tbuckley/cabot-search huggingface dataset:
Extrapulmonary small cell carcinoma (EPSCC): Retrospective review from a single institution
Authors: M. Raja, S. Akhtar, A. El Weshi, I. Maghfoor
Journal: Journal of Clinical Oncology (2004)

6108 Background: EPSCC is an uncommon entity. No clear guidelines exist for its management. Two retrospective series have been reported to date. We therefore decided to review our institution's experience with EPSCC with special emphasis on treatment considerations. Methods: We used tumor registry records to identify all patients diagnosed with EPSCC at our institution. Data were collected on demographics, site/s of disease, management, and outcome. Lung disease at presentation and Merkel cell carcinoma of skin were excluded. Disease confined to organ of origin and regional nodes was designated localized disease and spread beyond this considered extensive. Results: 24 patients were included in this study. There were 11 males and 13 females. Median age was 59. Sites of origin were esophagus 7, cervix 6, parotid gland, lacrimal gland, urinary bladder, pancreas, and anal canal 2 each, and prostate 1. Ten patients had localized disease, and 14 had extensive. Initial therapy consisted of chemotherapy in 11, surgery in 6, radiation therapy in 6, and no treatment in 1. Fourteen patients received chemotherapy (including 11 as initial treatment). Chemotherapy regimens included etoposide/platinum in 8, etoposide combinations in 2, cytoxan/doxorubicin/vincristine/etoposide in 4. At the completion of all therapy complete response was observed in 9, partial response in 3, stable disease in 1, progressive disease in 4 and not evaluable in 7. Median survival was 8 months. Patients presenting with limited disease had a median survival of 17.5 months. Of those presenting with limited disease, five are alive and free of disease (9–151 months; median 80). Four of these were treated with combination of chemotherapy and local treatment. Those presenting with limited disease but treated with single modality did not achieve long term survival. Conclusion: Our data highlights inconsistency in the management of EPSCC over the last decade. Patients presenting with localized disease should be treated aggressively with combined modality therapy including chemotherapy. Prognosis & survival of those presenting with extensive disease is poor. No significant financial relationships to disclose.
Bench-to-bedside research and the human tumor stem-cell assay--bridging the credibility gap.
Authors: G P Browman, M N Levine, R S Roberts
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.12.1730 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3783200 Bench-to-bedside research and the human tumor stem-cell assay--bridging the credibility gap. G P BrowmanxG P BrowmanSearch for articles by this author , M N LevinexM N LevineSearch for articles by this author , R S RobertsxR S RobertsSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.12.1730 PDF "Bench-to-bedside research and the human tumor stem-cell assay--bridging the credibility gap.." Journal of Clinical Oncology, 4(12), pp. 1730–1731© 1986 by American Society of Clinical Oncology
High Levels of the Adhesion Molecule CD44 on Leukemic Cells Generate Acute Myeloid Leukemia Relapse After Withdrawal of the Initial Transforming Event
Authors: Ronan Quere, Silja Andradottir, Ann Brun, Roman Zubarev, Göran Karlsson, Karin Olsson, Mattias Magnusson, Jörg Cammenga, Stefan Karlsson
Journal: Blood (2010)
O-0030 Long Term Survival Data from EORTC Study 40983: Perioperative Chemotherapy for Resectable Liver Metastases from Colorectal Cancer
Authors: Bernard Nordlinger, Halfdan Sorbye, Bengt Glimelius, Graeme John Poston, Peter M. Schlag, Philippe Rougier, Wolf Bechstein, John Neil Primrose, Euan Thomas Walpole, Meg Finch-Jones, Daniel Jaeck, Darius Mirza, Rowan W. Parks, Laurence Collette, Michel Praet, Eric Van Cutsem, Werner Scheithauer, Murielle E. Mauer, Thomas Gruenberger
Journal: Annals of Oncology (2012)
Biweekly docetaxel and carboplatin as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). Finally results of a phase II study
Authors: J. L. Fírvida, G. Esquerdo, M. Amenedo, M. Salgado, C. LLorca, E. Pérez, J. Cervera Grau, M. Ramos
Journal: Journal of Clinical Oncology (2008)

19097 Background: Platinum-based therapy remains a key component in the firs-line treatment of patients (pts) with advanced NSCLC. The docetaxel-carboplatin combination is active and well tolerated on a biweekly schedule. The primary objective of this phase II study was overall response rate (ORR). Secondary objectives were time to progression (TTP), safety and survival. Methods: Pts with stage IIIB (pleural effusion) and IV NSCLC, measurable disease according RECIST criteria, aged >18, ECOG PS 0–2, adecuate bone marrow, renal and hepatic function were included. Pts received docetaxel 50 mg/m2 and carboplatin AUC-4 each 2 weeks for a maximum of 8 cycles. Results: Between March 2004 and July 2005, 50 pts were included, 84% were male, median age 63 years old (range 48–77), 78% had ECOG PS 0–1, and 64% of pts stage IV. Squamous cell 54%, adenocarcinoma 36% and large cell 10%. A total of 316 cycles were administrated (median 7, range 1–12). Toxicity: Grade 3–4 per pt was neutropenia (22%), asthenia (16%), anaemia (10%), thrombocytopenia (2%), mucositis (2%) and emesis (2%) Activity: The ORR was 30.5% (95% CI:17.2–43.8%), with a median TTP of 6.2 months (95% CI:2.8–9.7) and median OS of 12.2 months (95%CI:9.3–15.2). The 1-year survival was 52.5% (95% CI: 37.8–67.2). Conclusions: The biweekly docetaxel-carboplatin regimen is effective in terms of response, median survival and 1-year survival in pts with advanced NSCLC. No significant financial relationships to disclose.
Phase I evaluation of carfilzomib (PR-171) in hematological malignancies: Responses in multiple myeloma and Waldenstrom’s macroglobulinemia at well-tolerated doses
Authors: K. A. Stewart, O. A. O’Connor, M. Alsina, S. Trudel, P. R. Urquilla, M. K. Vallone, C. J. Molineaux, A. Goy, R. Z. Orlowski
Journal: Journal of Clinical Oncology (2007)

8003 Background: Carfilzomib is a novel, irreversible tetrapeptide proteasome inhibitor derived from the natural product epoxomicin. Carfilzomib was well tolerated in preclinical animal studies when administered on a two-week cycle, QDx5; proteasome inhibition one hour after dosing at the MTD was &gt;80%. Two Phase I dose-escalation studies are ongoing, aimed at determining the safety, tolerability, and biological response to carfilzomib. Methods: Carfilzomib was administered according to two different dose-intensive schedules. In PX-171–001, carfilzomib was administered on a two week cycle, QDx5 with nine days rest; in PX-171–002, carfilzomib was administered on a four week cycle, QDx2 weekly for three weeks with 12 days rest. Eligible patients have multiple myeloma (MM), Non-Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD), or Waldenström's Macroglobulinemia (WM). Results: Thus far, a total of 54 subjects have been enrolled. Although the maximum tolerated dose (MTD) has not yet been identified on either study, responses seen on both protocols have established 11 and 15 mg/m 2 as the minimal effective doses (MEDs) on PX-171–001 and 002, respectively. Of 3 patients with MM or WM treated on the 001 protocol, one MM patient has had a Partial Response (PR) and one WM patient had a Minimal Response (MR). Of 8 patients with MM treated on the 002 protocol, 3 patients have had PRs. 6 additional patients have had Stable Disease lasting longer than 6 months and symptomatic improvement has been seen in patients on both protocols. 11 subjects remain on study with stable disease or better. Proteasome inhibition in whole blood at the highest dose levels exceeded 80% one hour after the first dose. Carfilzomib has been well tolerated at doses at and above the MED thus far. There has been no incidence of painful peripheral neuropathy on either study. No dose-limiting toxicities (DLTs) have occurred on PX-171–001; one DLT (Gr 4 anemia and thrombocytopenia) was observed at 27 mg/m 2 on PX-171–002. Conclusions: Thus far, intensive dosing with carfilzomib is well-tolerated at proteasome inhibition levels of more than 80%. Five responses have been observed, and several subjects have achieved long lasting SD and/or symptomatic improvement. No significant financial relationships to disclose.
A Combined Patient and Provider Intervention for Management of Osteoarthritis in Veterans
Authors: Kelli D. Allen, William S. Yancy, Hayden B. Bosworth, Cynthia J. Coffman, Amy S. Jeffreys, Santanu K. Datta, Jennifer McDuffie, Jennifer L. Strauss, Eugene Z. Oddone
Journal: Annals of Internal Medicine (2015)

Background: Management of osteoarthritis requires both medical and behavioral strategies, but some recommended therapies are underused. Objective: To examine the effectiveness of a combined patient and provider intervention for improving osteoarthritis outcomes. Design: Cluster randomized clinical trial with assignment to osteoarthritis intervention and usual care groups. (ClinicalTrials.gov: NCT01130740) Setting: Department of Veterans Affairs Medical Center in Durham, North Carolina. Participants: 30 providers (clusters) and 300 outpatients with symptomatic hip or knee osteoarthritis. Intervention: The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved delivery of patient-specific osteoarthritis treatment recommendations to primary care providers through the electronic medical record. Measurements: The primary outcome was total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 12 months. Secondary outcomes were WOMAC function and pain subscale scores, physical performance (Short Physical Performance Battery), and depressive symptoms (Patient Health Questionnaire-8). Linear mixed models that were adjusted for clustering of providers assessed between-group differences in improvement in outcomes. Results: At 12 months, WOMAC scores were 4.1 points lower (indicating improvement) in the osteoarthritis intervention group versus usual care (95% CI, −7.2 to −1.1 points; P = 0.009). WOMAC function subscale scores were 3.3 points lower in the intervention group (CI, −5.7 to −1.0 points; P = 0.005). WOMAC pain subscale scores (P = 0.126), physical performance, and depressive symptoms did not differ between groups. Although more patients in the osteoarthritis intervention group received provider referral for recommended osteoarthritis treatments, the numbers who received them did not differ. Limitation: The study was conducted in a single Veterans Affairs medical center. Conclusion: The combined patient and provider intervention resulted in modest improvement in self-reported physical function in patients with hip and knee osteoarthritis. Primary Funding Source: Department of Veterans Affairs, Health Services Research and Development Service.
Single dose per cycle pegfilgrastim successfully supports full dose intensity CHOP-14 in patients over 60 years with non-Hodgkin's lymphoma (NHL) and successfully mobilises peripheral blood progenitor cells (PBPC).
Authors: M Bentley, P Marlton, N Horvath, ID Lewis, A Spencer, R Herrmann, C Arthur, S Durrant, M van Kerkhoven, J MacMillan, R Mrongovius, MW Wolf
Journal: Blood (2003)
Detection of methylation in the CpG islands of the RASSF1A and RAR2b gene promoters in breast cancer (BC)
Authors: K. Desiris, S. Voyatzi, P. Stravoravdi, I. Boukovinas, A. Kiziridou, D. Paikos, E. Stergiou, G. Sibilidis
Journal: Journal of Clinical Oncology (2009)

e14632 Background: Aberrant methylation of CpG islands of cancer-related genes has emerged as an important epigenetic mechanism during carcinogenesis. We examined the methylation of RASSF1A (Ras-association domain family 1, isoform A) and RAR2b (Retinoic Acid Receptor 2b) genes in BC. The knowledge of their role in BC is limited and confused to date. Methods: Promoter methylation was measured in 37 pts, 26 with BC and 11 with benign lesions. The specimens were obtained from archive formalin-fixed paraffin-embedded tumors. After DNA extraction, the methylation was determined by chemical modification of DNA with sodium bisulfite and subsequent double “hot start” Methylation-Specific PCR (MSP), followed by detection on agarose gel. Results: Methylation of at least one of the genes was observed in 18/26 pts (p&lt;0.05). Methylation of RASSF1A gene was observed in 15/26 and RAR2b in 11/26 pts. Both genes were methylated in 8/26 pts. Correlation between methylation and clinicopathological features revealed an association of the RASSF1A gene with T2 tumors (12/15 pts, p&lt;0.05) and ER (+) status (12/15 pts, p&lt;0.05). T2 tumors and ER (+) status presented together in 9/15 pts. The methylation of RAR2b gene was not associated with any known clinicopathological features. In benign lesions methylation of at least one of the genes was observed in 8/11 pts (p&lt;0.05). Methylation of RASSF1A gene was observed in 5/11 pts and RAR2b in 7/11 pts. Both genes were methylated in 4/11 pts. Conclusions: Both genes are frequently methylated in both benign and malignant breast lesions. The association of methylation of RASSF1A gene with tumor size and ER status is noteworthy. The small number of pts does not allow us to confirm the exact role of gene methylation in BC yet. Larger studies are required in order to assess if these epigenetic alterations point out new BC markers, which could be helpful for BC control. No significant financial relationships to disclose.
Acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) and overall mortality with chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF): A meta-analysis of randomized controlled trials (RCTs)
Authors: G. H. Lyman, D. C. Dale, E. Culakova, M. S. Poniewierski, D. Wolff, N. M. Kuderer, K. Lambert, J. Crawford
Journal: Journal of Clinical Oncology (2009)

9524 Background: To evaluate the risk of AML/MDS and overall mortality in patients receiving CT ± G-CSF, a meta-analysis of RCTs were conducted. Methods: Electronic databases searched through August 2008 identified 3,794 articles for initial screening. Eligibility included RCTs of solid tumor or lymphoma patients randomized to CT ± primary G-CSF support, ≥2 years follow-up and reporting AML/MDS or all second malignancies. Pre-specified study categories included: a)same dose/schedule, b)dose-dense or c)dose-escalated CT. Primary outcomes were AML/MDS and mortality. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk difference (ARD) were estimated by Mantel-Haenszel. Results: Median follow-up was 54 months. 12,642 patients were randomized to CT ± primary G-CSF support. Second malignancies were reported in 3.3% and 3.2% with and without G-CSF, respectively (P=.942). RR for AML/MDS with CT+G-CSF compared to control was 1.92 [P=.006] with ARD increase of 0.4% [P=.008]. RR for AML/MDS in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 1.95 [P=.346], 1.20 [P=.666] and 2.47 [P=.006], respectively. RR for mortality with CT+G-CSF was 0.898 [P&lt;.0001] with ARD decrease of 3.3% [P&lt;.0001]. RR for mortality in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 0.95 [P=.140], 0.84 [P&lt;.001] and 0.91 [P=.019], respectively. Delivered relative dose intensities (RDI) were 1.18, 1.46 and 1.23 in studies planned to receive the same, dose-dense or dose-escalated CT, respectively. A significant association was observed between delivered RDI and reduced mortality [P=.013]. No differences in estimates of AML/MDS or mortality were observed between industry and non-industry-funded studies. Conclusions: Risk of AML/MDS is increased with dose escalated CT+G-CSF. Nevertheless, CT+G-CSF is associated with greater reductions in overall mortality. Dose-dense regimens are associated with the greatest RR reduction in mortality and lowest risk of AML/MDS. Further research is needed to differentiate any impact of G-CSF on the risk of AML/MDS from that due to increased CT intensity. [Table: see text]
Characteristics of patients referred to a community-based palliative care consultation service.
Authors: Adriana L. Alvarez, Renato Verayo Samala, Mona Gupta, Lisa A. Rybicki
Journal: Journal of Clinical Oncology (2014)

132 Background: Home-based palliative care programs by multi-disciplinary providers improve patient and caregiver satisfaction, enhance symptom control, increase hospice use, and decrease acute care encounters. We launched a community-based consultation service to deliver high-quality palliative care to patients who are homebound or staying in various post-acute care facilities. The study described the characteristics of our patients, and determined the relationship between certain demographic features and outcomes. Methods: We conducted a restrospective chart review of patients seen on initial consultation and subsequent visits between January 1, 2011 and December 31, 2011. All patient encounters were done by 4 palliative care physicians. Data pertaining to demographics, diagnosis, hospice use, and death were obtained and analyzed. Results: A total of 221 patients were evaluated. The median age was 75 years, 61.1% were female, 51.1% had cancer, 79.1% were seen at home, and 57% possessed advance directives at initial consultation. Almost half (45.2%) of the referrals were made by primary care physicians. Majority (82.4%) of the referrals were for symptom management, while 37.6% were for goals of care discussion. Many patients had several reasons for consultation, as well as multiple symptoms, such as pain (65%), fatigue (54.8%), and dyspnea (22.6%). The mean number of follow-up visits was 0.62 + 1.08. During the study period, 33.5% of patients died, and 42.5% enrolled in hospice. Of the deaths, 48.7% occurred within 30 days of initial consultation, and 50.0% died at home. Age, gender, race and marital status were not related to hospice enrollment, death, and time and site of death. Patients with advance directives were more likely to enroll in hospice (50.0% vs 32.2%, p=0.009), while those seen at home were more likely to die at home rather than in a facility or hospital (61.0% vs 16.9% vs 22.0%, p&lt;0.001). Conclusions: Patients referred to our community-based palliative care consultation service were mostly homebound older adults needing symptom management and goals of care discussion. Our program may have been helpful in providing quality end-of-life care by facilitating hospice enrollment and death at home.
Impact of FISH and Cytogenetics On Overall and Event Free Survival in Myeloma: An IMWG Analysis of 9,897 Patients.
Authors: Herve Avet-Loiseau, Brian G M Durie, Jeff Haessler, John Crowley, Antje Hoering, Bart Barlogie, John D Shaughnessy, Orhan Sezer, Chaim Shustik, Roman Hajek, Harmut Goldschmidt, Pieter Sonneveld, Philippe Moreau, Michel Attal, Antonio Palumbo, Mario Boccadoro, Jae Hoon Lee, Jan Westin, Ingemar Turesson, Jesús F. San Miguel, Joan Blade, Juan José Lahuerta, Santiago Pavlovsky, Dorotea Beatriz Fantl, S.Vincent Rajkumar, Rafael Fonseca
Journal: Blood (2009)
Association between early palliative care referrals, inpatient hospice utilization, and aggressiveness of end-of-life care: An investigation of cancer decedents in a cancer-designated hospital in Japan.
Authors: Koji Amano, Ryohei Tatara, Hirofumi Katayama, Teruaki Uno, Ibuki Takagi
Journal: Journal of Clinical Oncology (2014)

39 Background: Palliative care has a positive effect on many clinical outcomes, yet most referrals to palliative care have occurred late. End-of-life (EOL) cancer care has become increasingly aggressive. There have been no studies investigating the association between early palliative care referrals and aggressive EOL care in Japan. Methods: This study was designed to explore the association between early palliative care referrals, inpatient hospice utilization, and aggressiveness of EOL care by investigating cancer decedents. A retrospective cohort study in a cancer designated hospital in Japan. This study examined 266 consecutive cancer decedents. Inclusion criteria were as follows: (1) adults and (2) patients who died from cancer or causes related to cancer. Patients who died from causes unrelated to cancer were excluded. A total of 265 patients met the criteria. We explored the association between early referrals (&gt;3 months before death) and inpatient hospice utilization and the relationship between the timing of referrals and aggressive EOL care measured by a composite score adapted from Earle et al. Results: Patients were divided into an early referral group (n=54) and a control group (n=211). The rate of inpatient hospice utilization was significantly higher in the early referral group (74% vs. 47%, P&lt;0.001). While each of six indicators of aggressiveness of EOL care did not differ significantly, the composite score was significantly lower in the early referral group (1.91 ± 0.59 vs. 2.14 ± 0.78, P=0.040). Conclusions: Early palliative referrals were associated with more inpatient hospice utilization and less aggressive EOL care.
CF101 enhances the apoptotic effect of chemotherapy on colon and pancreatic carcinoma cell lines: Molecular mechanisms involved
Authors: P. Fishman, S. Bar Yehuda, S. M. Stemmer, L. Madi
Journal: Journal of Clinical Oncology (2004)

3173 Background: The A3 adenosine Gi protein-coupled receptor is highly expressed in tumor as compared to normal cells. Targeting the A3 adenosine receptor (A3AR) with the highly selective agonist CF101 induces growth inhibition of colon carcinoma and other tumor cell types via down-regulation of PKB/Akt and NF-kB. High expression level of these two signaling proteins is associated with the development of chemo-resistance in various tumor cell types, thus it prompted us to explore whether CF101 would enhance the anti-tumor effect of chemotherapy. Methods: HCT-116 human colon and Bx-PC3 human pancreatic carcinoma cell lines were used. Cells were cultured for 48h in the presence of 5-FU (0.625 μM), oxaliplatin (0.5 μM) or gemcitabine (0.02 mM) and CF101 (10nM) was introduced for an additional 24h. Proliferation assay (MTT) and protein expression profile were conducted at 72h. In vivo studies included nude mice that were inoculated with the tumor cells. Treatment with chemotherapy alone or in combination with CF101 was initiated when tumor reached a size of 150 mm3. Tumor size was monitored each 4 days and study was terminated after 35 days. Results: In HCT-116 human colon and Bx-PC3 human pancreatic carcinoma cells, CF101 enhanced the cytotoxic effect of 5-FU, oxaliplatin and gemcitabine in vitro by 20% 25% and 32% respectively (P<0.01). The molecular mechanism involved a marked decrease in the level of PKB/Akt and NF-kB followed by an increase in caspase-3 level resulting in apoptosis, as observed by DNA ladder analysis. In xenograft models of HCT-116 colon carcinoma, CF101 doubled the time to tumor progression (p<0.002) when given in combination with 5-FU. Conclusions: CF101 enhanced the chemotherapeutic effect in vitro and doubled the time to tumor progression in xenograft models. It is thus suggested that CF101 may be further developed as an add-on treatment to chemotherapy for colon and pancreatic carcinoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Can-Fite BioPharma