tbuckley/cabot-search huggingface dataset:
Oncolytic wild-type reovirus infection in brain tumors following intravenous administration in patients.
Authors: Adel Jebar, Emma West, Karen Scott, Simon Thomson, Robert Corns, Matthew C. Coffey, Ailsa Rose, Gerard Nuovo, Matthew Ryan, Fiona Errington-Mais, Christy Ralph, Christopher Twelves, Stephen Griffin, Kevin J. Harrington, Hardev S. Pandha, Olly Donnely, Peter John Selby, Richard Vile, Susan Short, Alan Melcher
Journal: Journal of Clinical Oncology (2014)

3104 Background: Oncolytic viruses preferentially replicate in, and kill cancerous cells. Wild-type reovirus is a proprietary isolate of reovirus type 3 Dearing, a double-stranded RNA human reovirus. In two trials using intralesional administration in gliomas and recurrent brain tumours, wild-type reovirus has been well tolerated, with early signs of efficacy. A recently completed trial in Leeds, UK (Adair et al. 2012 Sci Transl Med) has proven that intravenous wild-type reovirus accesses colorectal cancer liver metastases. Intravenous delivery to brain tumours would be easier, cheaper and more acceptable to patients than intralesional administration. To date, no oncolytic virus has been shown to infect brain tumours following intravenous delivery. This trial aims to identify whether wild-type reovirus can cross the blood brain barrier and infect brain tumours following intravenous administration. Methods: This is an open-label, non-randomised, single centre study of intravenous wild-type reovirus administered to patients prior to planned surgery for recurrent high grade glioma or metastatic brain tumours. In total, 12 patients will be treated with a single infusion of 1x1010 TCID50of wild-type reovirus. The primary objective is the presence of wild-type reovirus in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions. Results: Three patients have completed the study to date, including one glioblastoma multiforme, one grade 3 oligodendroglioma and one colorectal brain metastasis. Two of the 3 patients were taking high dose steroids. All 3 resected patient tumours contained wild-type reovirus RNA and protein. There was evidence for wild-type reovirus productive infection in 2 of the tumours. Grade 3-4 adverse reactions were neutropaenia in 1 patient and lymphopaenia in all 3 patients. Conclusions: We have shown for the first time that an oncolytic virus, wild-type reovirus, infects and replicates in brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using wild-type reovirus in patients with high grade gliomas and brain metastases. Clinical trial information: ISRCTN70443973.
Choice of therapy and time to first treatment for patients with colon cancer: A National Cancer Database analysis.
Authors: David C. Olson, Khaled Mohamed Abou El-Ezz, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2013)

e14642 Background: Insurance status has been shown to affect adherence to guidelines in the treatment of colon cancer1. This study aims to investigate trends in management of colon cancer and time to first treatment in patients with various insurance types using the National Cancer Database (NCDB). Methods: Treatment data for 845,121 patients and time to first treatment data for 497,993 patients diagnosed with colon cancer between 2000 and 2010 were identified using the NCDB. Reported utilization of treatment and time to first treatment were analyzed by insurance status. Results: Among all stages of colon cancer, no treatment was received more often by Veteran Affairs (10.5%) and Medicare (10.9%) patients than uninsured (8.8%), managed care (4.5%), private insurance (4.7%), Medicaid (8.4%) or Medicare with supplement (7.7%). Among stage I colon cancer, surgery was received less often by uninsured (90.9%) than other insurance types. Stage III colon cancer patients enrolled in Medicare with/without supplement received chemotherapy less often than other insurance types (49.9% and 46%). Stage IV Medicare patients with/without supplement also received chemotherapy less than other insurance types (59.5% and 52.9%). Surgery as monotherapy was the most common treatment received among all insurance types and stages. More uninsured patients received treatment within 3 days than any other insurance types (61%). A delay of at least 17days occurred more in Veteran Affairs patients than other insurance types (40.6%). Conclusions: This is the largest study to date to have examined treatment trends and time to first treatment. Among all insurance types, Medicare without supplement and Veteran Affairs patients were most likely to receive no treatment. Uninsured were less likely to receive the standard of care treatment with stage I cancers. Medicare patients were less likely to receive the standard of care for stage III and stage IV cancers than other insurance types. Veteran Affairs patients had treatment delayed significantly more than other insurance types. Future studies are needed to assess factors leading to receipt of substandard care.
Long-term androgen deprivation therapy (ADT) with leuprorelin and quality of life in patients with advanced prostate cancer (PCa).
Authors: Peter Hammerer, Lukas Manka, Manfred Wirth
Journal: Journal of Clinical Oncology (2017)

268 Background: LHRH analogs are the gold standard for treatment of patients with hormone-sensitive advanced PCa. In this study, we investigated the quality of life (QoL) of PCa patients under long-term treatment with leuprorelin acetate in microcapsules (1, 3, and 6 month depot formulation) for up to 19.8 years. Methods: Observational and retrospective analysis of data from 536 PCa patients treated with leuproreline and 116 patients of a control group (CG, ≥ 77 years of age, &gt; 5 years urological treatment, no cancer, no ADT). Data was collected in 30 German office based urological practices using EORTC questionnaires QLQ-C30 and QLQ-PR25. Results: Mean treatment duration was 8.6 years (range: 4.5 - 19.8 years). Mean age ± SD of PCa patients (79.6 ± 6.3 years) was comparable to CG (80.5 ± 3.1 years), as were body height, weight, BMI, and Karnofsky-Index (88.0 ± 12.7 vs. 88.4 ± 12.0). The general health status (QLQ-C30) was comparable for PCa patients vs. CG: 64.6 ± 20.5 vs. 66.8 ± 20.3; p = 0.3117. Marginal differences were observed regarding physical functioning (73.2 ± 23.1 vs. 78.1 ± 21.0; p = 0.0402) and role functioning (70.6 ± 30.4 vs. 74.4 ± 25.7; p = 0.1648). PCa patients rated fatigue (33.6 ± 25.1 vs. 28.8 ± 23.3; p = 0.0629), dyspnoea (24.0 ± 28.5 vs. 19.6 ± 26.9; p = 0.1307), and insomnia (28.9 ± 32.6 vs. 23.7 ± 27.2; p = 0.0751) slightly worse than CG. As assessed by QLQ-PR25, PCa patients scored lower on sexual activity (12.0 ± 20.6 vs. 23.7 ± 25.7; p &lt; 0.0001) and sexual function (43.3 ± 25.8 vs. 55.9 ± 27.0; p = 0.0067) compared to CG. PCa patients had less urinary tract symptoms (28.2 ± 19.8 vs. 31.2 ± 19.2; p = 0.1472) but stronger symptoms of androgen deprivation (21.4 ± 17.3 vs. 10.8 ± 13.2; p &lt; 0.0001), and they had a higher need of incontinence aids (29.6 ± 34.2 vs. 16.7 ± 20.5; p = 0.0056) – however, 136 of the 536 PCa patients had a prostatectomy. Conclusions: In this study, PCa patients treated with leuprorelin for up to 19.8 years (8.6 years on average) had an overall QoL comparable to an age-matched control group. As expected, sexual activity and sexual function were lower in PCa patients under ADT. Overall, treatment with leuprorelin is a well-tolerated long-term therapy for patients with hormone-sensitive advanced PCa. Clinical trial information: ENA E005(a) / DE-N-LEU-019(a).
Safety and tolerability of lanreotide autogel/depot (LAN) in patients (pts) with neuroendocrine tumors (NETs): Pooled analysis of clinical studies.
Authors: Alexandria T. Phan, Edward M. Wolin, George A. Fisher, Philippe B. Ruszniewski, Marianne E. Pavel, Nilani Liyanage, Kristina Strutt, Stephan Braun, Martyn E. Caplin, Aaron Vinik
Journal: Journal of Clinical Oncology (2017)

398 Background: Two international randomized double blind (DB) phase 3 trials provided evidence on LAN 120mg/4wks vs placebo in NETs: CLARINET reported on PFS improvements in metastatic intestinal/pancreatic NETs; ELECT on reduced use of short-acting rescue medication for carcinoid syndrome (CS) symptoms. ELECT and CLARINET open-label (OL) extensions recently provided further long-term (LT) data. Here, we pool all current data from LAN trials, to provide an overview of safety in functioning and nonfunctioning NETs. Methods: Data were pooled from CLARINET (96wk DB, ≤6yr LTOL), ELECT (16wk DB, 32wk initial OL, ≥2yr LTOL) and three other OL studies: 6mo study for CS symptom relief; 7–8mo study of self-administered LAN; and 92wk study of tumor-growth control. Occurrence of AEs was examined in all studies (except for diarrhea/flushing, an efficacy measure in ELECT DB + initial OL). Results: Of all 378 pts, 90% received LAN 120 mg (10% ≤90 mg). AE profiles were similar across DB, OL and all studies. GI events were most frequent AEs: 56% of pts reported GI events, excluding diarrhea, across all studies; 28% reported diarrhea in all studies excluding ELECT DB + initial OL. No study withdrawals occurred due to diarrhea or other GI AE. No deaths were considered treatment related. Long-term (&gt;12mo) treatment produced no additional safety signals vs ≤6mo. Conclusions: This comprehensive safety analysis supports the positive benefit–risk profile of LAN both for CS control in symptomatic NET and for tumor control in metastatic intestinal/pancreatic NET. Clinical trial information: NCT00353496, NCT00842348, NCT00774930, NCT00681187, NCT00326469. [Table: see text]
Final results from a trial of a combination herbal supplement for biochemically recurrent prostate cancer.
Authors: Tanya B Dorff, Denice D Tsao-Wei, Debra Hawes, Shigang Xiong, David I. Quinn, Mitchell E. Gross, Gary Lieskovsky, Nicholas J. Vogelzang, Susan G. Groshen, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2013)

e16020 Background: No standard exists for the treatment of bcrPC. Concern over deleterious effects of androgen deprivation (ADT) and lack of proven survival benefit in this setting makes initiation of ADT inappropriate for some patients. A non-hormonal, non-toxic agent to reduce PSA would be a welcome alternative to observation. We tested Prostate Health Cocktail (PHC), a supplement containing vitamin D &amp; E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could decrease PSA. Methods: Eligible men had a rising PSA with doubling time between 3 and 36 months, with no evidence of metastases on CT and bone scan. After IRB approval, 40 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after cycle 1, then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase above baseline/nadir AND absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: 60 men screened, 17 failed (28%). Median age was 67 (range 54-84) and baseline PSA 2.8 ng/mL (1.1-84.1). 23% had primary radiation only, 25% had prostatectomy, and 52% had both; 23% had Gleason 8-10. The median # of cycles was 8 (1-13). 15/40 men (37.5%) had a PSA decline (1.1%-55% maximum decrease). 43% stopped therapy for PSA progression, with median time to progression 10.2 months. Circulating tumor cells were detected in 5 of the first 23 subjects; complete CTC data will be presented. There was no significant change in testosterone or DHT during treatment. Toxicities possibly related to PHC included grade 1 or 2 liver enzyme elevations [transient], grade 1 or 2 gastrointestinal symptoms (9), grade 1 weakness/dizziness/pain (5), and grade 1 fatigue (2). 5 men continue on study, 3 lost to f/u, 16 have developed metastases, median time to mets 31.5 months from bcr. Conclusions: PHC induced PSA declines in 37% of patients with bcrPC, and was not associated with changes in serum androgens or significant toxicities. PHC is a potential alternative to observation in select patients with bcrPC. Clinical trial information: NCT00669656.
National trends in local excision and esophagectomy for cT1N0 esophageal cancer.
Authors: Emily C. Sturm, Whitney Zahnd, John D. Mellinger, Sabha Ganai
Journal: Journal of Clinical Oncology (2017)

62 Background: Esophageal cancer management has evolved due to improvements in staging and treatment strategies. Endoscopic local excision presents an attractive option for definitive management of T1 cancers, avoiding the morbidity of esophagectomy. We hypothesized that for cT1N0 cancers, patients who underwent local excision would have lower survival compared to esophagectomy due to potential discordant staging. Methods: The National Cancer Database was queried for esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) with AJCC T1N0 clinical stage who underwent local excision (n = 1625) or esophagectomy (n = 3255) between 1998 and 2012. Chi-square analysis was used to compare demographic and clinical characteristics by procedure. Chi-square trend analysis was performed to assess trends in procedure type over time. Cox Regression analysis was performed to assess survival by procedure controlling for demographic and clinical characteristics. Results: Between 1998 and 2012, the proportion of patients who underwent local excision increased from 12% to 50% for all patients (p &lt; 0.001); from 17% to 40% for SCC patients (p &lt; 0.001); and from 9% to 51% for AC patients (p &lt; 0.001). Surgical procedure varied significantly by demographic, socioeconomic status, facility, and tumor-related factors. 65% of cT1N0 cancers had concordant clinical and pathological staging after esophagectomy, with 11% having positive nodal disease; 44% were concordant after local excision. While no significant difference was seen in unadjusted survival, adjusted Cox Regression analysis indicated worse survival after esophagectomy compared to local excision for all cases (HR 1.67; 95% CI, 1.40-2.00) and for ACs with concordant staging (HR 1.54; 95% CI, 1.11-2.14). Conclusions: Local excision for cT1N0 esophageal cancer has increased over time. Staging concordance for esophagectomy is seen in two-thirds of cases. Contrary to our hypothesis, patients undergoing local excision for T1N0 cancers have better overall survival than those undergoing esophagectomy, which may reflect early differences in mortality and/or selection bias. As this study was unable to distinguish T1a from T1b, further analysis is warranted.
Peanut oleosins associated with severe peanut allergy—importance of lipophilic allergens for comprehensive allergy diagnostics
Authors: Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe
Journal: Journal of Allergy and Clinical Immunology (2017)
Regulated in development and DNA damage responses 1 (REDD1) links stress with IL-1β–mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps
Authors: Panagiotis Skendros, Akrivi Chrysanthopoulou, François Rousset, Konstantinos Kambas, Athanasios Arampatzioglou, Alexandros Mitsios, Veronique Bocly, Theocharis Konstantinidis, Philippe Pellet, Iliana Angelidou, Eirini Apostolidou, Dimitrios Ritis, Victoria Tsironidou, Sotiris Galtsidis, Charalampos Papagoras, Dimitrios Stakos, Georgios Kouklakis, Vasiliki Dalla, Maria Koffa, Ioannis Mitroulis, Ioannis Theodorou, Konstantinos Ritis
Journal: Journal of Allergy and Clinical Immunology (2017)
Use of pretreatment serum CA9 (carbonic anhydrase 9) to predict PFS and survival in trastuzumab-treated metastatic breast cancer
Authors: K. Leitzel, H. Y. Hou, V. Shrivastava, U. Anyanwu, S. M. Ali, W. Koestler, E. Fuchs, S. Brown-Shimer, W. Carney, A. Lipton
Journal: Journal of Clinical Oncology (2009)

11092 Background: Approximately half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a vexing clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), CA9, VEGF-165, and endoglin were measured using ELISA assays in 66 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, uPA, CA9, and VEGF-165 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA; and the endoglin ELISA was from R&amp;D Systems, Minneapolis, MN. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.005), TIMP-1 (p&lt; 0.0001), uPA (p= 0.006), endoglin (p= 0.008), and CA9 (p &lt;0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy, but VEGF was not. In multivariate analysis for PFS with all six biomarkers, only serum CA9 (p= 0.002) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.018), TIMP-1 (p&lt; 0.0001), uPA (p&lt; 0.0001), endoglin (p= 0.002), and CA9 (p&lt; 0.0001) were all significant as univariate continuous biomarkers for prognosis, but serum VEGF was not. In multivariate analysis for OS with all six biomarkers, only serum CA9 was a significant independent prognostic covariate (p= 0.001). Conclusions: Elevated pretreatment serum CA9 (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. [Table: see text]
Survival of thick melanoma in a Spanish university hospital: Analysis of 15 years experience.
Authors: Jose Antonio Aviles Izquierdo, Celia Horcajada, Paloma Sanchez-Mateos, Ana Alvarez, Enrique Mercader, Veronica Parra, Jose Luis Escat, Ivan Marquez Rodas
Journal: Journal of Clinical Oncology (2014)

e20012 Background: Breslow thickness (BT) is the most important independent prognosis factor for melanoma. Although an effort in campaigns for melanoma early detection has been made all over the world, thick melanoma (TM) frequency still prevails. Both adjuvant and surveillance strategies for high-risk relapse melanoma are under discussion, so knowledge about frequency and pathological characteristics of thick melanoma are of clinical interest Methods: We analyze the clinical and pathological characteristics and overall survival (OS) of TM (BT >2 mm, non-metastatic, non-clinically positive node at diagnosis) treated in our institution from 1994-2008 (N=146) Results: The table summarizes the findings. 41% of patients have died due to melanoma at the time of analysis. Ulceration and positive sentinel node (PSN) were the only factors influencing OS. Adjuvant interferon did not influence OS Conclusions: Even for patients with bad prognosis factors (ulceration and PSN), up to 40-60% TM are cured only with surgery. Deeper molecular and immunological characterization of the different subgroups is needed to better select the post-surgery strategies for these patients. Clinical factor N (%) No differences in OS Pathologic factor N (%) OS difference (months) Male 81 (65.5) BT mm, mean (SD) 4.57 (2.98) NS Age at diagnosis (years) Mean, (SD) <=65 >65 60.54 (16.42) 80 (54.8) 66 (55.2) T stage T3 (2.01-4mm) T4 (>4mm) AJCC stage IIA IIB IIC IIIA 91 (62.3) 55 (37.7) 55 (37.7) 60 (41.1) 14 (9.6) 17 (11.6) Ulceration 57 (39) Ulcerated: 90.4 months (95%CI 75-105.7) Non-ulcerated: 142.6 months (95% CI 117.8-167.3) p<0.05 Melanoma location Head and neck Body Limbs 32 (21.9) 53 (36.3) 61 (41.8) Nevus associated 5/33 (15) NS PSN 16/81 (19.8) PSN: 81.7 months (95%CI 62.3-101.2) Non PSN: 114.6 months (95% CI 101.9.-127.3) p<0.05 Adjuvant interferon Yes No 48/146 (32.9) 98/146 (67.1) Histhologic subtype Superficial spread Nodular Lentigo M Acral Other Nonspecified 42 (28.8) 59 (40.4) 13 (8.9) 13 (8.9) 10 (6.8) 9 (6.2) NS Metastatic relapse Cutaneous Ganglionar Visceral 22 (15.1) 34 (23.3) 22 (15.1)* 78.3 (95% CI 54.5-102.1), 75.4 (95% CI 51.7-99) 40.9 (95% CI 32.4-49.4) *p<0.05 Family history of melanoma 9 (6.2) Second primary melanoma 4 (2.7) NS
Risk of coronary heart disease and ischemic stroke in thyroid cancer patients taking levothyroxine.
Authors: Dong Wook Shin, Beomseok Suh, Jae Moon Yoon, Youngmin Park
Journal: Journal of Clinical Oncology (2017)

105 Background: Many thyroid cancer patients are exposed to long-term TSH suppression, in many cases as lifetime treatment, and are consequently subjected to risk for cardiovascular disease. We investigated incidence of CHD and ischemic stroke among thyroid cancer patients and explored possible pathophysiological mechanisms involved. Methods: A total of 182,419 subjects who received thyroidectomy for thyroid cancer during 2004-2012 were selected from the Korean National Health Insurance data, which covers approximately 97% of the entire Korean population. Propensity score matching was used to select non-cancer controls. Cox proportional hazards regression analysis was used to determine relative risk of coronary heart disease (CHD), and ischemic stroke. Mean follow-up was 4.32 years. Results: Thyroid cancer patients had elevated risk for CHD and ischemic stroke with HR 1.15 (95% CI 1.10-1.22), and 1.15 (1.09-1.22), respectively. This risk was marked in those who received total thyroidectomy and in those who took higher dosage of levothyroxine (HR 1.47, 95% CI 1.34-1.60 for CHD and HR 1.56, 95% CI 1.42-1.72 for ischemic stroke among those who took ≥ 170mcg/d). Atrial fibrillation risk was dose-dependently associated with levothyroxine dosage; however, once patients developed atrial fibrillation, ischemic stroke risk was not significantly greater in those who took higher dosage. Conclusions: The risk for CHD and ischemic stroke was higher in thyroid cancer patients who received thyroidectomy, and the dosage of levothyroxine administered appears to play a major role. More caution is suggested for the choice of thyroidectomy and TSH suppression therapy, as well as proper management for cardiovascular disease prevention.