tbuckley/cabot-search huggingface dataset:
Potentially modifiable influences on cancer family history-taking among primary care physicians in Vermont and Massachusetts
Authors: B. S. Flynn, M. E. Wood, G. S. Dana, T. Ashikaga
Journal: Journal of Clinical Oncology (2006)

6067 Background. Taking a complete family history is key in identifying individuals at increased risk for cancer. The objectives of this study were to test hypothesized relationships between potentially modifiable factors and family history-taking by primary care physicians. Methods. Primary care physicians (family medicine, internal medicine, gynecology) were surveyed by mail in Vermont, urban and suburban Boston (n=880) using comprehensive rosters from employers or state-wide networks, with a response rate of 70%. Measures of family history-taking quality and factors that may influence this behavior were developed systematically and validated using factor analysis methods. The primary outcome variable was either extent of history-taking or age of cancer diagnoses. These dependent variables were regressed on scales measuring physician perceptions of the advantages and disadvantages of history-taking, confidence in taking cancer family histories, supportive resources, and knowledge of management for patients at high risk for breast and colon cancer; relevant factors controlled in these multiple regressions included type and location of practice. Results. Most physician perception factors hypothesized to influence quality of history taking were found to be significantly associated in the analysis. The strongest predictor of extent of family history-taking was perceived disadvantages of taking a cancer family history (p&lt;.001). Reports of supportive resources ((p&lt;.01); perceived advantages (p=.02); and confidence (p=.02) were also associated with this behavior. Gathering age of cancer diagnoses was significantly associated with perceived advantages, supportive resources and confidence (all p&lt;.0001). Knowledge of high risk management was not associated with quality of family history-taking in either analysis. Conclusions. Potentially modifiable resource and perception factors were significantly associated with quality of family history in a large and diverse sample of primary care physicians. Improving family history quality for identification of high risk individuals among primary care providers will need to address multiple factors. No significant financial relationships to disclose.
Weekly topotecan for platinum resistant ovarian cancer
Authors: F. Abushahin, E. C. Grendys, J. R. Lurain, D. K. Singh, A. W. Rademaker, J. C. Schink, J. C. Schink
Journal: Journal of Clinical Oncology (2006)

15040 Background: Topotecan is currently used to treat recurrent ovarian cancer after failure of platinum-based therapy. The FDA-recommended regimen (1.5 mg/m 2 for 5 consecutive days of a 21-day cycle) is associated with a high incidence of grade 3/4 myelosuppression. Alternate dosing and scheduling may increase patient convenience and reduce toxicity. The objective of this study is to evaluate toxicity, response and progression free survival of weekly topotecan therapy in women with primary and secondary platinum resistant ovarian cancer after failure of 1 or more regimens. Methods: A retrospective analysis of 59 patients that received weekly topotecan with a median dose of 3.75 on days 1, 8, and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate by imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. Results: Response to therapy was noted in (22%) 13 of 59 patients (complete 6.75%, partial 15.25%). Stable disease was noted in 19 patients (32.2%) and progression in 25 patients (42.4%). Two patients (3.4%) had significant side effects that warranted the discontinuation of therapy. There was no significant difference in response to therapy between patients with primary and secondary platinum resistance. A total of 204 cycles were given with a median of 3 (1–12) cycles per patient. Grade 3 and 4 myelosuppression were rare with 1 cycle (0.5%) with grade 3 leukopenia, 15 cycles (6.4%) with grade 3 or 4 neutropenia, 1 cycle (0.5%) with grade 3 anemia, and 1 cycle (0.5%) with grade 3 thrombocytopenia. No patients were admitted with neutropenic fever. The Median Progression-free-survival for responders was 195 days (56–471). Conclusions: Weekly topotecan is a well tolerated and effective regimen for platinum resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen. [Table: see text]
Patient-reported symptom complaints associated with 5FU + irinotecan (IRI) or oxaliplatin (OXALI) in colorectal cancer (CRC)
Authors: J. Blakely, B. V. Fortner, K. Kulig, Q. Mao, S. Wagner, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2005)

3649 Background: While toxicities have been documented in CRC clinical trials, less has been done to explore patient-reported severity of these same toxicities in actual clinical practice. Medicare’s recent emphasis on quality of supportive care further highlights the need to understand and treat these symptoms. This study describes results of preliminary analyses in CRC chemotherapy patients (pts) through use of a validated patient report tool. Methods: A database generated from two large community oncology practices was accessed. CRC pts who completed at least one Cancer Care Monitor (CCM), a patient report measure including 38 physical cancer-related symptoms, were eligible. CCM scores reported within 28 days of a 5FU + IRI or OXALI administration between 8/1/03 and 7/31/04 were selected. Pts indicated severity on an 11-point Likert scale (0 = No problem; 1–3 Mild; 4–6 Moderate; 7–9 Severe; 10 = As bad as possible). Results: 57 IRI pts (mean age = 57 male = 63%) and 113 OXALI pts (mean age = 58 male = 50%) contributed 9 and 10 CCM administrations per patient, respectively. Frequencies of selected symptoms are tabulated below. Conclusion: A wide range of high severity symptoms were reported at even greater frequencies than in clinical trials relying on clinician-rated toxicity. A pt self-report tool is valuable for longitudinal assessment of frequency and severity of symptoms and can emphasize the need for quality supportive care. Our ongoing study will delineate treatment-specific differences in symptom reporting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
Abstract 17062: Adequacy of Primary Care Screening of Women with Adult Congenital Heart Disease
Authors: Margarita Castro-Zarraga, Mitalee Patil, Ami B Bhatt
Journal: Circulation (2011)

Introduction: Adults with congenital heart disease (ACHD) face non-cardiac healthcare challenges as the population ages. The 2008 ACC/AHA guidelines called for every ACHD patient to have a primary care physician and receive preventive screening, often underemphasized in chronic disease populations. Hypothesis: We assessed the hypothesis that women with ACHD have lower compliance rates for preventive screening compared with control subjects seen in a cardiac practice and with norms in the US population. Methods: IRB approved retrospective review of females over age 18 years seen in a cardiac care center in 2009-2011. Data on history, Pap smears, mammograms, colonoscopy, and bone densitometry were obtained from medical records. Adequacy of screening was defined according to US guidelines (as of November 2009). Results: We reviewed data of 164 women with ACHD, with 89 women meeting criteria with adequate data, and compared with 39 age-matched control subjects. Women with ACHD had lower rates of preventive screening compared with controls (p &lt; 0.001 for comparison across 4 screening categories, see Table 1). Compliance rates of both groups with colonoscopies were better than nationwide statistics, surpassing the Healthy People 2010 target. Women with ACHD had low screening rates for cervical cancer, breast cancer, and osteoporosis, below national averages. Follow-up for abnormal results was adequate, with lowest rates of follow up for colonoscopies. Individuals with “moderate” ACHD per Bethesda conference guidelines had the lowest rates of adequate screening (37%) compared with simple (50%) or complex (47%) disease patients. Conclusions: Women with ACHD need increased primary care screening with Pap smears, mammograms, and DEXA scans. Primary care physicians, cardiologists, and gynecologists should collaborate to ensure appropriate health maintenance screening for this growing and aging patient population.
A phase I study of intravenous tetra-O-methyl nordihydroguaiaretic acid in patients with refractory malignancy
Authors: S. Goel, H. Burris, D. Mendelson, R. Gollamudi, J. Stern, N. Frazer, S. Jones, M. Gordon, S. Mani
Journal: Journal of Clinical Oncology (2007)

3584 Background: Tetra-o-methyl nordihydroguaiaretic acid (terameprocol-also EM-1421 or M4N) is a semi-synthetic derivative of a naturally occurring plant lignan. Terameprocol blocks cell cycle progression by inhibiting expression of the Sp1-dependent cdk1 gene and promotes apoptosis by inhibiting survivin. Methods: A dose escalation, open-label study enrolled patients (pt) with malignancies refractory to surgery, radiation therapy, and/or chemotherapy. Terameprocol was administered daily by intravenous infusion for 5 days (d) every 28 d over 30 minutes, with dose escalation (100, 200, 375, 750, 1,500, 2,200, and 3,300 mg) in cohorts of 3–6 pt. Tumor measurement (CT and PET scans) was performed at baseline and every 2 to 4 cycles. Pt at the 2,200mg and 3,300mg doses had circulating tumor cells (CTC) measured prior to dosing. Pharmacokinetics (PK) was evaluated for the first 2 cycles. Results: Twenty nine pt (17 male), median age 61 years, with gynecological (21%), lung (17%), colorectal (17%), or other cancer (45%) were enrolled. All pt were evaluable for toxicity and 21 pt for efficacy. At the highest dose (3,300 mg/d), dose limiting toxicity (DLT) of metabolic acidosis/respiratory failure considered drug related was observed in 1 of 3 pt, and no additional pt was enrolled at this dose. The next lower dose cohort (2,200 mg/d) was expanded (11 pt) and no DLT has been observed. Best response by RECIST criteria included a partial response in 1 pt and stable disease in 6 pt. Three pt discontinued for reason other than progression, and 11 had progressive disease. Pharmacokinetics demonstrated dose linearity. The volume of distribution was 300–1,000 liters, and the half-life ∼ 20–30 hours. No obvious trend was seen in CTCs. Across all doses, 108 adverse events, with 10 severe events, were observed. Conclusions: Terameprocol is well tolerated up to a dose of 2,200 mg and warrants further evaluation. Expansion continues at this dose level. There is clinical benefit in this refractory population that warrants further investigation. No significant financial relationships to disclose.
Oxaliplatin and raltitrexed combined with leucovorin-modulated 5-fluorouracil i.v. bolus every two weeks: A dose finding study in advanced previously treated colorectal carcinoma
Authors: P. Comella, F. De Vita, L. De Lucia, R. Casaretti, A. Avallone, M. Orditura, F. Rivellini, S. Palmeri, G. Catalano, G. Comella
Journal: Annals of Oncology (2000)
Bone loss in early, active rheumatoid arthritis : effects of corticosteroids, gender and menopausal status in the cobra trial: abstract
Authors: P. Geusens, A.C. Verhoeven, M. Boers, J.M. TeKoppele, W.H. van der Laan, H.M. Markusse, S. van der Linden
Journal: Annals of the Rheumatic Diseases (2000)

Maastricht Univ, Acad Hosp, Dept Rheumatol, Maastricht, Netherlands. Limburgs Univ Ctr, Biomed Res Inst, Diepenbeek, Belgium. Vrije Univ Amsterdam, Univ Hosp, Amsterdam, Netherlands. TNO, Prevent & Hlth, Vasc & Connect Tissue Res Div, Leiden, Netherlands. Zuider Hosp, Dept Rheumatol, Rotterdam, Netherlands.
Deliberate Self-harm Following Bariatric Surgery
Authors: Xiulu Ruan, Katherine Bydalek, Srinivas Chiravuri
Journal: JAMA Surgery (2016)

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Preliminary phase II safety evaluation of ZD6474, in combination with carboplatin and paclitaxel, as 1<sup>st</sup>-line treatment in patients with NSCLC
Authors: B. E. Johnson, P. Ma, H. West, R. Kerr, D. Prager, A. Sandler, R. S. Herbst, D. J. Stewart, I. W. Dimery, J. V. Heymach
Journal: Journal of Clinical Oncology (2005)

7102 Background: ZD6474, a selective inhibitor of VEGFR and EGFR tyrosine kinase activity, is being evaluated in an ongoing randomized, double-blind Phase II study, alone and in combination with carboplatin/paclitaxel (CP), as 1st-line treatment for patients with locally advanced or metastatic (IIIB-IV) NSCLC. Methods: A safety run-in phase was conducted to establish the appropriate dose of ZD6474 to be administered in combination with CP, and comprised 21-day treatment cycles in which 10 subjects per cohort received daily oral doses of ZD6474 (1st cohort, 200 mg; 2nd cohort, 300 mg) in combination with CP (carboplatin, target AUCss = 6 mg/ml · min; paclitaxel, 200 mg/m2 i.v.). After six subjects in the 1st cohort completed at least 6 weeks’ treatment with no safety concerns, the ZD6474 dose was escalated to 300 mg. Objective tumor assessments (revised RECIST) and pharmacokinetic (PK) assessment of ZD6474 and carboplatin levels were also performed. Results: During the run-in phase, 24 patients have received ZD6474 (n = 14, 200 mg; n = 10, 300 mg) in combination with CP. Safety data are reported for the 13 patients who have completed at least 6 weeks’ treatment to date (n = 7, 200 mg; n = 6, 300 mg). Two patients in the 200 mg cohort developed a serious adverse event that was considered to be treatment related (rash with desquamation, n = 1; dehydration, n = 1); both cases responded to standard management. In addition, non-serious grade 3 drug-related skin rash (n = 1) and asymptomatic QTc prolongation as per protocol (n = 1) were reported in the 300 mg cohort. Based on the investigators’ assessment, partial responses have been observed in 7/18 patients (n = 3, 200 mg; n = 4, 300 mg) and stable disease for ≥12 weeks in a further two patients (both 200 mg). Preliminary PK data indicate that mean steady-state plasma levels of ZD6474 after 200 mg dosing are comparable when given alone (684 ng/ml ± 272) or in combination with CP (568 ng/ml ± 206). Conclusions: Results to date from the safety run-in phase show that combining ZD6474 200 mg or 300 mg with CP was generally well tolerated, without mutually additive toxicity. The randomized component of the study has been initiated and continues to recruit. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Genentech, Ligand AstraZeneca Amgen, AstraZeneca, Genentech Amgen, AstraZeneca, Eli Lilly, Genentech, Genta
The impact of hormone receptor status on pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy with or without trastuzumab
Authors: F. Peintinger, A. Buzdar, H. Kuerer, A. Gonzalez-Angulo, C. Hatzis, L. Pusztai, F. Esteva, M. Green, G. Hortobagyi, W. Symmans
Journal: Journal of Clinical Oncology (2007)

533 Background: The aim of this study was to compare the extent of pathologic response in HER2-positive patients treated with standard neoadjuvant chemotherapy with or without trastuzumab according to hormone receptor (HR) status. Methods: The study included 199 patients with HER2-positive disease treated in clinical trials of neoadjuvant chemotherapy. Eighty-nine patients treated with 3- weekly paclitaxel and concurrent trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) were compared with 110 patients treated with weekly or 3-weekly paclitaxel followed by FEC or FAC. Residual cancer burden (RCB), a measurement of residual disease (RD) from pathologic review of the primary tumor and lymph nodes, was classified as pathologic complete response (pCR), RCB-I (near-pCR, minimal RD), RCB-II (moderate RD), or RCB-III (extensive RD). RCB was compared between treatment groups according to HR status. Results: In HR-negative patients, similar pCR rates were achieved with weekly T/FAC as with 3-weekly T/FEC and trastuzumab (61% and 65%, respectively). However, in HR-positive patients, higher pCR rates were achieved with 3-weekly T/FEC and trastuzumab (47%) than with the weekly T/FAC (25%; p=0.04) or 3-weekly T/FAC (19%; p=0.01) ( Table 1 ). Near pCR (RCB-I) was slightly higher in HR-positive (26%) than in HR-negative patients treated with 3-weekly T/FEC and trastuzumab (11%; p=0.07). Conclusions: Patients with HR- negative/HER2-positive breast cancer had similar pathologic response rates from addition of trastuzumab to 3-weekly T/FEC or from weekly T/FAC chemotherapy. Patients with HR-positive/HER2-positive breast cancer obtained significant benefit from addition of trastuzumab to 3- weekly T/FEC, compared to 3-weekly T/FAC or weekly T/FAC. The combination of weekly T/FEC with trastuzumab as neoadjuvant chemotherapy should be evaluated. [Table: see text] [Table: see text]
Sildenafil citrate suppresses disease progression in patients with Waldenstrom’s macroglobulinemia
Authors: C. J. Patterson, J. Soumerai, Z. Hunter, X. Leleu, I. Ghobrial, S. P. Treon
Journal: Journal of Clinical Oncology (2006)

7556 Background: Responses to sildenafil citrate (Viagra), a phosphodiesterase-5 inhibitor used to treat erectile dysfunction, have been observed in patients with Waldenstrom’s Macroglobulinemia (WM). Moreover, sildenafil citrate induces apoptosis of WM lymphoplasmacytic cells (Clin Lymphoma 5:205, 2004). We therefore conducted a prospective phase II study of sildenafil citrate in patients with slowly progressing WM who did not meet consensus eligibility for active therapy (Semin Oncol 2003; 30:116). Intended therapy was as follows: Week 1 25 mg po qD Week 2 50 mg po qD Week 3 75 mg po qD Week 4, then Months 2–24 100mg po qD or Maximum Tolerated Dose Methods: Thirty patients were enrolled, 18 of whom were previously untreated. All patients demonstrated progressing disease prior to enrollment. Median age was 66 (range 43–85 yrs), baseline BM involvement was 30% (range 5–90%), serum IgM was 3,640 (range 790–6,720 mg/dL), hematocrit was 37.1% (range 32.7–58.5%), and B 2 M was 2.3 (range 1.5–8.9 mg/dL). Patients were evaluable for response after 3 months of therapy. Results: At a median of 3 months, serum IgM levels declined in 19/30 (63%) patients from a median of 3,640 (range 790–6,720 mg/dL) to 2,965 (range 1,170–6,110 mg/dL). 5/30 patients (17%) demonstrated at least a minor response (≥25% IgM decrease). Two patients were taken off study for non-response to therapy. Toxicities were mild and included headaches, sinus congestion, facial flushing, dyspepsia, and generally resolved on their own with prolonged sildenafil citrate usage. Only two patients required dose modification to 25 mg and 75 mg po qD, respectively. Corollary studies to determine putative mechanisms of action for sildenafil citrate in WM were also performed and will be updated at the meeting. Conclusions: This prospective clinical trial provides preliminary evidence for activity of sildenafil citrate in patients with advancing WM. With minimal toxicity, sildenafil citrate appears to have suppressed disease progression in more than half of patients and has resulted in objective responses, thus warranting further investigation in WM and possibly other B-cell disorders. No significant financial relationships to disclose.
Evolution of Minimum Mortality Temperature in Stockholm, Sweden, 1901–2009
Authors: Daniel Oudin Åström, Andreas Tornevi, Kristie L. Ebi, Joacim Rocklöv, Bertil Forsberg
Journal: Environmental Health Perspectives (2015)

The mortality impacts of hot and cold temperatures have been thoroughly documented, with most locations reporting a U-shaped relationship with a minimum mortality temperature (MMT) at which mortality is lowest. How MMT may have evolved over previous decades as the global mean surface temperature has increased has not been thoroughly explored.
Ten-year experience with weekly chemotherapy in metastatic breast cancer patients: Multivariate analysis of prognostic factors
Authors: C. Nistico’, F. Cuppone, E. Bria, D. Giannarelli, M. Mottolese, F. Novelli, G. Natoli, P. Astorre, E. Terzoli
Journal: Journal of Clinical Oncology (2006)

10652 Introduction: Weekly administration of chemotherapy represents an emerging option for the treatment optimization of metastatic breast cancer (MBC). Moreover, evidences suggest a intriguing mechanism of action for weekly paclitaxel, which involves pro-apoptotic and anti-angiogenetic pathways. In order to identify clinical and biological prognostic factors for weekly chemotherapy outcome, we performed a multivariate analysis in a 10-years experience of weekly 1 st line chemotherapy for MBC patients. Methods: The original databases of phase II trials of MBC patients undergone 1 st line weekly chemotherapy were collected. Clinical and biological co-variables were screened for the eventual relationship with time to progression (TTP) and overall survival (OS) into a Cox model. Results: From 1990 to 2003, 184 patients were enrolled in 3 consecutive phase II studies, to evaluate activity and tolerability of weekly epirubicin with lonidamine, or vinorelbine or paclitaxel, for 24 weeks. All patients were evaluable for clinical variables, while histological samples were available in only 40 patients. At a median follow-up of 24 months, median TTP was 9 months (95% CI 8–10) and median OS 34 (95% CI 24–42). Independent variables were: response (HR 2.34, p &lt; 0.0001), receptor status (HR 1.62, p = 0.01) Performance Status (PS) (HR 2.31, p &lt; 0.0001) for TTP, and response (HR 1.86, p = 0.005), PS (HR 2.81, p &lt; 0.0001), dominant metastatic site (HR 2.27, p &lt; 0.0001), enrollment period (HR 2.51, p = 0.001) for OS. Although no biological factors entered the Cox model due to the small sample size, some sub-populations showed negative trend in survival. Conclusions: In our series of patients undergone weekly chemotherapy for MBC, independent prognostic factors for survival improvement were responders, PS 0–1, non-visceral dominant metastatic site, and enrollment period. Further greater populations are needed to extensively screen for biological prognostic factors. No significant financial relationships to disclose.