tbuckley/cabot-search huggingface dataset:
An open-labeled, randomized, multicentered, phase IIa study for advanced cancer treatment by gambogic acid injection (THS).
Authors: J. Wang, Y. Chi, X. K. Zhan, G. R. Xie, Z. Z. Wang, W. Xiao, Y. G. Wang, J. F. Hu, H. Yu, L. Yang, C. X. Cui, F. X. Xiong
Journal: Journal of Clinical Oncology (2011)

e13095 Background: Gamboge acid is a pure active compound isolated from the Camboge (Garcinia Morella Desv.), a traditional Chinese herb medicine. Based on preliminary results of the completed phase I study, this phase IIa study intends to compare the efficacy and safety of different dosage schedule. Methods: The patients according to enrollment criteria were randomly signed into two arms. Arm A: a daily intravenous infusion of gamboge acid injection (THS) 45mg/m2 for 5 days for every two weeks with 21 patients. Arm B: THS 45mg/m2 intravenous infused every other day for 5 times, per every couple of weeks with 26 patients. All patients in both arms have received two consecutive courses of treatment prior the safety and efficacy evaluation. Results: Observed an objective remission rate (ORR) of 14.29% and an overall disease control rate (DCR) of 76.2% in arm A compare to observed an ORR of 0.00% and a DCR of 61.5% in arm B. Except ORR with an insufficient number of zero, DCR comparison was statistically significant (p=0.0456) with a positive RR and OR and its 95% confidence intervals. The observed adverse events or reactions mostly were grade I and II rather than grade III and IV, and those adverse events or reactions were observed in most cases after patients have received the trial drugs. There was no statistically significant difference in incidence rate of adverse events or reactions between the two armed groups. Conclusions: The preliminary results of the exploratory study indicated favorable safety profiles at 45mg/m2 in this phase IIa clinical study. The 76.19% DCR observed in Arm A is superior to that in Arm B. There was no statistically significant difference in incidence rate of adverse events or reactions between the two arms.
Allogeneic Hemopoietic Stem Transplant for Patients with Idiopathic Myelofibrosis Using a Reduced Intensity Thiotepa Based Conditioning Regimen.
Authors: Andrea Bacigalupo, Alida Dominietto, Sarah Pozzi, Giovanna Piaggio, Maria Teresa van Lint, Simonetta Zupo, Anna Maria Raiola, Marco Gobbi, Francesco Frassoni, Francesco De Stefano, Simonetta Verdiani, Giovanni Barosi
Journal: Blood (2007)
Oxaliplatin and capecitabine initially concomitant to radiotherapy then administered in the resting period in high-risk locally advanced rectal cancer.
Authors: Pei-Rong Ding, Yuan-Hong Gao, Xin An, Gong Chen, Feng-Hua Wang, Mu-Yan Cai, Zhi-Fan Zeng, Ling-Heng Kong, Jun-Zhong Lin, Xiaojun Wu, Zhen-Hai Lu, Li-Ren Li, De-Sen Wan, Zhi-Zhong Pan
Journal: Journal of Clinical Oncology (2013)

581 Background: Although neoadjuvant chemoradiotherapy (CRT) has dramatically reduced the risk of local recurrence in locally advanced rectal cancer (LARC), it fails to reduce the risk of systemic failure. To enhance systemic control, we develop an alternative approach, combining intense chemotherapy using Oxaliplatin and Capecitabine (XELOX regimen) concomitant to radiation and extending the chemotherapy regimen to the resting period (consolidation chemotherapy) for high risk LARC. The aim of the present study was to evaluate the efficacy and toxicities of this strategy. Methods: Patients with high risk LARC were treated with CRT. Two cycles of XELOX regimen was administered concomitant to radiation. Then an additional cycle of the same regimen was extended to the resting period one week after completion of chemoradiation. Tumor response, toxicities associated with CRT and consolidation chemotherapy, and surgical complications were recorded. Results: Thirty-six patients with high risk LARC were identified treated with the strategy from 2010 to 2012. All patents completed the planned dose of radiation and concurrent chemotherapy, and two patient was unable to complete the consolidation chemotherapy because of grade 3 toxicities. Grade 3 acute toxicities were 2.8% leucopenia, 2.8% diarrhea, and 2.8% radiation dermatitis. All patients underwent optimal surgery with TME, among whom sphincter-saving procedure was performed in 27 patients (75%). There was no peri-operative mortality in this cohort. Seven patients (19.4%) developed postoperative complications. Complete regression (pCR), major regression (nearly pCR), and moderate or minimal regression were achieved in 13 (36.1%), 16 patients (44.4%), and 7 patients (19.5%), respectively. Conclusions: The preliminary results suggest that XELOX regimen concomitant to radiation and extended to the “resting period” after radiation completion are well tolerated. This strategy is associated with high pCR and nearly pCR rates. The promising results warrant further investigation of the impact of consolidation chemotherapy following CRT for LARC in future clinical trials.
Induction of apoptosis by the BRAFV600E kinase inhibitor PLX4032 in BRAFV600E melanoma cells through regulation of endoplasmic reticulum stress-related genes.
Authors: F. E. Meier, D. Beck, H. Niessner, K. T. Flaherty, J. Iovanna, D. Kulms, D. Schadendorf, C. Garbe
Journal: Journal of Clinical Oncology (2011)

8518 Background: In a previous study, we showed that the pan-RAF inhibitor sorafenib induces upregulation of endoplasmic reticulum (ER) stress-related genes and apoptosis in melanoma cells in vitro. Methods: In this study, we posed the question whether PLX4032, which selectively inhibits the BRAFV600E kinase and demonstrated potent antitumor activity in melanoma patients with the BRAFV600E mutation, induces ER stress-mediated apoptosis in metastatic melanoma cells harboring a BRAFV600E mutation. Results: The BRAFV600E kinase inhibitor PLX4032 inhibited growth, induced apoptosis and upregulated the ER stress-related genes p8, CHOP, ATF4, ATF3 and TRB3 exclusively in BRAFV600E mutated melanoma cell lines. Furthermore, electron microscopy showed morphological features of ER stress, in particular significant swelling of the ER lumen of BRAFV600E melanoma cells treated with PLX4032 compared with BRAFV600E melanoma cells treated with vehicle. siRNA inhibition of p8 reduced melanoma cell apoptosis induced by PLX4032, overexpression of p8 enforced melanoma cell apoptosis induced by PLX4032. Furthermore, classical ER stress inducers such as thapsigargin and tunicamycin potently inhibited growth, induced apoptosis and suppressed invasive tumor growth of melanoma cells. Moreover, both thapsigargin and tunicamycin upregulated p8 and CHOP and induced apoptosis in PLX4032-resistant melanoma cells. Conclusions: These data suggest that the BRAFV600E kinase inhibitor PLX4032 induces apoptosis in BRAFV600E melanoma cells through upregulation of ER stress-related genes, and that melanoma cells which acquired resistance to PLX4032 may be sensitive to agents which induce ER stress-mediated apoptosis through a different mechanism.
Effectiveness and safety in very elderly patients treated by bevacizumab (BV) plus chemotherapy in first-line therapy of metastatic colorectal cancer: Results of ETNA, a French cohort study.
Authors: D. Smith, M. Rouyer, P. Noize, R. Lassalle, O. Bernard, F. Burki, P. Guichard, A. Ravaud, N. Moore, A. Fourrier-Ráglat
Journal: Journal of Clinical Oncology (2011)

555 Background: In view of the ageing population, oncogeriatrics has become a priority for public health. Elderly cancer patients are often excluded from clinical trials and there is no therapeutic standard for their care management. Cohort studies have been conducted in US and Europe but not in France. The ETNA study aimed to describe BV use and survival outcomes in real-life practice. Here, the population aged &gt;75 years was compared to that aged &gt;75. Methods: ETNA is a cohort study conducted in 28 French centers that included 411 patients initiating BV between Jan 2006 and Dec 2007, with 24 month follow-up. Results: Fifty-one patients (12.4%) of the cohort were over 75 years old: mean age 78.3 years (vs 61.9 years for the rest of the cohort), male 66.7% (vs 56.1%), ECOG≥2 17.6% (vs 10.8%). BV was combined with FOLFIRI/XELIRI in 88.2% of patients aged &gt;75 years (vs 87.5%) and FOLFOX/XELOX in 11.8% (vs 12.2%). Median duration of BV treatment was 5.6 months (m) (vs 5.5 m), and median duration of the 1st-line was 10.3 m (vs 9.8 m). More patients &gt;75 years had treatment-free intervals (39.2% vs 28.6%), and 13.7% had a maintenance therapy (vs 12.8%). Curative surgery performed in 15.7% of patients (vs. 20.6%). Among the 43 patients who discontinued the 1st-line, only 9.3% discontinued BV prematurely (vs 18.2%). The incidence of any grade-3/4 adverse event was 43.1% (vs 41.7%). In-line with the known safety profile of BV (any grade), hypertension was observed in 21.6% (vs 18.9%), proteinuria 23.5% (vs 27.2%), there were no GI perforations (vs 0.3%), thrombotic events 5.9% (vs 7.8%), and grade 3/4 arterial thrombotic events 2.0% (vs 0.6%). The 1-year OS rate was 78.0%, 95%CI [63.9-87.2] (vs 80.5%, 95%CI [76.0-84.2]) and the median OS was not reached for both groups. The median PFS was 10.6 m, 95%CI [9.0-12.8] (vs 9.9 m, 95%CI [9.3-11.1]). Conclusions: Effectiveness and safety of BV plus chemotherapy in elderly patients were similar to those of the rest of the ETNA cohort. Estimations of survival outcomes (1-year OS rate, median OS and PFS) were also comparable to those found in elderly patients (75-80 years) from the BRITE cohort (72.0%, 20.3 m and 10.0 m, respectively). No significant financial relationships to disclose.
DNA ploidy is a stronger prognostic variable compared to microsatellite instability or 18q allelic loss in patients with stages II and III colon cancer
Authors: F. A. Sinicrope, K. C. Halling, A. French, L. J. Burgart, N. Foster, D. J. Sargent, R. M. Goldberg, M. J. O’Connell, T. E. Witzig, S. N. Thibodeau
Journal: Journal of Clinical Oncology (2005)

9523 Background: We have shown that DNA ploidy is a significant prognostic marker in stage II and III colon cancer patients. Given that diploidy and microsatellite instability (MSI) are highly correlated, we determined if MSI status accounts for the prognostic impact of ploidy. The relationship between ploidy and chromosome 18q allelic loss was also studied. Materials & Methods: Data were obtained from six completed, randomized 5-fluorouracil-based adjuvant studies conducted by the North Central Cancer Treatment Group (n=528). TNM stage II (30%) and III (70%) colonic adenocarcinomas had been analyzed for ploidy by flow cytometry and were categorized as diploid or non diploid (aneuploid and tetraploid). MSI status was determined using 10 microsatellite markers and classified as MSI-H (instability at ≥ 30% of loci), MSI-L and MSS. 18q allelic loss was analyzed as reported (JNCI 91:1295–1303, 1999). Relationships among variables were sought using the chi-square test. Overall survival (censored at 8 yr) was analyzed in univariate and multivariate Cox models adjusting for stage and stratifying by study. Results: Diploidy was detected in 223 (42%) colon cancers. Ninety-five (18%) tumors were MSI-H and 433 (82%) were MSS/MSI-L. 18q allelic loss was detected in 185 (77%) and absent in 55 (23%) tumors. Seventy (74%) MSI-H tumors were diploid compared to153 (35%) MSS/MSI-L cases (p< 0.001). Patients with diploid tumors had an improved overall survival versus those with non diploid tumors (HR=0.62, p= 0.001). A similar result was found in the subset of MSS/MSI-L cases (p=0.005). Survival curves for diploid MSS/MSI-L and MSI-H patients overlapped (p= 0.66). Neither MSI status (p= 0.18) nor 18q allelic loss (p=0.78) were prognostic. When stratifying by ploidy, 18q status failed to add additional prognostic information. In a multivariate model, DNA ploidy (p=0.005), but not MSI (p=0.61), was an independent prognostic variable. Conclusion: DNA ploidy was the strongest stage-adjusted prognostic variable. Diploid MSS/MSI-L patients had similar survival as patients with MSI-H tumors. Neither MSI status nor 18q allelic imbalance were significant prognostic variables. No significant financial relationships to disclose.
Cytotoxicity of<i> nab</i>-paclitaxel and SPARC expression in ovarian cell lines: An in vitro and in vivo study.
Authors: M. B. Sawyer, V. L. Damaraju, S. Mcquarrie, H. Steed, J. Meza-Junco
Journal: Journal of Clinical Oncology (2011)

e13529 Background: Nab-paclitaxel (NP) is a solvent-free, albumin-bound nanoparticle formulation; it binds to albumin receptor on endothelial cells, which in turn activates caveolin-1. Lack of solvents and receptor-mediated delivery results in decreased toxicity and increased antitumor activity of NP. Tumors expressing SPARC, and albumin-binding protein may have increased efficacy of NP. In this study we evaluated paclitaxel (P) and NP toxicities; SPARC’s role in NP sensitivity; intraperitoneal NP effect and maximum tolerated dose (MTD) in mice with ovarian cancer. Methods: Human ovarian cancer (OC) cell lines OVCAR-3, SKOV-3, AG-6000 and A-2780 were seeded in 96-well plates and after 24 hours (h) of seeding, varying concentrations of NP or P were added for 72 h, after which viability was evaluated by MTS assay. SPARC expression was determined in all 4 OC lines by Western blotting. In an in vivo study, intraperitoneal injections of NP were evaluated at different doses (50, 75, 100, and 125mg/Kg) on growth of tumors in mice with OC. Results: Mean IC50 (concentration of drug that inhibits 50% of cell growth) for A-2780 cell line treated with P vs. NP was 16.2 vs. 0.12 nM respectively (fold difference 131); for AG-6000 was 19 vs. 0.15 nM respectively (fold difference 124); for OVCAR-3 was 2.04 vs. 1.77 nM respectively (fold difference 1.15); and for SKOV-3 was 9.5 vs. 9.04 nM (fold difference 1.05). SPARC protein was present in cells (AG-6000 and A-2780) that were more sensitive to NP but not in OVCAR-3 and SKOV-3 cell lines. All NP doses were well tolerated in mice with OC and no significant difference in post treatment recovery was noted. All mice had reduced activity and squinting for 1-1.5 hours post NP injection; and they all seemed anemic at the necroscopy. Conclusions: NP had higher cytotoxic effects compared to P in AG-6000 and A-2780 cell lines which directly correlated with higher SPARC expression in these two 2 cell lines. Intraperitoneal NP was well tolerated in an OC mouse model.
Trends in health care utilization, cost, and aggressive care at end of life among older cancer patients in the Deep South.
Authors: Elizabeth Ann Kvale, Gabrielle Rocque, Kerri S. Bevis, Aras Acemgil, Richard A. Taylor, Wendy Demark-Wahnefried, Kelly Kenzik, Yufeng Li, Karen Meneses, Michelle Martin, Mona N. Fouad, Maria Pisu, Edward E. Partridge
Journal: Journal of Clinical Oncology (2015)

155 Background: Healthcare utilization and costs escalate near diagnosis and in the final months of life. There is a national trend toward aggressive care at end of life (EOL). We examined patterns in utilization and cost across the trajectory of care and during the last two weeks of life during implementation of a lay navigation intervention. Methods: Claims data were obtained for Medicare beneficiaries ≥ 65 years old with cancer in the UAB Health System Cancer Community Network (UAB CCN). For 10 quarters from January 2012 -June 2014, we examined healthcare utilization for the population at large, navigated patients, and decedents. All analyses included ER visits, hospitalizations, and ICU admissions and use of chemotherapy in the last 2 weeks of life, and hospice utilization (admission or less than 3 days of hospice) in the quarter of death for decedents. Descriptive analyses and linear regression were used to test trends over time; general linear models evaluated changes in health care utilization and cost. Results: Across the population reduction of 13.4% to 11% for hospitalization (18% decrease, p &lt; 0.01), 8.0% to 7.1% for ER visits (12% decrease, p &lt; 0.01), 2.9% to 2.5% for ICU admissions (14% decrease, p = 0.04) and an increase of 3.9% to 4.3% for hospice (9.2% increase p = 0.37) were found. Among 5,861 decedents, in the last 2 weeks of life, there were decreases in ICU admissions (14.6% decrease, p = 0.11), from 39.2% to 32.0%, ER visits (18.4% decrease, p = 0.03), and chemotherapy, from 4.7% to 3.5% (25.5% decrease, p = 0.11).Over the 10 quarters, hospice enrollment increased from 70.7% to 77.4% (9.48% increase; p = 0.06), and the proportion of patients on hospice for less than 3 days changed from 7.8% to 7.5% (3.85% decrease, p = 0.30). Costs decreased about $158 per quarter per beneficiary. A significant pre-post decrease of $952 per beneficiary (p &lt; 0.01) led to an estimated reduction in Medicare costs of $18,406,920 for the 19,335 beneficiaries in the UAB CCN for the five quarters post-implementation. Conclusions: We observed decreased healthcare utilization and cost and trends toward decreased aggressive care at EOL in the UAB CCN. Further work is needed to determine the impact of navigation on utilization trends.
Characterization of nTreg in patients with metastatic renal cell carcinoma (RCC) undergoing DC-vaccination and cytokine therapy
Authors: T. Schwaab, A. Schwarzer, B. Wolf, J. Gui, J. L. Fisher, N. A. Crosby, J. D. Seigne, M. S. Ernstoff
Journal: Journal of Clinical Oncology (2008)

16038 Background: CD4+CD25+FoxP3+ Regulatory T cells (nTreg) play a pivotal role in suppression of anti-tumor immune responses. We analyzed the subpopulation of nTreg in patients enrolled in a Phase II autologous dendritic cell (DC) vaccine trial. Methods: Consented and eligible patients received up to 5 cycles of intranodal DC-autologous tumor vaccine (1 × 107 cells) followed by 5 days of continuous i.v. infusion of IL-2 (18 MiU/m2) and s.c. Interferon alpha 2a (6 MiU) every other day. Samples were collected via leukapheresis at baseline and after two cycles. Five-color flow cytometry was performed on lymphocytes utilizing a comprehensive panel of cell surface and intracellular markers. Treg function was assessed in a Treg assay. Cytokines in supernatants of this assay were quantified using Luminex® ELISAs. Patients were divided into responders (R: complete and partial, n=9 using WHO criteria) and non-responders (NR: stable and progressive disease, n=9) and compared with age matched healthy donors (HD, n=12). P-values were assesed using Student's t-test. Values are expressed as mean±StD. Results: At baseline, cancer patients had a significantly higher percentage of CD4+CD25+FoxP3+ cells than HD (% of CD3+: 2.7% ± 1.2 vs. 1.3% ± 0.7, p<0.001). After two induction cycles, an increase in this percentage was observed (% of CD3+ Pre: 2.7% ± 1.2 vs. Post: 6.6% ± 4.5, p=0.006). After induction, significantly higher levels of Treg were detected in NR vs. R (% of CD3+: 9.2% ± 5.4 vs. 4.4% ± 1.6, p=0.036). Treg assays demonstrated preserved suppressor function before and after therapy. Cytokine analysis demonstrated a treatment related increase in Th2-related cytokines IL-4 and IL-10 (46 pg/ml ± 28 vs. 143 pg/ml ± 77, p=0.001 and 212 pg/ml ± 133 vs. 902 pg/ml ± 386, p=0.005), and a decrease in the Th1-related cytokine IL-2 (5785 pg/ml ± 5824 vs. 381 pg/ml ± 510, p=0.005). Conclusions: RCC patients showed higher levels of Treg cells than healthy donors. Lower levels of Treg cells were detected in responding RCC patients treated with an immunotherapeutic regimen. This data implies a threshold of Treg cells in the peripheral blood, which may affect clinical outcome and has implications for the design of future immunotherapeutic approaches to RCC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Berlex Oncology, NIH
Developing an IT infrastructure for the National Radiation Oncology Registry.
Authors: Todd McNutt, Jatinder Palta, Carl Bogardus, Walter Bosch, Jeffrey Carlin, Henry Chou, Bruce Curran, Joel Goldwein, Ken Hotz, Rishabh Kapoor, Marc Kessler, Charles Mayo, Sasa Mutic, William Tulskie, Peter Gabriel
Journal: Journal of Clinical Oncology (2012)

300 Background: The National Radiation Oncology Registry (NROR) is developing an IT infrastructure to support the efficient collection, aggregation, and analysis of data concerning cancer patients treated with radiotherapy across the United States. Methods: Detailed requirements were developed to emphasize the following distinguishing goals for the system: 1) streamline the process of data collection by minimizing manual data entry; 2) support the collection of patient-reported outcomes (PROs) and their linkage with clinician-observed outcomes; 3) facilitate data integration within the NROR and between the NROR and other registries; 4) allow for evolution of the system in response to new learning; and 5) promote sustainability and ongoing improvement through an open standard of interoperability. Results: An innovative technical architecture has been designed to meet the goals described. The system maximizes efficiency through automated extraction and electronic transfer of data from radiation oncology information systems. PROs are collected directly from patients via a web-based portal and linked to data submitted from participating institutions. A data dictionary has been developed based on national standards and controlled vocabularies to facilitate data integration. Contemporary forms-based database technology is used in combination with traditional relational technology to permit both flexible evolution of the system and efficient data analysis. A unique “gateway” architecture and open transmission standard makes it possible for commercial products to interoperate with the registry in the future. Conclusions: The NROR prototype system will be launched later this year to collect data for a pilot registry of prostate cancer patients. Its performance and usability will be important factors in the success of the pilot. If effective, the platform will support the expansion of the NROR to benefit patients, clinicians, researchers, payors, device manufacturers, and policy-makers by capturing reliable, population-based information on radiation treatment delivery and health outcomes.