tbuckley/cabot-search huggingface dataset:
Breaking barriers for T cells by targeting the EPHA2/TGF-β/COX-2 axis in pancreatic cancer
Authors: Jose R. Conejo-Garcia
Journal: Journal of Clinical Investigation (2019)

Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related death and is largely resistant to immunotherapies. The tumor microenvironment, largely composed of heterogeneous myeloid cells, creates a physical, metabolic, and immunosuppressive barrier that prevents T cells from infiltrating cancer beds. In this issue of the JCI, Markosyan and colleagues have reported a tumor-intrinsic mechanism that excludes T cells from the vicinity of tumor cells. They showed that a receptor tyrosine kinase, ephrin-A receptor 2 (EPHA2), regulates prostaglandin endoperoxide synthase 2 (PTGS2) (encodes COX-2) expression in a TGF-β signaling-dependent manner. Genetic ablation of Epha2 or Ptgs2 in preclinical models or pharmacological inhibition of COX-2 elicited the transformation of this immunosuppressive microenvironment into a T cell-permissive milieu. Consequent T cell relocation rendered this immunoresistant malignancy responsive to combinations of checkpoint blockers and CD40 agonists. Because the association between T cell infiltration and the EPHA2/TGF-β/COX-2 axis is supported by independent clinical data, these results provide a rationale for ensuing clinical trials aimed at incorporating pancreatic cancer into the range of immunotherapy-responsive tumors.
The effects of Oncotype DX recurrence scores on chemotherapy receipt in a multi-institutional breast cancer cohort.
Authors: F. O. Ademuyiwa, A. Miller, S. B. Edge, M. A. Thorat, G. W. Sledge, S. S. Badve
Journal: Journal of Clinical Oncology (2010)

669 Background: The use of traditional clinicopathologic features in decision making in early stage estrogen receptor (ER)-positive breast cancer (BC) may lead to over or under treatment. We investigated the effect of the Oncotype Dx (ODX) genomic profile on receipt of chemotherapy (CTX) in two tertiary cancer centers. Methods: 276 cases of node-negative ER positive BC from two tertiary cancer centers had ODX performed on tumor blocks between 2005 and 2009. Age at diagnosis, tumor size, grade, histology, presence of lymphovascular invasion, and PR status were abstracted from records and provided to 2 medical oncologists specializing in breast cancer. The Adjuvant! Online (AO) relapse risk and the Nottingham Prognostic index (NPI) were calculated. Results: Median age was 55 years (range, 29-82). 13% of patients had a negative PR status. Mean tumor size was 1.58 cm. Fifty percent had grade 2 BC, 38% and 12% were grade 1 and 3. The median 10 year AO relapse risk was 23 (range, 13-60). The median NPI was 3.4 with 80% of patients in the excellent or good category. The median ODX recurrence score was 17. 51%, 40%, and 9% of patients were in the low, intermediate, and high risk categories respectively. Prior to obtaining ODX, medical oncologists were more likely to recommend CTX to women who were younger (p < 0.0001), had negative PR status (p < 0.0001), higher NPI (p < 0.012), and tumors greater than 1 cm (p < 0.015). The average tumor size of patients recommended CTX was 2.0 cm versus 1.2 cm in the group not recommended CTX. The mean AO for those recommended CTX was 28.6 versus 18.9 for those not recommended CTX. ODX resulted in a change in management for 38% of individuals. Of 188 total patients who ultimately DID NOT receive CTX, 71 of them had an initial CTX recommendation. Of 88 patients who DID receive CTX, 34 of them did not have an initial recommendation. CTX was administered to 13/142 patients with low ODX, 52/110 with intermediate ODX, and 23/24 with high ODX. Only 3/24 women with high-risk ODX did not have an initial CTX recommendation. Conclusions: In our multi-institutional cohort, the ODX score had a significant impact on adjuvant chemotherapy decisions. No significant financial relationships to disclose.
5-alpha reductase inhibitors and risk of male breast cancer.
Authors: Mahyar Etminan, James Brophy, Abraham Hartzema, Joseph Delaney, Steven Bird
Journal: Journal of Clinical Oncology (2013)

e16013 Background: 5-alpha reductase inhibitors (5ARIs), finasteride and dutasteride, are one of the most popular classes of medications used by older men. The drugs are mainly used for the treatment of benign prostatic hyperplasia (BPH). There have been 50 cases of breast cancer potentially linked to both finasteride and dutasteride reported to the FDA. However, to date, no epidemiologic study has examined this potential link. Methods: We used the LifeLink database (IMS, USA) as the main source of data for this study. The database captures information on approximately 70 million US residents who are enrolled in a private healthcare plan. The database captures information on prescription drugs, hospitalizations, physician visits and demographics. Breast cancer cases were defined as those with a diagnosis (ICD-9-CM 175.X) on two days and either a procedural code (CPT-4) for a mastectomy or a lumpectomy/partial mastectomy with evidence of follow-up treatment (radiation/chemotherapy). The index date was deemed the first diagnostic or procedural code for breast cancer. This definition has been found to have a 93% positive predictive value for incident breast cancer. For each case, twenty controls were selected from the database using risk set sampling and matched on age within 5 years, date of diagnosis within six weeks and follow up time prior to the index date. We used logistic regression to compute adjusted rate ratios. The model was adjusted for the following covariates: age, calendar year, alcoholism, gynecomastia, Klinefelter’s disease, liver damage, obesity, oral estrogen, orchiectomy, and prior radiation. Results: There were 429 male breast cancer cases and matched them to 13,240 controls. 341 (79.5%) met our primary ascertainment, while 88 (20.5%) additional cases met our secondary criteria. We found no increased risk with male breast cancer and use of 1 year (RR=0.70, [95% CI0.34-1.45]) or 3 years of 5-ARIs therapy (RR=0.71, [95% CI:0.25-1.98]). Conclusions: We found no harmful association between sue of 5-ARIs and risk of male breast cancer. Future studies are needed to refute or confirm these findings.
Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) in unresectable advanced head and neck squamous cell carcinoma: Retrospective analysis of 300 cases and proposal for a prognostic index.
Authors: Alexandre Bozec, Nicolas Fakhry, Charlotte Dupuis, Benjamin Lallemant, Marc Alfonsi, Karen Benezery, Christian Righini, Bruno Guelfucci, Michel Beltran, Delphine Borchiellini, Gilles Poissonnet, Olivier Dassonville, Clara Schori, Antoine Giovanni, Frederic Peyrade
Journal: Journal of Clinical Oncology (2012)

e16055 Background: Phase III studies have demonstrated that induction chemotherapy with TPF followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced unresectable head and neck squamous cell carcinoma. These studies have been done in highly selected patients. The aim of our study is to confirm these data in unselected patients and to identify prognostic factors of tolerance and survival. Methods: Between October 2005 and June 2010, 300 patients from 5 institutions with locally advanced neck and head cancer received at least one induction cycle, followed by locoregional radiotherapy (R) associated or not with platinum (P) or cetuximab (C)-based chemotherapy. Results: Mean age was 56 years old (range 31-76). Performance status was 0 or 1 in 97% of patients and 50 % of them presented current alcohol intoxication. 69% (n=208) received 3 cycles of TPF, and 91% (n=268) underwent R associated or not with P (n=167) or C (n=51). 52% of patients (n=156) received the conform treatment (ie 3TPF + RP or RC). Grade 3-4 toxicities have been reported in 19% (n= 57), including 3% febrile neutropenia (n=9) and 7% kidney failure (n=22). Grade 3-4 toxicity, during TPF induction, led systematically to permanently discontinuation of the chemotherapy. Overall response rate after TPF induction was of 88% with 23% of complete response. After a median follow-up of 21 months, median progression-free survival and cause-specific survival (SS) were not reached. Median overall survival (OS) was 49 months (95% CI 31.2-66.8). SS and OS were significantly improved (p&lt;0.0001) in patients who received the conform treatment. In multivariate analysis the probability of death related to cancer or to toxicities induced by treatment was increased for hemoglobin level ≤ 12.6g/dl or GGT level ≥ 77U/I [HR = 3.45 (95% CI: 1.50-7.93) p=0.0029]. Conclusions: We propose to use a biological index based on baseline hemoglobin and GGT levels to select patient for induction therapy in SCCHN. This simple index, predictive of treatment conformity and specific survival, needs further prospectives investigations.
Randomized phase III trial of docetaxel and cisplatin combination chemotherapy versus mitomycin, vindesine and cisplatin combination chemotherapy with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer: Preliminary report
Authors: K. Kiura, Y. Segawa, M. Tabata, N. Takigawa, H. Kamei, S. Harita, H. Ueoka, S. Hiraki, K. Matsuo, M. Tanimoto
Journal: Journal of Clinical Oncology (2006)

7101 Background: Standard treatment of locally advanced non-small cell lung cancer (NSCLC) is cisplatin-based chemotherapy with concurrent thoracic radiation therapy (TRT). Furuse et al. demonstrated a superiority of mitomycin, vindesine and cisplatin (MVP) chemotherapy with concurrent TRT over that with sequential TRT (JCO 17, 1999). We demonstrated that docetaxel plus cisplatin (DP) chemotherapy with concurrent TRT shows better response rate and survival (Kiura K et al. BJC 89, 2003). We conducted a randomized phase III trial that compared DP with MVP in locally advanced NSCLC patients when concurrently administered with TRT. Methods: We randomly assigned patients with good performance status (PS)-stage IIIA/IIIB NSCLC to receive DP or MVP chemotherapy. Chemotherapy consisted of docetaxel 40 mg/m 2 and cisplatin 40 mg/m 2 on days 1, 8, 29, &amp; 36 in the DP arm and mitomycin 8 mg/m 2 on days 1 &amp; 29, vindesine 3 mg/m 2 on days 1, 8, 29, &amp; 36, and cisplatin 80 mg/m 2 on days 1 &amp; 29 in the MVP arm. In the both groups, TRT began on day 1 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Results: Two hundred patients entered the trial between July 2000 and July 2005. Pretreatment characteristics were well balanced between the two treatment arms as follows: male/female 92/7, 88/13; median age (range) 65 (40–75), 64 (34–75); stage IIIA/IIIB 33/66, 33/68; and PS of 0/1 46/53, 50/51, for the DP arm and for the MVP arm, respectively. The response rates for the DP arm and the MVP arm were 78.8% and 70.3%, respectively. The 1- and 2-year survival rates were 81.8% and 59.9% for the DP arm, and were 68.8% and 49.1% for the MVP arm, respectively. Median follow up time is 1.4 years in January 2006. Complete analysis will be fixed in July 2007. Conclusions: The DP arm is exactly reproducing the response rate and survival of the phase II trial we have previously reported. The MVP arm seems to reveal better results than that we expected. Radiation dose and schedule might explain the difference because Furuse et al. splitted 56 Gy of TRT in the MVP arm whereas we did not split 60 Gy of TRT. No significant financial relationships to disclose.
Patient Assistance Programs and Anti-Kickback Laws
Authors: Katherine Kraschel, Gregory Curfman
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lung cancer screening: enhancing risk stratification and minimising harms by incorporating information from screening results
Authors: Emma Louise O'Dowd, Kevin ten Haaf
Journal: Thorax (2019)

Two large randomised controlled trials of screening for lung cancer with low-dose CT (LDCT)—the National Lung Screening Trial (NLST) and the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial)—have both shown substantial lung cancer mortality reduction in the LDCT arm.1 

Although there is now strong evidence that screening for lung cancer with LDCT reduces lung cancer mortality, concerns have been raised about the potential costs and harms of implementing annual lung cancer screening programmes. Annual screening with LDCT has been recommended in the USA, based on the evidence provided by the NLST design and modelling extrapolations.2 3 However, uptake of screening has been poor, with the latest data showing only 3.9% of those eligible have actually been screened.4 A cost-effectiveness analysis for Ontario, Canada, showed that annual screening scenarios were more cost-effective than biennial screening,5 but there is ongoing debate about whether all of those eligible for lung cancer screening actually require an annual LDCT.

NELSON was the only trial to compare the effects of different screening intervals between rounds. While the proportion of advanced stage cancers increased somewhat, a 2-year interval still had a good performance compared with a 1-year interval. However, there was an increase in interval cancers and a higher proportion of more advanced stage cancers for a 2.5-year interval compared with a 2-year interval suggesting that this may be too long.6 

Risk prediction models have been suggested to select eligible participants at high risk of lung cancer and have been shown to be superior to selection using age and smoking status alone.7 8 Incorporating information from LDCT results may allow them to aid in the personalisation of the screening regimen. In NELSON, participants with negative LDCT results were less likely to have lung cancer detected at a …
Evidence for the Full Potential of Daily Food Choices to Minimize Premature Mortality
Authors: William J. McCarthy, Folasade May
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The Relevance of Hospital Rankings in the Laparoscopic Era
Authors: Samer G. Mattar
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations
Authors: Andrea Visentin, Francesca Romana Mauro, Serena Rosati, Silvia Imbergamo, Edoardo Scomazzon, Stefano Pravato, Federica Frezzato, Veronica Martini, Filippo Severin, Flavia Raggi, Robin Foà, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2018)
Preoperative chemotherapy followed by resection vs. surgery alone for locally advanced esophageal carcinoma: Interim analysis of a randomized study
Authors: I. Stilidi, V. Bokhyan, A. Tryakin, E. Suleymanov, P. Kononets, O. Malikhova, S. Tjulandin
Journal: Journal of Clinical Oncology (2006)

4055 Background: Outcome of the patients (pts) with locally advanced esophageal cancer is poor. A prospective trial was undertaken to investigate whether preoperative chemotherapy (CT) followed by surgery results in increase of disease free survival (DFS) in pts with locally advanced resectable thoracic esophageal cancer. Methods: Previously untreated pts with stage T 3–4 N 0–1 M 0 , T 1–2 N 1 M 0 resectable esophageal cancer were eligible for the study. After clinical evaluation (incl. chest CT-scan, endosonography) they were randomized into CT (two cycles of FLEP: cisplatin 80 mg/m 2 , day 1; etoposide 80 mg/m 2 d 1–3, leucovorine 20 mg/m 2 and 5-fluorouracil 425 mg/m 2 , bolus, days 1–3; every 21 days) followed by surgical resection (Ch-S group), or resection alone (S group). Four weeks after completion of CT pts underwent transthoracic extended 2 or 3-field esophagectomy with intrapleural esophago-gastrostomy through I. Lewis approach. Results: From March 2001 to September 2005 78 pts (Ch-S group, n=38; S group, n=40) were treated in our center. Median f.-up for survived pts was 20 (range, 3–53) months. All pts but one had squamous cell carcinoma. Pts’ characteristics (tumor stage and histology, coexisting disorders, age and gender) were well balanced between the two treatment groups. Main toxicity of CT was hematological, with neutropenia gr. 4 was observed in 7 (18%) pts. There was no other serious toxicity as well as preoperative toxic deaths. Complete response was observed in 3 (7,9%) pts, partial response in 23 (60,5%) pts, progression of disease in 3 (7,9%) pts of Ch-S group. Rate of R0 resection was higher in Ch-S group (86,8%) compared with S group (65%, p=0,03). There was no difference in postoperative mortality between both groups. 3-year DFS was 58,3% vs. 27,7% (p=0,01) and 3-year overall survival was 62,9% vs. 39,8% (p=0,08) in Ch-S and S groups, respectively. Conclusions: Two cycles of preoperative CT improve DFS in pts with resectable locally advanced thoracic esophageal cancer. Accrual is continuing. No significant financial relationships to disclose.
Phase I/II trial of intraperitoneal implantation of agarose-agarose macrobeads (MB) containing mouse renal adenocarcinoma cells (RENCA) in patients (pts) with advanced colorectal cancer (CRC).
Authors: Allyson J. Ocean, Tapan Parikh, Nathaniel Berman, Juliet Escalon, Manish A. Shah, Zoe Andrada, Eugene Akahoho, Janice M. Pogoda, George B. Stoms, Verula B Escobia, Joseph T. Ruggiero, Thomas J. Fahey, Barry H. Smith
Journal: Journal of Clinical Oncology (2013)

e14517 Background: RENCA tumor cells encapsulated in two concentric agarose layers which release signals to treat advanced cancers is a novel concept that has been substantiated in in vitro and in vivo models as reported in Cancer Research 71(3), 716-735, 2011.We report results of a phase I/II study in advanced CRC pts. Methods: Previously-treated advanced CRC pts (ECOG PS 0-2) were enrolled with informed consent obtained. Pts had intraperitoneal implantation up to 4 times via laparoscopy with 8 (37/40 pts- established dose) or 16 (3/40 pts) RENCA MB/kg. Serial exams, lab profiles, and imaging were done pre- and 3 months (mo.) post-implant to assess efficacy. Endpoints of safety, tumor marker decrease, response, and overall survival (OS) were evaluated. Results: 40 pts were implanted with RENCA MB (12 pts phase I; 28 pts phase II); 17M: 23F. Mean age 58.3. 14/40 pts had &gt;1 implant (≥2: 14 pts; ≥3: 2 pts; =4: 2 pts). Response to MB is marked by a prominent initial rise in CRP, ESR, and IL-6, indicating a systemic inflammatory response (SIR) (100% of pts) and a parallel decrease in CEA and/or CA 19-9 in approximately 70%. SIR including its accompanying fatigue and anorexia lasts days to 3 wks. Overall, there was a statistically significant difference (p=0.009) in OS between the 70% of pts showing a decrease in tumor markers by at least 20% during the first 30 days post-implant (OS; 9.7 mo., C.I. 6.5-13.5) and those who did not (OS; 4.4 mo., C.I. 1.1-7.6). On PET-CT imaging, a striking feature of response, most often seen in pts with the longest OS, is tumor necrosis. MB were well-tolerated and no Grade ≥3 adverse events were treatment-related. Conclusions: For advanced, treatment-resistant CRC pts, early response to MB implantation characterized by tumor marker decrease in association with SIR correlates with a statistically significant increase in OS. RENCA MB represent a possible new therapeutic option for late-stage CRC. Clinical trial information: NCT01053013.
Abstract 18094: Cost-effectiveness of Cardiac Magnetic Resonance Imaging Used in Suspected Coronary Ischemia - A Post-hoc Analysis of a Natural Experiment
Authors: George Petrov, Sarah Kern, Sebastian Kelle, Eckart Fleck, Ernst Wellnhofer
Journal: Circulation (2012)

BACKGROUND: Stress cardiac magnetic resonance imaging (SCMR) was not established as a test for coronary ischemia in 2003. Thus SCMR was an optional step in the decision on coronary angiography (CA)...