tbuckley/cabot-search huggingface dataset:
Immune Response to HPV16 E6 and E7 Proteins and Patient Outcomes in Head and Neck Cancer
Authors: Heather H. Nelson, Michael Pawlita, Dominique S. Michaud, Michael McClean, Scott M. Langevin, Melissa N. Eliot, Karl T. Kelsey
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Pathology-based measures of human papillomavirus (HPV) status are routinely obtained in the care of head and neck cancer and are clearly associated with patient outcome for cancers of the oropharynx. However, it is unclear if HPV status is of high value for cancers of the larynx and oral cavity. In addition, it is possible to assess HPV infection using serology-based methods; however, the suitability of this pathology-independent measure for predicting patient outcome in head and neck cancer is unknown. <h3>Objective</h3> To investigate whether immunologic response to HPV16 is associated with patient survival across anatomic sites, independent of smoking and drinking history. <h3>Design, Setting, and Participants</h3> This was a population-based study of 1054 patients with head and neck cancer in the greater Boston, Massachusetts, area (1999-2003, 2006-2011). <h3>Main Outcomes and Measures</h3> All-cause survival in relation to HPV16 E6 and E7 seropositivity. <h3>Results</h3> The 1054 patients reflected the demographics of those treated in this timeframe (75% male; mean age, 59 years). Seropositivity was very strongly associated with improved survival overall (hazard ratio HR], 0.33; 95% CI, 0.24-0.45;<i>P</i> &lt; .001), with no evidence that the magnitude of immune response, as assessed by titer levels, effected outcome. Seropositivity was associated with improved patient survival across all head and neck cancer sites: HR for oropharynx cancer<sub>,</sub>0.26; 95% CI, 0.18-0.39; for oral cavity cancer, 0.45; 95% CI, 0.18-0.80; and for larynx cancer, 0.29; 95% CI, 0.10-0.85. In addition, the associations with seropositivity were similar across smoking and/or drinking exposure groups: HRfor low exposure, 0.52; 95% CI, 0.20-1.36; for moderate exposure<sub>, </sub>0.42; 95% CI, 0.25-0.70; for heavy exposure, 0.51; 95% CI, 0.36-0.73. In a subset of 162 patients with both HPV serology and p16 immunohistochemical (IHC) measures available, both measures were similarly associated with survival in the oropharynx (HR for serology, 0.16; 95% CI, 0.03-0.47; for p16 measures, 0.16; 95% CI, 0.03-0.46), whereas only serology was associated with outcome when considering all head and neck cancer cases (HR for serology,0.49; 95% CI, 0.23-1.04; for p16, 0.65; 95% CI, 0.30-1.42). <h3>Conclusions and Relevance</h3> Collectively, these data suggest that a positive serologic response to HPV16 oncoproteins may be the best approach to assess HPV-disease for clinical outcome because it is associated with survival for all types of disease and is a marker that is not dependent on pathology material.
Suppression of Myocardial 18F-FDG Uptake Through Prolonged High-Fat, High-Protein, and Very-Low-Carbohydrate Diet Before FDG-PET/CT for Evaluation of Patients With Suspected Cardiac Sarcoidosis
Authors: Yang Lu, Christopher Grant, Karen Xie, Nadera J. Sweiss
Journal: Clinical Nuclear Medicine (2016)

A major obstacle in using FDG-PET/CT to diagnose cardiac sarcoidosis (CS) is the unpredictable physiological myocardial FDG uptake. We hypothesized that a prolonged 72-hour pretest high-fat, high-protein, and very-low-carbohydrate (HFHPVLC) diet preparation could suppress physiologic myocardial uptake of FDG and thus help to identify active CS.This retrospective study included 215 FDG-PET/CT tests from 207 patients with biopsy-proven sarcoidosis and clinical suspicion for CS between July 2014 and December 2015. The patients were classified into 2 groups. Group 1 included 12 FDG-PET/CT scans from 12 patients who had 24-hour or less pretest HFHPVLC diet preparation. Group 2 included 203 FDG-PET/CT scans with 72-hour HFHPVLC diet before FDG-PET/CT. Nonadherent patients and patients with cancer were excluded. Cardiac FDG uptake was classified as: "none" and "ringlike diffuse at base" (negative for CS), "focal" (positive for CS), and "diffuse" (indeterminate for CS). FDG uptake in myocardial lesions was measured as SUVmax and compared with SUVmean of mediastinal blood pool. Final diagnoses were made with consensus among physicians in view of all available clinical information including cardiac MRI and echocardiogram results.In group 1, there were 1 (1/12, 8.3%) positive, 5 (5/12, 41.7%) indeterminate, and 6 (6/12, 50.0%) negative for CS. In group 2, 10 patients were excluded (6 patients because of noncompliance with diet, 2 patients with concurrent diagnosis of cancers, 2 patients because of insulin and steroid use within 4 hours before PET/CT); the remaining 185 patients had 193 FDG PET/CT tests (8 repeats), of which there were 19 (19/193, 9.8%) positive, 7 indeterminate (7/193, 3.6%), and 167 (167/193, 86.7.%) negative for CS. The SUVmax of PET-positive myocardial lesions ranges from 3.4 to 12.5, whereas mediastinal blood pool SUVmean ranges from 1.1 to 3.6. The indeterminate rate was significantly lower in group 2 compared with group 1 (P < 0.001).The prolonged 72-hour HFHPVLC diet preparation protocol successfully suppressed physiological myocardial FDG uptake and may permit a more sensitive and accurate method of diagnosing active CS using FDG PET/CT.
Creatinine clearance and serum albumin as factors for encephalopathy with ambulatory 14-day infusional ifosfamide for advanced liposarcomas.
Authors: S. M. Alam, C. Benson, R. L. Jones, E. Thanopoulou, S. Mitchell, O. Al-Muderis, A. Dunlop, C. Propert-Lewis, I. R. Judson, M. R. Scurr
Journal: Journal of Clinical Oncology (2011)

10087 Background: Ifosfamide (IFO) has recognised activity in soft tissue sarcomas (STS). There is preliminary evidence for improved cytotoxicity utilising a prolonged 14 day infusional regimen of IFO (PIR) compared with the standard 3-day regimen. Since September 2008 the PIR has been used at the Royal Marsden Hospital, principally for advanced de-differentiated liposarcomas (D-LPS) and shows activity. For many pts PIR is well tolerated, however, we noted serious neurotoxicity and this retrospective review was undertaken to more accurately determine the toxicity profile and define potential predictors of toxicity. Methods: A retrospective analysis of the Royal Marsden Hospital sarcoma database was performed to identify all pts who received PIR. IFO was given via central access through an ambulatory pump at 1G/m2/day with mesna, for 14 days every 4 wks. Oral sodium bicarbonate was used to maintain alkaline urine, oral mesna for haematuria and thiamine for symptoms of encephalopathy. Baseline characteristics and toxicities were graded according to CTCAE-4. Baseline serum creatinine (sCr), creatinine clearance (CrCl), albumin, LDH, gender and PS were evaluated as predictors of toxicity. Results: 22 pts were treated with PIR; median age 56yrs (29-76), M:F=11:11, 17 with advanced D-LPS. At baseline: PS (0=1, 1=17, 2=4), sCR (Gr 0=19), CrCl (Gr 0=2, Gr1=11, Gr2=6), albumin (Gr0=14, Gr3=3). Median no cycles 2 (1-8) with 10 pts receiving only 1 cycle (5 stopping due to neurotoxicity). Ten patients developed encephalopathy (Gr3/4=6), 9 in cycle 1. Toxicity was otherwise tolerable, with Gr 2-3 nausea (15 pts) and vomiting (9 pts) and only 2 Gr 3 episodes of myelotoxicity for all cycles. Significant predictors of encephalopathy were decreased CrCl and low albumin. Conclusions: Prolonged infusional ifosfamide is well tolerated for most pts; however a significant number develop neurotoxicity. Baseline CrCl and albumin have both been shown to predict those most at risk. This regimen has significant clinical potential and this study allows early identification of those who may need dose reduction from the outset. These predictors will be incorporated into a phase II study of this regimen.
A multicenter randomized phase III trial of nonpegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide (MC) versus liposome-encapsulated doxorubicin citrate plus vinorelbine (MV) as first-line treatment in locally advanced (LABC) or metastatic breast cancer (MBC).
Authors: V. Lorusso, F. Giotta, R. Bordonaro, E. Maiello, S. Del Prete, V. Gebbia, G. Filippelli, S. Pisconti, S. Cinieri, S. Romito, F. Riccardi, G. Cairo, V. E. Chiuri, M. Ciccarese, R. Forcignano, L. Petrucelli, V. Saracino, G. Colucci
Journal: Journal of Clinical Oncology (2011)

1041 Background: The combination MC demonstrated to be effective and safe in MBC. Vinorelbine, in combination with anthracyclines, is an active drug as well. This is a multicenter randomized phase III trial to assess the efficacy and tolerability of the regimen MC versus MV. Methods: Patients (pts) must have LABC or MBC, PS (ECOG≤ 2) and measurable disease. Previous anthracyclines, as adjuvant, or endocrine therapy were allowed. Treatment A: M 60 mg/m2 plus C 600 mg/m2 on day1 of a 21 day cycle; treatment B: M 50 mg/m2 plus V 25 mg/m2 i.v. on day 1 and V 60 mg/m2 orally on day 8 on a 21 day cycle. Primary endpoint was PFS, secondary endpoints were ORR, safety and OS. Results: Between July 2006 and December 2010, 253 women were enrolled, 228 are currently evaluable for efficacy and safety. Patient characteristics: arm A 126 pts, median age 59 (range 37−71), ER status +/−/unk 77/18/5%, Her-2 status +/−/unk 7/81/12%, PS 0/1/2 70/25/5%, prior treatment with anthracyclines 34 pts (27%), dominant site of disease visceral 88 pts (71%). Arm B 127 pts, median age 58 (range 25−71), ER status +/−/unk 74/21/5%, Her−2 status +/−/unk 7/84/9%, PS 0/1/2 63/30/7%, prior treatment with anthracyclines 49 pts (39%), dominant site of disease visceral 92 pts (73%). Pts received a median of 6 cycles (range 2−10) of therapy. Median follow-up time was 66 weeks. Overall response rate was 53/116 (45.7% [95% CI, 36.5−54.7%]) for arm A and 51/112 (45.5% [95% CI, 36.3−54.7%]) for arm B respectively. Median PFS was 41 (95% CI, 32−51) and 34 (95% CI, 26−39) weeks respectively for arm A and arm B (p=0.0234). OS data are still not mature. With regard to toxicity, MV showed a slight increase of haematological and non hematological toxicity. No clinical signs of cardiotoxicity evaluated by echocardiogram were observed even in pts pretreated with anthracyclines. One patient in arm B died for sepsis, due to drug-related pancytopenia. Conclusions: Although MC and MV showed similar response rate, a significant difference in PFS was observed in favour of MC. The combination MC remains as an unbeaten “standard” in first line treatment of MBC.
Detection of circulating miRNAs in serum from patients with breast cancer and their association with the presence of metastatic disease.
Authors: E. van Schooneveld, M. Wouters, I. Van der Auwera, D. Peeters, P. Huget, P. A. van Dam, P. B. Vermeulen, S. J. Van Laere, L. Y. Dirix
Journal: Journal of Clinical Oncology (2011)

10506 Background: miRNAs are small non-coding RNAs involved in the regulation of gene expression. Dysregulation of miRNAs is associated with tumorigenesis. In this study we have evaluated the clinical utility of circulating miRNAs as biomarkers for the detection and staging of breast cancer. Methods: miRNAs were extracted from a set of 84 surgical tissue samples from breast cancer patients and 8 tissue samples from breast reductive surgery. 768 pre-amplified miRNAs were profiled using the TaqMan Low-Density arrays. After data normalization, principal component analysis (PCA) was used to investigate global differences in miRNA expression between cancerous and normal samples. Using fold-change analysis, the most discriminating miRNAs between both tissue types were selected to be analyzed on serum samples from 20 healthy volunteers and 75 patients with different stages of breast cancer (localized breast cancer (N=4), treated (N=55) and untreated (N=16) metastatic breast cancer). miRNAs were extracted and the selected miRNAs were analyzed in duplo using qRT-PCR. Results: PCA demonstrated major differences in miRNA expression between tissue samples from breast cancer patients and tissue samples from breast reductive surgery (p<0.0001). Generally, miRNA expression in tumor samples is repressed when compared to healthy controls (p=0.045). The most discriminating miRNAs by fold-change (miR-215, miR-299-5p, miR-411, and miR-452) were selected for further analysis on serum samples. 3/4 miRNAs revealed a differential expression profile between serum samples from cancer patients and healthy controls (miR-411: p=0.004; miR-452: p=0.001 and miR-299-5P: p=0.001). For all these miRNAs, the greatest difference in expression was observed between healthy controls and untreated metastatic breast cancer patients. Conclusions: Our study provides a basis for the establishment of miRNAs as biomarkers for the detection and eventually staging of breast cancer through blood-borne testing. We identified a set of putative biomarkers of breast cancer and demonstrated that altered levels of these miRNAs in serum from breast cancer patients are associated with metastatic disease.
The effect of trastuzumab on pCR in locally advanced HER2-positive breast cancer.
Authors: S. M. Lavasani, K. I. Pritchard, A. Kiss, S. Verma, F. Wright, J. Boileau, M. E. Trudeau, G. J. Czarnota, R. A. Dent
Journal: Journal of Clinical Oncology (2011)

286 Background: Neoadjuvant therapy (NAT) is now standard of care for locally advanced breast cancer (LABC). Evidence shows that pathological complete response (pCR) predicts for disease free and overall survival. The pCR rates for LABC vary widely in the literature but prognosis still remains poor for this group of pts. Increases in pCR have been reported in clinical trials with the addition of trastuzumab (T) but these studies have predominantly included operable pts. The aim of this study was to evaluate whether the addition of T to NAT has improved the rates of pCR in HER2+ LABC pts at our center. Methods: Pts from the LABC prospective database at the Sunnybrook Odette Cancer Center in Toronto were included if they had confirmed HER2+ LABC [primary tumors greater than 5cm (T3) with skin or chest wall involvement (T4) or with matted axillary adenopathy (N2)]. Two cohorts of LABC pts, pre-T and post-T groups were compared for baseline characteristics and pCR. Chi square tests and p values were used for comparing proportions. Results: 43 pts were diagnosed between Jan 2002 to Dec 31, 2006 who had HER2+ breast cancer and received NAT without T (pre-T cohort). 17 HER2+ pts were diagnosed with LABC between Jan 1, 2007 to Dec 31, 2009 who received neoadjuvant T (post-T cohort). Baseline characteristics were similar in two cohorts (Table) except more pts in pre-T cohort received neoadjuvant hormonal therapy. The rate of pCR in the pre-T cohort was 9.3% and in the post-T cohort 29% (p value=0.02). Conclusions: The pCR rate dramatically improved in our LABC patients with the addition of T to NAT. The pCR rates still remain lower than in published clinical trials likely reflecting the more advanced nature of LABC in clinical practice. [Table: see text]
Epstein-Barr Virus Related Classical Hodgkin Lymphoma Reveals a Pro-Inflammatory RNA Expression Profile at Diagnosis
Authors: Priscilla Brito Silva, Juliana Monte Real, Ludmila Rodrigues Pinto Ferreira, Adriana M. Damasco Penna, Gustavo Henrique Esteves, Joao Garibaldi Junior, Fabio Nascimento Brito, Egyla Cavalcante, Otavio C. G. Baiocchi
Journal: Blood (2016)
Cerebrospinal Fluid Flow Cytometry in Acute Lymphoblastic Leukemia/Lymphoma: Is It Beneficial?.
Authors: Fuad El Rassi, Zahi Mitri, Leonard T Heffner, Amelia Langston, Edmund K. Waller, Elliott F. Winton, Morgan L. McLemore, Leon Bernal, Martha Arellano, H. Jean Khoury
Journal: Blood (2012)
Peripheral Neuropathy (PN) in Multiple Myeloma (MM) Responder Patients during Maintenance Therapy with Low-Intermittent Doses of Thalidomide (TAL).
Authors: Michele Bibas, Teresa Mignogna, Carla Gualandi, Claudio Geraldini, Nicoletta Villivà, Daniela Tarquini, Alessandro Andriani
Journal: Blood (2007)
Characteristics of multifocal and multicentric breast cancers detetected by preoperative MRI.
Authors: B. K. Killelea, B. J. Grube, L. Philpotts, M. Sowden, N. Horowitz, D. R. Lannin
Journal: Journal of Clinical Oncology (2011)

67 Background: Many newly diagnosed breast cancer patients undergo preoperative MRI to define the extent of their disease, as well as to evaluate the contralateral breast. The purpose of this study was to determine the number of patients who were diagnosed with a second malignancy detected solely on MRI at our institution, to compare them to a control group of patients who had an MRI not leading to a diagnosis of cancer, and to compare tumor characteristics of the primary and secondary tumors. Methods: A breast center database was searched for all newly diagnosed breast cancer patients who underwent preoperative MRI from January 2005 to March 2010. Among those who were diagnosed with a biopsy-proven second malignancy based on suspicious MRI findings, pathology and imaging reports were reviewed and data regarding patients and tumors was collected. Results: Out of 624 patients with newly diagnosed breast cancer who had a preoperative MRI, 53 (8.5%) had a second tumor identified solely by MRI. Of these, 40 were ipsilateral, 12 were contralateral, and 1 bilateral. Thirty seven percent were multifocal and 56% were multicentric. Patients who had an MRI were younger than those who didn’t, but there was no difference by age or race for those who had a second tumor found compared to those who didn’t. Tumor size, nodal status, PR status, and Her2 status were significantly associated with the group who had a second tumor. Among the group with additional tumors found on MRI, histology, ER/PR status and grade were strongly correlated between the primary and the secondary lesion. Conclusions: Tumors that were larger, node positive, lobular histology, hormone receptor positive, or HER2-negative had a higher chance of having a second tumor on preoperative MRI. [Table: see text]
Mycobacterium chimaera colonisation of heater–cooler units (HCU) in Western Australia, 2015: investigation of possible iatrogenic infection using whole genome sequencing
Authors: James Owen Robinson, Geoffrey Wallace Coombs, David John Speers, Terillee Keehner, Anthony David Keil, Victoria D’Abrera, Peter Boan, Stanley Pang
Journal: Eurosurveillance (2016)

Following the reported link between heater–cooler unit (HCU) colonisation with Mycobacterium chimaera and endocarditis, mycobacterial sampling of all HCUs in use in Western Australia was initiated from August 2015, revealing M. chimaera colonisation in 10 of 15 HCUs. After M. chimaera was isolated from a pleural biopsy from a cardiothoracic patient who may have been exposed to a colonised HCU, a whole genome sequencing investigation was performed involving 65 specimens from 15 HCUs across five hospitals to assess if this infection was related to the HCU. Genetic relatedness was found between the 10 HCU M. chimaera isolates from four hospitals. However the M. chimaera isolate from the cardiothoracic patient was not genetically related to the HCU M. chimaera isolates from that hospital, nor to the other HCU isolates, indicating that the HCUs were not the source of the infection in this patient.
High Frequency of Copy Number Variations in Myeloid Leukemia of Down Syndrome.
Authors: Marjolein Blink, Marry M van den Heuvel-Eibrink, Brian Balgobind, Iris H.I.M. Hollink, Valerie de Haas, Gertjan Kaspers, Dirk Reinhardt, Henrik Hasle, C. Michel Zwaan
Journal: Blood (2009)
SNPs in the Promoter of the Gene Encoding Transmembrane Transporter SLC22A4 (hOCTN1) Are Significantly Associated with an Alteration of Gene Expression and with Resistance to the Imatinib Treatment in Chronic Myeloid Leukemia
Authors: Monika Jaruskova, Rajna Hercog, Nikola Curik, Vladimir Benes, Hana Klamova, Katerina Machova Polakova
Journal: Blood (2015)
A Pilot Study of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Relapsed and Refractory Classical Hodgkin Lymphoma (HL): Delivering Cross Fire Radiation by Targeting Reactive B Cells in the Microenvironment.
Authors: Anas Younes, Jorge E. Romaguera, Peter McLaughlin, Franklin Wong
Journal: Blood (2005)
Blood Cells Derived Microparticles and Vascular Markers Study in Essential Thrombocythaemia Patients
Authors: Andrea Piccin, Irene Pusceddu, Luigi Marcheselli, Ciaran Murphy, Elva Eakins, Giovanni Amaddii, Carlo Moesender Frajria, Dino Veneri, Omar Perbellini, Enrica Pacquola, Michele Gottardi, Filippo Gherlinzoni, Flaviano Favaro, Diego Faggian, Mario Plebani, Giovanni Pizzolo, William Murphy, Sergio Cortelazzo
Journal: Blood (2012)
Navigating Ethical Tensions in High-Value Care Education
Authors: Matthew DeCamp, Kevin R. Riggs
Journal: JAMA (2016)

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