tbuckley/cabot-search huggingface dataset:
Treatment of invasive lobular carcinoma with breast conserving therapy
Authors: A. H. Tulusan, M. Bühner, M. Popovich
Journal: Journal of Clinical Oncology (2007)

11046 Background: Invasive lobular carcinoma (ILC) is the second most common histological type of breast carcinoma .There is still a persisting concern regarding the use of breast-conserving therapy(BCT) in patients with ILC.Difficulty to identify the exact size , location of ILC and multifocality and/or multicentricity are the reasons to suggest that patients with ILC might be poor candidates for BCT. The aim of our current study was to evaluate the possibilty of risk adapted BCT for patients with ILC with or without breast irradiation. Methods: 277 patients with ILC pure or mixed type between 1994 and 2006 were accrued for pospective risk adapted therapy. Contraindications for BCT are multicentricity , inability to obtain negative margins or poor cosmesis. Palpation, mammograpy,ultrasound were routinely done and preoperative MRI in cases with no sharp tumor image. Breast conserving surgery was standardised by performing a radial segmental resection. Inking margins,histological semiserial step sections and specimen radiography was done. Sharp dileneated ILC with a free margins of &gt;/= 1cm and no lymphvesel invasion(LVI) were treated by BCT without breast irradiation(Rx). Patients with ER + were treated with endocrine therapy.Mean follow-up time was 74 months. Results: Of the 277 ILC cases , 55(19,8%) were treated by mastectomy and five patients palliatively because of distant metastases. 217 ILC (79%) were treated with BCT (T1:108/48%;T2:45(21%);T3:67/31% ; NO:135/62%; ER+: 295/94%). 6 patients(2,8%) had local recurrence(LR). 161 ILC (T1 38%; T2 22%; T3 39%; N0 55%) were treated with BCT with Rx. Patients mean age was 57 years. 6(3,7%) of the patients had local recurrence (4 LR only, 2 LR and distant metastases). 56 ILC (T1 69%; T2 15% T3 22% ; NO 81%) were treated with BCT without Rx. Mean age 66 years. There were no LR , 2 patients had distant metastases. Conclusions: Using strict selecting criteria with a standardized breast conserving surgical procedure, thorough histological examination and using all breast imaging possibilities risk adapted BCT for ILC are not more likely to fail than BCT of other types of breast cancer. These results support the use of BCT for ILC patients. No significant financial relationships to disclose.
Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women &amp; Infants’ Hospital
Authors: J. R. Schwartz, A. Bradley, C. Bandera, L. Brard, P. Disilvestro, R. Legare, R. Moore, T. Tejada-Berges, C. O. Granai, D. S. Dizon
Journal: Journal of Clinical Oncology (2006)

5082 Background: Carboplatin (C) is a standard treatment for gynecologic cancers, but its use in recurrence is associated with an increased risk of hypersensitivity reactions (HSR) in those previously treated with C. However there is no way to predict those at risk for a C-HSR. We sought to evaluate whether the time between C was predictive of incidence and severity of HSRs. Methods: Patients treated with C between 1/1997 and 12/2005 were identified through our chemotherapy database. Records were reviewed for: dates and number of C regimens and cycles, age, drug allergies, cancer type, and date and symptoms of HSR. Severity was defined as mild if symptoms were rash, pruritis or severe for hypo/hypertension, vomiting, dyspnea, wheezing, chest pain, edema, rigors or generalized hives. Fisher’s exact test or Chi Square was used to compare categorized variables. Results: 126 patients were identified who had multiple C regimens. The median age was 60 (range, 40–90) and 89% were treated for ovarian cancer. 63 (50%) experienced C HSRs of which 36 (29%) were severe. The mean time between C regimens was 21 months for those with no HSRs and 24 months for those with HSRs (p = 0.1). The time between C regimens significantly predicted the incidence of HSRs (see table ). Of those receiving a 3 rd regimen of C, 8/8 had a HSR and these were severe in seven (88%). Neither age nor presence of other drug allergies was associated with a risk of C HSR. Of interest, 60 patients received &gt;8 (range 9–19) cycles with the first C regimen, and none of the patients reacted after cycle 8. Conclusions: A duration of greater than 12 months between C regimens is associated with an increased risk of both any- and severe- HSR. Our data also suggests that upfront treatment with C beyond eight cycles is not associated with an increased risk of HSR. Strategies for decreasing the risk of C HSR may be best focused on women receiving a repeat regimen after a platinum-free duration over 12 months or those receiving a 3 rd regimen of C. [Table: see text] No significant financial relationships to disclose.
CDC Grand Rounds: Addressing Preparedness Challenges for Children in Public Health Emergencies
Authors: Cynthia F. Hinton, Stephanie E. Griese, Michael R. Anderson, Esther Chernak, Georgina Peacock, Phoebe G. Thorpe, Nicole Lurie
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Recent public health emergencies including Hurricane Katrina (2005), the influenza H1N1 pandemic (2009), and the Ebola virus disease outbreak in West Africa (2014–2015) have demonstrated the importance of multiple-level emergency planning and response. An effective response requires integrating coordinated contributions from community-based health care providers, regional health care coalitions, state and local health departments, and federal agency initiatives. This is especially important when planning for the needs of children, who make up 23% of the U.S. population (1) and have unique needs that require unique planning strategies.
Phosphodiesterase 10A in Schizophrenia: A PET Study Using [<sup>11</sup>C]IMA107
Authors: Tiago Reis Marques, Sridhar Natesan, Flavia Niccolini, Marios Politis, Roger N. Gunn, Graham E. Searle, Oliver Howes, Eugenii A. Rabiner, Shitij Kapur
Journal: American Journal of Psychiatry (2016)

Phosphodiesterase 10A (PDE10A) is an enzyme present in striatal medium spiny neurons that degrades the intracellular second messengers triggered by dopamine signaling. The pharmaceutical industry has considerable interest in PDE10A inhibitors because they have been shown to have an antipsychotic-like effect in animal models. However, the status of PDE10A in schizophrenia is unknown. Using a newly developed and validated radioligand, [(11)C]IMA107, the authors report the first in vivo assessment of PDE10A brain expression in patients with schizophrenia.The authors compared PDE10A availability in the brains of 12 patients with chronic schizophrenia and 12 matched healthy comparison subjects using [(11)C]IMA107 positron emission tomography (PET). Regional estimates of the binding potential (BPND) of [(11)C]IMA107 were generated from dynamic PET scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding.There was no significant difference in [(11)C]IMA107 BPND between schizophrenia patients and comparison subjects in any of the brain regions studied (thalamus, caudate, putamen, nucleus accumbens, globus pallidus, and substantia nigra). There was also no significant correlation between [(11)C]IMA107 BPND and the severity of psychotic symptoms or antipsychotic dosage.Patients with schizophrenia have normal availability of PDE10A in brain regions thought to be involved in the pathophysiology of this disorder. The findings do not support the proposal of an altered PDE10A availability in schizophrenia. The implication of this finding for future drug development is discussed.
Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults
Authors: Ervin R. Fox, Tandaw E. Samdarshi, Solomon K. Musani, Michael J. Pencina, Jung Hye Sung, Alain G. Bertoni, Vanessa Xanthakis, Pelbreton C. Balfour, Satya S. Shreenivas, Carolyn Covington, Philip R. Liebson, Daniel F. Sarpong, Kenneth R. Butler, Thomas H. Mosley, Wayne D. Rosamond, Aaron R. Folsom, David M. Herrington, Ramachandran S. Vasan, Herman A. Taylor
Journal: JAMA Cardiology (2016)

Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain.
Phase II study of volociximab (M200), an α5β1 anti-integrin antibody in metastatic adenocarcinoma of the pancreas (MPC)
Authors: J. W. Valle, R. K. Ramanathan, R. Glynne-Jones, A. Anthoney, J. Berlin, S. Yazji, T. Evans
Journal: Journal of Clinical Oncology (2006)

4111 Background: Tumor angiogenesis occurs when pro-angiogenic growth factors are released, stimulating endothelial cell proliferation and migration to form neovessels. A critical survival step for angiogenesis is the ligation of fibronectin in the extracellular matrix to α5β1 on endothelial cells. M200 is an IgG4 chimeric monoclonal antibody targeting α5β1, thereby inducing apoptosis of proliferating endothelial cells. M200 activity is independent of growth factor stimulus, suggesting that binding of fibronectin to α5β1 occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, single cohort pilot Phase II study of 40 patients (pts) in MPC. Pts received M200 10 mg/kg IV every 2 weeks with Gemcitabine (Gem) 3 weeks on 1 week off for up to 13 cycles or disease progression. Pts were evaluated for efficacy every 8 weeks by objective response using RECIST criteria. An independent data safety monitoring board was utilized to review safety data. Results: A total of 20 pts have been enrolled. All pts were evaluable for safety and 16 pts for objective response (to date) using ITT population. Median age was 59.8 years. ECOG score was 0–1 in 19 (95%) and 2 in 1 (5%) pts. The most frequent side effects for M200 were vomiting in 7 (35%) pts and nausea in 8 (40%) pts and for (Gem) were nausea in 8 (40%) pts and vomiting in 8 (40%) pts. Eight pts died in the study, seven with progressive disease and 1 with GI perforation (possibly related to M200). One partial response was noted to date. Best overall response was (PR) 1/16 and stable disease in 8/16 pts. Median time to progression was 112+ days. Conclusions: M200 appears to be well tolerated at 10 mg/kg Q2W in combination with (Gem). Based on preliminary data from this trial and safety data from other trials, a higher dose level of M200 will be explored. [Table: see text]
Accelerated hyperfractionated radiotherapy weekend less (CHARTWEL) in combination with cisplatin and vinorelbine versus conventional radiotherapy combined with the same drugs in the treatment of locally advanced (stage IIIA and IIIB) NSCLC
Authors: S. El Mesidi, A. Ali Hassan, M. Moussa, W. Makar
Journal: Journal of Clinical Oncology (2008)

7551 Background: The aim of this prospective randomized study was to evaluate the effect of accelerated hyperfractionated radiotherapy weekend less (CHARTWEL) when combined with chemotherapy (cisplatin and vinorelbine) versus conventional radiotherapy combined with the same drugs in the treatment of locally advanced (stage IIIA and IIIB) NSCLC. Methods: Forty eligible patients were randomized to be treated in two arms (arm A and arm B) during the period from April 2003 to April 2005. Arm A included 20 eligible patients who received conventional radiotherapy 6,120 cGy to the primary tumor and mediastinal lymph nodes,180 cGy/ fraction once per day, 5 days per week in 5.5 weeks combined with cisplatin 60 mg/m2 D1 and vinorelbine 16 mg/m2 D1 and D8 to be repeated every 21 days during the course of irradiation. Arm B included 20 eligible patients who received CHARTWEL protocol 5400 cGy to the primary and mediastinal lymph nodes, 150 cGy / fraction 3 times/ day over 16 days combined with the same drugs and same doses given in Arm A. Patients who responded or even showed stable disease completed on chemotherapy to a total of six cycles but with cisplatin 80 mg/m2 D1 and vinorelbine 25 mg/m2 D1 and D8 every 3 weeks. Results: One patient (5%) in each Arm reached CR, 70% of patients in Arm A had PR while 25% of patients in Arm B had PR (P=0.011), 20% had S.D in Arm A and 5% had S.D in Arm B (P=0.399). Thirty percent of patients in Arm A experienced GI-II neutropenia while 40% in Arm B. Grade III to IV esophigitis was experienced by all patients in Arm B and resolved in only 40% of patients and was the cause of death in the remaining 60% of patients. The 1 and 2 year survival rates for arm A were 60% and 25% respectively while for Arm B were 25% and 15% respectively. Median PFS was 10 months in Arm A and one month in Arm B (P=0.0001). Median OAS was 5 months in Arm A and 3 months in Arm B (P=0.002). Conclusions: Combination of cisplatin and vinorelbine conventional radiotherapy is well tolerated by patients with locally advanced NSCLC with PS 0 to 1 and gives satisfactory results, while the combination of CHARTWEL with chemotherapy is very toxic to the patients. No significant financial relationships to disclose.
Outcomes after breast cancer in an ethnically diverse cohort of high-risk patients: Differences in survival based on <i>BRCA1/BRCA2</i> mutation status
Authors: R. Nanda, D. Huo, M. Cook, L. Chen, K. Hope, S. Cummings, O. I. Olopade
Journal: Journal of Clinical Oncology (2007)

21116 Background: Most studies of hereditary breast cancer report that BRCA1 associated tumors are characterized by high grade and hormone receptor negativity, while those associated with BRCA2 are more similar to sporadic cases. Several groups have demonstrated that BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in women with breast cancer. These studies have primarily included women of European and Ashkenazi Jewish heritage. No study to date has assessed outcomes in an ethnically diverse cohort of high-risk individuals. Methods: High-risk individuals were identified through the University of Chicago Cancer Risk Clinic (UCCRC). Clinicopathologic data was collected on all patients with breast cancer who had undergone genetic testing and consented to inclusion in research protocols. Recurrence-free survival (RFS) and overall survival (OS) for BRCA1, BRCA2 and non-carriers was compared using the log-rank test. Hazard ratios (HR) and 95% Confidence Intervals (95% CI) were calculated from Cox proportional hazard models. Results: 280 patients from 258 families were studied. 67 were BRCA1 mutation positive, 36 were BRCA2 positive and 177 were non-carriers. 65% of patients were non-Hispanic non-Jewish whites, 15% African American, 15% Ashkanazi Jewish, 3% Hispanic and 2% Asian. At a median follow up of 5 years, 40 patients had relapsed and 22 had died. HRs (95% CI) for RFS of the BRCA1 and BRCA2 carriers relative to non-carriers were 1.6 (0.77–3.33) and 1.3 (0.55–3.09) respectively, when adjusted for year at diagnosis. The adjusted HRs (95% CI) for OS for the BRCA1 and BRCA2 carriers relative to non-carriers were 1.82 (0.48–3.02) and 0.67 (0.15–3.04), respectively. Conclusions: In this study of an ethnically diverse cohort of high-risk individuals, BRCA1 mutation carriers had a poorer outcome as compared to those with BRCA2 mutations or those without identifiable mutations in either gene, although this difference was not statistically significant. This observation is consistent with previous studies of women of predominantly Ashkenzi Jewish and European ancestry. This study was funded by the Falk Medical Research Trust, the Breast Cancer Research Foundation and the Entertainment Industry Fund. No significant financial relationships to disclose.
Phase II study of irinotecan + 5FU/FA for patients with previously treated advanced gastric cancer
Authors: M. Peeters, J. L. Van Laethem, F. Baert, J. L. Canon, J. De Grève, H. Kalantari, P. Dhont, E. Van Cutsem
Journal: Journal of Clinical Oncology (2004)

4076 Background: Pozzo et al. (ASCO 2001) reported substantial activity of irinotecan combined with 5-fluoro-uracil + folinic acid (5FU/FA) in chemonaive patients with locally advanced (LA) or metastatic gastric cancer. An ongoing Belgian multicentre phase II study was set up to evaluate the safety and efficacy of irinotecan + 5-FU/FA in patients with pretreated advanced gastric cancer. Methods: Patients with confirmed LA or metastatic gastric adenocarcinoma, including oesophagogastric junction, written consent obtained, adequate performance status, intact organ function. Failure of prior ciplatin-5FU based chemotherapy. Patients were treated with a regimen of irinotecan 180 mg/m2 i.v. infusion followed by LV5FU2 every 2 weeks. Results: Up to date 38 patients are evaluable for safety and 33 for efficacy. Median age: 62 years. A total of 283 cycles (median 6, range 1–31) were administered with an overall relative dose intensity of 95%. Severe (grade 3/4) drug-related adverse events were rare (% of cycles): neutropenia (<1%) and fatigue (<1%). In general, these events didn't jeopardise further treatment. Efficacy: Three PR and 15 SD were seen with a tumour growth control rate (PR + SD>6 months) of 30.3% and median time of tumour growth control in these patients of 8.3 months (range 5.8–13.4). These patients received a median of 14.0 cycles (range 7–31). Overall median TTP was 3,7 months (range 0.5–13.4). Conclusions: These preliminary data indicate that irinotecan + 5FU/FA is active in patients previously treated for advanced gastric cancer with tumour growth control (PR + SD>6 months) achieved in 30.3 % patients during 8.3 months and with a very acceptable toxicity profile. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharma Aventis; Amgen
Final analysis of GIDEON (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma [HCC] and of Its Treatment with Sorafenib [Sor]) in &gt;3000 Sor-treated patients (pts): Clinical findings in pts with liver dysfunction.
Authors: Jorge A. Marrero, Riccardo Lencioni, Sheng-Long Ye, Masatoshi Kudo, Jean-Pierre Bronowicki, Xiao-Ping Chen, Lucy Dagher, Junji Furuse, Jean-Francois Geschwind, Laura Ladrón de Guevara, Christos Papandreou, Arun J. Sanyal, Tadatoshi Takayama, Seung Kew Yoon, Keiko Nakajima, Alan Paul Venook
Journal: Journal of Clinical Oncology (2013)

4126 Background: GIDEON is a prospective, non-interventional study. Completion of GIDEON creates a large, global database of &gt;3000 Sor-treated unresectable HCC (uHCC) pts, allowing for evaluation of a broad pt population, including Child-Pugh (CP) B pts with more advanced liver dysfunction. Methods: Baseline characteristics were collected in pts for whom a decision to treat with Sor had been made in clinical practice. Adverse events (AEs), dosing, and outcomes data were collected during follow-up. Results: 3,202 pts were evaluable for safety. Overall, the incidence of AEs and drug-related (DR) AEs was similar across CP subgroups, although serious AEs (SAEs) were more common in CP-B than CP-A pts. The rate of DR AEs (event per patient-year) was also comparable between CP-A and CP-B pts. The average daily Sor dose was slightly higher in CP-B than CP-A pts; duration of treatment was longer in CP-A (Table). In the intent-to-treat population (n=3,213), median overall survival (OS) (months [95% CI]) was longer in CP-A (13.6 [12.8-14.7]) than CP-B pts (5.2 [4.6-6.3]); time to progression was similar: CP-A (4.7 [4.3-5.2]); CP-B (4.4 [3.5-5.5]). Median OS was shorter in pts with a higher CP-B score: 7 (6.2 [4.9-8.7]); 8 (4.8 [4.1-6.9]); 9 (3.7 [3.0-5.1]). Conclusions: Sor safety and dosing during treatment are generally consistent across pts irrespective of liver function. As anticipated, CP status is a strong prognostic factor for OS in uHCC pts. [Table: see text]
Effect of renin-angiotensin system (RAS) inhibition on survival in advanced ductal adenocarcinoma (PDAC).
Authors: Rachel Winston, Glen J. Weiss, Ashley Baldwin, Samuel Frank, Lucas Tims, Nakia Lashawn Brooks, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2015)

464 Background: Advanced PDAC portends a poor survival due to several factors including development of resistance to therapies via tumor-stromal interactions. In preclinical studies, RAS inhibition has been implicated in PDAC development due to its anti-inflammatory effect by reducing pancreatic inflammation and fibrosis via suppressed activation of pancreatic stellate cells. Methods: A retrospective analysis was conducted at two institutions in North America of patients (pts) with advanced PDAC receiving palliative chemotherapy. Data collection included age, gender, ECOG, prescription for an angiotensin I-converting enzyme inhibitors (ACEIs) and/or angiotensin II type-1 receptor blockers (ARBs), and overall survival (OS). Statistical analysis included Kaplan Meier survival analysis along with the log-rank test to compare treatment strata. Additionally, multivariate analyses were performed using a Cox proportional hazard model. Results: The 403 pts included had a median age of 61 years (range: 25-86 yrs); 176(43%) were women and 329 (&gt;80%) had an ECOG performance status of 0 or 1. A majority of patients received combination therapy that was either gemcitabine or 5-flurouracil based. 57 (14%) received ACEIs and 25(6.2%) received ARBs. There was no statistically significant difference in median OS between those prescribed ACEI or ARB and those who were not (13.7 vs. 14.2 months; p=0.432). Subgroup analysis of ACEI vs. no ACEI or ARBs vs. no ARBs was similar (ACEI =13.8 vs. 14.2 months (p=0.741) and ARB=13.7 vs. 14.2 months (p=0.405). In addition, ACEI vs. ARB showed similar results 13.8 months (ACEIs) vs. 13.7 months (ARBs) (p=0.687). Conclusions: Our study did not demonstrate a statistically significant difference in OS between advanced PDAC patients in North America that were prescribed ACEI, ARB, or to those who were not. Compliance with taking prescribed ACEI or ARB medications could not be determined. A prospective phase 2 study in a Japanese population using the combination of gemcitabine and candesartan (an ARB) did not demonstrate a survival benefit with the combination. Based on these clinical evaluations, use of ACEI or ARB to take advantage of blocking RAS in advanced PDAC cannot be supported.