tbuckley/cabot-search huggingface dataset:
Program development in palliative care: Results from the NCI Community Cancer Centers Program (NCCCP).
Authors: Lynne Slaughter Padgett, Mary Helen Davis, Colleen Tallen, Angela Carrigan, Julia Howe Rowland
Journal: Journal of Clinical Oncology (2014)

42 Background: Growing national attention to the need for metrics to document delivery of quality palliative care has resulted in a proliferation of measures and standards (e.g., Commission on Cancer, Quality Oncology Practice Initiative). While these standards offer benchmarks to strive for, there are few resources for programs to self-assess development of organizational infrastructure to achieve them. Methods: The NCCCP Cancer Palliative Care Matrix (PCM) is a performance measure and evaluation tool to aid palliative care program development in the community setting. The PCM was completed annually by 21 NCCCP sites from 2010 to 2013. Four domains related to quality measures are reported here. Proportional-odds logistic regression models were used to evaluate the relationship between year and level of response. Results: Variations in program development were seen in the quality domains of symptom assessment, palliative care services offered across the continuum of care, identification for palliative care services, and use of quality measures. In 2010, 13/21 sites reported that symptom assessment were not performed or performed inconsistently. By 2013, 13 sites reported consistent assessment with standardized tools, with 5 of these 13 able to review sequential patient assessment (p=0.002). Similar gains were seen in the domains of providing services across the continuum of cancer care and utilization of quality measures such as patient/provider satisfaction and service utilization (p=0.004, p&lt;0.0001). Despite three years of effort, little change was seen in patient identification processes for palliative care services with only 6 of 21 sites in 2013, compared to 5 in 2010, reporting improvement in "upstream" patient identification regardless of cancer stage (p=0.065). Conclusions: Data suggest the utility of the PCM to evaluate process and quality outcomes in palliative care program development. In addition, identification of challenge and growth areas can be used to develop interventions to address quality performance in both clinical and research contexts.
Prospective evaluation of megestrol acetate after aromatase inhibitor failure in advanced endocrine responsive breast cancer: Preliminary results.
Authors: J. Bines, R. Dienstmann, O. Metzger, A. C. Gonçalves, W. M. Claudino, M. F. Costa, R. M. Obadia, I. Á. Small
Journal: Journal of Clinical Oncology (2010)

1137 Background: There is a recent interest in the evaluation of “old” endocrine treatments in advanced breast cancer. Based on our retrospective data showing median time to treatment failure of 16 weeks with megestrol acetate (MA) after aromatase inhibitor (AI) failure in patients (pts) with endocrine responsive breast cancer, we evaluated the benefit of MA in a prospective setting. Methods: Phase II single- institution study. Eligibility: pts with advanced breast cancer that received AI in the palliative setting for more than 6 months or as adjuvant therapy for more than 12 months and had documented disease progression while on endocrine therapy. Treatment: MA 160 mg/day continuously until disease progression or toxicity. RECIST response evaluation and doppler ultrasound of lower extremities for prospective deep venous thrombosis (DVT) assessment every 8 weeks. Results: Accrual started January 2007 and is still ongoing. As of December 2009, 36 pts entered the trial (out of 46 planned), with 34 pts evaluated for response and toxicity. Median age was 64 years (45-90). Nine pts (25%) had visceral metastasis and 27 (75%) had soft tissue, bone, or pleural disease. Previous treatment included neo/adjuvant tamoxifen in 16 pts (44%), palliative tamoxifen in 17 pts (47%), adjuvant AI in 5 pts (14%), and palliative AI in 31 patients (86%). Median time on palliative AI was 21 months (6-91). One patient had partial response and 11 pts had stable disease for more than 6 months, resulting in a clinical benefit rate of 35%. Median time to progression (TTP) was 16.6 weeks (3-77). Patients with visceral metastasis had median TTP of 12 weeks (7-72) and those without visceral disease 17 weeks (3-77). Treatment was well tolerated and no patient developed grade 3 toxicity or required therapy interruption. Two pts (6%) developed DVT while on MA. Conclusions: This is the first prospective evaluation of MA after AI failure in endocrine responsive breast cancer. Clinical benefit rate and median time to progression are in agreement with approved alternatives in this setting, such as exemestane and fulvestrant (J Clin Oncol 2008;26:1664). Incidence of DVT has been low. Accrual will continue as planned. No significant financial relationships to disclose.
Course of hospitalization for preterm neonates born at a tertiary hospital in Brazil
Authors: Inalu Silva, Paola Cunha, Maria Beatriz Linhares, Francisco Martinez, Júnior José Simon Camelo
Journal: European Respiratory Journal (2013)

Background:  In newborn preterm infants, especially those small for gestational age, low birth weight, respiratory control disorders are frequent.   Objective:  To study the clinical characteristics and course of hospitalization of infants preterm healthy.   Methods:  The sample consisted of neonates with gestational age    Results:  The mean gestational age of the sample was 32.04 ± 2.02 weeks, mean birth weight was 1490 ± 393.08 grams and as the distribution of sexes, 55% female and 45% male. Compared to neonatal clinicians evaluated, the mean Apgar score at 5 minute was 9.31 ± 1.05, Clinical Risk Index for Babies I was 1.45 ± 2.29 and the mean of the Neonatal Medical Index which assesses the entire hospital stay was 2.33 ± 1.07. Analyzing complications during hospitalization, respiratory diseases were the most frequent, with 75% of the sample had some kind of respiratory complication. Among them, 32.73% of neonates had apnea and 27.27% had hyaline membrane disease. Furthermore, 62% of the sample required ventilatory support and 51% used oxygen therapy. The mean hospital stay was 28.96 ± 17.89 days and neonatal ICU was 9.22 ± 13.87 days. When compared neonates born small or appropriate for gestational age, there were no differences in any of the variables.   Conclusion:  In a tertiary hospital in Brazil, the most frequent complication was respiratory, despite the present sample neonatal clinical indices showing good prognosis.
Phase I dose-escalation study of E7080, a selective tyrosine kinase inhibitor, administered orally to patients with solid tumors.
Authors: D. S. Hong, B. S. Koetz, R. Kurzrock, N. N. Senzer, W. Hanekom, A. Naing, J. J. Wheler, J. Mink, M. Ren, J. J. Nemunaitis
Journal: Journal of Clinical Oncology (2010)

2540 Background: E7080 is a potent, orally administered, receptor tyrosine kinase inhibitor of KDR, VEGFR1, VEGFR3, FGFR2, and RET. Antiangiogenic and antiproliferative activity were seen in human cancer xenograft models, suggesting that E7080 may be a promising anticancer agent. We report the MTD and DLT determination of E7080 administered in a continuous twice daily (bid) schedule. Methods: Escalating doses of E7080 ranging from 0.1 mg to 12 mg bid were studied in patients (pts) with advanced solid tumors. Tumor assessments were made after every two 28-day cycles, and responses investigator reported. Results: As of December 2009,77 pts (age range 28-85 yrs) have been treated with E7080 in this study for a mean of 6 cycles (range 1–35 cycles). DLTs occurred at the 12 mg bid dose level and consisted of grade 3 hypertension (HT), grade 3 fatigue, and failure to administer ≥75% of E7080 in the 1st cycle due to recurrent grade 2 proteinuria (PU). The MTD was determined to be 10 mg bid, and an expanded cohort of 26 pts with melanoma was treated at this dose level. The most frequent treatment-emergent adverse events (TEAE) were HT and PU (Table). Other ≥ grade 2 TEAEs were fatigue (30.7%), anorexia (19.2%), decreased weight (19.2%), diarrhea (11.5%) and dysphonia (7.7%). 43 pts were evaluable for response: 9 pts (21%) achieved a PR with 56% pts having clinical benefit (CB = PR + SD ≥6 months). PRs were observed in melanoma (n=3), endometrial (n=1), renal (n=1), thyroid (n=3), and islet cell (n=1) cancers. 9 pts with melanoma were ongoing in the expansion cohort at data cutoff, and 7 out of 17 evaluable melanoma pts achieved SD ≥6 months. Conclusions: The MTD of E7080 is 10 mg bid administered continuously in pts with advanced solid tumors. E7080 has manageable toxicities related mainly to VEGF inhibition. Antitumor activity was observed in melanoma, thyroid, endometrial, and renal cancer. These cancer types will be prospectively studied in clinical trials with E7080. Incidence of PU and HT: 10 mg bid cohort (n=26) Incidence of PU and HT: 10 mg bid cohort (n=26) CTC AE grade PU, n (%) HT, n (%) Total 15 (57.7) 13 (50.0) 1 7 (26.9) 0 (0.0) 2 5 (19.2) 9 (34.6) 3 2 (7.7) 4 (15.4) 4 1 (3.8) 0 (0.0) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai Eisai Eisai
Intra-arterial hepatic bio-chemotherapy for the treatment of melanoma patients with liver metastasis: A phase II clinical study
Authors: Z. Chi, C. Cui, X. Yuan, L. Si, X. Sheng, L. Shen, J. Guo
Journal: Journal of Clinical Oncology (2009)

e20014 Background: To investigate the efficacy and safety of hepatic intra-arterial infusion of cisplatin, fotemustine combined with systemic dacarbazine for the treatment of melanoma patients with liver metastasis. Methods: From 2005.7 to 2008.7, thirty-six melanoma patients with liver metastatic were enrolled. Systemic dacarbazine (250mg/m 2 d1–5) and intra-arterial hepatic (i.a.h.) of cisplatin (75mg/m 2 d6) and fotemustine (100mg/m 2 d7) were given repeated for 4-weeks. Response, progress free survival(PFS), and toxicity were analyzed. Results: 27 of the 36 patients were evaluable, with mean cycle 2.16±1.19, one achieved CR, one PR and seven SD. The disease control rate was 33.3% (9/27) with a median PFS of 3.5 months (95% CI 3.45–7.02months), overall survival of 7.5 months (95 CI 6.87–11.06 months, following to 2008.8). The Grade 3/4 toxicity was mainly myelosuppression, with occurrence rates of 40.7% (10/27). Conclusions: Intra-arterial hepatic chemotherapy show its efficacy and may prolong PFS in melanoma patients with liver metastasis. No significant financial relationships to disclose.
Proposal for a new risk model in myelodysplastic syndrome (MDS) that accounts for events not considered in the original International Prognostic Scoring System (IPSS)
Authors: G. Garcia Manero, S. M. O'Brien, F. Ravandi, J. E. Cortes, J. Shan, J. M. Bennett, A. F. List, P. Fenaux, G. Sanz, J. P. Issa, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2008)

7029 Background: The IPSS is applicable only to newly diagnosed patients (pts) with MDS at the time of initial diagnosis. These constitute a small fraction of pts referred to tertiary centers or accrued on research studies. Aims: To develop a prognostic model that addresses problems of the IPSS (e.g. cytogenetic categories, cut offs for cytopenias, prior therapy), that is applicable to any pt with MDS and CMML. Methods: We analyzed 1915 pts with MDS referred to MDACC from 1993 to 2005 (including CMML, secondary MDS, MDS with prior therapy). Only 507 pts (26%) had primary MDS without prior therapy (i.e. patients categorizable by IPSS). Pts were randomly divided into a study (n=958) and a test (n=957) group. Results: The IPSS tested in the total population was prognostic but demonstrated significantly different and worse survivals in the subsets of pts with non-newly diagnosed MDS. Multivariate analysis in the study group identified the following adverse prognostic characteristics: poor performance status (ECOG ≥ 2), older age (cut offs 60 and 65 years), thrombocytopenia (cut offs 30 and 50x109/L), anemia (cut off 12g/dl), increased marrow blasts percent (cut offs 5% and 10%), leukocytosis (cut off 20x109/L), chromosome 7 or complex (more or equal 3 abnormalities), and prior transfusions. Although several factors were part of IPSS, cutoffs for anemia, thrombocytopenia and blasts, and cytogenic subsets, were different. Based on this, an MDS prognostic model was developed that divided pts into four prognostic groups (Table). The model was validated in the test group. Applying the prognostic model within the four IPSS risk groups was highly prognostic in each, regardless of whether pts had primary MDS without prior therapy. Applying IPSS within each of the 4 risk groups of the new MDS model was not prognostic. Conclusion: The new proposed MDS model is more precise than IPSS, and applies to all pts with MDS or CMML regardless or prior therapy or duration of MDS MDS risk group Percent Median Survival (mos) / % 3-year survival Study group Test group Low 16 54/65 45/58 Intermediate 1 24 25/35 23/35 Intermediate 2 24 14/18 13/18 High 36 6/5 6/5 No significant financial relationships to disclose.
Reduction in platelet counts as a mechanistic biomarker and guide for adaptive dose-escalation in phase I studies of the Bcl-2 family inhibitor ABT-263
Authors: A. Roberts, L. Gandhi, O. A. O'Connor, C. M. Rudin, D. Khaira, H. Xiong, Y. Chiu, R. Greco, A. P. Krivoshik, W. H. Wilson
Journal: Journal of Clinical Oncology (2008)

3542 Background: ABT-263 is a novel, BH3 mimetic that binds with high affinity (Ki 1 nanoM) and inhibits multiple antiapoptotic Bcl-2 family proteins. ABT-263 displays potent mechanism-based toxicity (EC50 1 microM) against human cell lines derived from lymphoid and small cell lung cancers (SCLC). Mechanistic toxicities observed pre-clinically include inhibition of spermatogenesis, reduction in circulating lymphocytes and decreased circulating platelet survival, presumably mediated by Bcl-w, Bcl-2 and Bcl-XL, respectively. Methods: Three enrolling Phase 1 dose-escalation studies are using either a modified Fibonnaci 3 + 3 design (M06–814: lymphoid malignancies) or a continuous reassessment method (CRM; M06–822: SCLC/solid tumors and M06–873: CLL). The CRM uses dose limiting toxicity (DLT) data to estimate MTD and guide dose escalation. ABT-263 was dosed for 14 days with a 7-day rest period. Results: Fifty-four subjects enrolled in the 3 studies at doses ranging from 10 mg to 315 mg. ABT-263 exposure was dose-proportional with plasma levels above the preclinical efficacy threshold achieved at 315 mg. The average half-life was 14 to 20 hours. Three DLTs were observed, one grade 3 URI at 160 mg, one grade 3 ALT elevation at 315 mg and one fatal respiratory failure at 10 mg in a SCLC patient. Dose- related thrombocytopenia consistent with preclinical models was observed. At 315 mg mean platelet reduction of 69% was observed. Typically, platelet nadir occurred on days 3 to 5 with recovery during continued dosing. This pattern is consistent with preclinical evidence of accelerated platelet senescence and compensatory increased production. Tumor regression was observed in 6 patients with CLL/SLL, NK/T cell or follicular lymphoma, with 3 patients showing > 50% tumor shrinkage. Conclusions: ABT-263 induces a transient decrease in circulating platelets via inhibition of Bcl-XL, without decreasing platelet production. This transient reduction in platelets is manageable, predictable and confirms on target activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
A phase II trial of oxaliplatin (L-OHP) and uracil-tegafur (UFT)/folinic acid (FA) for advanced colorectal cancer (ACC) in elderly patients
Authors: G. Rosati, S. Cordio, A. Tucci, G. Blanco, R. Bordonaro, C. Pizza, G. Reggiardo, L. Manzione
Journal: Journal of Clinical Oncology (2004)

3681 Background: Colorectal cancer is usually diagnosed in elderly patients (pts). Since the increase of life expectancy makes chemotherapy more appealing in this setting, we test the activity and toxicity of L-OHP and oral UFT/FA as first-line therapy in pts with ACC aged 70 or older. Methods: A two-stage trial was planned with an accrual goal of 44 pts. The treatment included L-OHP 65mg/m2 as an intravenous 3-hours infusion on day 1 and 8 plus UFT 300mg/m2 and FA 90mg in three divided doses given orally on days 1–14 of each three-week cycle. Pts with ACC with age ≥ 70 years, measurable lesions, adequate renal, hepatic and hematologic function and no previous treatment for advanced disease (adjuvant chemotherapy more than 6 months and/or radiotherapy out of the target lesion were allowed) were included. Pts were followed by a geriatric and a quality of life assessment with specific scales and EORTC-QLQ-C30 questionnaire. Results: A total of 46 pts were enrolled. All pts were evaluable for toxicity and 40 (too early) for response, M/F 26/20, age 70 to 89, performance status 0/1/2 25/20/1, colon 29 and rectum 17. Metastases locations: liver 32, local (recurrent) 15, lung 11, peritoneal carcinomatosis 6. 14/46 had had prior adjuvant chemotherapy and 7 radiotherapy outside on target lesions. Only one case of unacceptable cardiotoxicity and one case of grade 4 diarrhea were registered. Grade 3 diarrhea and neutropenia occurred in 13%, and 2%, respectively. Most common grade 2 toxicities were thrombocytopenia and nausea/vomiting 15%, anemia 11%. On evaluable pts, 20 (50%) objective responses were observed; 15 pts (37.5%) had stable disease and progressive disease was diagnosed in 5 cases (12.5%). Median overall survival and median time to progression have not yet been reached. Conclusions: These preliminary results confirmed that this tested chemotherapy combination is active and tolerated in elderly pts with ACC. The updated analysis will be presented at the meeting. No significant financial relationships to disclose.
Serum biomarker discovery for ovarian serous carcinoma using novel proteomic methods
Authors: J. A. Borgia, C. Frankenberger, K. Kaiser, S. E. McCormack, L. Usha, J. Rotmensch, J. S. Coon
Journal: Journal of Clinical Oncology (2007)

16058 Background: Ovarian serous carcinoma (OSC) is the most common ovarian cancer sub-type and fourth leading cause of cancer-related deaths for women in the US. Unfortunately, more than two-thirds of women with ovarian cancer present at an advanced stage, when prognosis is poor. Developing methods to detect ovarian cancer at stage I, when it is 90% curable by surgery, or at stage II where survival is 70%, offers the best prospect for changing the clinical course of this dread malignancy. Methods: Serum specimens were collected both before and 3–6 weeks after tumor resection for patients with Stage I/ II high-grade serous carcinoma. None suffered recurrence within 6 months. We collected 98 ‘paired’ (pre- and post operative) serum specimens; including 41 benign paired specimens for comparison. A SELDI-TOF mass spectrometer was used to generate the serum proteomic profiles, optimized for the 2,000–40,000 m/z range. All data analyses were performed in a blinded manner using Bioconductor, an extension of the R-project statistical platform (v2.2.0). Raw spectra were processed as follows: baseline subtraction, spectra normalization, and differential peak detection. Aligned peaks were sorted into groups, based on tumor pathology and pre- vs. post-operative specimen type, and compared using a two tailed homoscedastic t-test. Results: The proteomes of pre- and post-operative serum from 10 patients with OSC were evaluated for significant changes in composition and compared with a set of 8 ‘normal’ specimens (i.e. patients undergoing major surgery for benign disease). We identified 18 serum components common to all OSC pre-op specimens that were extensively reduced or absent (p &lt; 0.05) after tumor resection and 26 components capable of discerning pre-op OSC from pre-op normal specimens (p &lt; 0.05). Most notable of these are components with m/z ratios of 2029.1, 2203.6, 6442.3, and 6851.9, based on level of significance (p &lt; 0.001). Conclusions: These results validate the power of our ‘pre- vs. post- operative’ analysis strategy for the identification of novel serum biomarker candidates. Efforts are currently focused on expanding the scope of our specimen bank and identifying the putative biomarker candidates via mass spectrometry. No significant financial relationships to disclose.
Tissue microarrays application in non-small cell lung carcinoma: Morphometric study of immunohistochemical expression of topoisomerase IIa correlating with molecular detection of the specific gene alterations and chromosome 17 instability
Authors: A. Stamatelopoulos, E. Tsiambas, E. Thanopoulou, A. Karameris, G. Vilaras, D. Bouros
Journal: Journal of Clinical Oncology (2005)

9648 Background: Aberrations of chromosome 17 are common in many cancers including NSCLC. Topoisomerase family which includes Topo I (20q11), Topo IIa (17q21) and Topo IIb (3p24) is a class of enzymes in the nucleus of all living cells, which affect the topological structure of DNA. Cells die when topoisomerase is inhibited and for this reason is a target for chemotherapy. Methods: Using Tissue Microarray Technology (Chemicon TMArrayer ATA100), we created a 50 tumor TMA. 50 NSCLC (30 Adenocarcinomas and 20 Squamous carcinomas) and 10 normal lung epithelia (as control group) were obtained and embedded into a single paraffin block (core diameter: 1mm). Immunohistochemical stain for anti-Topoisomerase IIa (Ki S1-DAKO Corp) combined with CISH for the detection of chromosome 17 instability (Chr 17 Centromeric probe, Zymed kit) and specific gene status (Topo IIa Amplification probe-Zymed kit) were performed in 2 and 5 μm sections. Finally using a semi-automated Image Analysis System we evaluated the nuclear features of number, optical density and the number of signals of chromosome 17 centromeres and gene copies per nucleus. Statistical analysis was performed by SPSS version 11.0 software. Results: A significant proportion of NSCLC showed over expression of the marker (24/50) and CISH application showed topo IIa amplification (high or low level) or deletion of one allele in 21/24 cases. The last three of them (3/24) did not showed gene alterations. Co-evaluating chromosome 17 instability we observed that 13/24 cases displayed aneusomy. Polysomy 17 correlated with multiple copies of Topo IIa gene in 5/34 cases and the others correlated with monosomy or stability of chr 17 (6/24). We observed that chr 17 instability co-appearing with Topo IIa amplification correlates with low differentiation and poor prognosis (p<0,001). Conclusions: The results indicate that topo IIa amplification or deletion is a critical genetic event correlating with biological behavior in NSCLC and determining chemosensitivity. No significant financial relationships to disclose.