tbuckley/cabot-search huggingface dataset:
Activity of sorafenib in radiation-associated breast angiosarcomas harboring MYC and FLT4 amplifications.
Authors: Sandra P. D'Angelo, Cristina R. Antonescu, Mary Louise Keohan, Richard D. Carvajal, Mark Andrew Dickson, Mrinal M. Gounder, Nicole H. Moraco, Samuel Singer, Gary K. Schwartz, William D. Tap
Journal: Journal of Clinical Oncology (2012)

10019 Background: Angiosarcomas (ASs) are rare, aggressive vascular malignancies of endothelial cell differentiation which arise de novo or secondary to radiation therapy (RAS.) A subset of patients(pts) with AS harbor mutations in KDR (VEGFR-2) or overexpression of MYC and/or FLT4(VEGFR-3). MYC &amp; FLT4 gene amplifications occur almost exclusively in RAS. These alterations provide a rationale for investigating agents that target angiogenesis in RAS. In a phase II trial of sorafenib, AS pts had a partial response (PR) of 14%; targeting the appropriate pt population may be essential. We hypothesize that co-amplification of MYC &amp; FLT4 may be predictive of response to sorafenib. Methods: Using our institutional sarcoma database &amp; data query system, we identified AS patients treated with sorafenib at Memorial Sloan-Kettering Cancer Center between 1992-2011. Molecular analysis performed on available tissue. With IRB approval, clinical information was collected. Results: We identified 10 women with RAS that received sorafenib. Average age 68 (range 51-84.) 7 pts had distant metastatic disease. Median lines of systemic therapy prior to sorafenib: 2 (range 1-4.) Sorafenib was first line in 60% of pts, administered at 400mg daily and adjusted for toxicity. Best responses included: complete response (CR) 2/9(22%), PR 1/9(11%), stable disease (SD) 5/9(56%) range 5-23m, progressive disease 1/9(11%) for a clinical benefit rate of (CR+PR+SD) 89%. Responses were seen in patients with lung metastases (n=2) and locally advanced disease (n=1) and were durable for 17, 42 and 26 months. Median duration on therapy was 15 months (range 0-42 months.) 7 pts underwent molecular analysis: co-amplification of MYC &amp; FLT4 3 pts (30%); MYC amplification 4 pts (40%); KDR mutation 0 patients. Of the 3 responders, MYC &amp; FLT4 co-amplification were observed in 2 patients and not evaluated in one. Conclusions: Sorafenib is active against RAS of the breast. In this small series, complete and partial responses were seen in patients with co-amplification of MYC &amp; FLT4. This observation requires further study. Performing molecular studies on all AS pts will help define the pathophysiology of this deadly disease to guide rationale clinical trials.
Milk and other dairy foods in relation to prostate cancer progression: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE).
Authors: David Tat, Erin Van Blarigan, Stacey A. Kenfield, Jenny Broering, Janet E. Cowan, Peter Carroll, June M. Chan
Journal: Journal of Clinical Oncology (2017)

168 Background: Recent research suggests a positive relationship between intake of high-fat dairy, particularly whole milk, and prostate cancer (PC) mortality. However, data are limited in men after PC diagnosis. Methods: We conducted a prospective cohort study among 1336 men with non-metastatic PC in CaPSURE. The men answered a food frequency questionnaire (FFQ) in 2004-2005 (median time from diagnosis to the FFQ: 2 y) and were followed for PC progression until April 2016. PC progression was defined as: prostate cancer death, bone metastasis from PC, biochemical recurrence, or secondary treatment. Multivariate Cox Proportional Hazards regression was used to calculate hazards ratios (HR) and 95% confidence intervals (CI) for associations between total, whole fat, and low-fat milk; total, high-fat, and low-fat dairy; and specific dairy items and PC progression. We adjusted for time from diagnosis to FFQ, calories, age at diagnosis, CAPRA score, smoking, BMI, walking pace, and primary PC treatment. Results: 314 events were observed (mean follow-up: 7.2 y). Whole milk was associated with an increased risk of PC progression when adjusting for age, calories, and time since diagnosis (HR ≥1 vs. &lt;1 serving/wk: 1.37; 95% CI: 1.03, 1.84; p-value: 0.03). This association was slightly attenuated, and not statistically significant, when adjusting for clinical and other lifestyle factors (HR: 1.27; 95% CI: 0.91, 1.77; p-value: 0.15). High-fat dairy intake also appeared associated with an increased risk of PC progression, but the association was not statistically significant (adjusted HR ≥4 vs. &lt;1 servings/day: 1.40; 95% CI: 0.92, 2.13; p-trend: 0.18). Post-diagnostic intakes of low-fat milk and other dairy foods were not associated with PC progression. Conclusions: Post-diagnostic intake of milk and other dairy foods was not associated with PC progression. Research in populations with greater intake of whole milk is warranted to further investigate whether post-diagnostic whole milk intake increases risk of PC progression. Funding: This work was funded by the DOD Prostate Cancer Research Program (W81XWH-13-2-0074) and the NIH (K07CA197077).
<i>PTEN</i> germline mutations in patients first tested for other hereditary cancer syndromes: Would use of risk assessment tools have reduced health care costs?
Authors: Jessica Mester, Rebekah Moore, Charis Eng
Journal: Journal of Clinical Oncology (2012)

1516 Background: PTEN Hamartoma Tumor Syndrome (PHTS) includes patients with Cowden (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) with germline PTEN mutation. Breast, colon, endometrial cancer and GI polyposis are associated, creating overlap with Hereditary Breast and Ovarian Cancer (HBOC), Lynch (LS) and adenomatous polyposis syndromes (APS). We reviewed our PHTS patient series to find how often testing criteria for these syndromes were met or testing was pursued before PTEN. Methods: Patients were prospectively recruited by relaxed International Cowden Consortium criteria or presence of known germline PTEN mutation; mutations were identified by mutation scanning or MLPA analysis and confirmed by sequencing or quantitative PCR, respectively. Families were excluded if diagnosed with CS or BRRS before 1998, family history was unavailable, or proband was &lt;18 yrs. Pedigree, genetic testing reports, and medical records were reviewed to determine if patients met HBOC testing criteria, Amsterdam II or Bethesda 2004 criteria, or had adenomatous polyps. Risk assessment was conducted for BRCA1/2 via the BRCAPRO, Myriad II, and Penn II models; for MLH1/MSH2/MSH6 via the PREMM1,2,6 and MMRPro models; and for PTEN via the Cleveland Clinic (CC) PTEN Risk Calculator. Results: 115 PTEN mutation-positive adult probands were identified among 3,405 patients. 53 (46.1%) met testing criteria for HBOC or LS and 34 (29.6%) underwent previous testing for HBOC, LS or APS. Average risk for BRCA1/2 and MLH1/MSH2/MSH6 mutations in tested patients were 7.5-16.9% and 33.1-41.4%, respectively; whereas PTEN mutation risks were 35.9% and 79.7%. No patient tested for APS (average PTEN mutation risk 73%) had &gt;5 adenomas. An estimated $89,700 was spent on negative analyses for HBOC, LS and APS among patients ultimately found to have germline PTEN mutations. Conclusions: PHTS should be part of the differential diagnosis for patients referred for question of HBOC, LS or APS. Pathology review is key for patients with polyposis. Using the CC PTEN risk calculator enables clinicians to understand when PTEN mutation risk is high, allowing testing to proceed in a step-wise and cost-saving manner.
Nab-paclitaxel salvage chemotherapy for metastatic ocular melanoma.
Authors: Alexander David Guminski, Adrian Lee, Sumit Lumba, Richard Maher
Journal: Journal of Clinical Oncology (2012)

e19042 Background: Metastatic ocular melanoma is an incurable malignancy characterised by liver predominant involvement. Conventional systemic chemotherapy using drugs such as fotemustine or dacarbizine have low response rates. In liver only disease hepatic arterial infusion of fotemustine has reported a higher response rate. Methods: We report four prospectively followed patients who all received salvage treatment with Nab-paclitaxel after previous intra-arterial fotemustine for metasatic ocular melanoma. Results: One patient who did not respond to to intra-arterial chemotherapy had a radiological response to Nab-paclitaxel with a duration of six months (5 cycles of treatment) with subsequent progression inliver and CNS. Another patient had rapidly progressing liver, peritoneal and nodal metastases with elevated bilirubin. He received dose reduced Nab-paclitaxel sith significant biochemical, radiological and functional improvement. He continues on Nab-paclitaxel in ongoing partial remission and remains clinically improved after six months. Two patients with similarly advanced disease, including one with abnormal bilirubin, did not respond. Subsequent treatments for the three patients progressing after Nab-paclitaxel have been SIR-Spheres followed by Ipilumumab, Ipilumumab and palliation respectively. Typical side effects of Nab-paclitaxel have occurred including alopecia, fatigue, peripheral neuropathy and neutropenia. Conclusions: In summary we have seen clinically useful responses in two of four patients treated. We continue to recruit further patients to better understand the role of Nab-paclitaxel as salvage chemotherapy for metastatic ocular melanoma.
Nanobody-based PET/CT imaging of HER2 expression in breast carcinoma: Phase I results and potential to assess tumor heterogeneity.
Authors: Marleen Keyaerts, Catarina Xavier, Johannes Heemskerk, Nick Devoogdt, Hendrik Everaert, Thierry Gevaert, Marian Vanhoeij, Francois P. Duhoux, Philippe Simon, Denis C. C. Schallier, Christel Fontaine, Ilse Vaneycken, Chris Vanhove, Jacques De Greve, Jan Lamote, Vicky Caveliers, Tony Lahoutte
Journal: Journal of Clinical Oncology (2015)

e11600 Background: A first-in-human study of 68GaNOTA-Anti-HER2 Nanobody for PET/CT imaging of HER2 expression in breast carcinoma has been completed. Nanobodies are the smallest antigen-binding antibody-fragments derived from heavy-chain-only antibodies. They offer ideal characteristics for imaging: fast blood clearance, high stability, easy labeling. Objectives: Primary: safety, human biodistribution and dosimetry. Secondary: tumor uptake in HER2-expressing lesions. Methods: Anti-HER2 nanobody was labeled with 68Ga via a NOTA derivative. In total, 20 female patients with primary or metastatic breast carcinoma (HER2 IHC 2+ or 3+) were included. Radioactive dose range was 53-174 MBq (average 107 MBq). Patients underwent 3 PET/CT scans (for dosimetry assessment) at 10, 60 and 90 min post administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 10 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Results: No related adverse events occurred. Blood clearance was fast, with 7.2 ± 2.0% of injected activity (%IA) remaining at 90 min. Tracer uptake was highest in liver (8.2 ± 3.1%IA) and kidneys (6.4 ± 1.3%IA). The effective dose was 0.043 mSv/MBq, resulting in on average 4.6 mSv per patient. SUVmean (mean standard uptake value) of lesions was between 1.8 and 7.3. Interestingly, two lesions ( > 4cm) showed a heterogeneous tracer uptake. In one, the pattern was not matched to FDG distribution, indicating it was not due to necrotic areas. In the second, heterogeneous expression was confirmed on IHC. Conclusions: 68Ga-HER2 PET/CT is a safe procedure with a radiation dose comparable to other PET tracers. Imaging at 90 min post tracer injection is advised. The wide range in SUVmean of lesions and the heterogeneous distribution in large lesions show potential for the in vivo assessment of HER2 expression levels and tumor heterogeneity, with potentially high impact on patient management. Clinical trial information: 012-001135-31.
Tumor infiltrative pattern predicts sites of recurrence after curative gastrectomy for gastric cancer.
Authors: Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2017)

38 Background: In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. Methods: The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. Results: Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. Conclusions: Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC.
Metabolic profiles of ketolysis and glycolysis in malignant gliomas: Possible predictors of response to ketogenic diet therapy.
Authors: Howard T. Chang, Lawrence Karl Olson, Kenneth A. Schwartz
Journal: Journal of Clinical Oncology (2013)

e13048 Background: The enzymatic differences in energy metabolism between normal brain tissues and malignant gliomas formed the basis for animal model studies that showed increased survival in mice with orthotopically transplanted glioblastoma multiforme (GBM) treated with energy restricted ketogenic diet (ERKD). To test the hypothesis that human brain tumors may also be sensitive to ERKD, we used immunohistochemistry reactions on formalin fixed paraffin embedded tumor samples to evaluate for the presence of enzymes important for the metabolism of ketones and glucose. Methods: Immunoreactivities were graded using a semi-quantitative scale based on the percentage of positive cells: low positive&lt;5% (LOW); intermediate (INT) 5-20%; and highly positive (HIGH) &gt;20%. Focal non-neoplastic “normal” brain tissue present within the specimens served as positive internal controls. Results: Succinyl CoA: 3-oxoacid CoA transferase (OXCT1) and 3-hydroxybutyrate dehydrogenase 1 (BDH1) are mitochondrial enzymes important for metabolizing beta hydroxy butyrate, the main ketone in blood. Both of these enzymes were either decreased or absent (INT or LOW) concordantly in 14 of the 17 (82%) GBMs, and in 1 of 6 (17%) anaplastic astrocytomas (AA). Two of the enzymes in the glycolytic pathway hexokinase-2 and pyruvate kinase M2 were concordantly LOW or INT in only 3 of the 17 GBMs that also were LOW or INT for both OXCT1 and BDH1. The remaining brain tumors were positive for at least one of these glycolytic enzymes. Mitochondrial enzymes were not globally deficient. The mitochondrial enzyme acetyl CoA transferase (ACAT1) was present in 9 of the 14 GBM specimens that were LOW or INT for the mitochondrial enzymes OXCT1 and BDH1. Conclusions: Our data showing that many, but not all, malignant gliomas lack ketolytic enzymes, support the rationale of ERKD as investigational treatment for patients with malignant gliomas. Moreover, we hypothesize that it is important to test individual tumor samples for the expression of these enzymes prior to ERKD, as patients with malignant gliomas that have diminished capacity to metabolize ketones likely may derive the most benefit from ERKD.
Evaluation of genes associated with undescended testes as predictors of TGCT susceptibility.
Authors: Ariela Marshall, Stephanie L. Ciosek, Saran Vardhanabhuti, Nandita Mitra, David J. Vaughn, Peter A. Kanetsky, Katharine Nathanson
Journal: Journal of Clinical Oncology (2012)

1539 Background: Testicular germ cell tumors (TGCTs) are highly heritable. Cryptorchidism (undescended testes; UDT) is a strong risk factor for TGCT, with increased risk to both the ipsilateral and contralateral testes. However, recent genome-wide association studies (GWAS) identifying genetic variants associated with TGCT susceptibility have not found differences in genotype carriage between TGCT patients with and without UDT. We investigated the role of potential risk variants for UDT as risk factors for TGCT. Methods: 1300 SNPs in and around 25 gene regions with published associations with UDT were evaluated in 474 TGCT cases (45 with UDT) and 919 controls. Genotype information was available from the Affymetrix Genome-Wide Human SNP Array 6.0. Statistical analysis was performed using PLINK, and statistical significance was assessed by Fisher's Exact test. Results: Comparing TGCT cases with and without UDT, variants in the region of four genes (EPHB2, ESR1, SEMA3C, TGFBR3) were suggestively associated with UDT. When TGCT cases with UDT were compared with unaffected controls, the associations all met the required level of significance (p &lt; 4 x 10 -5 ). Only variation at ESR1 approached significance (P=0.0004) when TGCT cases and unaffected controls were compared. Conclusions: We identified variants at three genetic loci - SEMA3C, TGFBR3 and EPHB2 - that were significantly associated with UDT, but not with TGCT. The association of variation in EPHB2 and SEMA3C with UDT are novel findings. While associated with UDT, variation at ESR1 is also potentially associated with TGCT risk. These data continue to suggest that genetic risk factors for UDT are largely independent of those for TGCT. Thus, screening for TGCT could be targeted in a UDT population to those with genetic risk factors. Further studies should be done to investigate the genetic link between UDT and TGCT.
The impact of neurocognitive function on health utility scores (HUS) in Stage 4 (S4) lung cancer patients (pts) with and without brain metastases (BrM).
Authors: Brandon C Tse, Vivian Tam, Tiffany Tse, Lin Lu, Michael Borean, Emily Tam, Catherine Labbé, Mark K. Doherty, Penelope Ann Bradbury, Natasha B. Leighl, M. Catherine Brown, Wei Xu, Doris Howell, Geoffrey Liu, Grainne O'Kane
Journal: Journal of Clinical Oncology (2017)

225 Background: As targeted therapies for S4LC pts have improved survival, the impact of health-related quality of life (HRQoL) in these pts grows in importance. In pts with BrM, loss of NCF may affect HRQoL significantly. We evaluated the relationship between NCF and HUS as a measure of HRQoL in S4LC pts. Methods: Self-reported HUS data from EQ5D-3L were obtained cross-sectionally from S4LC pts with (BrM) or without BrM (non-BrM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B). NCF scores were correlated with HUS (Pearson Coefficient, R). Results: BrM (n = 54) and non-BrM (n = 40) patients had similar demographics- overall median age was 61 (range 33-89) years; 59% were female; 45% had EGFR/ALK alterations; BrM pts were treated with whole brain (n = 20), stereotactic radiation (n = 19), both (n = 6), or sole use of systemic agents (n = 6); 3 were observed; 7 had BrM resection. Overall HUS were similar between BrM and non-BrM groups (mean HUS (mHUS): 0.77 vs. 0.78; p = 0.86). However, pts with stable brain disease had higher HUS than those with progressive brain disease (mHUS: 0.80 (n = 36) vs 0.69 (n = 17); p = 0.045). There was a trend towards lower HUS in symptomatic vs. asymptomatic BrM (mHUS: 0.70 (n = 10) vs. 0.78 (n = 43); p = 0.07). Multiple correlations between NCF scores and HUS were found. HLVT-Total Recall correlated with HUS in BrM but not non-BrM (R=0.35, p = 0.01; vs. non- R=0.04, p = 0.84 respectively) as did the HLVT-Recognition (BrM: R=0.32, p = 0.03 vs. non-BrM: R=0.13, p = 0.51). In contrast, TMT-A/B were associated with HUS in both BrM (p = 0.03, 0.06) and non-BrM pts (p = 0.001, 0.03). COWAT was associated with HUS only when all pts were analyzed together (p = 0.04). Conclusions: In S4LC pts, HUS were correlated with multiple measures of NCF. The impact of uncontrolled brain disease and poor NCF on HUS demonstrates that this measure has clinical utility, with important HRQoL implications as metastatic lung cancer pts live longer.
ESTUDIO DESCRIPTIVO DE LAS COMPLICACIONES DE LAS ESOFAGOGASTRODUODENOSCOPIAS Y COLONOSCOPIAS EN PACIENTES AMBULANTES EN EL HOSPITAL UNIVERSITARIO DE NUESTRA SEÑORA DE LA CANDELARIA (HUNSC): 1416 EXPLORACIONES
Authors: JA Márquez Rodríguez, H Salata Schusterman, CA Tardillo Marín, I Redondo Zaera, X Arguiñarena Ruíz, E Rodríguez González, L Díaz Hernández, D García, P Bennemann, M Vela González, E Borja Gutiérrez, A Amorós Tenorio, L Navazo Bermejo, A Arencibia, P Borque Barrera, M San Juan Acosta
Journal: Endoscopy (2015)

Introducción: La endoscopia gastrointestinal es una técnica altamente extendida por su importancia diagnóstico-terapéutica y como técnica invasiva no está exenta de complicaciones.
Unexpected Evidence That Dimethylsulphoxide (DMSO) Upregulates Expression of CXCR4 on Hematopoietic Stem/Progenitor Cells (HSPC), Increases Their Responsiveness to an SDF-1 Gradient and Enhances Homing to Bone Marrow.
Authors: Marcin Majka, Danuta Jarocha, Marcin Wysoczynski, Duygu Sag, Ewa Zuba-Surma, Jacek Kijowski, Jolanta Gozdzik, Mariusz Z. Ratajczak
Journal: Blood (2005)