tbuckley/cabot-search huggingface dataset:
Use of a comparative database to identify excessive hematology/medical oncology hospital days and readmissions.
Authors: Brian Halbert, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2017)

131 Background: Reducing length of stay and readmissions are important goals to improve healthcare quality and decrease costs. We identified diagnostic categories accounting for excessive hospital days and readmissions on our hematology/medical oncology (HO) service. Methods: We used a third-party comparative clinical database (Vizient Inc, Clinical Data Base/Resource Manager) to identify discharges from our HO service in 2015. Cases were categorized by All Patients Refined Diagnosis Related Groups (APR DRG), and we calculated excess hospital days attributed to each using the number of cases and their observed/expected length of stay. We also collected 30-day readmission rates for each APR DRG on our HO service and hospital wide. Readmission rates were compared using Fisher exact tests. Results: We identified 1,361 discharges from our HO service with 134 APR DRG codes and 880.5 excess hospital days. Fourteen APR DRGs accounted for over 80% of the excess hospital days. Readmission rates ranged from 0% to 66.7%, and were generally higher than rates hospital wide. Readmissions for septicemia and major operating room (OR) procedures for lymphatic neoplasms were significantly higher on the HO service. Conclusions: Relatively few APR DRGs accounted for the majority of our excess hospital days, and also had high readmission rates. We will conduct additional review of these APR DRGs to identify opportunities to improve quality and reduce cost. [Table: see text]
A phase II trial of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP) in patients with metastatic breast cancer
Authors: D. M. Atieh, M. Modiano, L. Shriberg, L. Brafman, M. Szno, L. Vahdat
Journal: Journal of Clinical Oncology (2004)

864 Background: 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine), a potent inhibitor of ribonucleotide reductase, demonstrates both in vitro and in vivo antitumor activity. This cytotoxic effect seems to be maximized by chronic, intermittent enzymatic inhibition. Methods: Patients(Pts) with measurable metastatic breast cancer(MBC) refractory to at least one regimen were eligible for enrollment. Pts were required to have an ECOG PS of 0–1, adequate organ function, no active brain metastases. Treatment: 2-hour IV infusion of 3-AP daily × 5 days every other week at an initial dose of 96 mg/m2/d. Four courses were considered 1 cycle of treatment. Based on interval and residual toxicities, dose modifications to 84mg/m2 or 72mg/m2 were employed. Dose escalation to 105mg/m2 was also permitted. Full staging to be completed every 8 weeks. Results: 9 pts with a median age of 58 were enrolled (range 36–68). Median # of prior chemotherapy regimens was 6 (range 4–10) and 44% of pts (4/9) were refractory to 6 or more chemotherapy regimens. Three of nine pts demonstrated stable disease and the remainder had progression of disease (2/9) or discontinued treatment (4/9) before restaging was required/performed. A total of 42 courses were administered and all pts completed at least 2 courses of treatment (range 2–12). Seven of nine (77%) pts required a cycle 2 dose reduction of 84mg/m2 and an additional two required a cycle 3 dose reduction to 72mg/m2. Dominant toxicity was hematologic with thirty Grade 3 or 4 toxicities documented. All pts experienced Grade 4 neutropenia (4/9 hospitalized with nadir fevers) and 3/9 had Grade 4 thrombocytopenia. Conclusions: Thirty-three percent of pts achieved stable disease following administration of 3-AP(Triapine®) on a daily for five days schedule. Hematological toxicity was significant and managed with dose reductions. Future studies are planned with a more convenient dosing schedule. No significant financial relationships to disclose.
What are the health care costs for chronic lymphocytic leukemia?
Authors: Matthew J. Matasar, Stacey DaCosta Byfield, Cori Blauer-Peterson, Melissa Montez, Carolina Reyes, Anthony Masaquel
Journal: Journal of Clinical Oncology (2017)

15 Background: New drugs for chronic lymphocytic leukemia (CLL) have recently been approved, including oral therapies. We examined total health care costs, including drug and patient out-of-pocket (OOP) costs, in patients (pts) initiating CLL treatment. Methods: This retrospective studyused a U.S. health insurance claims database. Adult commercially insured and Medicare Advantage pts from 5/2013 - 6/2015, with ≥2 medical claims for CLL were included. Pts required ≥1 claim for NCCN-recommended systemic cancer therapy. Pts were categorized based on first-line of therapy. Aggregate costs during a fixed 9-month follow-up period (treatment switch or discontinuation were possible) were investigated. Mean and standard deviation (SD) of total healthcare costs, regimen costs, and pt OOP regimen costs are presented. Results: A total of 707 CLL pts met all study criteria during the study period; 40% were commercially insured and 60% had Medicare Advantage. Mean age was 70 years (SD 11). Some of the most common regimens received included Bendamustine+Rituximab (BR) (N=186), Ibrutinib (Ibr) (N=101), Fludarabine, Cyclophosphamide, and Rituximab (FCR) (N=62), and Obinutuzumab +/- Chlorambucil (Ob+/-Chl) (N=51). Mean length of therapy varied by regimen; BR 4.2 months (m) (SD 2.7), Ibr 6.7m (SD 4.8), FCR 4.7m (SD 2.1), and Ob±Chl 4.0m (SD 2.1). The table shows aggregate costs among pts with ≥ 9 months follow-up. Ob±Chl had lower costs compared to other cohorts. Ibr had the highest drug costs. Conclusions: While the study has limited follow-up, Ob+/-Cl had the lowest drug and total costs. Oral therapy with Ibr had the highest drug and OOP costs compared to those associated with a prescribed fixed number of cycles. The magnitude of the difference between orals and infusions is expected to be greater with a longer follow-up and is a consideration in patient treatment decision-making in CLL.[Table: see text]
Evaluation of elderly patients with extended disease small-cell lung cancer.
Authors: Tatiane Caldas Montella, Marina Mendes Vasco, Ana Licia Maia Silva, Morgana Stelzer Rossi, Carla Valéria Santos Sena, Leandro Nascimento Oliveira, Clarissa Serodio Baldotto, Carlos Gil Moreira Ferreira
Journal: Journal of Clinical Oncology (2013)

e18515 Background: At diagnosis approximately 25-40% of patients with small cell lung cancer (SCLC) are over age 65 and more than 60% of them have extended disease (ED). There is a scarcity of data on this subpopulation. The aim of this study was to report clinical characteristics of this subpopulation, highlighting some challenges in their clinical management. Methods: In this retrospective cohort, data from 96 patients aged &gt;65 years with SCLC diagnosed between 1997 and 2007 at a single institution were analyzed. Results: At diagnosis median age at presentation was 71, and most patients (n=65; 67.7%) had ED_SCLC and became the focus of our analysis. In this particular population the median survival time was 5 compared to 9 months for limited disease patients. Further, 63% of these patients had performance status (PS)≥2 and that was correlated with worse survival (PS0-1=9 months, PS2=4 months and PS3-4=3months; p=0.05). Additionally, 70% of this group with ED had at least one comorbidity and 30% had more than one. Of note, chemotherapy (CT) or radiotherapy (RT) were not administered in 23% of those patients, due to the lack of clinical conditions. CT was administered in 49 patients (75%), being carboplatin and etoposide the preferred regimen in contrast to cisplatin and etoposide (71 vs 28%). However, 44% of patients received less than 4 cycles of CT and 34% received only one cycle. Number of CT cycles were correlated with survival (1 cycle 1.5 months and 2-4cycles 8.7 months). Conclusions: Our data show that elderly patients with ED-SCLC constitutes a frail subpopulation, with poor PS and associated comorbidities, leading to suboptimal treatment and a dismal prognosis. Moreover, most of those patients were considered unfit for current treatment. These results highlight the urgent need for an individualized approach and clinical trials focused on elderly patients, in order to provide them an optimal care and improve their outcomes.
Mechanism of action of ingenol mebutate gel in reconstructed human skin assessed by transcriptomics.
Authors: John Robert Zibert, Maria Helena Hoeyer-Hansen, Andre Huss Eriksson, Marianne Begtson Loevendorf, Josselyn Matthews, Thomas Litman
Journal: Journal of Clinical Oncology (2012)

e19056 Background: Ingenol mebutate (IM) gel topical applied once daily for 2-3 consecutive days, has recently been approved by FDA in treating actinic keratoses (AK), as a safe, tolerable and effective treatment. IM, a highly active biological diterpene ester, has shown in vitro and in vivo to induce a dual mechanism of action characterized by, first, cell death induced at high micromolar concentrations and, second, a protein kinase C dependent immune activation in the nanomolar range. The aim of this study was to investigate the mechanism of action of IM in reconstructed human skin (RHS). Methods: IM 0.05% gel or vehicle was applied topically to RHS (EpiDermFT) and normal pigskin and IM concentrations were measured after 2 and 24 hrs. In RHS, biopsies were obtained 1, 6 and 24 hrs after treatment and global transcriptomic profiling (Affymetrix HG 1.0 ST) was assessed. The analysis included transcription factor binding site (TFBS) and gene set enrichment analysis (GSEA). Results: We compared IM’s penetration through normal skin to RHS and found a 10-fold higher permeability in RHS, which likely models the increased permeability of AK lesions. Consequently we further investigated IM’s effects on RHS. Based on GSEA, we identified the major effects of IM to comprise: cell death, inflammation and wound healing responses, indicated by differential expression of e.g. caspases, DAPK1, chemokine ligands, HAS2, MMPs, SERPINs, ILs (and their receptors). A TFBS analysis identified E2F regulated genes as overrepresented, albeit in opposite directions in dermis (up-regulated) compared to epidermis (down-regulated). IM transiently activates PKC, and via this activation causes transcriptional silencing of E2F-responsive genes. The differential effect on dermis and epidermis could be due to different levels of PKC isoforms in the different skin layers. Indeed, a specific, inflammatory response was observed and several genes, including MMP10 and IL1R2, displayed a time-dependent increase in expression, reaching a maximum at 24h. Conclusions: In conclusion, IM displays pleiotropic effects, of which many are identified on a transcriptional level. Our data suggest involvement of in particular PKC, ERK2, and E2F regulated genes.
Prediction of late metastasis in node-negative breast cancer.
Authors: Marcus Schmidt, Birte Hellwig, Mathias Gehrmann, Heinz Koelbl, Daniel Boehm, Christina Cadenas, Joerg Rahnenfuehrer, Jan G Hengstler
Journal: Journal of Clinical Oncology (2012)

10551 Background: Prediction of late metastasis is of clinical relevance in breast cancer. However, systematic genome-wide studies to identify genes associated with increased risk of metastasis 5 or more years after surgery are scarce. Methods: We examined the natural course of disease in three previously published cohorts (Mainz, Rotterdam, Transbig) including 766 node-negative breast cancer patients with gene array data who did not receive systemic chemotherapy in the adjuvant setting. We established a Cox regression based method adjusted for multiple testing that identified genes predicting late metastasis (5 or more years after surgery). Only those genes were accepted that showed similar results in all three cohorts. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Results: We identified 9 genes [ABCC5 (Hazard Ratio (HR) 2.19, p=0.003), EDDM3B (HR 3.58, p=0.044), RAD23B (HR 0.37, p&lt;0.001), XYLT2 (HR 2.19, p=0.027), DDX18 (HR 0.35, p=0.006), GPBP1L1 (HR 0.20, p=0.018), UBB (HR 9.73, p=0.025), RPS24 (HR 0.20, p=0.050), GPC1 (HR 2.36, p=0.013)] predicting late metastasis. These genes retained their independent prognostic significance after adjustment for established clinical factors (age, tumor size, grade, hormone receptor status, HER2) and biological motives like estrogen receptor, proliferation, B or T cells. These late-type genes are largely associated with resistance to hypoxia, apoptosis and DNA damage, suggesting that they might contribute to persistence of disseminated tumor cells. Conclusions: Genes associated with late metastasis offer a perspective to identify breast cancer patients suitable for additional and prolonged therapies.
Peptide receptor radiotherapy (PRRT) with [Y-90-DOTA,Tyr3]octreotide: Toxicity and efficacy of 4-cycle and single-cycle regimens
Authors: R. Valkema, L. K. Kvols, S. Pauwels, F. Jamar, R. Barone, J. Lasher, E. P. Krenning
Journal: Journal of Clinical Oncology (2004)

3046 Background: PRRT with [Y-90-DOTA,Tyr3]octreotide (Y-90-SMT487, OctreoTher) has potential benefit in patients with somatostatin receptor positive tumors. We investigated whether toxicity (tox), mainly renal and red marrow (RM), and effects on tumor size are different when the total radioactivity (RA) is given in 4 equal cycles (4-cy) or in fewer cycles (cy), but with higher activity per cy (Hi-cy). Methods: 60 patients (pts) with neuroendocrine tumors were treated with 1 or more cy of Y-90-SMT487 escalating from 4 x 25 to 4 x 100 mCi/m2 (4-cy, n=34; 32 completed 1, 28 completed 4 cy) or 1 to 3 x 100 to 250 mCi/m2, up to a renal limit of 27 Gy (Hi-cy, n=26). The individual RA for a renal dose of 27 Gy had been determined prior to entry by PET using Y-86-SMT487. All pts received concomitant infusion of amino acids for renal protection. The first dose of RA was 60 ± 27 mCi/m2 (mean ± SD) in the 4-cy group, and 164 ± 41 mCi/m2 in the Hi-cy group (P<0.001). The cumulative RA was 219 ± 108 mCi/m2 (4-cy) and 224 ± 58 mCi/m2 (Hi-cy), similar in both groups, as were other baseline parameters. Results: Overall, 9 pts had transient WHO grade 3 and 1 pt grade 4 RM tox; 1 pt had myelodyplasia after 2 years. During the first cy, nadir platelets (Hi-cy: 111 ± 45 x 10E9/L, 28% ± 29% less than baseline) and nadir leukocytes (Hi-cy: 3.2 ± 1.2 x 10E9/L, 38% ± 27% less than baseline) were lower in the Hi-cy than in the 4-cy group (P<0.01), but differences were NS between groups after full dose. Renal tox included 2 pts with radiation nephropathy (late grade 3) and 2 with suspected radiation nephropathy; no pts required dialysis. Pts with follow-up of >30 months (n=13) showed a mean decrease in calculated creatinine clearance of 10.9 ± 4.1 mL/min, or 13.0 ± 4.9% from baseline. Differences between 4-cy and Hi-cy groups were NS. 5 pts had PR, 7 minor response, and 30 SD. In 12 4-cy pts with measurable tumor shrinkage, the smallest size occurred after 17 ± 11 months; in 10 Hi-cy pts after 13 ± 8 months (NS). Conclusions: PRRT with Y-90-SMT487 after individual dosimetry is well tolerated. Except for reversible early RM tox, we did not observe major differences in tox or efficacy between the 4-cy and Hi-cy groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.
Caspase-3 controls AML1-ETO–driven leukemogenesis via autophagy modulation in a ULK1-dependent manner
Authors: Na Man, Yurong Tan, Xiao-Jian Sun, Fan Liu, Guoyan Cheng, Sarah M. Greenblatt, Camilo Martinez, Daniel L. Karl, Koji Ando, Ming Sun, Dan Hou, Bingyi Chen, Mingjiang Xu, Feng-Chun Yang, Zhu Chen, Saijuan Chen, Stephen D. Nimer, Lan Wang
Journal: Blood (2017)
Hepatocyte nuclear factor 1α suppresses steatosis-associated liver cancer by inhibiting PPARγ transcription
Authors: Cecilia Patitucci, Gabrielle Couchy, Alessia Bagattin, Tatiana Cañeque, Aurélien de Reyniès, Jean-Yves Scoazec, Raphaël Rodriguez, Marco Pontoglio, Jessica Zucman-Rossi, Mario Pende, Ganna Panasyuk
Journal: Journal of Clinical Investigation (2017)

Worldwide epidemics of metabolic diseases, including liver steatosis, are associated with an increased frequency of malignancies, showing the highest positive correlation for liver cancer. The heterogeneity of liver cancer represents a clinical challenge. In liver, the transcription factor PPARγ promotes metabolic adaptations of lipogenesis and aerobic glycolysis under the control of Akt2 activity, but the role of PPARγ in liver tumorigenesis is unknown. Here we have combined preclinical mouse models of liver cancer and genetic studies of a human liver biopsy atlas with the aim of identifying putative therapeutic targets in the context of liver steatosis and cancer. We have revealed a protumoral interaction of Akt2 signaling with hepatocyte nuclear factor 1α (HNF1α) and PPARγ, transcription factors that are master regulators of hepatocyte and adipocyte differentiation, respectively. Akt2 phosphorylates and inhibits HNF1α, thus relieving the suppression of hepatic PPARγ expression and promoting tumorigenesis. Finally, we observed that pharmacological inhibition of PPARγ is therapeutically effective in a preclinical murine model of steatosis-associated liver cancer. Taken together, our studies in humans and mice reveal that Akt2 controls hepatic tumorigenesis through crosstalk between HNF1α and PPARγ.
Phase I/II study of exisulind and gemcitabine in patients with recurrent advanced non-small cell lung cancer (NSCLC)
Authors: T. Hoang, K. Kim, J. Merchant, A. M. Traynor, H. G. Ahuja, G. A. Masters, J. D. McGovern, K. R. Oettel, F. A. Sanchez, J. H. Schiller
Journal: Journal of Clinical Oncology (2004)

7103 Background: Exisulind is an oral selective apoptotic antineoplastic drug which inhibits the cyclic GMP phosphodiesterase. The combination of exisulind and gemcitabine produced an additive anti-tumor effect in preclinical studies. The objectives of this study were to determine the maximally tolerated dose (MTD) (Phase I) and clinical efficacy (Phase II) of this combination in patients (pts) with recurrent advanced NSCLC. Methods: In phase I, exisulind was escalated in 3 dose levels (from 125mg BID up to 250mg BID) in combination with a fixed dose of gemcitabine 1250mg/m2 IV days 1 and 8 of a 3 week cycle. Plan for phase II is to accrue 24 pts (95% power to detect a 50% increase in TTP from 3 months to 4.5 months with the level of significance of 0.1). Eligibility: Disease recurrence of more than 3 months from completion of first-line therapy, only one prior chemotherapy regimen, PS 0–1. Results: To date, 33 pts (24men, 9 women) have been enrolled; 15 in phase I and 18 in phase II. Median age was 65. 30% had PS 0, 70% had PS 1. 60% had distant metastasis. All pts received platinum-based doublets as first-line therapy, of which 94% were third-generation regimens. Phase I: Six pts were entered to dose level 1, 3 in dose level 2 and 6 in dose level 3. Of 14 evaluable pts, 1 achieved PR, while 4 had SD after 6 cycles of treatment. The regimen was well tolerated (MTD not reached) with grade 3 fatigue and grade 3 constipation being DLTs (1 patient each). Myelotoxicities were mild. Phase II (ongoing): Dose level 3 was chosen for testing. Of 18 pts, 7 have died, 11 survived including 4 who are still on treatment. PR was seen in 2/18 pts, SD in 10/18. Toxicities included G3/4 leukopenia in 4 pts (22 %), G3/4 neutropenia 7 (39 %), G3 neutropenic infection 1 (6%), G3 anemia 2 (11 %), G3 thrombocytopenia 3 (17 %), G3 transaminases 3 (17 %). As of 8/03, of 32 evaluable pts enrolled in both phase I/II, disease was controlled in 17 pts (53%) including 3 with PR (9 %) and 14 with SD (44 %). Median and one year survival was 10 months and 40% (standard error 13%) in phase I. Conclusions: The study regimen is well tolerated and the phase I results are promising. Phase II is still ongoing; survival and TTP will be updated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly
Long-term follow-up of patients with CLL treated with the selective Bruton’s tyrosine kinase inhibitor ONO/GS-4059
Authors: Harriet S. Walter, Sandrine Jayne, Simon A. Rule, Guillaume Cartron, Franck Morschhauser, Salvador Macip, Lionel Karlin, Ceri Jones, Charles Herbaux, Philippe Quittet, Nimish Shah, Claire V. Hutchinson, Christopher Fegan, Yingsi Yang, Siddhartha Mitra, Gilles Salles, Martin J. S. Dyer
Journal: Blood (2017)
Changes in survival and time to progression in metastatic breast cancer (MBC) patients enrolled into clinical trials from 1983 to 2001
Authors: A. Gennari, P. Conte, C. Orlandini, V. Guarneri, R. Rosso, P. Bruzzi
Journal: Journal of Clinical Oncology (2004)

634 Background: Despite the widespread perception that the availability of new drugs improves prognosis in MBC, survival gains were rarely reported in randomised clinical trials of 1st line chemotherapy (CTX) with last generation agents. We evaluated the survival of MBC patients enrolled into trials conducted by the GONO during a 20 year period, to detect any improvement potentially attributable to the use of newer drugs. Methods: Between 1983 and 2001, 790 patients were entered into 6 consecutive trials of CTX coordinated by the data center at the National Cancer Research Institute in Genoa, Italy (2 phase II and 4 randomised phase III). In trials started after 1994, a taxane was part of the CTX regimen. This analysis was limited to 640 patients, as patients metastatic ab initio were excluded. Five cohorts of patients according to 3-yr periods of diagnosis of relapse were identified. Kaplan-Meier estimates of overall survival (OS) and time to progression (PFS) were computed from enrolment, and compared by the log rank test. Multivariate PH models were used to adjust for differences in baseline factors, including age, nodal and receptor status, adjuvant CTX, relapse free survival, metastatic site and PS. Results: The following differences in baseline characteristics in the 5 cohorts were observed: the proportion of patients pretreatead with adjuvant anthracyclines increased from 4% to 26%; that of patients with a RFS>5 years increased from 19% to 33% and the proportion of patients with dominant visceral disease increased from 57% to 74%. Median PFS was 306 days, 294 days, 237 days, 328 days and 348 days in cohorts 1983–86, 87–89, 92–94, 95–97 and 98–2001, respectively (p < 0.0001). Median OS in the same cohorts was 546 days, 522 days, 584 days, 793 days and 713 days, respectively (p < 0.0001). These data were confirmed in multivariate analyses, when prognostic variables were adjusted for. Conclusions: It appears that the prognosis of MBC patients enrolled in CTX clinical trials since 1995 is significantly improved as compared to patients enrolled during 1983–94. A possible role of drugs introduced in the '90s is suggested. No significant financial relationships to disclose.
Interleukin (IL)-17A and IL-22-producing neutrophils in psoriatic skin
Authors: B. Dyring-Andersen, T. V. Honoré, A. Madelung, M. Bzorek, S. Simonsen, S. N. Clemmensen, R. A. Clark, N. Borregaard, L. Skov
Journal: British Journal of Dermatology (2017)