tbuckley/cabot-search huggingface dataset:
Racial and ethnic disparities in presenting stage and overall survival in women treated for breast cancer.
Authors: A. L. Salner, I. Staff
Journal: Journal of Clinical Oncology (2011)

187 Background: Over the past 20 years, we have recognized racial/ethnic disparities in breast cancer outcomes, and have attempted to develop outreach, screening, and care strategies to address these. This study explored changes in these disparities over twenty years in presenting stage and overall survival at a single large urban teaching and community hospital with an active cancer outreach program, a member of the NCI Community Cancer Centers Program. Methods: Between 1990 and 2009, 9733 women were diagnosed and treated with breast cancer at our institution. 8918 women with complete race/ethnicity and clinical data were analyzed. The women were grouped into four five-year cohorts, and 3 subgroups-Caucasian, African American, and Latina. All four cohorts were compared for stage migration, while only the initial three cohorts were compared for 5 year overall survival to allow follow-up. Chi-Square tests of proportions were utilized to compare subgroups. Results: Of the 8918 women analyzed, 91.5% are Caucasian, 4.5% African American, and 4% Latina. Over the 20 years of the study, significant stage migration occurred; the total number of women diagnosed with early stage disease(in-situ and localized) increased from 71.7% to 78.7%. Significant stage migration was found for all subgroups of women. Stronger trends were found focusing only on in-situ disease—an overall increase from 14.4% to 30.8%. Five year overall survival of the entire group improved from 78.7% to 85.4%, and also improved for each of the subgroups. Caucasian women were significantly older (60 vs. 54) but the cohort and ethnic findings remained in multivariate analysis. Significant disparities between Caucasians and Latinas for stage and between Caucasians and African American for 5 year survival gradually diminished. Conclusions: Significant improvements are seen in earlier stage presentation and five year overall survival amongst women treated for breast cancer between 1990 and 2009, as well as in subgroups of Caucasian, African American and Latina women. Differences between subgroups diminish and in many cases disappear by the end of the study period, suggesting that strategies may have helped reduce breast cancer disparities.
The Histone Deacetylase (HDAC) Inhibitor PCI-24781 Decreases Pro-Inflammatory Cytokine Secretion In Vitro and In Vivo and Protects Against Endotoxemia In a Sepsis Model
Authors: Sriram Balasubramanian, Mint Sirisawad, Susanne Steggerda, Wangsen Cao, Charles Lowenstein, Joseph J Buggy
Journal: Blood (2010)
Tumor volumes measurement (3D) versus Response Evaluation Criteria in Solid Tumors (RECIST version 1.1, 1D) and Choi criteria (C) in assessing response of gastrointestinal stromal tumors (GIST) to imatinib (IM).
Authors: G. Schiavon, A. Ruggiero, S. Sleijfer, K. Eechoute, G. P. Krestin, J. Verweij, R. Mathijssen
Journal: Journal of Clinical Oncology (2011)

10059 Background: Assessing antitumor effect of treatment is particularly important to guide treatment changes and to assess novel treatments in early clinical trials. We compared the sensitivity of 3D and 1D measurements in detecting size changes of liver metastases from GIST and assessing response to treatment. Methods: IM was given until progressive disease (PD) as assessed by RECIST. We evaluated liver metastases from 58 GIST patients (pts) by manual (2 independent readers) and semi-automated measurements on CT-scans at baseline, after 6 and 12 months (mo) of IM. Bland-Altman plots were used to evaluate agreement between readers and techniques. Percentages of cases with size changes ≥20% assessed by 3D and 1D were compared by McNemar's test (Pietanza et al, ASCO 2008). The ability of 3D, 1D and C to evaluate response was based on 2 target lesions. Minimally relevant changes by RECIST (+20/-30%) were related to a volume scale to obtain corresponding change cut-offs of +73/-65% and +20/-30%, considering lesions as sphere- or ellipsoid-like, respectively. Association with overall survival (OS) was determined by log-rank test. Results: Mean inter-observer variability for manual measurements was very low: 0.77% for 3D and 0.06% for 1D. 3D detected a size change ≥20% more frequently than RECIST at 6 mo (82 vs 44%, P=0.0001) and 12 mo (29 vs 12%, P=0.0005). Manual and semi-automated methods provided clinically consistent similar measures (variability 0.55 and 0.28% for 3D and 1D respectively, with R2 = 1.0 and 0.99, respectively). At 6 mo, 3D was more sensitive than RECIST in assessing partial response (PR) (60 vs 14% pts, P<0.0001) by using ellipsoid cut-off. OS correlated with PD at 6 mo (P=0.02 for both 3D and 1D and 0.01 for C) and 12 mo (P=0.001 for 3D, 0.002 for 1D, not significant for C). Conclusions: In detecting PR, 3D (ellipsoid cut-off) and C are superior to RECIST 1.1. 3D is a better discriminator of size changes than RECIST 1.1 in GIST, rendering it an interesting method to apply in early clinical trials.
Multicentric phase II clinical trial evaluating the role of everolimus (RAD001) in endemic or classic Kaposi’s sarcoma (C06-46).
Authors: R. Porcher, D. Kerob, N. Dupin, B. Guillot, T. Jouary, A. Mathieu-Boue, K. Slimane, V. Furlan, M. Battistella, F. Agbalika, S. Mourah, C. Lebbé
Journal: Journal of Clinical Oncology (2011)

10067 Background: Classic Kaposi’s sarcoma (CKS) is an angioproliferation associated with human herpes virus 8 (HHV8), which sometimes requires systemic treatment. Rapamycin and everolimus are mTOR inhibitors. The PI3K-AKT-mTOR pathway is activated in CKS.The aim of this study was to evaluate the rate of clinical response and tolerance to everolimus 10mg/d in CKS. Methods: Patients suffering from CKS were enrolled in a multicenter two-stage phase II trial. At inclusion, all patients had at least 10 lesions or more than one limb or 3% of body surface affected, in the absence of symptomatic visceral CKS. The primary endpoint was objective response to everolimus after 6 months therapy (complete or partial response per ACTG criteria). The trial was planned using Simon’s minimax two-stage design to demonstrate a response rate of 50% as compared to 20% with type I error rate 2.5% and power of 90%. Accordingly, 11 patients were to be enrolled in the first stage and provided at least 3 patients responded, 15 patients would be accrued in the second stage. Results: At the planned interim analysis, 11 patients (10 men and 1 woman of median age 74 years (56-81) were included. Only one partial response was achieved.Two patients had stable disease, 7 showed progressive lesions and 1 was not evaluated due to early serious adverse event (SAE) and death. Two patients had a SAE leading to early withdrawal: 1 gastric cancer complicated by bleeding and 1 lethal infectious bacterial pneumonia. We observed increased HHV8 viral loads in blood during treatment suggesting that everolimus may have induced HHV8 reactivation in some cases. Conclusions: The study was stopped in accordance with preset rules. In this study, everolimus 10mg/d did not demonstrate any advantage in CKS and could be responsible for CKS progression in some patients. Increased HHV8 viral loads seen in some patients could be related to immunosuppressive properties of mTOR inhibitors. Further development should focus on lower dosage and/or combination with antiviral drugs. The promoter was INSERM (C06-46) with the support of Novartis.
Appeal for sight
Authors: Richard Hurley
Journal: BMJ (2016)

Pinki’s cataracts had gone unnoticed until her grandfather recognised them because he had had cataract surgery himself. The pair visited the Sadguru Netra Chikitsalaya Hospital, which is supported by the eye care charity Orbis, in Chitrakoot, Madhya Pradesh, India. Pinki was assessed and scheduled for surgery. Both eyes were operated on, and her sight was restored. Left untreated, cataracts can …
Syndrome of Inappropriate Secretion of Anti-Diuretic Hormone in Children with Acute Lymphoblastic Leukemia.
Authors: Anupama S. Borker, Sabrina Hutchins, Robin Grant, Nobuko Hijiya, John T. Sandlund, Monika L. Metzger, Sima Jeha, Bassem I. Razzouk, Raul C. Ribeiro, Jeffrey E. Rubnitz, Melissa M. Hudson, Mary V. Relling, Ching-Hon Pui, Scott Howard
Journal: Blood (2006)
A study of atherosclerosis in patients after radiation for early breast cancer.
Authors: V. G. Kirtani, M. Chang, A. M. Dobrescu, S. Zeldis, J. A. Haas, A. A. Hindenburg
Journal: Journal of Clinical Oncology (2011)

260 Background: Radiation therapy (RT) is widely used as part of curative treatment of breast cancer. However, older studies have shown increased cardiac morbidity and mortality from breast RT. A screening method is needed to detect early cardiac damage in this population. Recent data have shown that Electron beam computed tomography (EBCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcification in the coronaries. In our study we employed this tool to detect occult atherosclerosis caused by breast RT. Methods: We evaluated 20 asymptomatic patients, less than 60 years of age, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right hemithorax. Average interval between RT and CT was 7.7 years (5-14). All patients were treated with external beam RT using tangential technique. The breast was treated to a dose of 4500-5040 cGy and the tumor bed was boosted to a total dose of 6000-6600 cGy. All patients underwent EBCT to compute the volumetric and agatston calcium scores in the coronary arteries and the aorta. Results: Of the 11 patients who had RT to right hemithorax, 8 had calcium score of 0, 2 had very minimally elevated scores and 1 had significantly elevated score (patient 19, interval -14 years). Of the 9 patients who had RT to left hemithorax, 7 had calcium score of 0. None had significantly elevated scores. In the aorta, 11 patients had score of 0 and 8 had minimally elevated scores. Conclusions: Occult atherosclerosis was not detected using EBCT calcium scores in coronaries and aorta in a significant number of patients treated with RT for breast cancer. However, the study is limited by a small sample size. [Table: see text]
Initial experience using percutaneous irreversible electroporation (IRE) in the treatment of locally advanced pancreatic adenocarcinoma (LAPC) with vascular encasement.
Authors: Peter Joel Hosein, Katuska J Barbery, Evelyn Perez-Rojas, Tatiana Froud, Caio Max S. Rocha Lima, Dido Franceschi, Alan S Livingstone, Jose M Yrizarry, Govindarajan Narayanan
Journal: Journal of Clinical Oncology (2012)

291 Background: Neoadjuvant chemoradiation therapy can convert some patients (pts) with borderline or unresectable LAPC to resectability. Persistent vascular encasement after neoadjuvant therapy usually contraindicates resection. IRE using the Nanoknife is more versatile than other ablative modalities in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of pts referred for IRE for LAPC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was safety. Secondary endpoints included survival and resection rate after the procedure. Results: Between 12/2010 and 8/2011, 8 pts with biopsy-proven PC underwent percutaneous ablation of pancreatic tumors using IRE. The median age was 53 years (range 51-72), the median time from diagnosis to IRE was 8.8 months (range 2.4-29.2) and the median tumor size treated was 2.8cm (range 2.5-6.8). All pts had prior chemotherapy and 7 had prior radiation, with a median of 2 lines of prior therapies (range 1-4). Two pts went to surgery after IRE after 4 and 5 months respectively. Both had margin-negative (R0) resections and one had a pathologic complete response. Both remain disease-free at 1 and 5 months after resection respectively. Among the 6 remaining pts, 2 were lost to follow-up, one had progressive disease after 3 months and 3 remain under follow-up to determine resectability. One of these 3 pts had a negative follow-up PET scan and surgery is planned. The procedure was complicated by a spontaneous pneumothorax during anesthesia in one patient, and another developed pancreatitis; both recovered completely. Conclusions: Percutaneous ablation of pancreatic tumors appears to be feasible and safe using the IRE modality. In our initial experience, 2 out of 8 pts with unresectable LAPC due to persistent vascular encasement after neoadjuvant therapy achieved a margin-negative resection after IRE. One had a pathological complete response. A prospective neoadjuvant trial in LAPC incorporating IRE is planned.
Post-Hoc Analysis of RE-MEDY™ Demonstrates Significant Real-World Net Clinical Benefit for Dabigatran Versus Warfarin in Prevention of Secondary Venous Thromboembolism
Authors: Sam Schulman, Henry Eriksson, Ajay Kakkar, Clive Kearon, Sebastian M Schellong, Patrick Mismetti, Martin Feuring, Stefan Hantel, Joerg Kreuzer, Samuel Z. Goldhaber
Journal: Blood (2014)
In Vitro Modeling of Ph-like ALL Fusions Identifies Novel Kinase-Domain Mutations As Mode of TKI-Resistance - Implications for Targeted Therapy
Authors: Kartini Asari, Susan L Heatley, Teresa Sadras, Tamara M Leclercq, Stephen Fitter, Chung Hoow Kok, Andrew C W Zannettino, Timothy P. Hughes, Deborah L White
Journal: Blood (2016)
Roles of miRNAs in breast cancer stem cells, drug sensitivity, and spontaneous metastases in orthotopic human-in-mouse models.
Authors: H. Liu, J. Bockhorn, R. Dalton, M. E. Dolan, C. M. Perou, O. I. Olopade, M. F. Clarke, G. Greene
Journal: Journal of Clinical Oncology (2011)

1082 Background: Our previous work showed that breast cancer stem cells (BCSCs) contribute to spontaneous metastasis and BCSCs were enriched in CD44+ cells from both primary tumors and lung metastases. We hypothesize that microRNAs (miRNAs) play important roles in breast cancer progression and chemotherapy response. Methods: To characterize miRNAs important for breast cancer progression and chemotherapy response, we generated breast tumor metastasis models, improved imaging and monitoring of breast tumor in vivo, profiled miRNAs of breast tumors, and screened miRNAs that regulate invasion and drug response. To identify miRNA target genes, we combined multiple algorithms prediction, mRNA analysis, westerns, luciferase assays and functional rescue experiments. Results: With clinical breast tumor specimens, we developed human-in-mouse breast tumor models with spontaneous metastases and transduced BCSCs with optimized fusion genes (Luc2-eGFP or –tdTomato), which enabled both bioluminescence imaging (BLI) and flow analysis. As few as 10 cells of stably labeled BCSCs can be tracked in vivo by BLI. When optical reporters are expressed along with miRNA precursors or inhibitors, the effects of introduced miRNA candidates can be evaluated by selective imaging of transduced tumor cells, thereby eliminating the noise of un-transduced cells. Using this model system and imaging technology, we have screened and identified miRNAs that regulate BCSCs (e.g. miR-200 family), tumor invasion and drug sensitivity. Conclusions: Our metastatic cancer models, combined with non-invasive imaging techniques, comprise an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of MCSCs, to explore therapeutic strategies targeting metastasis in general, or to evaluate individual patient tumor cells and predict response to therapy. Supported in part by the NIH T90, DOD BC087695 and Chicago Fellows Program at The University of Chicago (H.L.), U Chicago Cancer Research Center Pilot Research Fund, UCMC/Northshore Collaborative Research Award and Ludwig Fund (G.L.G and H.L). NIH R01 and Breast Cancer Research Foundation (M.F.C. and H.L.).
A SERPINE1 (PAI-1) Single Nucleotide Polymorphism Predicts Osteonecrosis in Children Treated for Acute Lymphoblastic Leukemia: Results of the Children’s Oncology Group (COG) Study AALL03B2.
Authors: Leo H. Hamilton, Leonard A. Mattano, Harland N. Sather, Mary V. Relling
Journal: Blood (2006)
Training overweight/obese older women at high risk for breast cancer to use web-based weight loss tools: The HELP pilot study.
Authors: L. A. Cadmus Bertram, J. P. Pierce, R. E. Patterson, H. Ojeda-Fournier, V. A. Newman, B. A. Parker
Journal: Journal of Clinical Oncology (2011)

233 Background: Excess weight is one of the few modifiable risk factors for incident breast cancer. Many programs can achieve a 7% weight loss but few can maintain it over time. Training women to use self-help resources over the internet has potential for reducing intervention costs and ensuring program maintenance. Methods: 50 overweight/obese (BMI≥27.5 kg/m 2 ) women at increased risk of breast cancer (Gail score≥1.7) were identified from a mammography registry and enrolled in the HELP pilot study and randomized with 2:1 probability to a 12-week lifestyle intervention or a comparison group. Twelve telephone-based coaching calls trained participants to use a free, publicly available website to set goals and track performance for dietary intake and physical activity. The comparison group received information but no training. At baseline and 12 weeks, participants were weighed, fitted with an accelerometer for physical activity pattern, and completed questionnaires. Results: At baseline, participants were 60.9±0.79 years of age with a BMI of 33.1±0.60 kg/m 2 ; 39% were daily internet users. Thirty-three were randomized to the intervention group with 91% completing follow-up. Fifty-four percent were able to use the website reliably and found it to be helpful, including 44% of previously nondaily internet users. At 12 weeks, intervention group participants who found the website helpful had lost 5.6±0.7 kg, or 6.7% of initial weight, intervention participants who did not find it helpful lost 0.8±0.9kg or 1.1% of initial weight and the comparison group gained 1.0±0.94 kg (89% follow-up) The between-group difference weight change was 4.2 kg (p&lt;.0001). 74% of intervention group participants lost weight, compared to only 34% of women assigned to the comparison group. Conclusions: A 12-session telephone coaching program to train women to use publicly available web-based weight loss programs effectively achieved a large short-term weight loss among the majority of participants. Further follow-up is needed to identify how well the initial weight loss is maintained without further intervention assistance.
Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).
Authors: Jennifer Anne Dorth, Christopher Willett, Brian G. Czito
Journal: Journal of Clinical Oncology (2012)

88 Background: Patterns of local-regional failure (LRF) after neoadjuvant chemoradiotherapy (CRT) and surgery for locally-advanced EC are poorly defined. Methods: This study reviewed pts treated with CRT followed by surgery for M0 esophageal cancer from 1995-2009. Staging and regional nodes (supraclavicular (SCV) through celiac) were defined based on AJCC 7 th edition. Patterns of first failure were analyzed. LRF included: 1) initially involved nodal failure (INF), 2) initially uninvolved (subclinical) nodal failure (SNF), and/or 3) anastomotic. Abdominal para-aortic failure (PAF) at or below the superior mesenteric artery was scored separately. Isolated SNF or PAF was defined as no other local or distant failure. Actuarial local-regional control (LRC), event-free survival (EFS), and overall survival (OS) were estimated by the Kaplan-Meier method. Results: 156 patients were identified with a median age of 60 years. Primary location was upper in 1%, middle 17%, lower 32% and gastroesophageal junction (GEJ) 50% (Adeno: 79%; SCC: 21%). Staging included EUS (73%), CT (46%), and/or PET/CT (54%). 40% had stage II and 60% stage III disease. Concurrent CRT was primarily cisplatin/taxane and/or 5-FU-based. Primary RT fields (median dose: 45Gy) encompassed the tumor with an approximate 5 cm proximal and distal margin and included standard regional nodes. Boost fields (median total dose: 50.4Gy) encompassed gross disease with a 2 cm margin. Surgical technique was transhiatial (28%), Ivor-Lewis (47%), or tri-incisional (25%) with a median of 8 nodes dissected. Median f/u was 1.3 years. 2-yr LRC, EFS, and OS were 83%, 36%, and 49%. 2-yr SNF was 15% (n=14); anastomotic failure was 7% (n=7). SNFs were SCV (n=5), mediastinal (n=12), and/or celiac (n=3). 95% of SNFs were outside or near the margin of the primary RT fields. 2-yr isolated SNF was 3% (n=3), PAF was 11% (n=9), and isolated PAF 6% (n=5). Conclusions: SNF is the most common type of LRF after tri-modality therapy for locally-advanced EC. A limited subset of patients experience isolated SNF or PAF as first disease recurrence. The potential benefit of targeting additional SN or PA regions with RT is small and likely eclipsed by high rates of distant failure.
Functional studies in two angiosarcoma cell lines.
Authors: R. J. Young, N. J. Brown, C. A. Staton, M. W. Reed, P. J. Woll
Journal: Journal of Clinical Oncology (2011)

e20511 Background: Angiosarcomas (AS) are rare vascular tumours. A series of studies were performed to characterise and contrast two human cutaneous AS cell lines (ASM and ISO-HAS) with human dermal micro-vascular endothelial cells (HuDMECs). The effects of inhibition of vascular endothelial growth factor (VEGF) receptors were investigated using the selective tyrosine kinase inhibitor (TKI) axitinib (A). Methods: The relative expression of angiogenic proteins and phospho-tyrosine kinases (pTK) were investigated using Proteome Profiler Arrays (R&D Systems). Basement membrane extract (Matrigel) tubule formation and Boyden chamber migration functional assays were performed and the effects of A studied. Cell proliferation assays compared A with chemotherapy (doxorubicin (D) and paclitaxel (P)) and drugs suggested by the pTK array (everolimus (E) and the checkpoint-2 (ChkII) inhibitor C3742 (C)). Results: The AS cell lines demonstrated an increased expression of angiogenin, coagulation factor III, fibroblastic growth factor (FGF) 1 and 2, HGF, TGF-β1, VEGF and the pTKs mTOR, p70 S6, p53 and ChkII relative to HuDMEC controls. On Matrigel HuDMECs developed a more extensive network of tubules than the malignant endothelial cells (total network length HuDMECs 810 units vs ASM 129 vs ISOHAS 589 (p=0.008)). ASM and ISO-HAS demonstrated significantly increased migration (mean migration HuDMECs 17 cells per hpf (x20) vs ASM 91 vs ISO-HAS 60.7 (p=0.018)). The addition of A 50ng/ml reduced tubule formation by 24% (p=0.005) and migration by 14% (p=0.071) across all cell lines. Results were not significant for individual cell lines. Estimated IC50 for single agent drugs (ng/ml) were P 6.5, D 21 and A 500. Single agent E reduced proliferation by 20% in all doses studied. A+P and E+D combinations showed an additive rather than synergistic effect. Single agent C and C+D combinations had no significant effect. Conclusions: ASM and ISO-HAS exhibited different responses compared to HuDMECs in the functional assays. The effects of single agent A on endothelial behaviour were modest but may be of benefit in the treatment of AS in combination with chemotherapy. mTOR is a potential drug target in AS. Results from array studies are being validated in AS tumor samples.