tbuckley/cabot-search huggingface dataset:
Hodgkin’s lymphoma in the elderly veterans: We need to do better
Authors: M. H. Al Sayyed, S. F. Maken, M. M. Safa, Z. A. Nahleh, J. R. Pancoast, A. F. Muhleman, A. R. Jazieh, R. S. Komrokji
Journal: Journal of Clinical Oncology (2006)

17554 Background: Recent studies demonstrated worse outcome in elderly patients diagnosed with Hodgkin’s Lymphoma (HL). The purpose of this study was to compare the presenting features, treatment, and outcome of elderly patients with HL within the Veteran Affairs Health care system (VA). Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with HL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. Data are entered by tumor registrars at the VA medical centers. This site aggregates the data collected by the medical centers’ cancer registries. Data was extrapolated and analyzed using bio-statistical software SPSS. Results: We analyzed 1009 patients in the Veteran Affairs (VA) database with the diagnosis of Hodgkin’s lymphoma. Patients were divided into two groups according to age, elderly group (&gt; 60 years) (n = 383) and young group (Age ≤ 60 years) (n = 626). The median age of presentation in elderly patients was 70 years; the most common stage at diagnosis was Stage IV. The most common histological subtype was nodular sclerosis and bulky disease was present in 89 (23.2%) of patients. Out of 383 patients 237 (62%) were treated with chemotherapy, 88 patients (23%) received radiation. Compared to patients ≤ 60 years of age, elderly patients were less likely to be current smokers, more likely to be caucasian, all other baseline characteristics were not statistically significantly different. Less elderly patients received chemotherapy compared to young patients (62% versus 74%) (P-value 0.004). No difference was observed in radiation therapy. The 5 year Overall survival in the elderly was 27 % compared to 70% in patients aged 60 or less. (P-value &lt;0.005). Conclusions: Outcome of HL among elderly veterans is poor. Elderly patients received less chemotherapy treatment. Novel strategies to better deliver treatment in elderly patients with HL are warranted. No significant financial relationships to disclose.
PWE-088 Frequency and function of anti-bacterial mait cells are significantly impaired in advanced alcoholic liver disease
Authors: A Riva, JM Ryan, R Williams, DL Shawcross, S Tarff, A Evans, G Wright, S Chokshi
Journal: Gut (2015)

<h3>Introduction</h3> Intestinal bacterial translocation and systemic gut-derived bacterial products play a central role in the immunopathogenesis of alcoholic liver disease (ALD), yet the mechanisms of susceptibility to infection and the link with intestinal immunity remain elusive. Mucosal associated invariant T cells (MAIT) are unconventional T cells which only respond to bacteria-derived metabolites and are found in large numbers in the blood, intestinal mucosae and liver. They represent a key sentinel system for the homeostatic control of the gut flora and for the control of bacterial infections. The aim of this study was to assess the role of MAIT cells in ALD. <h3>Method</h3> Peripheral blood mononuclear cells from subjects with acute alcoholic hepatitis (AAH, Maddrey’s discriminant function &gt;32; n = 9), compensated alcohol-related cirrhosis (ARC, n = 9) and healthy controls (HC, n = 9) were examined by FACS. MAIT cells were identified as CD161<sup>+</sup>/Vα7.2+ CD8<sup>+</sup>T cells and MAIT-presenting cells (MPC) as MR1+ monocytes or B cells. We quantified (1) frequency, activation status (CD69/HLA-DR) and immunoinhibitory signatures (PD1/TIM3/LAG3) of MAIT cells; (2) frequency and immunoinhibitory status (PD1/PDL1/TIM3/mGal9) of MPC; (3) cytokine/cytotoxicity profiles (IFNγ/TNFα/IL17; GranzymeB (GrB)/Perforin/CD107a) of MAIT cells after in-vitro stimulation with fixed E. Coli. Plasma cytokines and endotoxin levels were assessed by ELISA. <h3>Results</h3> MAIT frequencies were reduced in ARC (p = 0.005) and dramatically lower in AAH (p &lt; 0.001) compared to HC. MAIT cells from AAH and ARC were activated and overexpressed immunoinhibitory receptors compared to HC (p &lt; 0.03). Frequencies of MR1+ MPC were comparable in all groups but expression of immunoinhibitory molecules was higher in AAH and ARC (p &lt; 0.03). Membrane-bound MPC Gal9 was lower in AAH and ARC (p &lt; 0.01) than HC whereas soluble Gal9 was higher (p = 0.004). Levels of E. Coli-stimulated IFNγ from MAIT cells were comparable in all groups, but in ARC they produced less TNFα (p = 0.024) than HC. IL17 responses were observed only in HC. The cytotoxic potential of MAIT cells (GrB) was higher in AAH than HC. <h3>Conclusion</h3> This is the first report addressing the role of MAIT cells in liver disease. We show that MAIT cells have quantitative and functional impairments in ALD, with defective TNFα and IL17 responses, increased killing potential and overexpression of immunoinhibitory receptors. MAIT cells may represent a novel immunotherapeutic target for ALD. <h3>Disclosure of interest</h3> None Declared.
Phase II trial of irinotecan (Ir) plus cisplatin (CDDP) in patients with recurrent or metastatic squamous carcinoma of the head and neck (SCCHN)
Authors: J. Gilbert, A. Cmelak, B. Burkey, R. Sinard, W. Yarborough, J. Netterville, V. Paty, C. Chung, T. Hudson, B. Murphy
Journal: Journal of Clinical Oncology (2007)

6041 Background: Prognosis for recurrent or metastatic SCCHN patients remains poor with median survivals of 6–9 months. Therapies targeting this group are needed. We conducted a single arm Phase II trial of Ir plus CDDP in patients with recurrent or metastatic SCCHN. The goal of this trial was to evaluate the efficacy and toxicity of this combination in advanced SCCHN. Methods: Eligible patients had incurable SCCHN, an ECOG PS of 0–2 and were chemonaive (no prior chemotherapy or chemotherapy for primary disease at least 6 months prior to study entry). A two-stage accrual design (Simon) was used. Irinotecan 65 mg/m 2 and CDDP 30 mg/m 2 were administered weekly for 4 weeks, followed by a 2 week rest for a 6 week cycle. Due to GI toxicity and neutropenia, the Ir was decreased to 50 mg/m 2 with CDDP 30 mg/m 2 . Response assessment was made after every cycle using WHO criteria. The primary endpoint was response rate. Results: Forty patients were enrolled (male: 33, female:7). Median age was 58 (33–79). Forty and 32 patients were evaluable for toxicity and response, respectively. Reasons for unevaluable: 7 without at least 1 full cycle of therapy; 1 patient with incomplete records. Overall response rate was 34% (11/32 PR) with 18% SD (6/32). Median progression free survival was 2.6 months. The median overall survival was 8.2 months. Toxicity was substantial at Ir 65 mg/m 2 with a rate of Grade (G) 3 or 4 toxicity of 82% compared to 56% at Ir 50 mg/m 2 . For both dose levels, G 3 or 4 nausea and vomiting (23%), diarrhea (15%) and neutropenia (35%) were the most common toxicities. Conclusions: The combination of irinotecan and cisplatin is active in a poor prognosis group of patients. Toxicity of irinotecan at 65 mg/m 2 with CDDP 30 mg/m 2 is substantial. Irinotecan 50 mg/m 2 and CDDP 30 mg/m 2 is tolerable and provides a 34% response rate. No significant financial relationships to disclose.
Involvement of ppGalNAc-T6, a new colon cancer marker, in the molecular basis of simple mucin-type <i>O</i>-glycosylated antigen expression
Authors: L. Ubillos, N. Berois, D. Mazal, V. Braña, C. Yacoel, A. Masllorens, E. Berriel, M. Rondan, L. Carriquiry, E. Osinaga
Journal: Journal of Clinical Oncology (2009)

e15060 Background: Abnormal O-glycosylation is one of the most common changes during colon carcinogenesis, leading to the expression of short truncated O-glycan antigens (such as Tn, sialyl-Tn, Tk, and core 6). These structures which are related with the malignant behavior are actively investigated as immunotherapeutic targets. The ppGalNAc-T family enzymes regulate the initial step of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. The objective of this work was to describe the abnormal expression of ppGalNAc-Ts in colon cancer comparing its relationship with incomplete O- glycosylated antigens. Methods: We studied the gene expression of ppGalNAc-Ts in colon cell lines by RT-PCR assays. Using immunohistochemistry we determined ppGalNAc-T6, Tn, sialyl-Tn, Tk, and core 6 expression in 64 colon cancer samples and in 10 normal colon tissues. Results: We found that ppGalNAc-T6 (an enzyme usually restricted to normal placenta, trachea, brain, and pancreas) is expressed by colon cancer cell lines. Using immunohistochemistry we detected ppGalNAc-T6 in 70.3% of cancer samples with no staining in normal colon tissues. Staining pattern was predominantly cytoplasmatic. Staining of Tn, STn, core 6 and Tk antigens was observed in 87,5%, 79,6%, 76,5% and 68.7% of tumors, respectively. We observed a statistically significant relationship between the enzyme expression and Tn antigen (p=0.009) and core 6 (p=0.001). No relationship was observed between the enzyme expression and sialyl-Tn (p = 0.406) and Tk (p= 0.18) antigens. Conclusions: ppGalNac-T6 is a new tumor marker for colon cancer and its expression is related with the accumulation of two O-glycosylated antigens such as Tn and core 6. This is the first evidence in human tissues suggesting that the abnormal expression of a ppGalNac transferase could be in the molecular basis of aberrant O-glycosylated antigens accumulation in cancer. No significant financial relationships to disclose.
Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site
Authors: D Scandella, GE Gilbert, M Shima, H Nakai, C Eagleson, M Felch, R Prescott, KJ Rajalakshmi, LW Hoyer, E Saenko
Journal: Blood (1995)
Phase II trial of anastrazole in combination with gefitinib in women with asymptomatic mullerian cancer
Authors: C. N. Krasner, R. L. Debernardo, M. Findley, R. Penson, U. Matulonis, T. Atkinson, M. Roche, M. V. Seiden
Journal: Journal of Clinical Oncology (2005)

5063 Background: Both the selective aromatase inhibitor, anastrazole, (Arimidex) and Gefitinib (Iressa), an oral epidermal growth factor receptor tyrosine kinase inhibitor have demonstrated modest single agent activity in the treatment of women with ovarian cancer. Preclinical studies studies demonstrate that interruption of both pathways simultaneously may be an effective therapeutic strategy. Methods: Open label phase II study performed in patients with recurrent Mullerian malignancy including ovarian, peritoneal or fallopian tube carcinoma. Eligible patients had tumors that were IHC + for expression of the estrogen and/or progesterone receptor. Additionally, patients must asymptomatic without an indication for immediate systemic chemotherapy, ECOG PS of = 1. Patients could have either measurable or evaluable disease or a rising CA-125, defined as a single value > 35 U/ml or 2 successively rising values with the most recent 3 times patient's nadir value. Archived tumor samples were also sent for quantitative EGFR expression, but this was not an eligibility requirement. Treatment consisted of anastrazole 1mg po qd and Iressa 250mg po qd. Monthly follow-up included interim history, physical exam and CA-125, with radiologic evaluation q 3 months. Results: Thirty five women with a median age of 60 (range 40–79 years) were enrolled. Included were 30, 4, and 1 women with ovary, primary peritoneal and fallopian tube cancers, respectively. To date 23 women are evaluable for response and 7 patients remain on study. Best overall response of patients who have completed the study includes 1 CR, 0 PR, 14 SD. Median TTT was 68 days (range 19–261), with 8, 2, 1 patients with stable disease at = 3, = 6, and = 9 months, respectively. An additional two patients remain on study with SD > 9 months. Toxicity was tolerable, including mild fatigue, nausea, hot flashes, skin rash (gr 1:17 pts, gr 2:5 pts, gr 3:1 pt), stomatitis (gr 1:4pts), and diarrhea (gr 1:15 pts, gr 2:5pts, gr 3:1 pt). Conclusions: Anastrazole in combination with Iressa is a well-tolerated oral regimen with modest activity in women with recurrent/persistent Mullerian cancers. Exploratory analysis regarding EGFR expression, EGFR mutations and response are underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Safety and tolerability of sunitinib (SU) initiated 24 h after the last dose of imatinib (IM) in advanced GIST
Authors: P. G. Casali, E. Fumagalli, A. Bello, S. George
Journal: Journal of Clinical Oncology (2008)

10557 Background: SU is an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, FLT3, CSF-1R and RET, approved multinationally for treatment of advanced IM-resistant/intolerant GIST at 50 mg/d on 6-wk cycles of 4 wk on treatment followed by 2 wk off. Results from a ph II trial have also suggested efficacy and acceptable tolerability of 37.5 mg SU on a continuous daily dosing schedule. Until now, SU GIST trials have been designed with ≥1 wk between the final dose of IM and initiation of SU therapy. As a lead-in sub-study of a multicenter ph IIIb trial that will evaluate the efficacy and safety of SU 37.5 mg/d vs. IM 800 mg/d following PD on IM 400 mg/d, we are evaluating the PK and treatment-related AEs associated with initiating SU 37.5 mg/d 24 h after a final dose of IM 400 mg/d. Methods: Endpoints in this on-going sub-study are treatment-related AEs in the first wk of SU treatment, and changes in QTc interval (using the Fridericia correction formula) and elevations in total drug (SU + active metabolite SU12662) plasma concentrations >150 ng/mL on d 1 of dosing. If treatment-related AEs of grade ≥3 are observed in ≤1/6 pts during the first 7 d of treatment, an additional 6 pts will be enrolled in the sub-study and the main study will commence. Results: As of Nov. 2007, 6 pts (3 M, 3 F) who had received 1.7–5.9 y prior IM therapy had been enrolled and treated with SU for 2–16 wk: 5 remain on study; 1 discontinued due to PD at 15 wk. During the first 7 and 14 d of treatment, no treatment-related grade ≥3 AEs were observed in these 6 pts. A total of 6 treatment-related grade 1/2 AEs occurred in 4 pts in the first 14 d; grade 2 AEs (asthenia, diarrhea and mucosal inflammation) occurred in 2 pts. To date, treatment-related grade 3 AEs (anemia and neutropenia) have occurred in 2 pts; no grade 4 events or dose reductions have occurred. No QTc prolongations considered severe or abnormal ECG assessments have been recorded. PK results and results obtained with the second cohort of 6 pts will be presented. Conclusions: SU administered 24 h after the last dose of IM appears to be safe and well tolerated. As no treatment-related AEs of grades ≥3 were observed during the first 7 and 14 d of SU therapy following transition from IM within 24 h, criteria for proceeding with the main trial and the next cohort of pts have been met. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer GlaxoSmithKline, MedImmune, Novartis, Pfizer, sanofi-aventis Pfizer Novartis, Pfizer, PharmaMar, SigmaTau Janssen-Cilag, Novartis, Pfizer, SigmaTau Novartis, PharmaMar
Phase II study of induction weekly paclitaxel, ifosfamide, and carboplatin (PIC) followed by chemoradiotherapy (CRT) in locally advanced head and neck squamous cell cancer (HNSCC): A Brown University Oncology Group study (HN-86)
Authors: R. Rathore, P. Chougule, H. Wanebo, K. Theall, C. Ruhl, A. Nadeem, J. Koness, N. Oldenburg, T. Kennedy, N. Ready
Journal: Journal of Clinical Oncology (2005)

5556
Complication of laparoscopy during early pregnancy.
Authors: Brudenell M
Journal: BMJ (1974)

This letter was written in reference to an earlier report of 3 cases of carbon dioxide gas embolism which occurred after puncture of the uterus by a Verres needle.  The author suggested an alternate technique which he believes renders the procedure relatively safe.  The verres needle should be introduced immediately below the umbilicus and the needle should not be connected to the source of gas.  This allows the physician greater sensitivity to the needle in making correct penetration of the peritoneal cavity.
The impact of Angelina Jolie's (AJ) story on genetic referral and testing at an academic cancer centre.
Authors: Jacques Raphael, Sunil Verma, Paul Hewitt, Andrea Eisen
Journal: Journal of Clinical Oncology (2014)

44 Background: In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but it’s not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading. Methods: We conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJ’s story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release. Results: The number of women referred for genetic counseling increased by 85% after the release of AJ’s story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family, and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJ’s story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after). Conclusions: This study clearly shows that the number of genetic referrals doubled after AJ’s story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJ’s story the current model of genetic counseling may need to be revisited.
Erythema Nodosum and Contraceptive Medication
Authors: M H Matz
Journal: New England Journal of Medicine (1967)

In 1964 erythema nodosum was seen in 2 patients each of whom was taking by mouth a contraceptive-norethynodral and mestranol (Enovid).  No clear relation could be established between the ingestion of the contraceptive and the development of erythema nodosum.  However in 1965 Holcomb reported that erythema nodosum occurred in a patient four separate times each after the administration of the same orally ingested contraceptive.  Erythema nodosum is not a common condition and physicians therefore may not associate the drug with erythema nodosum or having made this association may experience difficulty in proving it.  It is this contraceptive or any other be made the subject of an adverse drug report.(Full text)
Accuracy of local data on skin cancer
Authors: D. L Roberts
Journal: BMJ (1995)

People are overusing sunbedsED1rOR,-David Shuttleworth drew attention to the question of whether sunbeds that emit ultra- violet A radiation cause skin cancer.'To determine the prevalence of use of sunbeds during 1994 the Department of Health commissioned the omnibus survey of the Office of Population Censuses and Surveys to interview British adults, who were randomly selected and stratified by socioeconomic variables.A balanced response rate of 76% was achieved, producing 2017 interviews.Of the 284 respondents aged 16-24, 68 (24%) had used a sunbed during the year, as had 106 (10%) of the 1056 respondents aged 25-54; the overall ratio of men to women who had used a sunbed was 7:1 1.A total of 184 people had used sunbeds.Half had used them at home (ratio of hired to privately owned equipment 1:2), and half had used commer- cial facilities, with about one fifth of the total use of sunbeds occurring on local authority premises.Information regarding use of sunbeds is available from, among others, the Health and Safety Executive (existing guidance is under revision),'
Hepatic arterial infusion (HAI) in gastric cancer (GC) liver metastases (mets): A pooled analysis of the reported results
Authors: B. Melichar, K. Melicharova, J. Cerman
Journal: Journal of Clinical Oncology (2004)

4211 Background: The prognosis of patients (pts) with GC liver mets is poor. HAI is rarely used in GC pts because of frequent extrahepatic disease, and most published experience are case reports. In the largest study to date (Kumada et al. Oncology 57, 1999, 216), only 43% of 83 eligible pts had no extrahepatic disease, and the median survival was 11 months. Because only 4 pts with GC isolated liver mets were treated in our center over a 12-year period, we performed a pooled analysis of reports with data on individual pts to assess the efficacy of HAI in GC liver mets. Methods: Reports on HAI in GC liver mets were identified through searching MEDLINE. A total of 47 reports (including our series) with a total of 192 pts were included in the pooled analysis. The survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and Cox regression, respectively. Results: Extrahepatic disease was present only in 6% of 192 pts. Complete response (CR) was reported in 19 % and partial response (PR) in 45% for an objective response of 64 %, 17% of pts had stable disease (SD), 18% progressive disease (PD) and 2% were not evaluable. The median survival of all pts was 14 months. The median survival times in pts with CR, PR, SD and PD were 42, 17, 8 and 5 months, respectively. Survival was significantly longer in CR pts than PR pts (p = 0.000) and in PR pts than SD pts (p = 0.004). Survival was also longer, on univariate analysis, in pts reported in papers describing 1 or 2 cases, males, pts with H1 or H2 mets, pts treated by HAI of anthracyclines and liver resection. No significant survival differences were observed according the age, synchronous or metachronous mets, HAI of fluoropyrimidines, platinum or mitomycin C. On multivariate analysis, objective response, HAI of anthracyclines and number of pts per report were independent indicators of survival. Conclusions: HAI may be effective in the rare pts with isolated GC liver metastases. The prognosis is significantly better in pts with objective response and in pts treated by anthracyclines. Longer survival of pts reported in papers describing 1 or 2 cases indicates a publication bias. No significant financial relationships to disclose.