tbuckley/cabot-search huggingface dataset:
Pleomorphic lobular carcinoma in situ: A distinct entity of controversial significance.
Authors: Marina De Brot, Shirin Muhsen, Victor P. Andrade, Starr Koslow Mautner, Melissa Murray, Dilip D. Giri, Rita A. Sakr, Edi Brogi, Tari A. King
Journal: Journal of Clinical Oncology (2012)

177 Background: Pleomorphic lobular carcinoma in situ (PLCIS) is an increasingly diagnosed variant of lobular carcinoma in situ. Histologically, it resembles ductal carcinoma in situ (DCIS), leading to controversy over proper management. Yet, the natural history of PLCIS is unknown. Here we describe our experience with PLCIS. Methods: Review of pathology reports (1995–2012) identified 233 cases of LCIS variants. Patients with synchronous ipsilateral DCIS or invasive cancer (IC) were excluded leaving 25 cases for review. Consensus review by 3 pathologists further excluded 7; leaving 18 cases, 12 of which were classified as PLCIS and 6 as LCIS with pleomorphic features (LCIS-PF). (Table) PLCIS was defined by cellular dyshesion, nuclear pleomorphism with a 2-3 fold size variation, conspicuous nucleoli, mitoses and abundant cytoplasm; lesions not meeting all parameters were classified as LCIS-PF. Loss of e-cadherin was confirmed; clinical data were obtained from medical records. Results: Mean patient age at diagnosis of PLCIS/LCIS-PF was 57 yrs (42-67 yrs). All cases presented with imaging abnormalities. A previous history of breast cancer was present in 7/18 (39%) pts (3/7, ipsilateral; 4/7, contralateral). Following PLCIS/LCIS-PF diagnosis, 6/18 (33%) pts underwent mastectomy and 12/18 had excision alone, with (n=3) or without chemoprevention (n=9). Margin status was negative in 4/12 pts; close in 3/12 pts and positive in 5/12 pts undergoing excision. At a median follow-up of 27 mos (2-148 mos), 2/12 pts treated with excision developed ipsilateral breast cancer (1 DCIS; 1 IC). Both had close margins at initial excision; median time to cancer, 54 mos. Conclusions: Pure PLCIS is an uncommon lesion. Synchronous malignancy or prior history of breast cancer are often present in patients with PLCIS, contributing to the difficulty in determining the actual risk conferred by this lesion and appropriate management. Efforts to systematically characterize LCIS variants and prospective documentation of outcomes are needed to clarify the significance of these lesions. [Table: see text]
Impact of BMI on clinical outcome of HER2-positive breast cancer.
Authors: V. Parolin, E. Fiorio, A. Mercanti, M. Riolfi, G. L. Cetto, E. Surmacz, A. Molino
Journal: Journal of Clinical Oncology (2010)

1130 Background: Obesity and HER2 overexpression are associated with poor prognosis in breast cancer (BC). Recent studies suggest the existence of functional crosstalk between leptin, a hormone correlated with adiposity, and HER2. Specifically, stimulation with leptin can transactivate HER2 and activate its downstream signaling, while chronic exposure to leptin increases HER2 stability in presence or absence of Herceptin. In our study we evaluated if excess adipocity (associated with leptin overexpression) can impact the clinical outcome in HER2-positive patients treated with Herceptin. Methods: We analyzed retrospectively 155 patients with HER2-positive BC treated with Herceptin for early stage or metastatic disease in the period 2003-2008. The patients were grouped into normal, overweight, and obese categories according to Body Mass Index (BMI) following WHO guidelines. Overall survival (OS) and time to progression (TTP) were calculated by the Kaplan-Meier method and comparisons were made using the log-rank test. Results: 103 patients were treated with adjuvant Herceptin. 12.5% of the population relapsed; of these, 31% and 23% were overweight and obese, respectively. Inrelapsed patients, OS and TTP decreased with increased BMI: the median OS for normal, overweight and obese patients was 40, 36.5, and 31 months, respectively (p=ns); median TTP was 11, 8, and 5 months, respectively (p=0.0351). 52 patients received Herceptin for metastatic disease in association with chemotherapy. In this population, 33% and 15% patients were overweight and obese, respectively; median OS was 65 months and TTP 10.5 months. Decreased OS and TTP were associated with increased BMI: median OS for normal weight, overweight and obese patients was 67, 54, and 39 months, respectively (p=0.0010); median TTP was 12, 7.5, and 7 months, respectively (p=0.0442). The negative impact of increasing BMI was confirmed in subgroups differentiated by hormone receptor and menopausal status. Conclusions: The results suggest that obesity is not only a risk factor and an indicator of poor prognosis in BC patients, but also a negative predictive parameter in HER2-positive subjects. Our in vivo data validate in vitro observation that leptin can impair response to Herceptin in BC cells. No significant financial relationships to disclose.
Abstract 18370: Role and Potential Impact of TEE in Detecting Markers of Thromboembolism in Non Valvular Atrial Fibrillation Patients with a CHADS2 score = 0?
Authors: Stéphane Ederhy, Sylvie Lang, Louise Boyer-Chatenet, Nabila Haddour, Catherine Meuleman, Guillaume Fleury, Saroumadi Adavane, Emanuele Di Angelantonio, Franck Boccara, Ariel Cohen
Journal: Circulation (2012)

Background: Transesophageal echocardiography (TEE) parameters (left atrial appendage, LAA thrombus or spontaneous echocardiographic contrast (SEC), aortic atheroma (AAA) are powerful markers of thromboembolism (TE) in non-valvular atrial fibrillation (NVAF) patients. However, the prevalence and potential impact of these abnormalities have not been evaluated in patients at very low risk of TE. We evaluated TEE-detected LASEC, thrombus and AAA in AF patients referred for cardioversion and analyzed the subgroup of patients with a CHADS 2 score=0. Methods: Among 763 consecutive patients hospitalized for NVAF, prior to cardioversion, TEE was systematically performed within 24h after admission; 205 patients had a CHADS 2 score=0. The following parameters were described: presence and severity of LASEC, LA thrombus, aortic atheroma (AAA). Results: Mean age was 54.5 ± 13.5 years. AF was paroxysmal in 101 patients (49.3%), persistent in 82 (40.0%) and permanent in 22 (10.7%). Transthoracic echocardiography showed LVEF&lt;40% in 12 (5.9%) and median of mean LA area was 18 (15-23) cm 2 . LA thrombus was found in 1 patient (0.5%), LASEC in 60 (29.3%), classified as mild in 43 (21.0%), moderate in 14 (6.8%) and severe in 3 (1.5%). AAA was present in 6 patients (2.9%). The table compares some baseline characteristics in patients with (LAASEC/thrombus or aortic atheroma ≥ 4 mm) or without TEE abnormalities, defined as an endpoint. In the multivariate analysis, age (OR, 1.04, 95% CI 1.01-1.07), non paroxysmal AF (OR, 3.23, 95% CI 1.54-6.78) and LA area (OR, 1.08, 95% CI 1.02-1.16) were predictors of TEE-detected LASEC/thrombus or aortic atheroma. Conclusions: TEE prior to cardioversion in NVAF found TEE-detected risk markers of thromboembolism (LASEC/thrombus or aortic atheroma) in one third of patients with a CHADS 2 score = 0.
Similar Efficacy and Toxicity Profile for Idarubicine and Mitoxantrone in Induction and Intensification Treatment of Children with Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS): Long-Term Results of the EORTC-CLG Randomized Phase III Trial 58921
Authors: Barbara De Moerloose, Stefan Suciu, Martine Munzer, Caroline Piette, Karima Yakouben, Genevieve Margueritte, Patrick Lutz, Anne Uyttebroeck, Pierre Rohrlich, Alina Ferster, Patrick Boutard, Marie-Françoise Dresse, Xavier Rialland, Lucilia Norton, Nicolas Sirvent, Matthias Karrasch, Yves Benoit, Yves Bertrand
Journal: Blood (2011)
Psychosocial impact of cancer-related symptoms among patients with lung cancer
Authors: M. Walker, G. Peltz, A. Houts, G. Pohl, L. Schwartzberg, E. Stepanski, M. Marciniak
Journal: Journal of Clinical Oncology (2009)

6621 Background: Patients with lung cancer may experience adverse physical symptoms due to cancer, cancer treatment, or comorbid medical conditions. These cancer-related symptoms (CRS) may be associated with functional impairment (FI), and may affect psychosocial functioning. Methods: We conducted a retrospective analysis of self reported symptom burden with the 38-item Patient Care Monitor survey (PCM), collected as part of routine clinical care in 1,384 lung cancer patients identified by ICD-9 codes at 8 community oncology practices in the US. Structural equation models were built among 672 randomly selected patients to examine the relationships of CRS and of FI on psychosocial symptoms and to determine whether FI mediates the effect of CRS. Results: Patients were 47.7% female, with mean age of 66 years (23–91), 65% Caucasian, 16% African American, 19% other/unknown race. Stage of disease was 19% stage IV, 22% stage I-III, and 59% unspecified. Histological type was 36% adenocarcinoma, 18% squamous cell, 37% unspecified, and 9% other. The most common comorbidities were anemia, other malignancies, and respiratory disease. Depressive disorder was recorded for &lt; 5% of patients. Surveys were collected between 2005 and 2008, ranging up to 5 years after the start of treatment (median 79 days after start of chemotherapy). Half (50.4%) of surveys were collected while the patient was in active treatment. Model findings supported a 1 factor measurement model of 19 CRS items, and a 1 factor measurement model of 8 FI items. Findings supported a 2 factor model of 11 psychosocial items, with resulting factors reflecting acute distress and despair. CRS were less severe longer after the start of chemotherapy, and not significantly worse during vs. off chemotherapy. More severe CRS significantly predicted more severe acute distress and despair, and more severe FI. In contrast to expectations and some previous research, FI was not significantly related to acute distress and despair, and did not mediate the effect of CRS on acutedistress and despair. Conclusions: Cancer related symptoms are associated with FI and with psychosocial outcomes in lung cancer patients. However, FI does not appear significantly related to psychosocial outcomes. [Table: see text]
Protocol performance metrics and resource utilization of phase II investigator-initiated trials.
Authors: H. Durivage, K. D. Bridges, J. Sauers, M. Wellons, L. Baker
Journal: Journal of Clinical Oncology (2010)

6066 Background: Investigator-initiated trials (IITs) are the backbone of cancer center (CC) clinical programs. They are essential to early testing of drug dosing, safety and early indicators of efficacy. Little is known about IIT performance metrics and associated resource use. We suspected many IITs are not being completed, that completed trials are taking a long time to finish enrollment and significant resources are used to implement and conduct IITs that are not completed. Methods: Implementation and accrual timelines, patients (pts) enrolled and reasons for study closure of phase II IITs were obtained from 5U.S. CCs. Data of IITs closed during the 4-year period from 2005 through 2008 was analyzed. Phase II IITs were classified as completed or not completed based upon the reason for study closure, which was available for all IITs in the dataset. Results: 1.939 patients (pts) were enrolled to 106 phase II IITs during the analysis time period. 54 of 106 (50.9%) phase II IITs were completed. 1316 of 1939 (67.8%) pts were enrolled to the completed phase II IITs. 36 of the 106 (33.9%) phase II IITs were not completed due to slow accrual. Phase II IITs closed due to slow accrual remained open for 28 months (median). There was no discernable difference in activation time between IITs completed and IITs not completed. Resource utilization: We estimate > 28,000 hours (median: > 7,800 hours per CC) were devoted to study implementation and conduct of the 36 phase II IITs not completed due to slow accrual (Guidance Document for Implementing Effective Cancer Clinical Trials, www.c-changetogether.org/pubs/default.asp). Conclusions: Approximately 34% of the phases II IITs from 5 CCs were not completed due to inadequate accrual. Approximately 15% of the total phase II IIT accrual was to phase II IITs closed due to inadequate accrual. Significant resources are used on phase II IITs that are not completed. Effective rules governing selection and closure of nonaccruing phase II IITs are needed. Early predictors of phase II IIT completion are needed. Effective rules and early predictors will enable centers to direct valuable resources to more useful activities. No significant financial relationships to disclose.
A Retrospective Multicenter Study from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) on Cerebral Sinus Venous Thromboses in Children with Acute Lymphoblastic Leukemia
Authors: Susanna Ranta, Nadine Gretenkort Andersson, Ulf R. Tedgard, Tony Frisk, Maria Winther Gunnes, Jon Helgestad, Ólafur G Jónsson, Birgitte Klug Albertsen, Anne Mäkipernaa, Kaie Pruunsild, Mats Heyman, Thomas Leth Frandsen, Sonata Trakymiene, Ellen Ruud, Ruta Tuckuviene
Journal: Blood (2014)
Familial risk, age at onset, and cause of end-stage renal disease in white Americans.
Authors: B J Spray, N G Atassi, A B Tuttle, B I Freedman
Journal: Journal of the American Society of Nephrology (1995)

A strong familial clustering of ESRD has been reported among African Americans, suggesting that factors predisposing to renal failure, whether genetic, environmental, or both, may disproportionately affect certain families. A case-control study was undertaken to determine if a familial risk of ESRD was present among white Americans, if this risk differed among causes of ESRD, and if variability in age at onset was attributed to familial factors. Data were obtained from 103 white American patients (cases) with ESRD receiving dialysis treatments at the Bowman Gray School of Medicine's affiliated dialysis facility in Winston-Salem, NC. One hundred three age-, sex- and race-matched non-ESRD controls were consecutively selected from the Wake Forest University Physicians internal medicine clinic. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated to signify the prevalence of a relative with ESRD among cases versus controls. The presence of either a first- or second-degree relative increased a white American's risk for developing ESRD nearly threefold (OR = 2.7, 95% CI 1.1 to 7.2; P = 0.038), whereas the presence of either a first-, second- or third-degree relative with ESRD increased the risk nearly fourfold (OR = 3.5, 95% CI 1.5 to 8.4; P = 0.004). Cases with chronic glomerulonephritis and Type II diabetic nephropathy as the cause of ESRD had relatives with ESRD more often than cases with Type I diabetic nephropathy, interstitial nephritis, or renal artery stenosis. The average correlation (f) of ages at onset of ESRD among individuals in a single family (cases and their relatives) was 55%.(ABSTRACT TRUNCATED AT 250 WORDS)
Second line treatment of hormone resistant prostate cancer (HRPC). A phase II trial of epirubicin (E), estramustine phosphate (EP) and celecoxib (C)
Authors: F. Zhong, B. Kasimis, S. Hwang, J. Cogswell, V. Chang, E. Morales, M. Gonzalez, I. Boholli, M. Ohanian, M. Blumenfrucht
Journal: Journal of Clinical Oncology (2005)

4754 Background: Cox-2 is over expressed in patients (pts) with HRPC and is an independent predictor of survival. C is a Cox-2 inhibitor. E is a derivative of doxorubicin with lower cardiotoxicity. Its activity is exerted through intercalations between DNA base pairs as well as topoisomerase II-DNA complex stabilization. Its activity in HRPC has been documented. EP is active in HRPC by inhibiting the mitotic microtubules and their depolymerization. All three induce apoptosis and their combination could be synergistic. In an ongoing trial, we study the effects of this combination on PSA, response, toxicity and survival. Methods: Fourteen (14) pts, progressing from first line chemotherapy with rising PSA and radiographic manifestations were treated with E 30mg/m2 iv on day 1 and 8 of each 4 weeks (wks) cycle; EP 280mg p.o., b.i.d daily x 3 (days-1, 0, +1) every wk x 2 followed by 2 wks rest; C 400mg p.o. b.i.d daily for 28 days. All pts were assessed for response every 2 cycles. Dose modifications for hematologic and hepatorenal toxicity were made. The RECIST criteria and PSA decline > 50% were used to assess for response. Results: Twelve (12) pts are evaluable for toxicity and response. Two (2) pts withdrew before completion of the first cycle. For the 12 evaluable pts the median (M) number of cycles was 3 (1–10). The M age was 79 years old (58–87), ECOG PS 1 (0–1), Gleason Score 7 (4–9), LDH 172 U/L (131–244), Hgb 10.8 g/d L (9.1–11.9), PSA 50.8 ng/dl (6.3–816.0). Soft tissue metastases were present in 9 pts (75%). Bone metastases were present in 11 pts (91.6%). Ten (10) pts are evaluable for response, 6 pts (60%) had PSA decrease >50%, one (1) pt (10%) had response by bone scan and 1 pt (10%) by CAT scan respectively. Two (2) pts (20%) developed DVT. Grade 2 neutropenia, thrombocytopenia and peripheral edema, grade 3 vomiting and decline of the ejection fraction were noted in 1 pt (10%) each. The renal and cardiovascular tolerance was excellent. Conclusions: The preliminary results indicate the combination of E, EP, and C is well tolerated. Its activity is manifested by both PSA and radiographic responses. Supported by Pfizer Pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Interim results for the phase II study of panobinostat (LBH589) in patients (Pts) with relapsed/refractory Hodgkin's lymphoma (HL) after autologous hematopoietic stem cell transplant (AHSCT).
Authors: A. Sureda, A. Engert, P. J. Browett, J. A. Radford, G. E. Verhoef, R. Ramchandren, N. Myke, A. Shen, C. Le Corre, A. Younes
Journal: Journal of Clinical Oncology (2010)

8007 Background: Panobinostat (PAN) is a pan-deacetylase inhibitor targeting epigenetic and non-epigenetic oncogenic pathways. In vitro, PAN decreases proliferation and induces apoptosis in HL cell lines at low nanomolar concentrations. In a Phase I study, promising activity was observed in pts with HL (EHA 2009, Abstract #1064). Methods: This international trial with Simon optimal 2-stage design has completed enrollment with 129 pts at 45 sites. Oral PAN is administered at a dose of 40 mg three times per week, every week, in 21-day cycles. Dose delay and modification is allowed for management of AEs. CT/MRI scans are conducted after every 2 cycles. Primary endpoint of the study is objective response rate. Secondary endpoints include time to and duration of response (TTR, DOR), PFS, and safety. Results: As of December 14, 2009, demographic data are available for 127 pts: median age was 32 years [18–75]; 37% had ≥5 prior lines of therapy; median prior regimen was 4 [2–6]; 37% had no response on last therapy; median time to relapse after first AHSCT was 8 months; 10 pts also had prior allogeneic transplant. In early analysis, 81 pts had ≥1 post baseline CT/MRI result available or discontinued early – 72% had tumor reduction, 5% had early PD, and 6% discontinued early (e.g. due to AE). 17 responses (2CR+15PR) have been reported; 14 of 17 responders continued on study, including 9 pts with DOR ranging from 12–52+ weeks. TTR ranged from 4–24 weeks. Median treatment duration for 127 pts was 78+ days [5–455+] and 64% of pts continued on treatment. 33% of pts have been treated for ≥8 cycles. Common G1/2 AEs were N/V/D, fatigue, anorexia, and neutropenia. Common related G3/4 AEs were thrombocytopenia (TCP) (55%) and anemia (11%). The TCP was reversible with dose hold or modification. No G3/4 QT prolongation has been reported. Conclusions: This is the first pivotal study initiated for a homogenous HL population in the post-transplant refractory/relapsed setting where there is no standard treatment. PAN is well tolerated and demonstrates encouraging activity in these heavily pretreated pts. Enrollment has been completed; updated results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Abbott Laboratories, Amgen, Biogen Idec, Genentech, MethylGene, Novartis, Pharmion, Sandoz, sanofi-aventis, Seattle Genetics, Trubion, Xencor Education Concepts Group
Randomized study of darbepoetin alfa as modifier of radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC): Final outcome of the DAHANCA 10 trial
Authors: J. Overgaard, C. M. Hoff, H. S. Hansen, L. Specht, M. Overgaard, C. Grau, E. Andersen, J. Johansen, L. J. Andersen, J. F. Evensen
Journal: Journal of Clinical Oncology (2009)

6007 Background: The study aimed to evaluate if correction of low hemoglobin (Hb) levels by means of the erythropoietin stimulating agent: darbepoetin alpha (Aranesp) during radiotherapy (RT) improves outcome in patients with HNSCC. Following a planned interim analysis which showed inferiority of the experimental treatment, the trial was stopped in November 2006. Methods: Pts with HNSCC eligible for primary RT alone and with Hb values below 14.0 g/dl were randomized to receive Aranesp together with accelerated fractionated RT. Pts. were stratified according to gender, T and N staging, tumor site, and institution. Aranesp was given subcutaneously in a dose of 150 micrograms weekly during RT, or stopped earlier if the Hb exceeded 15.5 g/dl. Results: In total, 522 patients (of a planned intake of 600) were included at the time of the interim analysis. Of these 514 pts were eligible for analysis (255 pts treated with Aranesp and 259 pts in the control group) with a median follow up of 49 months. Among these, 201 developed a loco-regional failure (primary endpoint). There have been 238 deaths of which 176 are due to HNSCC. The patients were evenly distributed according to the stratification parameters (gender, T and N staging, tumor site, institution).Aranesp resulted in the expected increase in Hb in more than 81% of the patients. The compliance to Aranesp was good with no significant difference in serious (cardiovascular) adverse events (3% vs. 1%). Overall, the results showed a poorer outcome in 5-year loco-regional control (59% vs. 68% (p = 0.04, RR: 1.47 [1.14–1.94]) for the Aranesp vs. control arm. This was also seen for the endpoint of disease-free survival (37% vs. 47%, p = 0.02, RR: 1.32 [1.04–1.68]), whereas there was no significant difference in overall survival (40% vs. 51%, p = 0.16, RR: 1.20 [0.93–1.55]). There were no differences in radiation related morbidity. All univariate analyses were confirmed in a multivariate setting. Conclusions: Correction of the Hb level with Aranesp in patients with HNSCC resulted in a significantly poorer tumor control after radiotherapy. The treatment principle was abandoned and the difference in outcome is being subjected to further examination. No significant financial relationships to disclose.