013. Conclusions: The Breast Cancer Adjuvant Treatment Plan and Summary Standard will improve quality by allowing providers to efficiently transmit clinical data with semantic meaning to health professionals, patients, quality improvement initiatives, and registries.
Targeting of endocrine therapy resistance through combined mTOR and histone deacetylase inhibition.
Authors: Peter Ordentlich, William McCulloch, Susanne Flechsig, Jens Hoffmann
Journal: Journal of Clinical Oncology (2012)

130 Background: Primary and acquired resistance to endocrine therapy in advanced breast cancer presents a significant barrier to maximizing the clinical effectiveness of these agents. We recently reported in a randomized, placebo controlled phase II study that entinostat (ENT), a class 1 selective HDAC inhibitor, combined with exemestane extended PFS and OS in postmenopausal women with ER+ positive breast cancer that had progressed on a prior nonsteroidal aromatase inhibitor. Likewise, everolimus (EVE), a mTORi, combined with exemestane or tamoxifen (TAM) also significantly extended PFS in a similar patient population. In order to determine the potential benefit of combining ENT with EVE plus hormone therapy we have piloted a series of xenograft studies in primary human tumor models of TAM sensitivity and resistance. Methods: Athymic nude mice bearing xenografts of tissue derived directly from patient tumors (MaCa4049 – TAM sensitive; MaCa3366/TAM – TAM resistant) were treated with A) vehicle B) 2 mg/kg EVE C) 2 mg/kg EVE + 10 mg/kg TAM D) 15 mg/kg ENT E) 2 mg/kg EVE + 10 mg/kg TAM + 15 mg/kg ENT. Tumor samples taken at the end of the study were cryoconserved for analysis of gene and protein expression and protein phosphorylation. Results: Growth of MaCa4049 tumors was inhibited in all treatment groups relative to vehicle in two independent studies conducted in this tumor model. Groups B, C and D demonstrated a similar level of activity while maximal inhibition was observed in Group E. All treatments were generally well tolerated with weight loss similar in groups C and E. Treatment of MaCa3366/TAM tumors is ongoing with similar levels of tumor growth inhibition in all groups observed relative to vehicle at week 7. Analysis of tumor samples from completed studies will be presented to provide insight into mechanism of action for the enhanced activity observed with the triple combination. Conclusions: Preclinical data demonstrating enhanced activity of entinostat combined with everolimus and hormone therapy provides the rationale for clinical investigation of this novel therapeutic approach to targeting hormone therapy resistance.
A phase II trial of preoperative paclitaxel, carboplatin, 5-FU and radiation in patients with resectable esophageal or gastric cancer (Ca)
Authors: P. R. Anne, R. Axelrod, E. Rosato, F. Rosato, J. Kairys, M. Ramirez, R. Cantor, A. Chapman, W. Curran, E. Mitchell
Journal: Journal of Clinical Oncology (2004)

4031 Background: Trimodality therapy has been shown in select series to be associated with an improved outcome over surgery alone for esophageal ca. A Phase I trial of preoperative paclitaxel (P), carboplatin (C), 5-FU and radiation (RT) was previously reported (IJROBP 45:3, supplement) and a phase II study initiated. The phase II study has now been completed with an endpoint of pathologic complete response (CR). Methods: Eligible patients had Stage IIA or III (AJCC 1992) esophageal or gastric cancer with adequate cardiac, pulmonary, renal and liver function. Karnofsky performance status had to be 60% or greater. Tumors were staged by CT scan and endoscopic ultrasound (when feasible). RTOG toxicity scoring was used. Paclitaxel 50 mg/m2 was given d 1,8,15,22,29 with carboplatin AUC 5 d 1, 29; 5-FU 225 mg/m2 /day 5 days per week during RT and 45 Gy RT in 25 fractions. Surgery was performed 4–6 weeks after completion of chemoradiation. Results: 36 patients are eligible and evaluable on the study. 33 patients had surgical resection, 2 had progressive disease prior to surgery. 11/36 patients had a pathologic CR (30%), 5 patients had minimal residual disease(Tis or T1) for a major response rate of 44%. 1 patient had a positive margin after resection. Therapy was well tolerated. There were 5 patients with Grade 3 and 1 with Gr 4 hematologic toxicity, 5 with Gr 3 esophagitis, 3 with Gr 3 dehydration, and 1 with a Gr 4 GI bleed. Conclusions: In conclusion, this treatment regimen is well tolerated with an excellent major response rate (44%) and pathologic CR rate (30%). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Pfizer Bristol-Myers Squibb
Complete Response After High-Dose Methotrexate-Based Chemotherapy as a Major Prognostic Factor for Primary CNS Lymphoma: An Exploratory Analysis of the LNHCP93 Trial of the Groupe d'Etude Des Lymphomes De l'Adulte.
Authors: Hervé Ghesquières, Celine Ferlay, Agathe Bajard, Catherine Sebban, David Perol, Andre Bosly, Olivier Casasnovas, Oumedaly Reman, Bertrand Coiffier, Herve Tilly, Pierre Morel, Bernard De Prijck, Eric Van Den Neste, Philippe Colin, Nicolas Ketterer, Thyss Antoine, Andre Delannoy, Corinne Haioun, Alain Devidas, Pierre Biron, Jean-Yves Blay
Journal: Blood (2009)
Real-time quality assessment of cancer care through information technology instruments incorporated into routine clinical practice
Authors: E. Galligioni, S. Forti, F. Berloffa, O. Caffo, A. Ferro, C. Eccher, A. Caldara, V. Murgia, B. Soini
Journal: Journal of Clinical Oncology (2009)

6620 Background: Information technology may provide complete and timely data, to monitor process-based and outcomes measurements, which are crucial for health care improvement. Since June 2000, we have developed an Electronic Oncological Patient Record (EOPR), which is routinely used in our Department, providing a powerful link between computer-based technology and clinical practice (Ann. Oncol. 2008). Recently EOPR was implemented with a Clinical Instrument Panel (OncoQual) which enables oncologists to explore clinical data and perform real-time process and outcome measurements, by applying a flexible module to formulate complex population queries. Methods: To evaluate the performance of OncoQual in our pts, we chose as quality indicator, the adherence to ASCO recommendations on adjuvant endocrine therapy (ET), in hormone receptor positive (HR+) breast cancer (BC) pts. In particular, we assessed pts treated from 2000 to 2004 for Tamoxifen (TAM) and pts treated from 2006 to 2007 for Aromatase Inhibitors (AIs). Furthermore TAM results were compared with the adjuvant treatments modalities of 77 italian centres, reported from a cooperative group (NORA) for the same period. Results: The results are shown in the table. Patients characteristics and Tam use in our series, were similar to those of the NORA group, while TAM use decreased and AIs increased in the 2006–07 series, as expected. It took few hours to collect and analyzed our series, which can be easily updated and adapted to different requirements. Conclusions: Our experience shows the feasibility of incorporating real-time process-based measurements into daily practice, to provide self assessment for continuous quality of care monitoring and improving. [Table: see text] No significant financial relationships to disclose.
Management of decreased bone mineral density (BMD) in men starting androgen deprivation therapy (ADT) for prostate cancer
Authors: A. H. Panju, H. Breunis, A. M. Cheung, S. Duff-Canning, N. E. Fleshner, M. Krahn, G. Naglie, G. Tomlinson, P. Warde, S. M. Alibhai
Journal: Journal of Clinical Oncology (2008)

16115 Background: Decreased BMD is a common side effect of ADT, leading to increased fracture risk. Little work has been done to determine (a) whether clinicians who prescribe ADT inform patients of this side effect; (b) whether lifestyle and drug interventions for low BMD are recommended; (c) whether interventions are dependent on baseline BMD. Methods: Men age 50+ with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual x-ray absorptiometry (DEXA) at baseline. Clinical interviews and chart reviews were conducted at the start of ADT and 6 months later to determine whether clinicians noted potential bone side effects in clinic notes and made lifestyle and/or medication recommendations. Patients were classified based on DEXA as normal BMD (T-score>-1), osteopenic (-2.5<T-score<-1), or osteoporotic (T-score<-2.5). Results: Data were available for 66 patients (mean age 70.6 y; range: 55–84); 53.0% were osteopenic and 4.6% were osteoporotic at baseline. Within 6 months of starting ADT, 25.8% of patients were informed of general side effects of ADT, and bone-specific side effects were documented in 15.2%. BMD test results were noted for 31.8% of patients. Clinicians recommended lifestyle interventions to 10.6% of patients. Calcium and vitamin D were prescribed to 16.3% of all patients within 6 months, and to 25.7% and 66.7% of osteopenic and osteoporotic patients, respectively. The use of calcium and vitamin D by 6 months was not associated with baseline BMD. Conclusions: A minority of patients are being informed of bone-specific side effects of ADT. Drug interventions to prevent BMD declines were uncommonly recommended. Practices around bone health for men starting ADT are suboptimal and do not consistently incorporate the risk of fracture. No significant financial relationships to disclose.