tbuckley/cabot-search huggingface dataset:
Abstract P083: Poor Health Behaviors Explain Increased Risk of Cardiovascular Events in Hostile Patients with Coronary Heart Disease: Findings from the Heart and Soul Study
Authors: Jonathan M Wong, Beeya Na, Mary A Whooley
Journal: Circulation (2012)

Background: Hostility is a significant predictor of adverse cardiovascular (CV) events in patients with coronary heart disease (CHD) but the mechanisms that explain this association are unknown. Hypothesis: We assessed the hypothesis that controlling for poor health behaviors (physical inactivity, medication nonadherence, and smoking) would eliminate the association between hostility and future CV events. Methods: We prospectively examined the association between self-reported hostility and CV events in 1022 outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was assessed using the 8-item Cynical Distrust Scale. Log hazard models were used to determine the extent to which candidate biological and behavioral mediators changed the strength of association between hostility and CV events (myocardial infarction, heart failure, stroke, transient ischemic attack, or death). Results: A total of 592 CV events occurred during 8 years of follow-up. Each standard-deviation increase in hostility score was associated with a 20% increased risk of CV events (age-adjusted hazard ratio [HR] 1.20; 95% CI, 1.09-1.31; P=0.0001). The age-adjusted annual rate of CV events was 10.4% among the 185 subjects in the highest quartile of hostility and 6.2% among the 333 subject in the lowest quartile of hostility (HR 1.67; 95% CI, 1.27-2.18; P=0.0002). After adjustment for comorbid diseases and cardiac disease severity, participants with hostility scores in the highest quartile had a 46% higher rate of CV events than those with scores in the lowest quartile (HR 1.46; 95% CI, 1.09-1.98; P=0.01). This association was no longer statistically significant after adjustment for smoking, medication non-adherence and physical inactivity (HR 1.12; 95% CI, 0.87-1.63; P=0.27). Conclusions: Hostility was a significant predictor of adverse CV events in this sample of patients with stable CHD, but the association was eliminated after adjustment for poor health behaviors. Association Between Baseline Hostility (Quartile IV vs. I) and Subsequent Cardiovascular Events * Model Adjusted for † HR (95% CI) P value Age 1.67 (1.27-2.18) 0.0002 Above + Male, White 1.70 (1.29-2.24) 0.0002 Above + depressive symptoms 1.56 (1.17-2.08) 0.003 Above + MI, diabetes, LVEF 1.46 (1.09-1.98) 0.01 Above + CRP 1.36 (1.00-1.84) 0.05 Above + smoking 1.31 (0.97-1.78) 0.08 Above + medication nonadherence 1.26 (0.92-1.72) 0.14 Above + physical inactivity 1.19 (0.87-1.63) 0.27 * Cardiovascular events include myocardial infarction, heart failure, stroke, transient ischemic attack, and death; † Each model adjusts for the variables from the preceding rows, such that the final row adjusts for every variable listed in the table
Effect of rH-erythropoietin-a on tumor vasculature and sensitivity to irradiation in epidermoid cancer xenograft
Authors: J. Timar, R. Gillyen, J. Lövey, B. Bereczky, J. Tovari
Journal: Journal of Clinical Oncology (2004)

5597 Background: Recent data indicate that Erythropoetin (EPO) regulates non-erythroid cells including endothelial- or cancer cells therefore may have direct effect on tumors. Methods: Embryonal vasculogenesis was tested in chicken chorioallantoic membrane assay and neoangiogenesis in A431 human epidermoid cancer xenograft. Tumor vasculature was visualized and measured (density and size) in frozen sections of A431 xenograft labeled by anti-CD31. Tumor cell proliferation was measured in vitro by MTT- and clonogenic assay. In vivo tumor growth was tested in SCID mice following s.c. implantation. Human recombinant erytropoetin-a (EPO) was administered i.p. into mice three times per week in a dose of 150 IU/bw, 5 mm sized tumors have been irradiated by 5 Gy on day 14 and tumor size was measured for another 10 day period. Results: We found that 72 hr EPO treatment (2–20 IU/egg) significantly enhanced blood vessel formation in the chicken embryo, however, in A431 xenograft EPO did not altere microvascular density. On the other hand, continuous EPO administration (100 and 1000 IU/bw(kg)) induced significant increase in the diameter of intratumoral blood vessels and the perfused area. EPO administration to cancer cells did not cause significant change in cell proliferation in vitro, unlike the irradiation of 5–8 Gy. However, irradiation in the presence of 1–10 IU/ml EPO became significantly more effective in inhibiting tumor cell growth. The radio-sensitizing effect of EPO was even more significant in a 14 day long clonogenic assay where 1–10 IU/ml EPO further enhanced the inhibitory effect of 5Gy from 30.7 to 49.3 %. In mice EPO administration alone did not affect tumor growth while irradiation inhibited by 42.4%, and EPO in combination with irradiation was the most effective reaching 63.2% growth inhibition. Conclusions: These data indicate that rh-erythropoetin-a has a dual effect on human epidermoid cancer xenograft: 1/ increases tumor vessel size and tumor perfusion, 2/ enhances direct antitumor effects of the irradiation. This work was supported by the Hungarian Ministry of Education (NKFP1/48/2001). No significant financial relationships to disclose.
Cancer in Mothers of Dizygotic Twins&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: G Wyshak, M S Honeyman, J T Flannery, A S Beck
Journal: JNCI Journal of the National Cancer Institute (1983)

For the determination of whether mothers of dizygous (DZ) male-female twins or other polyzygous (unlike sexed) multiple births have cancer incidence different from that of controls, a cohort study was conducted with the use of the records of the Connecticut Twin Registry and the Connecticut Tumor Registry (CTR). A total of 3,982 women born between 1885 and 1935 who had borne DZ (male-female) twins or who had experienced other polyzygous multiple births in Connecticut during 1925-59 and a control group of 3,982 women, matched pairwise on year of childbirth, age, number of previous children, race, and national origin, were searched in the CTR for the incidence of cancer of all sites. Women who have DZ twins have a higher level of gonadotropins than women in the general population. A hypothesis that mothers of DZ twins may have a higher incidence of breast cancers than other women was investigated; the results did not support the hypothesis. There was, however, an excess incidence of cancer of the pancreas among mothers of twins. The relative risk was 3.2 (P = 0.026, exact two-tail probability) with exact 95% confidence limits (1.12, 11.16). These results are consistent with findings from autopsy data which suggested that among women but not among men with pancreatic duct cell carcinoma, there is excessive gonadotropic activity. These results are also consistent with early findings of high follicle-stimulating hormone (FSH) in the urine of diabetics and high FSH in the urine of postmenopausal women.
Economic and demographic patterns influence access to high volume hospitals for surgical resection of colorectal cancer in New York City 2000
Authors: D. Graham, M. Weiser, D. Schrag, D. Wong
Journal: Journal of Clinical Oncology (2005)

3547 Background: A large body of research has demonstrated improved surgical outcome in centers with high clinical volume. However, the extent to which baseline difference in demographic and clinical characteristics is the reason for volume-outcome associations remains unclear. This study characterized the differences in sociodemographic characteristics of patients operated on at New York City Hospitals performing low versus high volume colorectal cancer surgery. Methods: The Statewide Planning and Research Cooperative System (SPARCS) database was queried for patient demographics, economic profile (average adjusted gross income by zip code-AGI), and surgical volume of treating hospital. The 60 hospitals included in the study were grouped by colorectal cancer surgical volume, into 6 groups labeled Hospital Volume (HV) #1 though #6. Distribution of factors within hospital groups was analyzed by an unadjusted Chi square. Results: Hospital volume directly correlated with in-house mortality. However, the higher volume hospitals treated younger, fewer minority, fewer Medicaid, and more patients with higher AGI than the lower volume hospitals (see Data Table). Conclusions: The improved outcome in high volume hospitals in New York City may, in part, be related to major differences in the sociodemographics of the patient populations treated at the various institutions. Additional research is needed to further characterize factors such as comorbidity that are also likely to contribute to volume-outcome associations. These differences must be considered when comparing outcomes across institutions. Data: Volume Categories (N= 2716) HV # 1 HV # 2 HV # 3 HV # 4 HV # 5 HV # 6 Univariate Chi Square Volume (year 2000) 350 200–349 150–199 100–149 50–99 1–49 # hospital 1 1 1 4 9 43 Age (%) 65 years old 48 38 29 34 31 36 65 years old 52 62 71 66 69 64 p<0.0001 Race (%)(N=2597 Reported Cases) White 85 69 77 81 54 46 Black 5 8 3 10 18 29 Asian 6 1 6 3 5 7 Other/Unknown 5 21 14 5 23 19 p<0.0001 Insurance Status (%) Medicare 47 50 52 56 59 51 Medicaid 5 6 1 6 10 17 Commercial Ins 39 17 44 29 14 17 p<0.0001 AGI by Zip Code (%) $18,999 $39,999 11 11 13 15 31 44 $40,000–$69,999 33 36 29 30 49 38 $70,000 56 53 58 55 19 18 p<0.0001 Outcome Data # Patients (% Total) 368 (13.5) 227 (8.4) 156 (5.7) 507 (18.7) 638 (23.5) 820 (30.2) 2716 (100) Median LOS (days) 7 8 6.5 8 8 10 In-hospital mortality (%) 0.3 1.8 1.9 2.8 2.0 3.9 p<0.008 No significant financial relationships to disclose.
Use of bevacizumab to reduce the rate of oxaliplatin-induced thrombocytopenia and splenomegaly.
Authors: Michael J. Overman, Binsah George, Karime Kalil, Renata Ferrarotto, Cathy Eng, Chris R. Garrett, Evelyn Loyer, Paulo Marcelo Hoff, Chusilp Charnsangavej, Scott Kopetz
Journal: Journal of Clinical Oncology (2012)

564 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. In the NSABP C-08 study a reduced rate of thrombocytopenia (1.4% vs 3.4%, P &lt;0.01) was seen in the bevacizumab arm. Evidence suggests that bevacizumab may protect against HSI, though the clinical impact of this has not been well examined. Methods: A retrospective review of metastatic colorectal cancer patients treated at MD Anderson Cancer Center from 1/2003 to 1/2010 with ≥3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab was conducted. Presence of known liver disease, prior liver surgery, absence of spleen, or adjuvant oxaliplatin were exclusion criteria. Splenic volumes pre, during, and post FOLFOX treatment were determined from CT scans and correlated with platelet counts and treatment. Results: 184 pts (138 FOLFOX/Bev; 46 FOLFOX) were identified. The median number of cycles (9 for each cohort) and the total oxaliplatin dose (P = 0.78) did not differ between the two cohorts. The development of splenomegaly (spleen volume increase of ≥30%) was more common in the non-Bev cohort, 48% vs 32%, P=0.013. The median time to splenomegaly was longer in the Bev cohort, 7.6 vs 5.5 months, P=0.023. When comparing patients with and without splenomegaly, the presence of splenomegaly correlated with thrombocytopenia (&lt;150 platelet count) at 3 months (40% vs. 16%, P=0.0005) and beyond (lower mean platelet counts during 3 to 6 months of treatment, P &lt;0.0001 by Two-way ANOVA). A correlation with thrombocytopenia was also seen in the non-Bev vs. Bev cohort at both 3 months (43% vs 24%, P = 0.006) and beyond (P = 0.003). Conclusions: The addition of bevacizumab to oxaliplatin chemotherapy reduces the frequency of splenic enlargement, which directly correlates with a reduced rate of thrombocytopenia. Further study to understand the hepato-protective mechanism of anti-VEGF therapy is needed.
Efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin (OX) in pre-treated advanced epithelial ovarian cancer (EOC) and relation to p53 status
Authors: M. O. Nicoletto, M. E. Donach, L. Borgato, F. Angelini, G. Artioli, P. Azzoni, A. Perin, C. Barile, R. Bertorelle, A. Cecchetto, G. Cartei
Journal: Journal of Clinical Oncology (2006)

15054 Background: The efficacy of PLD+Ox in pre-treated advanced EOC in third and fourth line suggests that the elevated survival in these patients might activate the p53 pathway. Methods: Inclusion criteria: Performance Status≤2, relapse or progression after 1–3 lines of therapy; ≤4 prior antiblastic drugs; life expectancy &gt;3 months; LVEF &gt;50%.Treatment consisted of 1 hr infusion of PLD 30–35 mg/m 2 on day 1 and 70 mg/m 2 of Ox in 2 hrs on day 2 for 8 cycles, then 2 cycles of PLD alone. Clinical response was evaluated by CT scan every 3 cycles. Primary endpoints were overall survival and its correlation with p53. Results: From June 2000, 65 pre-treated pts were enrolled. They were divided according to platinum sensitivity into sens, part-sens and res (time to progression after platinum therapy of ≥12, ≥6 or &lt;6 months). Median age = 65 yrs, range 41–84, (23 pts &gt;70 yrs). 56 pts were evaluable for response: 28 sens with an ORR = 79%, 15 part-sens ORR = 47%, and 12 res ORR = 50%. 445 cycles were administered (median = 6 cycles/pt). Median survival from 1 st cycle was 19 months, 10 and 8 months in sens and part-sens and res groups respectively (p = 0.00021). Major (G3–4) toxicities were: neutropenia (6 episodes), gastrointestinal (3 episodes). G1–2 neurosensorial toxicity was seen in 18 pts and PPE in 10 pts. 1 toxic-related death was recorded. Median LVEF showed no significant changes during treatment. There is no clear correlation between OS and amount of Platinum/Taxol administered previously. p53 was analyzed for expression and mutations. Mutations were sought in exons 5, 6, 7 and 8. Immunohistochemistry of 11 amplified samples showed p53 overexpression in 8 pts, of these 7/11 had a CR and/or PR (64%). The analysis is ongoing. The 5-yr survival after first relapse is 64%, 24% and 0% for sens, part-sens and res respectively. 6/6 (100%) evaluable patients with BRCA mutations responded to therapy (5 BRCA1 pts, 1 BRCA2 pt): 4 CR and 2 PR, presently all living. Conclusions: The therapy is effective in increasing OS in Platinum-sensitive patients after re-exposure to Carboplatin and Taxol and may be effective in p53+/mutated pts and for pts with BRCA mutation. For Pt-refractory and Pt-partially-sensitive pts an optimized use of this treatment must be identified. No significant financial relationships to disclose.
Safety analysis of a randomized phase II trial of hedgehog pathway inhibitor (HPI) GDC-0449 versus placebo with FOLFOX or FOLFIRI and bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC).
Authors: J. C. Bendell, L. L. Hart, I. Firdaus, I. Gore, R. C. Hermann, H. M. Mackey, R. A. Graham, K. Zerivitz, J. A. Low, J. Berlin
Journal: Journal of Clinical Oncology (2010)

3530 Background: GDC-0449 is an HPI that has shown clinical activity in advanced basal cell carcinoma and preclinical activity in CRC. Methods: 199 previously untreated mCRC patients (pts), received either FOLFOX (oxaliplatin 85 mg/m2, LV 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) or FOLFIRI (irinotecan 180 mg/m2, LV 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) with bevacizumab (bev, 5 mg/kg) every 2 weeks and were randomized 1:1 to receive GDC-0449 150 mg/day or placebo. The study remains blinded pending completion of the primary analysis of PFS. A blinded analysis of adverse events (AEs) is reported here with GDC-0449 and placebo-treated cohorts blindly designated as groups X or Y. Results: Between May 2008 and July 2009, 199 pts were randomized. As of Oct 1, 2009, 191 were safety evaluable; median time on study was 8.5 mos. 121 received FOLFOX-bev; 70 received FOLFIRI-bev. 57% of pts were male; 26% received prior adjuvant chemotherapy. FOLFOX and FOLFIRI pts received a median of 7 (range 1-29) and 9 (range 1-53) 2 week cycles containing oxaliplatin or irinotecan, respectively. Grade 3-5 AEs occurring in more than 5% of patients in any treatment arm are listed in the Table. Plasma concentrations of GDC-0449 were similar to those in phase I patients receiving GDC-0449 alone. Conclusions: This is the first report that summarizes the adverse events seen with GDC-0449 in combination with oxaliplatin- and irinotecan-based regimens, and suggests the feasibility of combining GDC-0449 with chemotherapy. Unblinded safety data will be presented. Grade 3-5 AE FOLFOX (%) FOLFIRI (%) Total (%) X, n=61 Y, n=60 X, n=35 Y, n=35 X, n= 96 Y, n=95 Neutropenia 16.4 10.0 31.4 22.9 21.9 14.7 Anemia 8.2* 0 5.7 0 7.3* 0 Fatigue/asthenia 4.9 13.3 8.6 28.6* 6.3 18.9* Diarrhea 9.8 5.0 11.4 20.0 10.4 10.5 Nausea 3.3 3.3 5.7 8.6 4.2 5.3 Decreased appetite 0 5.0 2.9 5.7 1.0 5.3 Dehydration 1.6 11.7* 0 5.7 1.0 9.5* Pulmonary embolism/deep vein thrombosis 1.6 10.0 14.3 2.9 6.3 7.4 Peripheral neuropathy 3.3 10.0 2.9 2.9 3.1 7.4 Infection (all sites) 4.9 6.7 8.6 5.7 6.3 6.3 Hypertension 4.9 0 5.7 2.9 5.2 1.1 * p <0.05 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Roche Roche Genentech
A phase I study of menogaril in patients with advanced cancer.
Authors: T D Brown, R C Donehower, L B Grochow, A P Rice, D S Ettinger
Journal: Journal of Clinical Oncology (1987)

Menogaril (7-con-O-methylnogarol) is a semisynthetic anthracycline analogue of nogalamycin that has shown good activity against a variety of experimental tumor systems as well as decreased cardiac toxicity when compared with doxorubicin in preclinical studies. Forty-one patients with refractory solid tumors received menogaril during a phase I trial at The Johns Hopkins Oncology Center (Baltimore). Menogaril was administered as an intravenous (IV) infusion on days 1 and 8 of a 28-day cycle in doses of 8 to 140 mg/m2. Eastern Cooperative Oncology Group (ECOG) grade 3 and 4 leukopenia was the principle dose-limiting toxicity and was occasionally accompanied by thrombocytopenia. Both WBC and platelet nadirs occurred between days 15 and 22. Anemia requiring transfusion was occasionally seen. Nonhematologic toxicities observed included frequent anorexia and malaise that was not dose related and postinfusion phlebitis that was dose related and occasionally dose limiting. Gastrointestinal toxicity and alopecia were infrequent and mild in severity. Three patients with cumulative doses of menogaril greater than 1,400 mg/m2 had no significant changes in ejection fractions as determined by serial gated blood pool scans. Two patients had greater than 10% decrements in ejection fractions without clinical changes at total doses of 128 and 288 mg/m2. One patient with prior anthracycline therapy and chest irradiation decreased her left ventricular ejection fraction from 52% to 30% and developed respiratory failure after two cycles of therapy in the setting of disease progression. No responses to menogaril therapy were observed. The recommended phase II dose for menogaril on this day 1 and 8 schedule is 140 mg/m2. A starting dose of 90 mg/m2 should be considered for heavily pretreated patients. In comparing results of this phase I schedule with those of other schedules, evidence for schedule-dependent toxicity differences should be sought.
The value of PET/CT with 18F-FLT and 18F-FDG in the management of metastatic germ cell tumors (GCT): A pilot study
Authors: J. T. Hartmann, P. Aschoff, H. Dittmann, M. Lichy, F. Mayer, G. Reischl, C. von Weyhern, L. Kanz, C. D. Claussen, C. Pfannenberg
Journal: Journal of Clinical Oncology (2009)

e16142 Background: The purpose is to assess the ability of [F-18]-3’-Fluoro-3’-deoxythymidin (FLT), a cell proliferation marker, for early response monitoring and prediction of histology of residual tumor masses in patients (pts) with metastatic GCT in comparison to the standard tracer F-18-FDG, CT-scans and tumor markers. Methods: 11 male pts, age 23–48 yrs, with metastatic GCT were evaluated with both FDG- and FLT-PET/CT prior to chemotherapy (CTh), after the first cycle (early response) and 3 weeks after completion of induction CTh. PET was analyzed visually and quantitatively. The results were validated by histopathology of resected residual masses after CTh in 7 pts or by clinical follow-up for at least 6 mos in 4 pts. Presence of necrosis was judged as responder, as well as CR/PRm- within a minimum progression-free interval (PFI) of 6 mos. In case of multiple resections, the worse histology was taken into account. Regarding early tumor response EORTC criterias were used. Results: 8 out of 11 pts had a PFI &gt; 6 mos (range, 206–1337 days). Examination of resected masses revealed necrosis in 3/7, teratoma in 2/7 as well as 2/7 pts with viable tumors. Prior to CTh the reference lesions showed increased FDG uptake (SUVrange/mean, 2.9–15.0/8.8) in all pts but moderate FLT uptake (SUVrange/mean, 1.7–9.7/3.7) in 10 out of 11 pts. SUVavg decrease in early response FDG monitoring was 64% in responders and 60% in non-responders (p = 0.8), as well as 57% vs. 48% for FLT (p = 0.5), respectively, and 85% vs. 72% (FDG, p = 0.1) and 67% vs. 65% (FLT, p = 0.8) in the final monitoring. Results of early and final response were inconsistent in 6/11 pts in FDG and in 4/10 pts in FLT-PET. In 2 pts with teratoma false negative results in both FDG- and FLT-PET have been seen. The sensitivities, specificities, positive and negative predictive values (%) of FDG and FLT-PET for early and final response monitoring were 60/33/43/50, 60/80/75/67, 20/100/100/60, and 0/100/0/50, respectively. Conclusions: PET negative residual masses after CTh of metastatic GCT still require resection, since the low negative predictive value of FDG-PET cannot be improved by application of the proliferation marker FLT. No significant financial relationships to disclose.
It may not be ethical to ask patients to participate in future trials
Authors: M. Harding
Journal: BMJ (1996)

EDITOR,—Meta-analysis suggests that chemotherapy may have a role in the treatment of non-small cell lung cancer.1 The authors note that the place of such treatment is uncertain, given the toxicity of platinum based combinations and the small survival advantage. An accompanying editorial suggests that, as the number of people with lung cancer worldwide is large, even a small individual chance of benefit is worth while in terms of population health gain.2

In the …
Autoimmune thyroid gland disease predisposes to orbital lymphoma
Authors: P. N. Plowman, C. Nutting, G. Rose
Journal: Journal of Clinical Oncology (2005)

6641 Of 369 consecutive, biopsy proven, orbital lymphoma patients presenting to Moorfield’s/Barts (1979–1999), 20 (5%) had a history of thyroid gland disease and adequate notes were available for scrutiny in ten. All ten patients had laboratory evidence of autoimmune thyroid disease at 11–27 (median 17.5) years prior to the diagnosis of orbital lymphoma and 6/10 had overt ophthalmopathy - none having received orbital radiotherapy. Using a calculated estimate of 0.4% prevalence of thyroid ophthalmopathy in UK (being 30% of 1.4% UK prevalence of autoimmune thyroid disease:Thyroid 1998;8:427–8; Brit Med J 2004; 329: 385–90), the probability of this occurring by chance is low (p=0.007) and our result is probably an underestimate. All lymphomas were solely orbital (unilateral IE) at presentation, being marginal zone in 9/10 and diffuse large B-cell lymphoma in the other. The tumour affected mainly conjunctiva (5/10), lacrimal gland (2/10) and retrobulbar tissues (1/10) - the anterior location cases being of interest in that thyroid ophthalmopathy mainly affects the retrobulbar tissues but MALT (and from our data most sporadic orbital lymphomas: Brit J Ophthalmol 2000; 84: 907–13; Eye 2003; 17: 809–820) occur anteriorly in the orbit. Conclusions: Autoimmune thyroid gland disease predisposes to orbital lymphoma. No significant financial relationships to disclose.