tbuckley/cabot-search huggingface dataset:
Induction chemotherapy, extrapleural pneumonectomy (EPP), and adjuvant hemithoracic radiation are feasible and effective for locally advanced malignant pleural mesothelioma (MPM)
Authors: R. M. Flores, L. Krug, K. E. Rosenzweig, A. Vincent, T. Akhurst, R. Heelan, V. W. Rusch
Journal: Journal of Clinical Oncology (2004)

7193 Background: Approximately 25% of patients (pts) with malignant pleural mesothelioma (MPM) prove unresectable at surgery and the median survival of stage III MPM is <12 months even after complete resection by extrapleural pneumonectomy (EPP). Improving chemotherapy for MPM led us to test induction chemotherapy followed by EPP and adjuvant hemithoracic radiation (RT) for locally advanced MPM to assess feasibility and estimate survival. Methods:From 1/2002 - 12/2003, pts with T3–4 or N2 MPM by CT and PET scans were enrolled on a phase II study. Induction therapy was: gemcitabine (1250mg/m2days 1, 8) and cisplatin (75mg/m2day 8) x 2–4 cycles. Pts underwent EPP 3–5 weeks after induction therapy, then 54 Gy RT 4–6 weeks postop. CT scans were followed every 3 months thereafter. Chemotherapy response was assessed by RECIST criteria. Overall survival was assessed by Kaplan-Meier. Results: 21 pts (15 men, median age = 60 years) were consented to study, 19 received chemotherapy. MPM histology was epithelial = 14, mixed or sarcomatoid =5. 10 pts completed 4 chemotherapy cycles, while 9 received 1–2 cycles. No grade 4 toxicities occured. Chemotherapeutic responses were: complete = 0, partial = 5 (26%), stable =11 (58%), progression = 3 (16%). At surgery, 8/9 pts had complete resection by EPP with no postop deaths. All of these pts received planned adjuvant RT. By Kaplan-Meier, pts undergoing EPP had a 75% survival at 18 months (median follow-up = 8 months), while no pts were alive at 18 months without surgery (log rank p=0.03). Conclusions: This combined modality approach is feasible for locally advanced MPM, and initial analysis suggests a favorable survival for pts rendered resectable. This experience supports additional studies of induction and multimodality therapy, especially with regimens such as cisplatin and pemtrexed which may be better tolerated and more effective. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly
Abstract 17400: Adiposity Over the Life-course and Risk of Sudden Cardiac Death in Women
Authors: Stephanie E Chiuve, Qi Sun, Roopinder K Sandhu, Usha Tedrow, JoAnn E Manson, Christine M Albert
Journal: Circulation (2013)

Background: Sudden cardiac death (SCD) is often the first manifestation of CHD among women, necessitating prevention strategies in this apparently healthy subset of the population. Elevated BMI has...
Interaction between STAT3 and immunosurveillance based on MICA.
Authors: A. Thiery-Vuillemin, R. Bedel, C. Grandclement, J. Balland, B. Kantelip, J. Pallandre, X. B. Pivot, C. Ferrand, P. Tiberghien, C. Borg
Journal: Journal of Clinical Oncology (2010)

e21055 Background: Evasion of cancer immunosurveillance (IS) is a hallmark of many malignancies. The role of NKG2D-expressing natural killer (NK) cells in tumor IS is now well established. Nevertheless, tumor progression occurs despite tumor immune surveillance leading to cancer survival in immune competent hosts. STAT proteins are a family of latent cytoplasmic transcription factors that can be considered as oncogenic proteins. STAT3 signaling affects the expression and functions of a variety of genes involved in cell survival, proliferation, invasion and angiogenesis. Then, we decided to investigate the role of STAT3 in NK cell-IS subversion. Methods: To initiate this study, we first selected a colorectal cancer cell line (HT29) poorly able to activate NK and constitutively expressing an active form of STAT3. STAT3 neutralization in HT29, using pharmacological inhibitors or siRNA, resulted in an increase of NK cytotoxicity and IFN-g production. This ability was partially restored in the presence of NKG2D neutralizing antibodies, suggesting that STAT3 activation in HT29 prevents NKG2D-mediated NK cell activation. Results: Therefore we investigated the expression of NKG2D ligands according to STAT3 activation in HT29, mesenchymal stem cells and activated-lymphoytes. Using quantitative real-time PCR, western blotting and flow-cytometry analyses, we observed that MHC class-I-chain-related protein A (MICA) was up-regulated following STAT3 neutralization. A direct interaction between STAT3 and MICA promoter was identified. Conclusions: The link between oncogenesis and NKG2D ligands expression has been showed previously by Raulet et al. implicating a cross-talk with DNA damage repair mechanism. STAT3 was shown to negatively regulate MICA expression in colon cancer cell line and mesenchymal stem cell following irradiation or heat shock exposition and in lymphocytes following CD3/CD28-mediated activation. Here we characterize a novel role of STAT3 in MICA expression regulation, that is part of NK immunoediting of colorectal cancer. No significant financial relationships to disclose.
Stat1 Is Induced and Activated by All-Trans Retinoic Acid in Acute Promyelocytic Leukemia Cells
Authors: Maurizio Gianni, Mineko Terao, Ida Fortino, Marco LiCalzi, Vincenzo Viggiano, Tiziano Barbui, Alessandro Rambaldi, Enrico Garattini
Journal: Blood (1997)
Use of metformin and lifestyle intervention to prevent ADT-related metabolic syndrome in prostate cancer
Authors: J. P. Nobes, S. E. Langley, R. W. Laing
Journal: Journal of Clinical Oncology (2009)

5159 Background: The association between androgen deprivation therapy (ADT) for prostate cancer and metabolic syndrome has been reported, with insulin resistance as the key to its development. This is the first study to investigate the effect of metformin and lifestyle changes on the development of ADT-related metabolic syndrome. Methods: Forty men with any stage of prostate cancer, due to receive ADT with a GnRH agonist, were recruited to a prospective randomised pilot study. The control arm comprised 20 patients receiving ADT alone. Men in the intervention arm (n=20) received ADT with 6 months of metformin, a low glycaemic index diet and a regular aerobic exercise programme. All patients were investigated pre-treatment and at 6 months for the metabolic syndrome, insulin resistance, and related biochemical and physical parameters. Results: After 6 months a significant reduction in metabolic syndrome cases (NCEP ATP III definition) was seen in the intervention arm (p=0.042), with an equal number seen in the control arm as at baseline. There was an increase in HDL cholesterol in both arms, which reached greater significance in the intervention arm (p=0.008) than the controls (p=0.015). The table shows an improvement in abdominal girth, weight, body mass index, and systolic blood pressure in the intervention arm, when measured as a % change over 6 months. Biochemical markers of insulin resistance did not significantly differ between each group. Conclusions: ADT is widely used in prostate cancer, but metabolic complications may be responsible for an increased cardiovascular mortality. The preventative role of metformin and lifestyle changes has been evaluated in this study, showing potential beneficial effects. However, the anticipated increased incidence of insulin resistance and metabolic syndrome has not been demonstrated in men receiving ADT alone, which may be due to small study size. Further studies will ascertain whether overall survival can ultimately be improved by this approach. [Table: see text] No significant financial relationships to disclose.
Preference and compliance of stool occult blood testing in a rural cancer-screening program
Authors: S. Waheed, T. A. Linthacum
Journal: Journal of Clinical Oncology (2006)

1030 Background: Colon cancer is the third most common cancer in men and women. Screening for colon cancer reduces the incidence of colon cancer; decreases mortality associated with colon cancer and should be an integral part of all comprehensive cancer screening programs. The impact of patient preference and compliance when given the option between guaiac-based fecal occult smear method and immunochemical assay testing was reviewed at a rural cancer-screening clinic. Methods: All cancer screening participants over age 50 were educated about colon cancer prevention and screening. The immunochemical assay test and the guaiac-based fecal occult blood test directions and costs were thoroughly explained. A sample test packet of the chosen method was shown to the participant for further explanation on the directions. Data was collected for over one year with documentation of type of preference of test taken and the return rates of those tests. Results: A total of 2170 immunochemical assay or guaiac-based fecal occult blood tests were offered to participants over age 50. The total percentage of tests taken was 39% (852 participants). 81% (688 participants) of the participants chose the immunochemical test over the guaiac-based fecal occult blood test 18% (155 participants). The return rate continued in favor of the immunochemical test with 86% (380 participants) return rate as compared with only 14% return rate for guaiac-based fecal occult blood test (60 participants). The total return rate for both test combined was 51%. Conclusion: This study revealed a surprising lack of acceptance of colon caner screening by means of stool occult blood testing despite vast efforts at thorough explanations and education. When occult blood testing was accepted immunochemical assay testing was the preferred method. Further research should focus on patient barriers in accepting colon cancer testing. No significant financial relationships to disclose.
Intraperitoneal or intraportal 5 FU combined with systemic chemotherapy for the adjuvant treatment of colorectal cancer: An EORTC (40911) and FFCD (9204) phase III study
Authors: B. Nordlinger, P. Rougier, J.-P. Arnaud, J.-C. Ollier, O. Grobost, J. Wals, B. Genicot, J. Lacourt, C. Milan, E. Van Cutsem
Journal: Journal of Clinical Oncology (2004)

3620 Background: A survival benefit has been demonstrated with adjuvant systemic (syst) chemotherapy (CT) using 5FU in patients (pts) with colon cancer. Administration of regional CT during one week is easier, but past studies have only shown a trend towards a benefit. The aim of this multicenter, intergroup study was to evaluate the efficacy of short term (1 week) regional chemotherapy in combination with long term (6 mo) systemic CT and to compare systemic 5 FU + Levamisol (FU+L) to 5 FU + folinic acid (FU+FA) in patients with stage II and III (Astler B2 and C) colorectal cancer. Methods: 1857 pts were randomized during surgery to one of 4 treatment arms (2 by 2 design) and, as per protocol, eligibility (stage II or III colon or rectum adenocarcinoma) was confirmed by pathology in 1501 pts as follows: A - Regional (reg) CT + syst FU+L, n = 380. B - Reg CT + syst FU+FA, n =368. C - syst FU+L only, n = 374. D - syst FU-FA only, n =379. Regional CT was either intraperitoneal (3600 mg/m2 in 6 days) or intraportal (3500 mg/m2 in 7 days). Results: Median follow up was 6.8 years. Tolerance was good. 79.7 % pts received full dose of reg CT, and 74.3 % full dose of syst CT. Overall survival at 5 years was 72.3% vs 72.0% in pts with or without regional CT (HR = 0.96, logrank p=0.68) and 72.3% vs 71.9% in pts with FU + FA vs FU + L (HR = 0.98, logrank p=0.81). Disease free survival at 5 years was 63.9% in pts who received regional CT and 61.4% in pts who did not receive regional CT (HR = 0.94, p=0.43) and 64.0% vs 61.8% in pts with FU + FA vs FU + L (HR = 0.92, logrank p=0.32). The data do not show any treatment differences according to stage (II vs III) or tumor location (colon vs rectum). Conclusions: 1 –combining regional and systemic adjuvant CT does not improve the efficacy of systemic chemotherapy. 2 –folinic acid when combined with systemic adjuvant 5 FU is not superior to levamisole. No significant financial relationships to disclose.
Adequacy of follow-up after an abnormal fecal occult blood test (FOBT) result
Authors: L. C. Richardson, Z. Berkowitz
Journal: Journal of Clinical Oncology (2006)

6035 Background: Annual fecal occult blood testing (FOBT) is the only colon cancer screening shown to reduce colon cancer incidence and mortality in randomized controlled trials. The true benefits of screening are only realized when total colon examination (TCE) is performed as follow-up to an abnormal screening result. Methods: We used the 2000 National Health Interview Survey (NHIS) Cancer Control Supplement, a nationally representative sample of households, to examine follow-up after abnormal FOBT and the content of this follow-up. Persons who reported undergoing an FOBT were the population of interest. Reasons for FOBT, results of test, and follow-up after an abnormal FOBT were examined. Inadequate follow-up after a positive FOBT included no follow-up or another FOBT. TCE was defined as sigmoidoscopy with double contrast barium enema (DCBE) or colonoscopy. We used SUDAAN to obtain population estimates. Results: We included 4,908 respondents who indicated they had undergone FOBT (79.8% as part of the routine physical examination, 14.7% for a specific problem, 2.0% as follow-up of a previous abnormal test/screening examine, 1.4% family history). Overall, 5.7% of respondents reported an abnormal test, varying by reason for test (3.5% for screening and 16.9% for those who had FOBT done for a specific problem). For those reporting an abnormal FOBT during screening, 62.9% had some follow-up diagnostic procedures. Fifty-three percent reported having a TCE as defined above. Forty-seven percent either had no further evaluation, another FOBT or incomplete colon examination with sigmoidoscopy alone, and DCBE only or a surgical evaluation. Those who had FOBT completed for a specific problem had more surgical evaluations (18.4%) and fewer TCEs (44.3%). Conclusions: Among a nationally-representative sample of adults who reported FOBT as a screening test for colorectal cancer, close to 63% had some type of follow-up. Only 53% of those with a positive screening FOBT had a TCE. These results suggest that the full potential of CRC screening is not being realized, and point to the need to improve follow-up of abnormal FOBT results. No significant financial relationships to disclose.
Phase I study of nelfinavir (NFV) in liposarcoma (LPS).
Authors: W. A. Chow
Journal: Journal of Clinical Oncology (2010)

e13538 Background: LPS's are the most common type of soft-tissue sarcoma. Chemotherapy for recurrent LPS is only modestly active. We began investigating the HIV protease inhibitor (PI), NFV, for LPS therapy because of its association with the HIV PI-induced Lipodystrophy Syndrome. We hypothesized that adipocytic tumors respond similarly to NFV as normal adipocytes. We report the results of a phase I study of NFV for LPS. Methods: Patients (pts) with recurrent, surgically unresectable LPS were eligible. There was no limit to prior chemotherapy regimens. Additional eligibility included: Age ≥ 18 y, ECOG 0-2, and normal organ function. The starting dose of NFV was 1,250 mg BID (level 1). Doses were escalated in cohorts of 3 up to a maximal dose of 4,250 mg BID (level 5). A cycle was defined as 28 days. Steady-state pharmacokinetics (PK) for NFV and its primary active metabolite, M8, were determined on Day 1 Cycle 2 at levels 4 (3,000 mg BID) and 5. Results: 20 pts (13 M; 7 F) were enrolled (age range 37-81y; median age 64y). 1 pt at level 1 experienced transient, grade 3 pancreatitis after 1 wk of NFV, and was inevaluable for response. No other dose-limiting toxicities were observed. The length of NFV treatment ranged from 0.6 to 13.5 mos (median 3 mos). Response data include: 1 PR (unconfirmed), 5 SD on fist evaluation after 3 cycles, 13 PD, and 1 inevaluable. PK data are available from six subjects at level 4 and three at level 5. Interestingly, mean peak plasma levels and AUCs for NFV were higher at the 3,000 (7.3 mg/L; 60.9 mg/L × hr) vs. 4,250 mg BID dose level (6.3 mg/L; 37.7 mg/L × hr). Additionally, time to peak plasma concentration of NFV and M8 occurred later (4-6 h) with 3,000 mg vs. 2 h for the 4,250 mg dose. The mean ratio of M8:NFV AUCs for both dose levels was ∼1:3. Peak plasma concentrations were within the range where anticancer activity was demonstrated in vitro. Conclusions: The PK data demonstrate auto-induction of NFV clearance at the doses studied, although the mechanism remains unclear. M8 metabolite is present at ∼1/3 the level of the parent NFV, and may also contribute to the anticancer activity seen. In accordance with the phase I results, a phase II study of NFV for LPS at 3,000 mg BID is ongoing to better define its activity. Supported by R01FD003006. No significant financial relationships to disclose.
Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin’s lymphoma: Results of a pilot study
Authors: G. Corazzelli, G. Capobianco, F. Russo, G. Marcacci, O. Villani, A. Pinto
Journal: Journal of Clinical Oncology (2006)

17533 Background: We evaluated a new short-course (biweekly), dose intensive, cytoreductive/mobilizing salvage regimen (R-GIFOX) combining the cross-synergistic agents Gemcitabine (G), Ifosfamide (Ifo), Oxaliplatin (Ox) and Rituximab (R), in patients with recurrent CD20+ NHL. Methods: Patients were scheduled to receive three courses of R-GIFOX followed by mobilization and ASCT or three more courses if ineligible for ASCT. Therapy was delivered on a compassionate basis after written informed consent. R-GIFOX consisted of R (375 mg/m 2 , d 1), G (1000 mg/m 2 , d 2), Ox (130 mg/m 2 , d 3), Ifo (5 g/m 2 , d 3), as a 24-hour single infusion in patients aged ≤ 65 yrs, or fractionated over 3 days (dd 3–5) in those older, G-CSF (5 mcg/kg/d, dd 6–11; 10 mcg/kg/d at the 3rd course). Responses were evaluated after three courses by the integrated FDG-PET/IWC criteria. Results: Twenty patients (median age 62 yrs, r 37–79) with relapsed (n = 15) or refractory (n = 5) aggressive [diffuse large cell (n = 8), mantle cell (MCL) (n = 5), follicular G3 (n = 7)], advanced (stage IV = 75%), poor risk (IPI 3–5 = 60%; previous therapies: median = 2, r 1-4) NHL, were accrued. Eighty-five total courses were given (median 4, r 1–6). Actual dose intensities of the first 3 courses were: G = 82%, Ifo = 83% and Ox = 86.5%. CTCAE v 3.0 toxicity (85 courses) was: G3/G4 thrombocytopenia = 23%; G3/G4 neutropenia = 21%; G3 febrile neutropenia = 5% and G3/G4 infections = 8%. The ORR after three courses was 80%, with 11 complete responses (55%; CR = 8; CRu = 3) and 5 partial; CRu converted to CR at BM biopsy after 6 courses. The ORR was 77 % (6 CR, 4 PR) for patients aged ≤ 65 yrs and 86% (5 CR, 1 PR) for those older. Also, the ORR was 40% (1 CR, 1 PR) for refractory patients and 93% (10 CR, 4 PR) for those relapsed. TTF was 79.4% at a median f.u. of 8 months (r, 2-16). CD34+ cells were harvested in 6 out of 8 eligible patients. Among patients with MCL 3 CRs and 1 PR were obtained, including 2 molecular remissions. Conclusions: R-GIFOX had limited toxicity and good activity in recurrent aggressive NHL. It may offer a less toxic alternative to Cisplatin/ARA-C-based regimens, also for patients aged or unfit for ASCT, and in “difficult” histotypes such as MCL. No significant financial relationships to disclose.
Familial hemolytic uremic syndrome and mutations in membrane cofactor protein (MCP; CD46) of the complement system.
Authors: A Richards, Yves Pirson, EJ Kemp, K Liszewski, JA Goodship, AK Lampe, R Decorte, H Muslumanoglu, S Kavukcu, G Filler, LS Wen, JP Atkinson, Thj Goodship
Journal: Journal of the American Society of Nephrology (2003)
A phase II open-label study of OSI-774 (NSC 718781) in unresectable hepatocellular carcinoma
Authors: M. B. Thomas, A. Dutta, T. Brown, C. Charnsangavej, A. Rashid, P. M. Hoff, J. Dancey, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2005)

4038 Background: Hepatocellular carcinoma (HCC) is the 4th most common cancer worldwide and is increasing in the United States and other western countries. HCC are chemotherapy-resistant tumors, and current systemic therapy has been unable to prolong survival. Epidermal growth factor receptor (EGFR) is overexpressed in a majority of HCC, thus it is rational to study OSI-774, a small molecule EGFR tyrosine kinase inhibitor, in this disease. Patients and Methods: Prospective Phase II study of OSI-774 in pts with previously untreated advanced HCC. A total of 25 patients (pts) have been enrolled to date. Patients accrue to 1 of 2 strata based on low (0–2+; 6 pts, 24%) or high (3–4+; 19 pts, 76%) tumor EGFR expression by immunohistochemistry (IHC). The primary endpoint is the rate of progression-free survival at 16 weeks of OSI-774 treatment. All patients received OSI-774 at 150 mg/po daily. Demographics: male 19, female 6, median age 66, cirrhosis 12 pts, no cirrhosis 13 pts, Childs-Pugh class A, 25 pts (100%); ECOG 0, 8 pts (32%); 1, 14 pts (56%); 2, 3 pts (12%); risk factors hepatitis C virus (HCV) 9 (36%), HBV 4 pts; other 12 (48%). Functional computed tomography (fCT) scans were performed on all pts at baseline, 4, 12, and 16 wks, to evaluate whether OSI-774 changed tumor blood flow. Results: 8 pts have met the study endpoint (8/25, 32%; 1 PR); 5 high EGFR (5/19, 26.3%), 3 low EGFR (3/6, 50%); 1 pt remained on study drug for 16 months. Toxicity: Grade (Gr)1–2: 23 pts; Gr 3: 7 pts. (abdominal pain, anemia, increased bilirubin and AST, skin infection, vomiting, diarrhea). No pts required dose reduction or removal from study for drug-related toxicity. 21 pts had Gr 1–2 skin rash. All responding pts developed Gr 1(5 pts, 62.5%) or Gr 2 (3 pts, 37.5%) skin rash. Median time to progression (TTP) for all pts: 9.1 wks; median TTP for responding pts: 26.3 wks. Median survival (MS) all pts: 25 wks; MS for responding pts: 44 wks. fCT analysis appears to indicate mixed response of tumor blood flow to OSI-774. Conclusions: OSI-774 is well tolerated in pts with HCC, and provides prolonged stable disease and apparently has the potential to improve survival. Accrual will continue to 40 pts total in each strata. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech NCI
Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura
Authors: Sun Bean Kim, Do Kyung Kim, Sun Jeong Byun, Ji Hye Park, Jin Young Choi, Young Nyun Park, Do Young Kim
Journal: Clinical and Molecular Hepatology (2015)

Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months. Keywords: Peliosis hepatis; Hepatomegaly; Steroids