tbuckley/cabot-search huggingface dataset:
A meta-analysis of health-related quality of life after primary treatment for prostate cancer as measured by the Expanded Prostate Cancer Index Composite.
Authors: Nicholas RIchard Cnossen, Amber Gail Orman, Deukwoo Kwon, Chad Ritch, Mark Gonzalgo, Adrian Ishkanian, Isildinha Reis, Alan Pollack, Matthew Abramowitz
Journal: Journal of Clinical Oncology (2015)

39 Background: Health-related quality of life (HRQoL) outcomes are important in treatment selection for prostate cancer. The Expanded Prostate Cancer Index Composite (EPIC) is a validated and widely-utilized HRQoL survey which accounts for newer radiotherapeutic, surgical, and hormonal treatment methods. We present a meta-analysis of patient reported HRQoL outcomes collected with EPIC and compare HRQoL trends with radiation therapy, surgery, or active surveillance as primary treatment. Methods: The PubMed database was systematically searched for all studies which presented data directly derived from the use of EPIC on patients with prostate cancer prior to 07/09/2014. All eligible studies were selected for either inclusion and analysis or exclusion based on pre-determined criteria. The data from included studies was compiled and a simulation-based estimation method using Approximate Bayesian Computation was performed to obtain missing standard deviation estimate. A longitudinal meta-analysis was conducted to estimate EPIC-profiles for each component using Bayesian p-spline method. Results: Over 4,000 studies were searched, 152 were deemed eligible, and 39 were included. The calculated mean summary score estimates are shown in the attached table. Conclusions: In the urinary domain, radical prostatectomy (RP) has lower acute scores than active surveillance (AS) or radiation therapy (RT) without long-term difference. In the bowel domain, RT has lower scores than AS or RP acutely and long-term. In the sexual domain, RT and RP have lower acute scores than AS. RP has lower scores than RT without long-term difference. In the hormonal domain, little difference was noted between modalities. [Table: see text]
Metachronous cancer after endoscopic submucosal dissection of gastric neoplasia.
Authors: Jae Myung PARK, Seung Bae Yoon, Kyo Young Song, Chun-Hyun Lim, Yu Kyung Cho, Sang Woo Kim, Myung-Gyu Choi
Journal: Journal of Clinical Oncology (2015)

559 Background: Metachronous recurrence after endoscopic resection (ER) of gastric cancer is known to be high. However, recurrence rate of metachrous lesions after ER of gastric adenoma has not been studied well. The aim of the study was to compare the metachronous recurrence between gastric carcinoma and adenoma patients. Methods: Four hundred eight carcinoma and 539 adenoma patients were enrolled in this study, and median follow-up period was 27 months (IQR: 16-45 months). Clinicopathological characteristics were assessed. At the follow-up endoscopy, the whole gastric mucosa was examined thoroughly to detect any gastric neoplasia. All suspicious lesions were evaluated histologically on endoscopic biopsies. Surveillance endoscopic schedule was as follows: every 3–6 months within 1 year, then once every year. Results: Forty three metachronous recurrence was diagnosed in in carcinoma patients and 45 in adenoma patients. There was no significant difference in the incidence of recurrent metachronous neoplasm between carcinoma and adenoma patients (p=0.728, log-rank test). After excluding metachronous adenoma, cancer recurrence was not different either between two groups (p=0.943). After adjusting for age, sex, multiplicity, and Helicobacter pylori status, the risk of the metachronous development of gastric cancer in adenoma patients was similar with that in carcinoma patients (HR, 0.96; 95% CI, 0.63-1.45). Conclusions: Metachronous gastric cancer after ER of gastric adenoma was as high as that of gastric carcinoma. Similar endoscopic surveillance program should be applied for both gastric carcinoma and adenoma patients after ER.
Improving quality of prostate cancer care in an integrated care delivery system.
Authors: Violeta Rabrenovich, Ronald Loo, Kirk Tamaddon
Journal: Journal of Clinical Oncology (2014)

147 Background: Kaiser Permanente (KP) is an integrated care delivery system that provides clinical services to over 9 million members in nine states and the District of Columbia with the goal of providing high-quality and affordable health care to our patients. Over the last decade, the rapid adoption of prostate cancer (Pca) screening practice and technology have resulted in increased detection of Pca and helped identify opportunities for care improvement. KP initiated improvements of continuum of services provided to Pca patients. Methods: Transforming the care provided to Pca patients evolved into the first population-based cancer program that manages the entire continuum of care by taking advantage of our integrated health delivery system. Major accomplishments include appropriate Pca screening to prevent over-diagnosis (Prostate Cancer Screening), improved patient safety and claims reduction to prevent missed abnormal cancer screening (PSA Safety Net), comparative effectiveness of cancer treatment choices to improve quality, and benchmark outcomes in efficiency and clinical quality utilizing a new technology (Robotic Surgery). In addition, the program has achieved superior outcomes and value through innovative chemotherapy management for advanced disease (Lupron Management). Evidence-based medicine, research, analytics and continuous quality improvementare cornerstones of the program, while the pinnacle is our patients, who receive informed, shared decision making and equitable unbiased care. Results: We strongly believe that measures of how well our patients are living with Pca are as important as the cancer-specific survival measures; because of this, we established a prospective registry to measure quality of life for every newly diagnosed patient and stratified by all treatment types. This practice is being disseminated across the Program. Conclusions: By systematically stratifying this diverse population, we have been able to achieve efficient reliable care, and spread each successful process to other regions through collaboration with KP’s Interregional Chiefs of Urology.
Final Results From a Phase II Trial of Triapine® Plus Fludarabine for Adults with Aggressive Myeloproliferative Disorders
Authors: Michael A McDevitt, Robert L Dilley, Keith W. Pratz, B. Douglas Smith, Alison R. Moliterno, Yun Yen, Lisa Malick, Steven D. Gore, Richard J. Jones, Jaroslaw P. Maciejewski, Igor Espinoza-Delgado, Judith E. Karp
Journal: Blood (2011)
Is measuring serum levels of microRNA miR-371a-3p superior to the classical biomarkers of testicular germ cell tumors?
Authors: Klaus-Peter Dieckmann, Meike Spiekermann, Christian G Ruf, Karin Oechsle, Gazanfer Belge
Journal: Journal of Clinical Oncology (2015)

376 Background: There is need for more serum biomarkers of testicular germ cell tumors (GCTs) because the management of GCT is largely based on marker monitoring but only 60% of patients express the classical markers AFP and beta HCG. We measured serum levels of microRNA miR-371a-3p (miR-371) in GCT patients with the aim of establishing a new biomarker. Methods: Serum samples of 130 consecutive patients with GCT (75 seminoma, 55 nonseminoma; 90 clinical stage 1, 40 higher stages) were examined for miR-371a-3p before and after treatment. 105 young males with nonmalignant testicular diseases and 10 patients with non-GCT testis tumors served as controls. Serum levels of miR-371a-3p were measured by quantitative polymerase chain reaction with quantification in relation to miR-20a as internal standard. Measurements were correlated with clinical data, analysis involved descriptive statistical methods. Results: Over 90% of all patients had higher serum levels of miR-371a-3p than controls. After treatment, all elevated levels decreased to the normal range. All metastasized patients had significantly higher mean levels than stage 1 patients, serum levels appear to correlate with tumor bulk. Upon chemotherapy levels decreased with each cycle of therapy. After orchiectomy in stage 1 cases, serum levels dropped by 95% within 24 hours. Nonseminomas had higher mean levels than seminoma. Teratoma does not express miR-371a-3p. The levels remained low during follow-up. Conclusions: Serum levels of microRNA miR-371a-3p appear to comprise of all attributes of a valuable serum biomarker of germ cell tumors. This marker is also expressed in seminoma and it apparently outperforms the classical markers. Evaluation in a large scale multicentric study is warranted.
Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.
Authors: H. Ishigami, J. Kitayama, S. Kaisaki, H. Yamaguchi, H. Yamashita, S. Emoto, H. Nagawa
Journal: Journal of Clinical Oncology (2011)

139 Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m 2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m 2 (level 1), stepped up to 30 or 40 mg/m 2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m 2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m 2 and 25 mg/m 2 , respectively, while keeping the dose of IP PTX at 20 mg/m 2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. No significant financial relationships to disclose.
Onset of CT scan morphological changes in metastatic lesions and associated responses in gastric patients treated with telatinib.
Authors: P. Bhosale, J. A. Ajani, J. S. Baker, M. Whiteside, J. Castillo, L. A. Kunkel
Journal: Journal of Clinical Oncology (2011)

81 Background: Response to the antiangiogenic agent, bevacizumab, by CT has been associated with a unique morphologic change in liver metastasis (mets) where heterogeneous attenuation, variable degree of enhancement and ill-defined borders before treatment transform into homogeneous, hypoattenuating lesions with well defined borders, mimicking a cyst. CT-based morphologic criteria in colorectal cancer (CRC) had a statistically significant association with pathologic response and overall survival, (Chun, JAMA 2009). The CT changes likely reflect the replacement of mets by fibroconnective tissue rather than tumor necrosis. Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Methods: TEL0805, a Phase 2 study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Response assessments were every 2 cycles (6 weeks). The ORR in response evaluable pts was 69% (1 CR, 21 PR in 32 pts). CT films from 16/32 response evaluable pts were analyzed and reviewed by a radiologist at a single institution, 10 pts had liver mets. Results: The median onset of response was 49 days. CT changes of mets at week 6 scans included: decreased attenuation and/or a sharp interface with rapid reduction of mets (n=6); mixed response, with decreased attenuation but persistent borders, and/or slight increase in mets followed by onset of response week 12 (n=3), and PD (n=1). CT changes correlate with durable responses. Conclusions: Telatinib + XP produces rapid onset of tumor response with morphologic CT changes in gastric cancer liver mets similar to those observed in CRC pts with bevacizumab, consistent with antiangiogenic activity. Further analyses in a randomized setting to correlate CT morphologic response with survival are planned. [Table: see text]
Phase II study of sequential topoisomerase (Top) targeting regimens (reg) with irinotecan/oxaliplatin (I/O) followed by etoposide/carboplatin (E/Crb) in patients with extensive small cell lung cancer (SCLC)
Authors: J. F. Rossman, V. Reddy, B. Prescott, D. Wang, F. Robert
Journal: Journal of Clinical Oncology (2008)

19095 Background: Top inhibitors are active agents in SCLC, and preclinical models indicate that sequential administration of Top I and Top II targeting drugs can result in additive or synergistic antitumor activity. Methods: The primary objective of this study is to determine the objective response (OR) rate of sequential I/O (Regimen A) followed by E/Crb (Regimen B). Secondary endpoints include toxicities (Tx), time to progression (TTP), overall survival (OS), and immunohistochemical (IHC) evaluation of Top I/II and excision repair cross complementation I (ERCC-I) expression in tumor specimens. Chemotherapy naïve patients receive 5 cycles of sequential therapy of reg A→B. Each cycle consists of I (150–200 mg/m2) and O (85mg/m2) on day 1 followed by Crb (AUC = 6) on day 15 and E (100mg /m2) on days 15, 16, and 17. Pegfilgastrim (6mg) is given on days 2 and 18 of each 28 day cycle. Response assessment is performed after every 2 cycles. Primary refractory or relapsed patients are treated with reg A only. Results: Demographic characteristics of the 26 enrolled patients are: median age 62; gender ratio 13/13 (male/female); 10 with performance status 0–1; and 3 have primary refractory disease upon enrollment. Four patients are not included in the response data, 3 are too early to evaluate and 1 was evaluable for Tx only. Data from chemotherapy naïve patients with > 2 cycles of treatment (n=16) indicate 1 complete response, 13 partial responses, and 2 with stable disease. The median TTP is 7.5 months in the 6 patients with progression. No OR are observed in previously refractory patients (n=3). Grade 3 and 4 Tx in the 1st cycle of regimen A are neutropenia (ANC) (n=3) and fatigue (n=13). Reg B Tx are anemia (HGB) (n=5), ANC (n=5), thrombocytopenia (PLT) (n=16), and fatigue (n=4). The most common overall Tx in reg A are mild to moderate nausea and vomiting and HGB. The main dose limiting Tx (DLT) is grade 4 PLT in reg B. Conclusions: Early data indicates that this sequential approach may enhance the efficacy of chemotherapy in newly diagnosed SCLC patients. This study is actively enrolling patients, and updated findings including efficacy and pharmacogenomic correlations will be presented. No significant financial relationships to disclose.
Eliglustat, An Investigational Oral Therapy for Gaucher Disease Type 1: Phase 2 Results After 3 Years
Authors: M. Judith Peterschmitt, Elena Lukina, Nora Watman, Marta Dragosky, Marcelo Iastrebner, Gregory Pastores, Elsa Avila Arreguin, Mici Phillips, Hanna Rosenbaum, Elena Sysoeva, Rasha Aguzzi, Leorah H Ross, Ana Cristina Puga
Journal: Blood (2011)
Outcome after high-dose therapy with autologous stem cell rescue with BEAM for relapsed follicular lymphoma.
Authors: S. Montoto, J. Matthews, D. Anderson, T. A. Lister, J. G. Gribben
Journal: Journal of Clinical Oncology (2011)

e18512 Background: The role of high-dose therapy with autologous stem cell rescue (HDT-ASCR) remains a major challenge in the management of patients (pts) with follicular lymphoma (FL), particularly in view of the undoubted clinical impact of rituximab and the advent of therapeutic options such as reduced intensity conditioning allotransplants. Cyclophosphamide/total body irradiation (Cy-TBI) is associated with a high incidence of secondary myelodysplasia/acute myeloid leukaemia (sMDS/AML) in heavily pretreated pts, but it is not known if the number of prior therapy lines also influences prognosis in pts treated with BEAM for relapsed FL. This is currently of special relevance to decide the best timing for this therapy as it is pts who did not receive 1st-line rituximab (R) that are presenting with recurrent FL. Methods: From 1997 to 2008, 80 pts (41M/39F; median age: 51 yrs, range: 31-67), including 30 with transformed FL (tFL), received HDT-ASCR with BEAM for relapsed FL at our center. Results: The median time from diagnosis to HDT was 41 months (range: 4-165). The median number of previous treatment lines was 3, 61% of the pts having received >3. Thirty-eight pts (49%) received R before HDT (as part of the 1st line therapy: 1; as part of the salvage therapy before BEAM: 28; as part of the HDT: 4). There was a trend for a higher use of R before BEAM in pts with FL (56%) in comparison with those with tFL (33%, p=0.05). After a median follow-up of 76 months (range: 14-160), 2 pts developed sMDS/AML. Five-year overall survival (OS) was 71% and progression-free survival (PFS) 44%. There were no differences in PFS or OS according to the number of previous treatment lines or episodes of disease. Likewise, histology at relapse did not impact on PFS or OS. Comparison with a historical control of pts treated with Cy-TBI showed no significant differences in PFS or OS. Conclusions: Deferring HDT with BEAM until 3rd response does not impair OS in pts with FL. 5-yr PFS (%) P value 5-yr OS (%) P value Histology FL (50) tFL (30) 43 45 0.5 75 63 0.1 Episodes 1-2 (58) >3 (22) 47 33 0.4 74 61 0.1 Treatment lines 1-2 (31) >3 (49) 49 41 0.5 79 65 0.1 Prior R Yes (38) No (42) 50 40 0.2 69 71 0.6 Conditioning regimen Cy-TBI (132) BEAM (80) 59 44 0.06 65 71 0.4
Phase I study of the aurora kinases (AKs) inhibitor PHA-739358 administered as a 6 and 3-h IV infusion on Days 1, 8, 15 every 4 wks in patients with advanced solid tumors
Authors: M. De Jonge, N. Steeghs, J. Verweij, J. W. Nortier, F. Eskens, J. Ouwerkerk, B. Laffranchi, M. Mariani, M. Rocchetti, H. Gelderblom
Journal: Journal of Clinical Oncology (2008)

3507 Background: Aurora proteins belong to a family of serine/threonine kinases that are key regulators of different steps in mitosis. AKs were found to be implicated in tumorigenesis and overexpressed in cancer. Methods: Objectives were to determine the recommended dose for phase II (RP2D) and dose limiting toxicities (DLTs) during cycle 1 for each schedule, to evaluate the safety and pharmacokinetics (PK) profiles, to document antitumor activity and evaluate histone H3 phosphorylation (pH3) in skin biopsies. DLTs were defined as grade 4 neutropenia (G4 ANC) >7 days, febrile neutropenia (FN), neutropenic infection, G ≥3 thrombocytopenia (≥ 7 days or with bleeding), G ≥3 non-hematological toxicity, dose omission for ≥ G3 drug related (DR) toxicities and 2-wks delay in starting Cycle 2. Sequential cohorts of 3–6 patients (pts) were treated per dose level (DL). Results: 6-h IV infusion schedule: 42 pts were included in 7 DLs (45, 90, 135, 190, 250, 330 and 400 mg/m2). The RP2D is 330 mg/m2. DLTs were observed in 6 pts: 1 at 90 mg/m2 (infusion did not resume due to G2 hypertension), 2 at 250 mg/m2 (G3 ANC), 1 at 330 mg/m2 (FN and G3 fatigue), and 2 pts at 400 mg/m2 (G4 ANC). Neutropenia was the DLT for this schedule. The most frequent (≥ 15 % pts) DR adverse events (AEs) were, anorexia, nausea, fatigue, diarrhea, all of G1/2 as maximum severity except for 1 case of G3 fatigue at 330 mg/m2. Disease stabilization (SD) was observed in 7 pts, lasting ≥6 months in 4 cases. Cmax and AUC increased with the dose, with a limited variability among pts; terminal half-life was about 20 hr. Inhibition of pH3 in skin biopsies indicated biomarker modulation starting from 190 mg/m2. 3-h IV infusion schedule: 10 pts were included in 2 DLs: 250 (3 pts) and 330 mg/m2 (7 pts). 2 DLTs were reported at 330 mg/m2: G4 ANC and G3 fatigue. The most frequent DR AEs were fatigue and diarrhea. SD was observed in 3 pts. Conclusions: The 6-h IV infusion schedule is well-tolerated and 330 mg/m2 identified as the RP2D. PK parameters are dose/time independent and characterized by a low variability. Clinically relevant SD is reported. pH3 modulation is seen at various DLs. The 330 mg/m2 dose over 3 hr is less well tolerated. No significant financial relationships to disclose.
Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer (mPC).
Authors: Daniel A. Goldstein, Kavya Krishna, Christopher Flowers, Bassel F. El-Rayes, Tanios S. Bekaii-Saab, Anne M. Noonan
Journal: Journal of Clinical Oncology (2015)

368 Background: Multiple chemotherapy regimens are now available for the treatment of mPC. With these regimens median overall survival ranges between 6-11 months. Choice of regimen is often based on the patient’s performance status (PS) and toxicity profile of the regimen. Newer combinations may be associated with high financial costs. The objective of this study was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value. Methods: We calculated the monthly cost for individual standard regimens. These included gemcitabine (G), FOLFIRINOX (5-FU, irinotecan and oxaliplatin), and gemcitabine/nab-paclitaxel (GN-P). Furthermore, we evaluated other novel regimens. These included our institutional experience with dose-modified GN-P (dmG-NP) which will be presented at the ASCO GI conference. We additionally evaluated the cost of 3-weekly carboplatin/paclitaxel (CP) which formed the control arm of a phase II trial in mPC (NCT01280058). The results of this trial are to be presented as Late Breaking Abstract 19 at the upcoming ESMO conference. In addition to the cost of drugs, we included administration costs, and costs of toxicities (including growth factor support, blood product transfusion and hospitalization for toxicities). Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on Medicare average sale prices (all 2014 US $). Results: The monthly cost of GN-P is $12,221. FOLFIRINOX costs $3.865 per month. G alone costs $1,363 per month. DmGN-P costs $6.716 per month. CP was the cheapest combination regimen ($2,154 per month) and in a recent phase II trial has been shown to have a similar efficacy to GN-P. Conclusions: Choice of chemotherapy regimen for mPC is usually based on tolerability and efficacy of the regimen individualized to patient’s PS. Healthcare systems have finite resources, thus, there is increasing emphasis on metrics to define value in healthcare These data provide useful financial information to incorporate into the decision-making process.