tbuckley/cabot-search huggingface dataset:
PrEP on demand cuts HIV transmission in high risk men, study finds
Authors: Michael McCarthy
Journal: BMJ (2015)

Pre-exposure prophylaxis (PrEP) taken by men when they have sex with other men reduced the risk of transmission of HIV-1 by 86%, a new randomized, placebo controlled trial published in the New England Journal of Medicine has found.1

Previous trials have shown that PrEP taken daily can reduce HIV-1 transmission among men who have sex with men, heterosexual men and women, intravenous drug users, and serodiscordant couples. However, adherence remains a challenge. The hypothesis of the new study, conducted in France and Canada, was that PrEP taken on demand instead of part of a once a day regimen would achieve greater adherence and thus greater efficacy.

In the trial, called the Intervention Preventive de l’Expostion aux Risque avec et pour les Gays (IPERGAY) trial, 400 men who had tested negative for HIV and who engaged in unprotected anal sex with men were randomized to take either …
Hereditary gastric cancer caused by germline CDH1 gene mutations in the Netherlands.
Authors: I. Kluijt, E. Siemerink, M. Ausems, M. Ligtenberg, D. de Jong, R. Sijmons, J. T. Plukker, R. van Hillegersberg, A. Cats, N. Hoogerbrugge
Journal: Journal of Clinical Oncology (2010)

4080 Background: Germline mutations in the CDH1 gene lead to the hereditary diffuse gastric cancer syndrome (HDGC), with strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). We report on the geno-/phenotypical data of all Dutch families with germline mutations in the CDH1 gene. Methods: Index patients of families suspect for HDGC were tested for CDH1 mutations in a central molecular genetics laboratory. Of families with CDH1 mutations all cancer data were retrieved. Surgical data of prophylactic gastrectomies were collected. Pathologic investigation was performed according to the Swiss roll technique by expert pathologists. Results: In 6 families 6 different CDH1 mutations were found. Symptomatic GC was diagnosed in 26 individuals. Mean age at diagnosis was 40 years (range 23-65 years), with 3 GCs < 30 years. Of 18 confirmed GCs, 17 were diffuse cancers, one intestinal type. Symptomatic LBC was diagnosed in 1 carrier. Forty out of 79 tested family members carried a CDH1 mutation. Twenty-four of these carriers, aged 18-61 years, underwent prophylactic gastrectomy, in 2/24 combined with prophylactic mastectomy. In 1 patient a small focus of invasive diffuse gastric cancer and an in situ carcinoma were found. Multiple foci of intramucosal cancer and one GIST were diagnosed in 13 other patients. In 8 patients no cancer cells were found. Foci of invasive LBC and multifocal LCIS were found in all mastectomy specimens. Two out of 40 carriers were diagnosed with GC or precursor lesions at gastroscopy before planned gastrectomies. Re-laparotomy was necessary in 3 subjects because of abdominal infection, anastomotic leakage or residual gastric mucosa. Clefts of lip and/or palate were reported in 6 individuals from 3 families (3 proven mutation carriers). Conclusions: The age at onset of GC in our families is highly variably, which has to be included in the counselling on planning prophylactic gastrectomies. A multidisciplinary approach is obligatory in the care for HDGC patients in order to maximize the quality and to minimize the physical impact of prophylactic procedures. Taking a family history should include clefts in gastric cancer families. No significant financial relationships to disclose.
Bevacizumab, erlotinib, and imatinib in the treatment of patients (pts) with advanced renal cell carcinoma (RCC): A Minnie Pearl Cancer Research Network phase I/II trial
Authors: J. D. Hainsworth, J. A. Sosman, D. R. Spigel, J. F. Patton, D. S. Thompson, V. Sutton, L. L. Hart, K. Yost, F. A. Greco
Journal: Journal of Clinical Oncology (2005)

4542 Background: Most pts with clear cell RCC have loss of Von Hippel Lindau (VHL) protein primarily due to gene mutation, ultimately resulting in overexpression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF-:), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). In a previous phase II trial, we demonstrated that combined VEGF/EGF receptor inhibition with bevacizumab and erlotinib was an active and well tolerated treatment for pts with metastatic RCC. In this phase I/II trial, we add imatinib, a PDGF receptor antagonist, to the combination of bevacizumab/erlotinib. Methods: Eligibility: metastatic clear cell RCC, 0–2 previous systemic regimens, ECOG PS 0–1, no previous anti-angiogenesis or EGF receptor inhibitor therapy, no active CNS metastases, adequate organ function, no history of thromboembolic disease, informed consent. All pts received bevacizumab 10mg/kg IV q 2 weeks, and erlotinib 150mg po daily. In the phase I portion of the trial, imatinib levels were escalated: 300mg qd (cohort 1), 400mg qd (cohort 2), and 600mg qd (cohort 3). Pts were evaluated for response after 8 weeks; treatment continued until tumor progression. Results: In the phase I portion of the trial, imatinib 400mg qd was identified as the maximum tolerated dose. At this dose level, 2 of 10 patients had reversible dose-limiting toxicity (diarrhea). Other grade 3 toxicity (1 pt each): nausea, vomiting, rash, pruritus, fatigue, arthralgia. Grade 1/2 toxicities included rash (77%), diarrhea (69%), nausea (61%), fatigue (54%), vomiting (31%), and proteinuria (23%). Amongst the 15 pts treated in the phase I portion of the study, 2 pts had partial response and 9 pts had minor response/stable disease after 8 weeks. At present, 25 pts have been entered on the phase II portion of the study, and accrual is expected to be completed within the next 2 months. Conclusions: The combination of bevacizumab 10mg/kg IV q 2 weeks, erlotinib 150mg po qd, and imatinib 400mg po qd is tolerable therapy for pts with metastatic RCC. Preliminary results also indicate activity with this 3-drug regimen. Updated results on the phase II study will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech
Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments
Authors: Mechthild Krause, Anna Dubrovska, Annett Linge, Michael Baumann
Journal: Advanced Drug Delivery Reviews (2016)

Inactivation of cancer stem cells (CSCs) is of utmost importance for tumor cure after radiotherapy. An increasing body of evidence complies with a higher radioresistance of CSCs compared to the mass of tumor cells, supporting the use of CSC related biomarkers for prediction of radiotherapy outcome. Treatment individualization strategies for patient groups with vastly different risk of recurrence will most likely require application of more than one biomarker. Specifically, inclusion of established biomarkers like tumor size for primary radio(chemo)therapy or human papilloma virus (HPV) infection status in head and neck squamous cell carcinoma seems to be of very high relevance. The high heterogeneity of CSC subclones along with changes of the functional behavior of individual tumors under treatment underlines the importance of the selection of the optimal timepoint(s) of biomarker evaluation, but also provides a potential therapeutic target for combined treatment approaches with irradiation.
EPID (etoposide, cisplatin, ifosfamide and dexamethasone) with or without rituximab as second line treatment in patients with non Hodgkin lymphoma not candidates for haematopoietic stem cell transplantation (HSCT): A single center retrospective study
Authors: F. Aldaco, P. Perez, G. Cervantes, L. Torrecillas, P. Cortes, B. Hernandez, A. A. Erazo
Journal: Journal of Clinical Oncology (2008)

19500 Background: The potentially curative rate in patients with failure to first line shown to be only from 5 to 10%, and the 2 years survival rate about 25% without haematopoietic stem cell transplantation (HSCT). We evaluate the efficacy and safety of EPID plus Rituximab (EPID-R) vs. EPID as second line treatment in patients with Lymphoma (NHL). Methods: Retrospective study in Patients with NHL and EPID (Etoposide 80/100 mg/m2 d1–3, q3w, Cisplatin 80/100 mg/m2 delivery in 3 days q3w, Ifosfamide (plus MESNA) 5 grs/m2 delivery in 3 days q3w and Dexamethasone 24 mg/m2 d1–3 q3w) or EPID-R (Rituximab 375 mg/m2 d1 q3w) as second line treatment and not candidates for HSCT between 1999–2005. Results: We included 50 patients (20 pts EPID-R/30 pts EPID). Pts characteristics (EPID-R vs. EPID respective): Median age 47.8 (range 39–75) vs. 52 years (range 21–76), >64 years 23% vs. 23% Female 55% vs 57%, Stage III/IV 40% vs. 46%, extra nodal 10% vs. 8% ECOG 0–1 80% vs. 77%, histological type (WF) I/HG 90% vs. 80%, First line chemotherapy CHOP 70% and CHOP-R 25% vs. CHOP 70% and CHOP-R 0%, Overall Response rate (ORR) first line chemotherapy 80% vs. 73% and time to progression (TTP) first line 11 vs 8.3 months.Efficacy: N of cycles EPID-R 4.15 (1–6) vs. EPID 4.4 (1–7), ORR: EPID-R 75% (CR 55%/PR 20%) vs. EPID 73% (CR 35%/PR 38%), TTP EPID-R 22 months vs. EPID 10 months, 2 years Overall Survival (OS) EPID-R 65% vs. EPID 26.9 %, Pts. EPID-R with CR OS 2 years 90% vs. 44% (OS EPID 22 months - less than 2 years-), Rituximab maintenance or after failure to EPID/EPID-R: EPID-R 70%, EPID 0%. Toxicity G3/4(EPID-R vs. EPID respective): Neutropenia 75% vs. 56%, neutropenia febrile 45% vs. 15%, anaemia 25% vs. 18%, Thrombocytopenia 20% vs. 15%, nausea and vomiting 10% vs 30%, mucositis 5% vs. 7%, diarrhea 5% vs. 3%, renal 5% vs. 7%, treatment death associated 0% vs. 3%. Conclusion: An unexpected increase in hematologic toxicity was shown with EPID-R, however, in our study the addition of Rituximab to EPID improves ‘dramatically‘ the OS. Further and prospective studies are required to evaluate the therapeutic potential of EPID-R, and may be to revaluate the HSCT indications. No significant financial relationships to disclose.
A multicenter randomized phase II (rPII)/III study comparing concurrent chemoradiotherapy (CRT) with low-dose cisplatin plus continuous infusion of 5-fluorouracil (LDPF) and standard-dose PF (SDPF) for locally advanced unresectable squamous cell carcinoma of the thoracic esophagus (JCOG0303).
Authors: M. Shinoda, N. Ando, H. Kato, Y. Tsubosa, K. Minashi, G. Watanabe, K. Ikeda, T. Kawano, K. Nakamura, H. Fukuda
Journal: Journal of Clinical Oncology (2010)

4053 Background: Cisplatin-based CRT is one of the standard treatments for locally advanced unresectable esophageal carcinomas. Although both cisplatin and 5-FU are known to enhance the efficacy of radiotherapy, the optimal chemotherapy regimen has not been established. Thus, we evaluated CRT with LDPF on effectiveness and adverse events for locally advanced unresectable esophageal carcinomas in a randomized study to determine if it is an acceptable alternative to SDPF. Methods: Eligibility criteria included histologically proven squamous cell, adenosquamous, or basaloid carcinoma; tumor located in thoracic esophagus; and definite T4 and/or unresectable regional lymph node metastasis. In arm A, two courses of standard chemotherapy of cisplatin (70 mg/m2, div day1, 29) plus 5-FU (700 mg/ m2, ci day1-4, 29-32) were given with external beam radiation (EBRT) in 30 daily fractions, 5 d/week to a total dose of 60 Gy. In arm B, low dose daily cisplatin (4 mg/ m2, div) plus 5-FU (200 mg/ m2, ci) was administered on the same days that EBRT was given. The primary endpoint was overall survival (OS). The rPII study was designed to evaluate the efficacy of LDPF to decide whether it warranted a phase III trial. Results: Between Apr. 2004 and Jun. 2009, 135 pts (Arm A/B; 67/68) from 40 institutions were randomized. Tumor depth (T1-3/T4) was 18/49 in arm A and 13/55 in arm B. The median follow-up time for all eligible pts was 9.9 mos. Toxicities were almost equivalent in both arms; however LDPF necessitated long hospitalization. Moreover, the OS of pts of LDPF group was slightly inferior to that of those treated with SDPF (hazard ratio, 1.048, 95%CI, 0.782-1.045; median OS (A/B), 13.0/13.6 mos.; 3-year OS (A/B), 30/26%). Because of the inferior efficacy of LDPF, the Data and Safety Monitoring Committee of the JCOG recommended the termination of the study at the end of rPII. Conclusions: CRT with LDPF is not recommended for pts with locally advanced unresectable esophageal cancer. No significant financial relationships to disclose.
Cost effectiveness of whole breast IMRT for reduction of moist desquamation
Authors: J. B. Strauss, S. S. Chen, A. T. Dickler, K. L. Griem
Journal: Journal of Clinical Oncology (2007)

17004 Background: Cost minimization studies have compared conventional whole breast radiation therapy (C-WBRT) to whole breast intensity modulated radiation therapy (IMRT). Consistently, IMRT has proved to be far more expensive. The weakness of cost minimization studies is that they assume the outcomes and toxicities of the treatment modalities in question are identical. Data from a case- control trial and a recent randomized controlled trial show that IMRT reduces the incidence of moist desquamation. We performed an analysis to estimate the cost effectiveness of breast IMRT to prevent moist desquamation. Methods: The direct medical costs of C-WBRT and IMRT were estimated using the 2006 Medicare Fee Schedule. We assumed rates of moist desquamation of 48 to 31% in accordance with Pignol, et al., ASTRO 2006. The cost effectiveness ratio (additional dollars spent per case of desquamation avoided) was calculated under two circumstances: 1) every patient received IMRT, or 2) only those patients destined to desquamate were treated with IMRT. Results: The direct medical costs of C-WBRT are $7,948 vs. $29,790 for IMRT. Thus, the marginal cost of IMRT is $22,142. In circumstance 1, the marginal cost to avoid one case of desquamation is $130,247. In circumstance 2, this cost is $62,518. Conclusions: The two circumstances described above are extremes that bound the range of cost estimates. Patient risk factors for desquamation, such as large breast size, can be used to identify high risk patients, obviating the need to treat all patients with IMRT. However, perfect prospective identification of all patients destined to desquamate is unlikely. Instead, the true marginal cost to avoid one case of moist desquamation will lie between $62,518 and $130,247. This cost may be too high to justify the benefit of reduced acute skin toxicity, but it is likely that the benefits of IMRT have been underestimated. IMRT may shorten the duration of moist desquamation. Late effects such as breast fibrosis and color variegation of the skin caused by desquamation as well as dose to the heart and lungs may be decreased by IMRT. If new data support these benefits, then IMRT may become a more cost effective option. No significant financial relationships to disclose.
Hot topics and networks in<i>Cardiovascular Research</i>
Authors: Diane Gal, Wouter Vandevelde, Karin R. Sipido
Journal: Cardiovascular Research (2015)

‘Publish or perish’ refers to the essence of journals as instruments for sharing novel and reliable information to advance scientific knowledge. Editors are expected to present high-quality, novel, and relevant studies to the community by a process of review and selection from submitted manuscripts. Peer review is an essential part of this selection process providing expert input on all three aspects for the final editorial decision. In addition, regular evaluation of the outcome of the editorial work is essential to guide the process. ISI provides metrics of which the impact factor is best-known, but there are many others. All of these give single numerical value to the aggregate of the articles but do not inform about the content of the journal.

Here, after 3 years in office, we wanted to take stock of the research published in Cardiovascular Research in 2013 and 2014. Are we on track for the impact and visibility we aim to achieve? What topics are emerging? Have publication policies provided more visibility to these publications? Taking a global view of the results of the first 2 years, the topics of the papers published and their visibility in the research community, is a useful step in analysing the decisions made in the past.

Overall, 379 original research articles and 80 reviews were published in Cardiovascular Research in 2013 and 2014. One of the main indicators of visibility of these publications is the number of citations obtained from Web of Science online on 21 September 2015, totalling 3199 citations.

Publications in Cardiovascular Research enjoy a high visibility, with an average citation rate of 7 citations per publication, a low percentage of only 7% that have …
Stereotactic radiation therapy in painful bone metastases.
Authors: Despina Katsochi, Chryssa Paraskevopoulou, Sophia Kosmidis, Ekaterini Fotopoulou, George Kollias
Journal: Journal of Clinical Oncology (2014)

74 Background: Disease local control and therefore pain relief is the main objective in patients with painful bone metastases. The introduction of Stereotactic Body Radiation Therapy in combination with image guided radiotherapy offers the opportunity to safely apply hypofractionated schemes. Methods: From May 2009 to May 2014, 104 patients with total 158 single or multiple bone metastases from several primary tumors were treated with Stereotactic Body Radiation Therapy with palliative intent. Concrete osteolytic or painful osteoblastic lesions of maximum length 3cm where treated with two hypofractionated schemes: 24Gy in 6 fractions or 21Gy in 3 fractions depending on lesion size and location. All patients were provided with MDStation software installed on a tablet that analyzes their behavioral change based on evaluation questionnaires on their clinical status and pain intensity. Results: All patients completed the treatment plan with no major toxicity. Follow up was scheduled at the end of the treatment, three and six months after. Total pain relief was achieved in 130 lesions (82%), while in the rest 28 sites (18%) pain was significantly less and patients decreased medication. Conclusions: Stereotactic Body Radiation Therapy for bone metastases is a very effective technique for pain management. Palliation is achieved quite promptly with minimal toxicity.
Epidermal growth factor receptor expression in and targeted therapy for metastatic squamous cell carcinoma of the penis
Authors: L. C. Pagliaro, W. Osai, P. Tamboli, F. Vakar-Lopez, C. A. Pettaway
Journal: Journal of Clinical Oncology (2007)

14045 Background: Penile carcinoma is highly fatal when associated with bulky regional or distant metastases, despite chemotherapy and surgery. Epidermal growth factor receptor (EGFR) is a potential target for systemic therapy, but little is known about its expression or significance in penile carcinoma. Methods: The results of EGFR immunohistochemistry in cases of metastatic squamous cell carcinoma of the penis performed in our Department of Pathology over a 2-year period were reviewed retrospectively. The antibody used in the assay was Zymed clone 31G7. To assess the biological significance of EGFR expression, we reviewed the charts of these patients for EGFR-targeted therapies and outcomes. Results: Thirteen cases were assayed for EGFR expression. The tissue was from a lymph node metastasis in 5 patients, inguinal or scrotal skin metastasis in 2 patients, and the primary tumor in six patients. Tumor cells in all cases were positive for EGFR, and 9 were scored as 3+ or strongly positive. The percentage of cells positive for EGFR was &gt;90% in six cases, 40–50% in one case, and not specified in six cases. All of the patients received one or more EGFR-targeted therapies including erlotinib (one patient), cetuximab (three patients), or cetuximab combined with one or more cytotoxic agents (nine patients). Six patients received a second or third EGFR-targeted therapy. Grade 3 or 4 adverse events were limited to cellulitis, thrombocytopenia, and tumor hemorrhage (one patient each). Two patients had disease progression during initial treatment with paclitaxel, ifosfamide, and cisplatin (TIP), then had partial responses to TIP plus cetuximab. Two patients had partial responses to cetuximab and cisplatin, also after having disease progression while receiving TIP. A patient with visceral metastases who had extensive prior chemotherapy received cetuximab and cisplatin as salvage treatment and experienced objective tumor regression lasting 3 months. Conclusions: High levels of EGFR expression are common in metastatic penile carcinoma. Five of 13 patients showed evidence of response to cetuximab in combination with cisplatin or TIP. These results indicate that EGFR plays a clinically important role in metastatic penile carcinoma and is a promising target for therapy. No significant financial relationships to disclose.
Randomized phase III study of carboplatin and paclitaxel versus vincristine, doxorubicin and cyclophosphamide chemotherapy in intermediate and poor prognosis small cell lung cancer: Preliminary results
Authors: S. Baka, S. Mullamitha, L. Ashcroft, S. Nagel, R. Board, P. Lorigan
Journal: Journal of Clinical Oncology (2006)

7059 Background: The combination of paclitaxel and carboplatin has been found to be effective in lung cancer and well tolerated. Method: This is a phase III randomized trial of paclitaxel and carboplatin (PC) versus vincristine, doxorubicin and cyclophosphamide (CAV) chemotherapy in limited or extensive stage disease patients but with a prognostic score in the intermediate or poor prognosis range.The aim of the study is to determine the one year survival rate, the objective response rate and toxicity. Patients were randomized to: four cycles of PC (paclitaxel 200mg/m 2 by IV 3 hour infusion), followed by carboplatin (AUC of 6) by IV injection, 3-weekly or four cycles of CAV (cyclophosphamide 750mg/ m 2 , doxorubicin 40mg/ m 2 , vincristine 1.3mg/ m 2 by IV injection) every 3-weeks. Thoracic radiotherapy was considered for appropriate patients. Results: 219 patients (110 for CAV and 109 for PC) patients were randomized. Pre-treatment characteristics were well balanced for stage, performance status, and age. There was significantly more grade 3/4 neutropenia in the CAV arm than the PC arm, 67% vs 38% (p &lt; 0.005), whereas the PC arm, had more grade 3/4 thrombocytopenia (19% versus 8% p = 0.012). The PC arm had more grade 2 and 3 neuropathy. 56% grade 3 and 4 infections were observed on CAV arm and 35% on the PC arm (p &lt; 0.005). Hospitalization required for severe neutropenia and infections was less with PC, compared to CAV (146 days for IV antibiotics compared to 308 days for CAV, p &lt; 0.005). Response rates for CAV and PC were 59% and 61% respectively. One-year survival rates for the CAV arm was 6% and 13% for the PC arm. The intention to treat analysis concluded that there is statistical difference on the overall survival time in favor of PC (P = 0.014). Median survival was 94 days (CAV) and 154 (PC). Conclusions: CAV chemotherapy in SCLC patients is associated with higher risk of neutropenic sepsis than taxane based PC chemotherapy with no significant difference on the response rate. The overall survival was better for the PC arm. Final results will follow. No significant financial relationships to disclose.