tbuckley/cabot-search huggingface dataset:
Risk of second primary cancers after treatment for locoregional rectal cancer.
Authors: Chaitali Singh Nangia, Thomas H. Taylor, Walter Tsang, Jason Wong, Joseph Carmichael, William Karnes, Jason A. Zell
Journal: Journal of Clinical Oncology (2013)

3578 Background: The risk of second primary colorectal cancers among rectal cancer patients has been described, but little is known about the risk of non-colorectal malignancies that may occur in the field of radiation. We attempted to quantify the risk, using data from the large population-based California Cancer Registry (CCR). Methods: We analyzed the CCR data for surgically-treated locoregional rectal cancer cases, diagnosed during the period 1988–2009. We excluded cases with second primary tumor (SPT) diagnosed within 12 months of initial diagnosis . Radiation treatment used was external beam radiation therapy. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to evaluate risk as compared to the underlying population after matching for age, sex, ethnicity, and time. Results: Of the study cohort of 13,418 rectal cancer cases, 1572 cases of SPTs were observed . The SIR was increased for small intestine cancer among cases receiving radiation treatment (4 cases observed vs. 1.01 cases expected; SIR=3.94, 95% CI 1.07-10.10) but not among cases lacking radiation treatment (4 observed vs. 4.45 expected; SIR=0.90, 5% CI 0.24-2.30). Among females treated with radiation, the SIR was increased for uterine cancer (12 observed vs. 5.59 expected; SIR=2.15, 95% CI 1.11 to 3.75) but not among cases lacking radiation therapy (23 observed vs. 26.17 expected; SIR=0.88, 95% CI 0.56-1.32). Among males receiving radiation treatment, the SIR for prostate cancer was decreased (23 observed vs. 69.78 expected; SIR=0.33; 95% CI 0.21 to 0.49) but of borderline significance among males lacking radiation therapy (243 observed vs. 276.97 expected; SIR=0.88, 95% CI 0.77-0.99). No significant differences were observed for cancers of the vagina, cervix, ovary, kidney, bladder, penis, testes, or leukemia based on prior radiation treatment for rectal cancer. Conclusions: Patients receiving pelvic radiation for treatment of rectal cancer have a subsequently higher than expected incidence of small intestine and uterine cancer. The incidence of prostate cancer appears to fall after pelvic radiation. These unexpected findings suggest complex relationships associated with radiation treatment for rectal cancer and SPT risk.
Development of invasive disease in 433 women treated for vulvar, vaginal or perianal intraepithelial neoplasia
Authors: M. K. Fehr, K. J. Dedes, S. Heinzl, M. D. Mueller, M. Baumann, D. Fink
Journal: Journal of Clinical Oncology (2006)

5043 Background: The incidence of intraepithelial neoplasia (IN) of the lower anogenital tract is increasing. Due to small case-series, the malignant potential of treated high-grade IN is not well defined and risk factors for progression are not established. Methods: Patients with IN of the vulva (VIN), vagina (VAIN) and perianal skin (PAIN) were identified in the electronic databases of three university colposcopy clinics. Inclusion criteria were biopsy proven IN grade 2–3 (high-grade) and no history of vaginal, vulvar or anorectal cancer. Excluded were patients with the diagnosis of invasive disease within one year from initial diagnosis of IN. Results: 442 patients were identified from 1977 to 2005 with a mean follow up of 69.9 ± 56.1 months. Initial diagnosis was VIN III in 75.3%, VIN II in 17.2%, VAIN II in 4.3%, VAIN III in 2%, and PAIN II/III in 1.1% of patients. Mean age at initial diagnosis was 47.1 ± 14.1 (range, 18–102). Initial treatment was biopsy and laser evaporation in 61.5%, surgical excision in 32.8%, and other locally destructive methods in 3.1% of patients. 9 patients refused any treatment (2.0%). In the 433 treated patients, recurrent disease (e.g. diagnosed &gt;1 year after initial diagnosis) occurred in 32.2%. In patients with a follow up longer than 5 years, 14.4 % were still experiencing recurrences. In multivariate analysis, immunosuppression (OR: 2.33, 95% CI 1.06–5.06, p = 0.035) was associated with recurrence but not smoking, age or histological grade. Progression to invasive disease occurred in 3.8% of treated patients within a mean time of 7.9 ± 6.8 years (range, 1.3–24.5). In multivariate analysis, immunosuppression (OR:3.31, 95% CI 1.01–10.93, p = 0.049) and smoking (OR:3.12, 95% CI 1.07–9.08, p = 0.037) were independent risk factors for progression. Conclusions: Anogenital IN is a chronic disease in a substantial proportion of patients. The malignant potential is remarkably high despite repeated treatments. Therefore, long lasting surveillance is mandatory, especially in immunosuppressed or smoking patients. No significant financial relationships to disclose.
BMA's representation of clinical and medical directors
Authors: M. Rosenberg
Journal: BMJ (1995)

agents in minimal change nephropathy is contro- versial.This implies that the benefits are unproved, whereas a definite, sustained effect has been shown in controlled trials.3There are, however, side effects associated with these agents, and the authors are correct in stating that their use should be carefully considered.The consensus statement lists two clear indications for second line treatment.(1) Relapse while taking prednisolone > 0 5 mg/kg on alternate days plus one or more of (a) unaccept- able side effects of corticosteroid treatment; (b) high risk of steroid toxicity-for example, in boys approaching puberty or in diabetes; (c) unusually severe relapses (hypovolaemia or thrombosis); and (ad) inadequate facilities for follow up or concern about compliance.(2) Relapse while taking prednisolone > 1 mg/kg on alternate days.The recommended dose of cyclophos- phamide is 3 mg/kg/day for eight weeks.The report describing fewer relapses in children treated with cyclophosphamide for 12 weeks was limited to patients with steroid dependent disease.4
Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk—Reply
Authors: Jae Jeong Yang, Danxia Yu, Xiao-Ou Shu
Journal: JAMA Oncology (2020)

In Reply We have carefully reviewed the letter from Wu and Leung regarding our recent JAMA Oncology article on fiber and yogurt consumption and lung cancer risk.1 We believe that there were misunderstandings and misinterpretations of the study design and results.
HOME-TIME AFTER DISCHARGE AMONG PATIENTS WITH TYPE 2 MYOCARDIAL INFARCTION
Authors: Cian P. McCarthy, Sean Murphy, Saad Rehman, Maeve Jones-O'Connor, David Olshan, Joshua Cohen, Avinainder Singh, Jinghan Cui, Muthiah Vaduganathan, James Januzzi, Jason H. Wasfy
Journal: Journal of the American College of Cardiology (2020)
Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types
Authors: Yu-Tong Chen, Jia-Yi Shen, Dong-Ping Chen, Chen-Fei Wu, Rui Guo, Pan-Pan Zhang, Jia-Wei Lv, Wen-Fei Li, Zi-Xian Wang, Yu-Pei Chen
Journal: Journal of Hematology & Oncology (2020)

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.
A phase II trial of neoadjuvant dasatinib (Neo-D) in muscle-invasive urothelial carcinoma of the bladder (miUCB): Hoosier Oncology Group GU07-122 trial.
Authors: Noah M. Hahn, Siamak Daneshmand, Edwin M. Posadas, Michael O. Koch, Richard Bihrle, Richard Foster, Timothy A. Masterson, Liang Cheng, Ziyue Liu, Timothy Breen, Mark T. Fleming, Ray Lance, Christopher W. Ryan, Christopher L. Corless, Matt D. Galsky, Ajjai Shivaram Alva, Carmen Mitchell, Steven S. Shen, Seth P. Lerner, Guru Sonpavde
Journal: Journal of Clinical Oncology (2012)

4586 Background: Neoadjuvant chemotherapy (NC) preceding radical cystectomy (RC) is an accepted standard for miUCB patients (pts). Dasatinib (D) is an oral tyrosine kinase inhibitor of Src mediated signaling, and has demonstrated promising preclinical anti-tumor activity, providing a rationale to evaluate Neo-D in human miUCB. Methods: A phase II trial was conducted to assess the safety and biologic activity of Neo-D in miUCB. Key eligibility criteria included: miUCB (T2-T4a, N0, M0), unsuitable or willing to forego platinum-based NC, adequate TURBT tissue available, ECOG PS 0-1, creatinine &lt; 2 x ULN. Pts received D 100 mg po once daily for 28 +/- 7 days followed by RC 8-24 hours after the last dose. The primary endpoint was feasibility defined as &gt; 60% of pts completing therapy without treatment-related dose limiting toxicity (DLT) specified as grade 4 hematologic toxicity, grade 3 non-hematologic toxicity, or any grade 2 toxicity &gt; 14 days. Secondary endpoints included the assessment of biologic activity as assessed by pre- and post-treatment tumor tissue immunohistochemistry analysis of Src, pSrc, EPHA2, pEPHA2, FAK, pFAK, AKT, pAKT, CD31, Ki67, TUNEL. Results: The study completed accrual with enrollment of 25pts. 22 and 24 pts were respectively evaluable for feasibility and toxicity endpoints. Patient demographics included: median age – 62, M/F – 20/5, ECOG PS 0/1 – 19/6. Baseline tumor staging included: T2 – 17, T3 – 7. The study achieved its primary endpoint with 15 pts (68%) completing therapy without treatment related DLT’s. DLT’s included: fatigue (2 pts), DVT/PE, abdominal pain, supraventricular tachycardia, enteric fistula, and hematuria (1 pt each). Frequency of highest observed toxicity on study included: Grade 1 – 13%, Grade 2 – 38%, Grade 3 – 46%, Grade 4 – 4%. Among 22 patients, pathologic stage at RC was T1/Tis in 3 pts (14%), ≥T2 in 19 pts (86%), and node positive in 6 pts (27%). Correlative analyses of pre- and post-treatment tumor Src signaling are ongoing and will be updated at the meeting. Conclusions: Neoadjuvant dasatinib preceding RC is feasible in miUCB patients. Tumor tissue correlative studies may provide directions for further development.
Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects
Authors: Inês Mahú, Andreia Barateiro, Eva Rial-Pensado, Noelia Martinéz-Sánchez, Sandra H. Vaz, Pedro M.S.D. Cal, Benjamin Jenkins, Tiago Rodrigues, Carlos Cordeiro, Miguel F. Costa, Raquel Mendes, Elsa Seixas, Mafalda M.A. Pereira, Nadiya Kubasova, Vitka Gres, Imogen Morris, Carolina Temporão, Marta Olivares, Yolanda Sanz, Albert Koulman, Francisco Corzana, Ana M. Sebastião, Miguel López, Gonçalo J.L. Bernardes, Ana I. Domingos
Journal: Cell Metabolism (2020)

Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PEGyAMPH) to exclude its central action. PEGyAMPH does not enter the brain and facilitates SNS activity via theβ2-adrenoceptor, protecting mice against obesity by increasing lipolysis and thermogenesis, coupled to higher heat dissipation, which acts as an energy sink to increase energy expenditure without altering food intake or locomotor activity. Thus, we provide proof-of-principle for a novel class of exclusively peripheral anti-obesity sympathofacilitators that are devoid of any cardiovascular and brain-related side effects.
RESTING ST SEGMENT ABNORMALITY IS AN INDEPENDENT PREDICTOR OF MORTALITY IN ASYMPTOMATIC PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Anwesh Poosala, Kolade M. Agboola, Sonia Fortin Gamero, Vuyisile Tlhopane Nkomo, Thomas G. Allison
Journal: Journal of the American College of Cardiology (2020)
Follicular lymphoma in the elderly: A different disease?
Authors: Judit Rubio, Fernando Franco, Andrea Ruiz-Valdepeñas, Magda Palka, Elena Almagro, David Perez, Miriam Mendez, Blanca Cantos, Isabel Millán, Mariano Provencio Pulla
Journal: Journal of Clinical Oncology (2013)

e19532 Background: The aim of this study was to evaluate the characteristics of patients older and younger than 70 years diagnosed with follicular lymphoma (FL). Methods: A review of the clinical database of 131 patients with LF treated in our hospital between May 1980 and January 2013 was performed. Clinical, treatment, and following items were obtained. Results: 34 patients were 70 years of age or older (70.6 to 83.9 years) and 98 were younger (23-69.3 years), without significant differences with respect to gender, histology grade, stage and Performance Status. The extranodal involvement sites in the younger group were more frequent in spleen (17.1%), liver (17.1%), bowel (14.3%) and head and neck (11.4%), meanwhile in the eldest were in lung (35.7%), bone (21.4%) and pleura (14.3%), with significant differences (p=0.007). The median Overall Survival (OS) was 8.1 years (1.2-31.4) in the younger group and 4.3 years (1.2-7.2) in the older group. The median of probability of Free Progression Survival (FPS) was 3.2 years (0.1-31.4) in younger patients and 1.7 years (0.1-5.5) in older patients. It exists significant differences in the probability of OS and FPS (both p&lt;0.001), with worse results in older patients. The analysis of the causes of death (FL, second tumour or other causes) does not demonstrate significant differences between both groups. Differences were not found between the age groups when CHOP versus CVP was used. Not using rituximab in addition to CHOP scheme implies a relative risk of relapse of 3.3 (95% IC 1.5-6.9 p&lt;0.001). Conclusions: It should be noted a worse OS and FPS in the older population. Nevertheless, the different extranodal involvement suggests a different biologic behaviour in both groups. [Table: see text]
Biweekly regimen of nonpegylated liposomal doxorubicin with cyclophosphamide, vincristine, and prednisone plus rituximab (R-COMP-14) as primary treatment for diffuse large B-cell lymphoma (DLBCL): Long-term follow-up of a phase II study.
Authors: Joaquin Herrero, Jose Gómez-Codina, Mariano Provencio, Antonio Rueda, Pilar Sabin, Marta Llanos, Francisco Lobo, David Vicente, Francisco Ramon Garcia Arroyo
Journal: Journal of Clinical Oncology (2012)

8062 Background: To evaluate the efficacy and toxicity of dose-dense biweekly schedule of (R-COMP-14) in patients newly diagnosed of agrressive diffuse B cell lymphomas (DLBCL). Methods: In this single-arm, open-label, multicenter trial, 60 pts were included between 2004 to 2008. Received rituximab (375 mg/m 2 ) D1 + cyclophosphamide (750 mg/m 2 )D1 + vincristine (1.4 mg/m 2 ; max. 2 mg)D1 + prednisone (100 mg/d D1 and D5) and non-pegylated liposomal doxorubicin (50 mg/m 2 ) every two weeks. Response was assessed at cycle 3, and patients with complete or partial response received 5 additional courses. Granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim was administered on day 2. The primary efficacy endpoint was (CR) and objective response rate (ORR). Survival follow-up data were updated. Results: 59 evaluable patients with a median age of 50 years (21-65) were analyzed. Clinical Characteristics: 22 Pts stage I-II (aaIPI≥1 (37%), 17 (29%) stage III, and 19 (32%) in stage IV. aaIPI=1 41(67%), aaIPI2/3= 18(33%).LVEF basal: 65,5[50-93]. Extra-nodal disease: 42%. B symptoms: 44.1%. The mean calculated dose intensities of cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and rituximab were 98,7%, 98,7%, 76,1% and 98,3% respectively. Among 60 eligible patients (96,7% completed six cycles and 74,4% completed all eight cycles. ORR was 81%, and CR rate of 54,2%. IC 95% [40,7-67,8]. The main toxicity was neutropenia Gr=III-IV/ and febrile neutropenia in 20% of patients. Neurotoxicity Gr=III-IV in 3,4%. No cardiac toxicity Gr: III-IV was reported. No toxic deaths. After a median follow-up of 25-64m(44m) the 5-year overall survival (OS), event-free survival, (EFS) and disease free survival (DFS) were 80%, 67%, and 77% respectively. Forty two patients (71%) had (&lt;60 y) and med. OS(p=0,017) and med EFS(p=0,014) was 72,3% and 68,1 in aaIPI=1 and 50,4% and 33,8 in aaIPI&gt;1. Conclusions: Dose dense R-COMP-14 is an effective regimen in patients with (DLBCL) comparable o R- CHOP-14. Good tolerability profile with no Gr: III-IV cardiac toxicity or reduction of LVEF.
Safety data of cabazitaxel in patients treated for metastatic castration-resistant prostate cancer after docetaxel treatment: Results of a cohort of patients during the temporary authorization for use in France (ATU).
Authors: Nadine Houede, Jean-Christophe Eymard, Zoubir Tahar
Journal: Journal of Clinical Oncology (2012)

e15142 Background: The TROPIC (Johann Sebastien de Bono et al ; Lancet 2010) study demonstrated that cabazitaxel (a novel tubulin-binding taxane drug) improves overall survival of patients (pts) with mCRPC who progressed during or after docetaxel-based chemotherapy, with a median survival of 15.1 months. Based on this result, a compassionate-use program has been established to provide pts with mCRPC the opportunity to receive the treatment, before licensing of the drug. Methods: ATU of cabazitaxel in France has been granted before its marketing authorization; all safety data from pts treated during this period were collected following a specific therapeutic use protocol. All participating physicians were instructed about the molecule by a company physician and contacted before the first treatment, on day 15 and at the end of treatment of each patient to make sure that all G3/4 and serious adverse events were collected. Results: We report baseline characteristics and safety data from the 184 pts treated in 92 French centers. Median age was 67.2 years (46 - 92), ECOG performance status was 0-1 for 85% of pts, 88% had bone metastases and 21% had visceral metastases. All the pts had received prior docetaxel, 55% had discontinued for disease progression; 85% of the pts received previously 1-2 lines of chemotherapy. Pts received a median of 3 cycles of cabazitaxel (1-6). Rates of grade 3-4 hematological toxicities were: neutropenia grade≥ 3 (4%), febrile neutropenia (3%), all resolved. All grade other toxicities were: nausea (0.5%), diarrhea (2.7%) and fatigue (0.5%). No treatment-related death was reported. Conclusions: The ATU program provides additional safety information on cabazitaxel in the real-life setting; they are consistent with the TROPIC study safety results. The incidence of neutropenia grade≥ 3 (4%) and febrile neutropenia (3%) appears to be lower than expected. Therapeutic use protocols such as these can be helpful for physicians when new therapies become available. Proactive education of healthcare givers on AEs management could be considered when new treatments are introduced.
Abstract 9682: Experience of Three Years of Balloon Pulmonary Angioplasty in a Single Centre: Safety and Short Term Results
Authors: Massimiliano Palazzini, Francesco Saia, Enrico Gotti, Nevio Taglieri, Fabio Dardi, Elisa Zuffa, Alessandro De Lorenzis, Filippo Pasca, Daniele Guarino, Ilenia Magnani, Andrea Rinaldi, Alessandra Manes, Nazzareno Galiè
Journal: Circulation (2019)

Introduction: balloon pulmonary angioplasty (BPA) has recently been developed as an alternative and less-invasive treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH) but th...
CLINICAL OUTCOMES OF PATIENTS WITH AND WITHOUT CHRONIC KIDNEY DISEASE UNDERGOING ENDOVASCULAR REVASCULARIZATION OF INFRAINGUINAL PERIPHERAL ARTERY DISEASE: INSIGHTS FROM THE XLPAD REGISTRY
Authors: Ryan Kabir, Bassel Bou Dargham, Yulun Liu, Ishita Tejani, Avantika Banerjee, Khusrow Niazi, Subhash Banerjee
Journal: Journal of the American College of Cardiology (2020)
LONG-TERM OUTCOMES AMONG PATIENT UNDERGOING PCI FOR OSTIAL LESIONS: AN INDIVIDUAL PATIENT-DATA POOLED ANALYSIS OF 4 RANDOMIZED CONTROLLED TRIALS
Authors: Mayank Yadav, Gary Mintz, Sorin J. Brener, Ajay Kirtane, Philippe Genereux, Mahesh Madhavan, Bjorn Redfors, Mengdan Liu, Pieter Smits, Clemens von Birgelen, Patrick Serruys, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow
Authors: Kelly L. Betterman, Drew L. Sutton, Genevieve A. Secker, Jan Kazenwadel, Anna Oszmiana, Lillian Lim, Naoyuki Miura, Lydia Sorokin, Benjamin M. Hogan, Mark L. Kahn, Helen McNeill, Natasha L. Harvey
Journal: Journal of Clinical Investigation (2020)

The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteolytic cleavage and activation of VEGF-C. The fact that FAT4, CCBE1, and ADAMTS3 mutations underlie Hennekam syndrome suggested that all 3 genes might function in a common pathway. We identified FAT4 as a target gene of GATA-binding protein 2 (GATA2), a key transcriptional regulator of lymphatic vascular development and, in particular, lymphatic vessel valve development. Here, we demonstrate that FAT4 functions in a lymphatic endothelial cell-autonomous manner to control cell polarity in response to flow and is required for lymphatic vessel morphogenesis throughout development. Our data reveal a crucial role for FAT4 in lymphangiogenesis and shed light on the mechanistic basis by which FAT4 mutations underlie a human lymphedema syndrome.