tbuckley/cabot-search huggingface dataset:
Adult participation in oncology clinical trials by indication, race, and age.
Authors: Austin James Combest, Dirk J. Reitsma, Angelena Moseley, Savanna D. Steele, Marie-Edith Anne Bonneterre
Journal: Journal of Clinical Oncology (2013)

e17586 Background: According to the National Cancer Institute (NCI), approximately 3 percent of adult cancer patients participate in clinical trials despite the NCCN guidelines frequently recommending clinical trials as standard of care in many circumstances (Mooney, 2010). In a large analysis of NCI Cancer Therapy Evaluation Program (CTEP) trials, 40 percent of trials failed to achieve minimum enrollment, including 3 of 5 phase III trials (Cheng, 2010). Additionally, concerns about unequal access to clinical trials led Congress to enact the National Institutes of Health (NIH) Revitalization Act 20 years ago (June 10, 1993). Using data from Ipsos’ Tandem Oncology Monitor, a robust, nationwide system that collects actual prescriptions and clinical trial participation by indication from 500 oncologists and hematologists from the United States, we evaluated current participation and ethnic diversity in clinical trials. Methods: We assessed adult clinical trial participation from October 2011 to September 2012. Age, ethnicity and practice type were also collected to identify descriptive trends. Results: With regards to indication, clinical trial participation ranged from 1 percent (prostate, renal cell and head and neck) to 12 percent (thyroid) averaging between 2 and 3 percent. We observed a decline in first-line metastatic melanoma participation between pre- and post- vemurafenib/ipilimumab approval (9%-pre versus 2%-post). Patient diversity results are included in the Table. Conclusions: Despite efforts to increase oncology clinical trial participation, we have observed overall low clinical trial participation. Additionally, we observed better trial participation in the youngest age groups and minor differences between ethnic categories. Continued focus on increasing trial participation and patient diversity is still needed. [Table: see text]
Health workers and the weaponisation of health care in Syria: a preliminary inquiry for The Lancet –American University of Beirut Commission on Syria
Authors: Fouad M Fouad, Annie Sparrow, Ahmad Tarakji, Mohamad Alameddine, Fadi El-Jardali, Adam P Coutts, Nour El Arnaout, Lama Bou Karroum, Mohammed Jawad, Sophie Roborgh, Aula Abbara, Fadi Alhalabi, Ibrahim AlMasri, Samer Jabbour
Journal: The Lancet (2017)
High-Altitude Pulmonary Edema
Authors: N. D. Menon
Journal: New England Journal of Medicine (1965)

HIGH-altitude pulmonary edema has, in recent years, aroused considerable interest all over the world. Houston1 and Hultgren and his co-workers2 , 3 have written papers on the subject. This new mountain malady was unrecognized in India until 1962. There had been occasional reports of "bronchopneumonia" occurring among persons going to high altitudes, and it had been noted with concern that, in spite of energetic treatment, the mortality in these cases was high. It was late in 1962 that it was realized that these were really cases of pulmonary edema. Since that time the incidence of the disease has gone up considerably, and . . .
Second cancer (SCa) risk among patients (pt) treated with abdomino-pelvic radiation (XRT) for epithelial ovarian cancer (EOC).
Authors: Aalok Kumar, Nhu Le, Cyril Blake Gilks, Jennifer Santos, Caroline Holloway, Anna Tinker
Journal: Journal of Clinical Oncology (2015)

e16535 Background: Prior studies suggest a survival benefit of adjuvant abdomino-pelvic XRT for the treatment of low stage, non-serous EOC. However, the long-term risk of a SCa from XRT is unknown. We examined the relationship between XRT use and the risk of SCas in a population-based cohort of EOC pt. Methods: We determined the rates of SCa in a previously described cohort of stage I-III (microscopic residual only) EOCs, diagnosed between 1984-2008 and treated with adjuvant chemotherapy +/-XRT(45 Gray to abdomen and pelvis) at any of 5 regional Cancer Centers in British Columbia. SCas were any non-skin cancer(ca) diagnosed > / = 12mo after the primary EOC. The site of SCa relative to the XRT field was determined by a radiation oncologist(in-field/field border/out-of-field)(CH). Cox regression accounting for age, stage and histotype comparing XRT vs. no XRT was used to determine the hazard for developing SCa as the event of interest. Competing risk analysis was carried out looking at either SCa or death due to XRT. Results: 703 pts were included in the analysis: median age 56 years (yrs)(range 25-89), 38% stage I, 44% stage II and 18% stage III, 37% high grade serous ca (HGSC), 25% endometrioid ca, 22% clear cell ca, 10% mucinous ca and 6% unknown. 351(49.9%) pt received XRT, while 352(50.1%) did not. XRT was associated with a longer median survival (14.1 vs 8.3 yrs,p < 0.0001). Median time to SCa was 8.4 yrs overall. The rate of SCa was 15%(53 pt) with and 10%(34 pt) without XRT, p = 0.04. Among pt who had XRT, 45% of SCas were in-field, 36% out-of-field, 11% along the field border and the remaining unknown. There was no difference in time to SCA between in-field/border vs. out-of-field SCa(p = 0.292). Cox regression analysis revealed no significant difference in the risk of SCa according to XRT use(HR 1.21,95%CI,0.77-1.90,p = 0.40). There was no increased risk of SCa on the basis of EOC histotype. Competing risk analysis did not demonstrate a significant increase in cumulative incidence of SCa due to XRT, p = 0.26. Conclusions: In this population-based cohort of low stage EOCs, XRT was not associated with a higher risk of SCAs. This study is limited by the small sample size and relatively short median follow up.
Febrile neutropenia with adjuvant docetaxel and cyclophosphamide (TC) chemotherapy for breast cancer.
Authors: Joanne Linda Yu, Michael Kurin, Mark Pasetka, Srikala S. Sridhar, Ellen Warner
Journal: Journal of Clinical Oncology (2013)

e17523 Background: The combination of docetaxel and cyclophosphamide (TC) for adjuvant treatment of early stage breast cancer has been shown to improve overall survival compared with doxorubicin and cyclophosphamide (AC) (Jones et al., 2006). Although cardiotoxicity is avoided with TC, the risk of febrile neutropenia (FN) is higher. For TC, reported rates of FN without prophylactic G-CSF range from 5% in the phase III trial to as high as 50% in retrospective chart reviews. As G-CSF is not covered by our provincial cancer funding agency for primary prophylaxis of FN with TC chemotherapy, we sought to determine the incidence of FN with TC chemotherapy in two comprehensive cancer centres in Ontario, Canada. Methods: Patients who received adjuvant TC chemotherapy between January 1, 2008 and December 31, 2012 were identified through the pharmacy databases. Electronic charts were retrospectively reviewed to abstract patient characteristics, treatment details including G-CSF use, and incidence of FN. Results: Preliminary results from one institution demonstrate that 187 patients were treated with TC over the study period. Of the 74 (40%) patients who did not receive primary G-CSF prophylaxis, 23 (31%) developed FN requiring hospitalization and treatment with intravenous antibiotics. However, none of the 113 patients who received primary G-CSF prophylaxis (funded by the patient or a third party payer) developed FN. Putative risk factors for FN in the absence of G-CSF including age, BSA, BMI, and pre-treatment absolute neutrophil count were examined and will be reported. Conclusions: The FN rate associated with TC chemotherapy exceeds 30%, higher than that reported in the clinical trial. As per ASCO guidelines, primary G-CSF prophylaxis should be given with TC chemotherapy, and in Canada this should be covered by provincial cancer funding agencies.
Treatment of advanced or metastatic hepatocellular cancer (HCC): Final clinical results of a single-arm phase II study of bevacizumab and everolimus.
Authors: Gerhard Treiber, Thomas Wex, Guenther Schneider, Cristoph Roecken, Jean-Francois Dufour, Juergen Geisel, S. Hardikar
Journal: Journal of Clinical Oncology (2012)

4107 Background: mTOR inhibitors are emerging drugs for treatment (Tx) of advanced hepatocellular cancer (HCC), their therapeutic effects may be potentiated by combination with anti-VEGF partners (Treiber G, Expert Rev Anticancer Ther 2009). Methods: Pts with histologically confirmed advanced HCC were included. Tx consisted of RAD001 in a daily start dose of 5 mg orally and bevacizumab 5mg/kg iv every 2 weeks, up to 24 weeks. Primary endpoint was TTP, secondary endpoints were OS, RR, changes in biomarkers, and safety and tolerability besides PK analysis. Pts with either a CPT Score &gt; 9, a CLIP score &gt; 3, or a Performance Status of ECOG &gt; 2 were not eligible. Radiological TTP was centrally evaluated by both, conventional(c)-, and modified(m)-RECIST criteria on a PP basis. Additionally, we included a combined endpoint (TTPcomb: time to either clinical or radiological progression leading to termination of treatment) as assessed by the local centers in all recruited patients. Results: 33 pts (ITT) were recruited (26 with Child A, 7 with Child B; median CLIP score was 2, mean age 67 y, and mean BMI 28). 17/33 pts. had previous Tx (including sorafenib &lt; 3 months). Drop out other than PD was due to consent withdrawl, lost to FU, and AE (n=5), therefore 28 patients had received study medication &gt;2 wks (PP). There were 65 CTC-AE grade 3/4 events occuring in 22 pts. Median Tx duration was 69 days on RAD001, and a median of 5 cycles of bevacizumab were applied. Dose adjustements for RAD001 were performed in 20 pts, mean cumulative individual RAD dose was 334 mg, there was no association between Cmin of RAD and TTP or OS. On ITT, median TTPcomb was 2.0 mo and median OS was 9.0 mo. On PP, median TTP approached 3.8 mo (conventional RECIST) and median OS 9.7 mo. Using (m)RECIST, 5 pts. achieved PR within the first 8 wks, and this was accompanied by a significant VEGF plasma decrease (median of -65%), on (c)RECIST best response seen was SD. Conclusions: Combination Tx of RAD001 and bevazicumab is tolerated acceptably. TTP and OS in our 1°/2°-line HCC patients on Tx is comparable to sorafenib monotherapy in the SHARP trial (1° line only).
Predictive factors for pathologic complete response (pCR) to trastuzumab (T)-based neoadjuvant chemotherapy in HER2+ breast cancer (BC) women treated in the National Cancer Institute (NCI) of Mexico.
Authors: Erika Sifuentes, Yanin Chavarri Guerra, F. Berenice Baez-Revueltas, Enrique Soto-Perez-de-Celis, Fernando Lara-Medina, Santiago Ruano, Cynthia Mayte Villarreal-Garza
Journal: Journal of Clinical Oncology (2013)

634 Background: Neoadjuvant treatment identifies subgroups of patients (pts) with different prognosis. In HER2+ BC, some tumors have been reported to be more sensitive to anti-HER2 therapy than others. We conducted an exploratory analysis in HER2+ BC women who received T-based neoadjuvant chemotherapy. Methods: Clinico-pathologic data from HER2+ BC pts who received neoadjuvant chemotherapy and T between January 2007 and May 2012 at the NCI were identified. Estrogen receptor (ER), progesterone receptor (PR) and HER2 expression were determined by immunohistochemistry and/or FISH. pCR was defined as complete absence of invasive tumor in breast and axillary nodes. Proportion differences were tested using the Chi-square test. A generalized linear model was used for multivariate analysis. Results: 243 pts received T-based neoadjuvant chemotherapy for localized HER2+ BC tumors. Median age was 49 (26-72) years. 96% had positive axillary nodes at diagnosis and median tumor size was 5.5 (1.5-20) cm. 49.4% had hormone receptor (HR) + (ER+ and/or PR+) and 50.6% HR negative (ER- and PR-) tumors. 63.4% pts achieved pCR. HR negative tumors reached significantly higher pCR rates than HR + tumors (69.9% vs. 56.7%, p=0.034). Pts with inflammatory BC (n=27) had a trend to achieve pCR less frequently than the non-inflammatory tumors (48.1% vs. 65.3%). Those who received taxane-anthracyline sequence chemotherapy (n=20) achieved pCR in 70% of the cases vs. 62.8% with anthracycline-taxane sequence. Differences among other variables (age, tumor size, nodes and HER2 positivity ++/+++) were not significant. Variables that positively influenced pCR were HR negative status (p=0.015), non-inflammatory BC (p=0.082) and chemotherapy sequence (p=0.086). Conclusions: HR negative HER2+ BC tumors were associated with higher pCR, consistent with neoadjuvant trial reports. Preclinical data suggest bi-directional crosstalk between HER2 and ER pathways, which might influence anti-HER2 agents and chemotherapy sensitivity for tumors co-expressing both receptors. New strategies are needed to overcome resistance for HER2+ HR+ BC tumors.
Prognostic significance of leukopenia at the time of diagnosis in acute myeloid leukemia (AML)
Authors: M. L. Arellano, E. Winton, L. Pan, L. Souza, S. Sunay, L. Lima, M. McLemore, L. T. Heffner, A. Langston, H. J. Khoury
Journal: Journal of Clinical Oncology (2009)

7070 Background: In contrast to the poor prognosis associated with hyperleukocytosis, the prognostic significance of leukopenia at the time of diagnosis of AML is unknown. Methods: Single institution retrospective analysis of 225 consecutive, newly diagnosed AML patients (pts), homogeneously treated between July 1996 and February 2005; and divided into 2 groups based on presenting WBC: &lt; 2,000/uL (30) and &gt; 2,000/uL (195). Simultaneously obtained peripheral blood and marrow blasts were analyzed for cell surface expression of CD34, cKit, CXCR4, PCAM, VLA-2, VLA-3, VLA-4, VLA-5, and FLT3 using flow cytometry. Results: Patients’ characteristics (gender, secondary vs. de novo, and cytogenetic [CTG] risk) were comparable between the 2 groups. Leukopenic AML pts were older (median 56 vs. 53 years, p = 0.02), and had lower induction complete remission [CR] rates: 63% vs. 81% (p = 0.03) by univariate analysis. Induction mortality was 0% for leukopenic and 5% for non-leukopenic pts. In primary refractory pts, median survival was longer for leukopenic (11) vs. non-leukopenic (34) pts: 137 vs. 81 d (p = 0.026). Median follow-up was 22 mos. Event-free (EFS), disease-free (DFS), and overall survivals (OS) were lower in the leukopenic group: 12 vs. 14; 14 vs. 17; and 17 vs. 19 mos, respectively; but did not reach statistical significance. By multivariate analysis, age (p &lt; 0.0001) and CTG risk group (p &lt; 0.0001) were independent predictors of OS, while CTG risk group predicted RFS (p &lt; 0.0001). The level of expression of cell surface adhesion molecules on blood and marrow blasts was comparable for the 2 groups. Conclusions: AML pts presenting with leukopenia have comparable outcomes to those presenting with normal or high WBC despite a lower likelihood of achieving remission. Leukopenic AML did not have over-expression of cell surface adhesion molecules. No significant financial relationships to disclose.
Outcomes for patients with advanced N3 penile cancer undergoing flap reconstruction and adjuvant chemo/radiotherapy.
Authors: Asif Muneer, Findlay MacAskill, Michelle Christodoulidou, Clare Akers, Ash Mosahebi, Ibby Younis, Raj Nigam, Peter Malone
Journal: Journal of Clinical Oncology (2017)

419 Background: Patients presenting with advanced penile cancer with significant inguinal disease requiring extensive resection. Reconstruction is required to cover the defect and protect underlying vascular structures when undergoingl adjuvant treatment. Often the performance status or the extent of the disease makes neoadjuvant chemo/radiotherapy difficult. Although this group of patients undoubtedly have a poor prognosis, palliative resection reduces the tumour burden and allows improved wound management and quality of life. The aim of this study was to present the techniques and report the outcomes for patients with N3 disease undergoing flap reconstruction. Methods: Medical records were reviewed for penile cancer patients with fixed inguinal nodal disease either at presentation or recurrence. Resection was performed by a team comprising urological and plastic surgeons. Cancer specific survival and the impact of adjuvant chemo/radiotherapy was recorded. Results: Seventeen patients were included; mean age 62 (range 37–85) years. Nine (53%) patients had a first presentation with penile cancer and advanced nodal disease, with 8 (47%) presenting with inguinal disease recurrence. The majority (n = 13) underwent a vertical rectus abdominis musculocutaneous (VRAM) flap. Of these, 3 required femoral vein reconstruction. Where defects were smaller, a tensor fascia latae (n = 2) or a scrotal advancement flap was used (n = 1). The average length of stay was 23 days (10-45 days) regardless of type of flap. Ten patients had adjuvant radiotherapy, 5 underwent neoadjuvant chemotherapy with a 4 undergoing adjuvant chemotherapy. The disease specific survival was 595 days (range 24-3881). Complications were related to wound healing and managed conservatively. Post operative lower limb lymphoedema occurred in the majority of patients. There were no flap failures and all but one patient was discharged home. Conclusions: Aggressive surgical management for patients with extensive nodal disease and flap reconstruction is feasible. This aids wound management and improves the quality of life for patients. Survival rates can extend to over 12 months following adjuvant treatment.
RNA profiling of neuroendocrine tumors (NETs) to define new targets and mechanisms of progression.
Authors: Namrata Vijayvergia, Suraj Peri, Karthik Devarajan, Jianming Pei, Yulan Gong, Steven J. Cohen, Igor A. Astsaturov, Paul F. Engstrom
Journal: Journal of Clinical Oncology (2017)

302 Background: NETs lack mutations in the “classical” signaling pathways but share mutations in regulators of gene expression (Jiao; 2011). We compared gene expression in PD &amp; WD NETs to identify novel targets and biomarkers of differentiation. Methods: High quality RNA, extracted from paraffin blocks of deidentified NETs under an IRB-approved protocol, was profiled using a 770 gene panel (nCounter PanCancer pathway, Nanostring Technologies). The resulting data was used to identify the differentially expressed genes between PD and WD NETs using limma software (Ritchie; 2015). Gene Set Enrichment Analysis (Subramanian; 2005) identified differential pathway enrichment by calculating a Normalized Enrichment Score (NES). Results: Analysis of 16 PD and 23 WD NET samples identified 154 genes as extreme outliers ( &gt; 2 fold up/downregulation between the subtypes). Compared to WD NETS, drug targets of interest overexpressed in PD NETs were histone lysine methyltransferase EZH2, and a cell cycle regulator CHEK1 (6.5x and 8.1x, respectively, p &lt; 0.001). In contrast, serine/threonine protein kinase PAK 3 was upregulated in WD (10.6x, p &lt; 0.001). These and other biomarkers will be further validated by immunolabeling of tissue sections. We also found differential enrichment of canonical pathways in PD versus WD NETs (table). Conclusions: Extreme outlier transcripts identified in PD &amp; WD NETs support investigation of inhibitors of EZH2 (e.g. EPZ6438) and CHEK1 (e.g. LY2606368) in PD and PAK3(e.g. FRAX597) in WD NETs. Genes involved in cell cycle regulation and DNA repair in PD NETs and calcium / G protein coupled receptor signaling in WD NET account for biological differences between the 2 molecular subtypes and warrant future investigation as classifiers for NETs. Our findings provide mechanistic insights into the biology of NET and targets for therapy with direct clinical implications.[Table: see text]
Ipilimumab-induced hypophysitis in melanoma patients.
Authors: Typhanie CarrÃ©, Caroline Gaudy-Marqueste, Frédérique Albarel, Sandrine Monestier, Stéphanie Mallet, Thierry Brue, Marie-Aleth Richard, Jean Jacques Grob
Journal: Journal of Clinical Oncology (2012)

8568 Background: Ipilimumab (Ipi) is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigene-4 (CTLA-4) recently approved for the treatment of metastatic melanoma (MM) and currently under investigation in the adjuvant setting. Methods: Retrospective analysis of patients treated with ipi between June 2006 and September 2011 in our department in Marseille. As some patients are still blinded in trials, the exact number of patient under ipi is unknown. We present a minimal percentage (&gt;%) assuming that the 120 patients received ipi. Results: A total of 120 patients were treated: 76 stages IV MM, from which 16 in the BMS clinical trials (CA184-022, -024, and-025 and MDX 010-20) and 44 stages III MM (in the BMS CA184-029 trial). Stage IV MM were administered 0.3, 3 or 10mg/kg IV dosage, while stages III MM were randomly assigned to receive 10 mg/ kg or placebo (1:1 ratio). Hypophysitis was diagnosed in 12 patients (&gt;10%): 2/76 patients with stage IV MM (&gt;2. 6 %) and 10/44 patients with stage III MM (&gt;22.7). Diagnosis was performed at the 1 st , 3 rd and 4 th administration in respectively 2 (1.6%), 6 (50%) and 4 patients (33.3%). Clinical symptoms included headaches (n=11; 91.6%), asthenia (n=7; 58.3%) and decreased libido (n=2; 1.6%). Adrenal, thyroidal and gonadal axis were affected in respectively 6 (50%), 9 (75%) and 7 patients (58.3%). MRI changes were observed in 7 patients (58.3%): pituitary swelling in 5 patients (41.6%) and heterogeneous enhancement in 4 patients (33.3%) including 2 patients with normal biology. Corticosteroids supplementation was required in 11 patients and thyroidian supplementation in 4 patients. Clinical symptoms regressed within one week in 8 patients (66.6%). Conclusions: Ipi-induced hypophysitis is detectable only if clinicians are aware of these unspecific signs. Only MRI can make diagnosis in some patients without clinical and/or biological signs. Our data suggest that it develops especially for 10mg/kg dosage, after the third administration, and that the rate could be higher in patients with a normal immune system (adjuvant treatment), than in metastatic ones. Hormonal supplementation usually controls the disease.