tbuckley/cabot-search huggingface dataset:
Phase Ib trial of lapatinib oxaliplatin and capecitabine in early HER2-overexpressing esophagogastric cancer.
Authors: H. Ford, D. Hochhauser, A. Paterson, L. Lovat, M. Jobanputra, R. C. Fitzgerald
Journal: Journal of Clinical Oncology (2010)

TPS339 Background: Expression of EGF family of receptors by tumor cells is linked with aggressive tumor growth, poor survival, and poor response to therapy. Overexpression of HER2 and EGFR has been reported in esophagogastric cancer. Activation of these receptors initiates a series of signaling cascades including MAP kinase, PI3Kinase, AKT and p70S6K. Our own data show up to 20% of gastroesophageal adenocarcinomas overexpress HER2. In vitro HER2 overexpression is associated with constitutive phosphorylation of HER2 and EGFR resulting in the formation of EGFR-HER2 hetero-dimers and increased activity of MAPK and AKT pathways. HER2 and EGFR constitutive phosphorylation is seen in patients with HER2 amplified tumors. When esophageal cell lines with HER2 amplification are treated with lapatinib the activity of HER2, EGFR, MAPK and AKT is silenced; proliferation is inhibited and apoptosis induced. Methods: Lapatinib is a dual inhibitor of EGFR and HER2 TK activity. In a two-center study (UCLH and Cambridge) we will recruit 25 patients with HER2 overexpressing early esophagogastric cancer and add lapatinib to standard preoperative chemotherapy. Patients with operable HER2-expressing esophagogastric cancer will undergo induction therapy consisting of lapatinib 1,250 mg od for 10 days followed by repeat biopsy and FDG-PET scan. They will subsequently receive 3 cycles of chemotherapy with oxaliplatin 130 mg/m2 IV d1 and capecitabine 850 mg/m2 bid d1-14 q21 before surgery. The following hypotheses will be tested: 1) Suppression of tissue HER-2, EGFR, MAPK, and AKT phosphorylation by lapatinib using an ex vivo treatment protocol will be a surrogate marker for equivalent suppression in vivo on the d10 biopsy. 2) The activation of specific RTKs (eg, C-met), will be associated with the failure of lapatinib to suppress EGFR/HER2 phosphorylation and continued activation of the MAPK and AKT pathways abrogating clinical benefit from lapatinib. 3) Molecular, clinical, and radiological response to lapatinib will correlate with reduced metabolic activity on FDG-PET scan. 4) Ability of lapatinib to silence phosphorylation of receptors EGFR and HER2 and downstream pathways MAPK and AKT will correlate with clinical benefit. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Treatment of skin rash in a phase II study of cisplatin, docetaxel, and erlotinib in patients with advanced head and neck cancer: A prospective algorithmic approach
Authors: J. S. Garey, K. J. Oishi, B. Burke, E. S. Kim
Journal: Journal of Clinical Oncology (2005)

8231 Background: Therapies targeting the epidermal growth factor receptor (EGFR) including small molecule inhibitors have promise but are accompanied by side effects, predominantly rash. As rash may be a predictor of response and prognosis, it is important to effectively manage patients who experience this toxicity. Prospective treatment of rash has not been described. Methods: We applied a treatment algorithm previously developed at our institution to prospectively study HNSCC patients enrolled in a phase II study in which they received erlotinib with chemotherapy. Patients were observed and questioned about rash development and were treated according to the algorithm based on grade of rash and characteristic (pruritic, macular, pustular, dryness, ulcerative). Treatments were per our abbreviated table listed. Our objectives were to observe response to rash therapy and tolerance of rash symptoms. Results: Nineteen patients have been enrolled. 16 patients are evaluable for rash and response to intervention. Eleven patients developed a grade 1 rash, four a grade 2, and one a grade 3. Response to rash included: 11/11 complete responses for grade 1; 3/4 partial responses for grade 2 (the non-responding patient was referred to dermatology and improved after several other treatments); 1/1 partial response for grade 3 (patient was complicated by hospitalization with neutropenic fever and sepsis and erlotinib was held). Conclusions: Side effects such as rash due to erlotinib therapy can be effectively treated per our algorithm. We will continue to follow and manage these patients. Trial accrual continues up to 50 patients. No significant financial relationships to disclose.
Text Message Support for Weight Loss in Patients With Prediabetes: A Randomized Clinical Trial
Authors: Henry H. Fischer, Ilana P. Fischer, Rocio I. Pereira, Anna L. Furniss, Jeanne M. Rozwadowski, Susan L. Moore, Michael J. Durfee, Silvia G. Raghunath, Adam G. Tsai, Edward P. Havranek
Journal: Diabetes Care (2016)

OBJECTIVE Although the benefits of in-person Diabetes Prevention Program (DPP) classes for diabetes prevention have been demonstrated in trials, effectiveness in clinical practice is limited by low participation rates. This study explores whether text message support enhances weight loss in patients offered DPP classes. RESEARCH DESIGN AND METHODS English- and Spanish-speaking patients with prediabetes (n = 163) were randomized to the control group, which only received an invitation to DPP classes as defined by the Centers for Disease Control and Prevention, or to the text message–augmented intervention group, which also received text messages adapted from the DPP curriculum for 12 months. RESULTS Mean weight decreased 0.6 pounds (95% CI −2.7 to 1.6) in the control group and 2.6 pounds (95% CI −5.5 to 0.2) in the intervention group (P value 0.05). Three percent weight loss was achieved by 21.5% of participants in the control group (95% CI 12.5–30.6), compared with 38.5% in the intervention group (95% CI 27.7–49.3) (absolute difference 17.0%; P value 0.02). Mean glycated hemoglobin (HbA1c) increased by 0.19% or 2.1 mmol/mol (95% CI −0.1 to 0.5%) and decreased by 0.09% or 1.0 mmol/mol (95% CI −0.2 to 0.0%) in the control group and intervention participants, respectively (absolute difference 0.28%; P value 0.07). Stratification by language demonstrated a significant treatment effect in Spanish speakers but not in English speakers. CONCLUSIONS Text message support can lead to clinically significant weight loss in patients with prediabetes. Further study assessing effect by primary language and in an operational setting is warranted.
Radium-223 chloride, a first-in-class alpha-pharmaceutical for patients with castration-resistant prostate cancer (CRPC) and bone metastases: Biodistribution/dosimetry compared to overall safety profile.
Authors: V. Lewington, C. Parker, C. Hindorf, G. Flux, S. Chittenden, G. Sgouros, G. O'Bryan-Tear, A. Aksnes
Journal: Journal of Clinical Oncology (2010)

e15009 Background: Radium-223 chloride (Alpharadin) is a first-in-class targeted alpha-pharmaceutical with a potent and highly targeted antitumor effect on bone metastases. It has shown a promising survival benefit, a benign safety profile and pain improvement in patients (pts) with bone metastatic CRPC. Biodistribution/dosimetry was evaluated in the context of safety. Methods: 6 pts with bone-metastatic CRPC received 2 radium-223 doses, 100 kBq/kg, 6 weeks apart. Blood, urine and feces were collected before and at regular intervals after injection. Whole body gamma camera imaging determined biodistribution. Radiation dose was calculated with adjustments for GI tract, heart wall, red marrow (RM) and osteogenic cells (OC). It was also taken into consideration that the product emits short range, high energy alpha particles. Overall safety and tolerability were evaluated in 292 pts across all Phase I/II trials. Results: Radium-223 wasrapidly eliminated from blood and taken up in bone (∼60% at 4hr) or excreted into the small intestine. There was <5% urinary and no hepato-biliary excretion. Highest calculated absorbed doses were to OC, RM and lower large intestine wall. In separate studies of 292 pts who had received range administered activities, <1% had CTC grade 4 hematological toxicity, 2-4% had grade 3 toxicity for HB, platelets, neutrophils, WBC. Mainly mild to moderate and reversible AEs were seen in the GI tract. Conclusions: Radium-223 was rapidly sequestered to bone/bone metastases and excreted in the GI tract. Due to the very short range of alpha particles (2-10 cell diameters), only a small volume of RM would have received a significant radiation dose, possibly accounting for the favorable hematologic safety profile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Algeta ASA Algeta ASA Algeta ASA
Economic value of disability adjusted life years lost to cancers: 2008.
Authors: R. M. John, H. Ross
Journal: Journal of Clinical Oncology (2010)

1561 Background: Cancer is one of the leading causes of premature death in the world today with 12.4 million new cases and 7.6 million deaths in year 2008 according to the World Cancer Report. With 53% of the new cancer cases and 60% of the cancer related deaths, developing countries share an increasing burden of cancer. However, the economic burden on cancer has never been estimated across the countries on a comparable scale. Methods: This paper estimates the economic value the disability adjusted life years (DALY) lost to cancer to measure the indirect economic burden of cancer in the world. Results: We find that 83 million DALYs with its economic value amounting to US$895 billion, roughly 1.5% of the world GDP, were lost to cancers globally in 2008. The top three cancers which account for the highest economic value of DALYs are lung cancer (19.9%) at US$ 178 billion, colon/rectum cancer (11.0%) at US$99 billion and breast cancer (9.8%) at US$88 billions. While the economic value of DALYs lost to cancer amounts to 2.22% of Gross Domestic Product (GDP) in low-income countries, it amounts to 1.69% in high-income countries. For nearly half the countries in the world, economic value of DALYs associated with cancers amounts to more than one percent of annual GDP. Conclusions: This finding suggests that cancer prevention warrants attention as a major health policy strategy. No significant financial relationships to disclose.
Other studies were misrepresented
Authors: J M Eagles
Journal: BMJ (1996)

Depression in carers of elderly people living at home Alcohol misuse could be a factor EDIToR,-In their study of the prevalence of depression in carers of elderly people living at home, Gill Livingston and colleagues used diagnoses according to ICD-10.1However, there was no mention of the ICD-10 category F1O-F19, disorders due to psychoactive substance use.I suppose this was due to it not being sought rather than it not existing, as excessive drinking is widespread-28% of men and 11% of women in the general population drink more than the recommended "safe" levels.2My clinical experi- ence suggests that this population of carers may be at increased risk.About 15% of men and 5% of women over the age of 65 drink more than the recommended weekly safe drinking levels.In community based
Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling
Authors: Alexios S. Antonopoulos, Marios Margaritis, Sander Verheule, Alice Recalde, Fabio Sanna, Laura Herdman, Costas Psarros, Hussein Nasrallah, Patricia Coutinho, Ioannis Akoumianakis, Alison C. Brewer, Rana Sayeed, George Krasopoulos, Mario Petrou, Akansha Tarun, Dimitris Tousoulis, Ajay M. Shah, Barbara Casadei, Keith M. Channon, Charalambos Antoniades
Journal: Circulation Research (2016)

Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium.To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart.EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase-derived O2 (-), whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2 (-). In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47(phox) from the cytosol to the membranes. Induction of O2 (-) production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ-mediated upregulation of ADIPOQ in EpAT.We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress.
Extramedullary Leukemia Relapse In Patients With Acute Myeloid Leukemia Allogeneic Stem Cell Transplantation: Risk Factors and Prognosis
Authors: Vinay Gupta, Krishna Gundabolu, Wilson I Gonsalves, Mark R. Litzow, William J Hogan, Naseema Gangat, Mrinal M Patnaik
Journal: Blood (2013)
Non-breast cancer mortality after a breast cancer diagnosis: A retrospective population-based study
Authors: G. F. Beadle, N. J. McCarthy, P. D. Baade
Journal: Journal of Clinical Oncology (2009)

6619 Background: Survivorship research after a breast cancer (BC) diagnosis has identified psychosocial, functional and comorbidity outcomes that adversely influence daily life. Little is known, however, about non-breast cancer (NBC) mortality after a BC diagnosis. Methods: This retrospective cohort study included Australian women aged 30–79 years diagnosed with BC between January 1982 and December 2004, with mortality examined from January 1993 to December 2005. The age-standardized mortality ratio (SMR) was used to compare NBC causes of death in the BC cohort and the age-matched Australian female population between January 1993 and December 2005. Results: The median follow-up time for the cohort of 159,550 Australian women diagnosed with BC was 7.04 years (range 0–24.7 years). During the follow-up period, 30,819 (19.3%) died of BC, 5,403 (3.4%) died of other cancers (OC), 18,349 (11.5%) died of non-cancer (NC) causes, while 104,979 (65.8%) were still alive at the end of the follow-up period. Excluding the first year after diagnosis, women with a prior BC diagnosis had a higher risk of mortality (SMR = 328.6.95% CI = 324.8–332.3, p &lt; 0.001) than the age matched female population. NBC mortality risk was elevated for OC (SMR = 103.7, CI = 100.1–107.5, p = 0.022) but reduced for NC causes (SMR = 94.9, CI = 92.3–97.5, p &lt; 0.001). For the age groupings 30–49 years (n = 46,736), 50–69 years (n = 82,967), and 70–79 years (n = 29,847), SMR's for NC causes were 168.2 (CI = 144.1–195.1, p &lt; 0.001), 100.9 (CI = 95.9–106.1, p = 0.355), and 90.5 (CI = 87.5–93.5, p &lt; 0.001) respectively. Following the first year of diagnosis, the SMR for OC was non-significantly elevated with time after diagnosis. In comparison, the SMR for NC causes reduced with time after diagnosis; SMR = 96.4 (CI = 92.1–100.8, p = 0.055) at 2–5 years after diagnosis, 98.2 (CI = 93.7–102.8, p = 0.222) at 6–10 years, 92.8 (CI = 87.2–98.7, p = 0.008) at 11–15 years and 82.2 (CI = 74.8–90.2, p &lt; 0.001) at more than 15 years. Conclusions: BC survivors have a higher risk of mortality from OC compared to the aged-matched Australian female population, but a reduced risk from NC causes. Although NC mortality is lower in older women and as time from BC diagnosis increases, women less than 50 years have a higher risk of NC mortality. No significant financial relationships to disclose.
A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide.
Authors: D A Scheinberg, D Lovett, C R Divgi, M C Graham, E Berman, K Pentlow, N Feirt, R D Finn, B D Clarkson, T S Gee
Journal: Journal of Clinical Oncology (1991)

Ten patients with myeloid leukemias were treated in a phase I trial with escalating doses of mouse monoclonal antibody (mAb) M195, reactive with CD33, a glycoprotein found on myeloid leukemia blasts and early hematopoietic progenitor cells but not on normal stem cells. M195 was trace-labeled with iodine-131 (131I) to allow detailed pharmacokinetic and dosimetric studies by serial sampling of blood and bone marrow and whole-body gamma-camera imaging. Total doses up to 76 mg were administered safely without immediate adverse effects. Absorption of M195 onto targets in vivo was demonstrated by biopsy, pharmacology, flow cytometry, and imaging; saturation of available sites occurred at doses greater than or equal to 5 mg/m2. The entire bone marrow was specifically and clearly imaged beginning within hours after injection; optimal imaging occurred at the lowest dose. Bone marrow biopsies demonstrated significant dose-related uptake of M195 as early as 1 hour after infusion in all patients, with the majority of the dose found in the marrow. Tumor regressions were not observed. An estimated 0.33 to 1.0 rad/mCi 131I was delivered to the whole body, 1.1 to 6.1 rad/mCi was delivered to the plasma, and up to 34 rad/mCi was delivered to the red marrow compartment. 131I-M195 was rapidly modulated, with a majority of the bound immunoglobulin G (IgG) being internalized into target cells in vivo. These data indicate that whole bone marrow ablative doses of 131I-M195 can be expected. The rapid, specific, and quantitative delivery to the bone marrow and the efficient internalization of M195 into target cells in vivo also suggest that the delivery of other isotopes such as auger or alpha emitters, toxins, or other biologically important molecules into either leukemia cells or normal hematopoietic progenitor cells may be feasible.
Variations in time to receiving first surgical treatment for breast cancer as a function of racial/ethnic background
Authors: R. Bustami, N. O'Donnell, E. D. Whitman
Journal: Journal of Clinical Oncology (2008)

6566 Background: Multiple studies have shown differences in the type of breast cancer treatment received, related to race/ethnicity or socioeconomic status. This study investigates racial disparities in time to receiving first surgical treatment (i.e., surgical delay) in patients with breast cancer. Methods: Patients admitted at two affiliated hospitals for breast cancer treatment during 2001- 2006 were identified. Time to receiving surgery or surgical delay was defined as the time in days between diagnosis (biopsy) and definitive surgical treatment (lumpectomy or mastectomy). Unadjusted comparisons between racial/ethnic groups were made using the Kruskal-Wallis Test (KW). A multivariate linear regression model was used to predict the natural logarithm of time to receiving surgery by racial/ethnic group. Adjustments were made for several factors including age, diagnosis year, AJCC stage, type of surgery, hospital, number of comorbidities and insurance status. Results: 2,845 patients who were first treated with surgery were identified. Racial background was classified as White, African American, or Asian/Other. Average age was 58.7 years (SD = 13.5). Overall median time to surgery was 16.5 days; 15.5 days in whites, 22.5 and 19.5 days in African Americans and Asian/others, respectively (p = 0.002, by KW). Multivariate linear regression analyses (table) showed that only African Americans, not Asian/others, had significantly increased surgical delay compared to whites (p = 0.001). Surgical delay also significantly increased with older age, more recent diagnosis year (not shown), mastectomy vs. lumpectomy, and for patients without comorbid conditions. Higher AJCC stage was also variably related to surgical delay. No statistically significant relationship to surgical delay was observed for either hospital or insurance status. Conclusions: This study demonstrates racial differences in time to first surgical treatment in a group of ethnically diverse breast cancer patients. Factor Mean or % Beta 95% CI p-value Race group (vs. White) African American 5.4% 0.50 (0.20,0.81) 0.001 Asian/Other 4.5% 0.05 (-0.29,0.38) 0.79 Age (per 10 years) 58.7 0.08 (0.03,0.13) 0.003 AJCC stage: 2 (vs. 0 or 1) 27.7% 0.15 (-0.01,0.32) 0.059 AJCC stage 3+ (vs. 0 or 1) 7.9% 0.28 (0.01,0.55) 0.042 Surgery type (mast. vs. lump.) 37.5% 0.33 (0.18,0.48) <0.001 Insurance (yes vs. no) 96.6% -0.19 (-0.71,0.33) 0.48 At least one comorbidity (vs. none) 31.5% -0.29 (-0.49,-0.09) 0.004 Model includes intercept (not shown) No significant financial relationships to disclose.
Therapeutic management of male breast cancer in Germany.
Authors: H. Eggemann, A. F. Taran, U. Altmann, A. Ignatov, S. Kuemmel, S. D. Costa
Journal: Journal of Clinical Oncology (2010)

e11036 Background: Male breast cancer (MBC) is a rare disease, representing less than 1% of all breast cancer cases. Due to the rareness of the disease and lack of prospective randomized trials, guidelines of therapeutic management are nonexistent. The aim of this retrospective population-based study was to analyze the current management of MBC in Germany. Methods: We identified all male patients with breast cancer recorded in the “Gießen Tumor Documentation System” (GTDS) between 2000 and 2009. The GTDS is a tumor registry, available in 40 cancer centers from Germany; data for this study were obtained from 23 cancer centers. A total of 669 cases of MBC were identified. We ascertained patterns of operative and pathologic findings as well as information on systemic therapy. A comparison of patterns of management of the cases treated between 2000-2004 and 2005-2009 was performed. Results: See Table. Conclusions: In this cohort of MBC patients from Germany we observed that 1) compared to 2000-2004 there has been a significant increase in sentinel node biopsies performed between 2005 and 2009; 2) compared to 2000-2004 there has been a switch to less CMF-containing chemotherapy regimes and more taxane-containing chemotherapy regimes between 2005 and 2009; 3) tamoxifen was the most commonly prescribed endocrine agent. The major limitation of this study is its retrospective design. However, it represents the largest cohort of MBC patients from Europe and describes trends in surgery and systemic therapy. 2000-2004 2005-2009 p value Number % Number % Mastectomy 253 89.4 280 89.5 NS BCT 30 10.6 33 10.5 NS Sum 283 313 No axillary surgery 30 10.5 46 13.8 NS Axillary dissection 253 88.2 246 73.7 NS Sentinel node biopsy 4 1.4 42 12.6 .001 Sum 287 334 CMF 32 38.1 7 9.0 <.004 Anthracyclin 43 51.2 43 55.1 NS Taxane 9 10.7 28 35.9 <.003 Sum 84 78 Tamoxifen 84 79.2 95 72.5 NS Aromatase inhibitor 16 15.1 32 24.4 NS Tam/AI 4 3.8 4 3.1 NS Fulvestrant 2 1.9 0 0.0 NS Sum 106 131 No significant financial relationships to disclose.