tbuckley/cabot-search huggingface dataset:
Impact on survival of primary tumor resection in patients with colorectal cancer and unresectable metastasis: Pooled analysis of individual patients’ data from four randomized trials.
Authors: Matthieu Faron, Abderrahmane Bourredjem, Jean-Pierre Pignon, Olivier Bouche, Jean-Yves Douillard, Antoine Adenis, Dominique Elias, Michel Ducreux
Journal: Journal of Clinical Oncology (2012)

3507 Background: In patients with colorectal cancer (CRC) and unresectable metastasis, the prognostic impact of primary tumor resection still remains a matter of debates. The goal of this study was to estimate, after adjustment for prognostic factors, the effect of primary tumor resection on survival. Methods: Individual patients’ data of the 1155 patients with metastatic CRC included in 4 first-line chemotherapy trials (FFCD 9601, FFCD 2000-05, ACCORD 13 and ML 16987) where retrieved. Patients were eligible for this study if they had synchronous metastasis judged unresectable. Primary endpoint was overall survival (OS), secondary endpoint was progression free survival (PFS). A Cox proportional hazard model stratified on the trial was used to estimate the impact on survival. Results: 810 patients beginning first-line chemotherapy with either fluoropyrimidine alone, oxaliplatin, irinotecan and/or bevacizumab were eligible. Patients with a history of resection (n = 478 (59%)), as compared to those without (n = 332 (41%)), were more likely to have colonic primary (p &lt; 0.0001), lower carcino embryonic antigen (CEA) (p &lt; 0.0001) or alkaline phosphatase (ALP) level (p=0.04) and normal white blood cell count (WBC) (p &lt; 0.0001). In the univariate analysis, stratified on the trial, primary tumor resection was associated with a better OS (Hazard Ratio HR: 0.73 [0.63-0.84]; p &lt; 0.0001) and PFS (HR : 0.73 [0.63-0.84]; p &lt; 0.0001). Multivariate analysis, adjusted for primary tumor location, CEA, ALP and WBC levels, OMS performance status and number of metastatic sites confirmed that primary tumor resection was an independent predictor of better OS (HR : 0.63 [0.53-0.75] ; p &lt; 0.0001), and PFS (HR : 0.82 [0.70-0.95] ; p = 0.0007). Significant interactions were found between resection and CEA level (p=0.02) and resection and primary tumor location (p=0.01) for OS (not for PFS) with a lower impact of resection with higher CEA levels or a colonic primary. Conclusions: This study confirmed the independent prognostic value on survival of primary tumor resection in patients with unresectable metastases of CRC.
Believe the H.I.P.E.: Hematology-Oncology Inter Professional Education to improve provider collaboration at an inpatient tertiary medical center.
Authors: Richard Lewis Martin, Anna Hux, Ryan Miller, Mario Davidson, Leora Horn, Jill Gilbert
Journal: Journal of Clinical Oncology (2019)

10538 Background: With projected provider shortages and increasing pharmaceutical complexity, Advanced Practice Providers (APPs) and Pharmacists are becoming increasingly utilized members of hematology/oncology teams. Despite significant interdependence in practice, inter-professional training remains rare. Medical IPE has been shown to improve learning satisfaction and attitudes, however, IPE has seldom incorporated inter-professionalism into content development nor has it been evaluated in terms of sustainability. Methods: We developed a pilot IPE curriculum consisting of six, 1-hour long, case-based sessions. A preparation phase required a lead APP, Fellow, and Pharmacist to collectively build a case around three teaching points; 1) diagnosis, 2) treatment, and 3) coordination of care. The APP and Pharmacist presented the case while the Fellow moderated to ensure active participation among all groups. Surveys on collaboration, interaction, interest, and connection, as well as open-ended comments on strengths and areas for improvement were collected after each session ( &gt; 80% completion rate). Results: With 3 of 6 sessions completed (02/19), attendance was stable, averaging 10 of 18 (Fellow), 5 of 8 (APP), and 3 of 6 (Pharmacist). Sessions were rated an average of 4.6/5 on collaboration, 4.5/5 interactive, 4.7/5 application, 4.3/5 communication, and 4.2/5 professionalism. 69% of attendees reported being more likely to attend future conferences. 65% reported feeling more connected to the care team. The most common suggestion for improvement was giving more teaching opportunities to the APPs. Session leaders were initially recruited but quickly transitioned to eager volunteers. Conclusions: Our IPE curriculum shows promising initial sustainability with perceived high marks in collaboration and applicability. Incorporating inter-professionalism into content development and longitudinal delivery to providers in practice provides a novel approach to educating IP teams. Future steps include ensuring continued sustainability, conducting qualitative and quantitative analysis, and dissemination to other units.
Combining tumor destruction by electrochemotherapy and innate immunity by CpG-ODN: Toward a new combination treatment for melanoma with skin metastases
Authors: S. Roux, B. Al Sakere, C. Bernat, P. Opolon, J. Garbay, V. Billard, L. Zitvogel, A. Carpentier, L. Mir, C. Robert
Journal: Journal of Clinical Oncology (2006)

12507 Background: Electrochemotherapy (ECT), consisting of electroporating cytotoxic agents (bleomycin or cisplatinum) in tumors, is effective in inducing destruction of cutaneous or subcutaneous tumors and can be used as a palliative treatment for patients with skin melanoma metastases. Our objective was to combine the antigen release induced by ECT with a potent and adapted stimulation of the innate immune system in order to induce a systemic anti-tumor response. Methods: The preclinical work was performed on murine models of skin tumors: fibrosarcoma (LPB) and melanoma (B16F10). We found that electrochemotherapy induced the recruitment of immune cells expressing CD11-c and Mac-1 in the first 48h after the treatment. By quantitative RT-PCR, we showed that this immune cell infiltrate was associated with an increase of TLR9 RNA expression. Therefore, we decided to combine ECT with intra-tumoral injection of TLR9 ligands: unmethylated CpG oligodeoxynucleotides (CpG-ODN). The distant and local antitumoral effect of this association (ECT + CpG-ODN) were tested in mice bearing a tumour on the two flanks (fibrosarcoma or melanoma). Animals were treated on the left flank only by a unique ECT course followed by intratumoral injection of CpG-ODN. Tumor growth rates were monitored on both treated (left) and non-treated (right) sides in order to assess direct and systemic antitumor effects of the association respectively. Experiments were also performed on nude mice, in order to investigate the role of lymphocytes in the systemic antitumor effect. Results: Compared to the separated treatments alone we found an increased local efficacy of the ECT-CpG-ODN, but, more importantly, we demonstrated a clear systemic effect of the combination on the controlateral tumors. In nude mice, no effect was observed in controlateral tumors suggesting a mechanism mediated by T lymphocytes. No significant financial relationships to disclose.
ENDURANCE SPORT PARTICIPATION IS ASSOCIATED WITH INCREASED SYNCOPE IN ADOLESCENTS: AN ANALYSIS OF THE HEARTBYTES SCREENING REGISTRY
Authors: Jennifer Wellings, Abhinav Nair, Max Weiss, Sean Dikdan, Drew Johnson, Renee Langstaff, Chris Koilor, Miller Stanton, David M. Shipon
Journal: Journal of the American College of Cardiology (2020)
CLO20-054: A Phase 2 Trial of Nivolumab and Temozolomide in Advanced Neuroendocrine Tumors (NETs): Interim Efficacy Analysis
Authors: Dwight H. Owen, Lai Wei, Ashima Goyal, Ye Zhou, Sheryl-Ann Suffren, Rajani Jacob, Carly Pilcher, Gregory A. Otterson, Claire F. Verschraegen, Manisha H. Shah, Bhavana Konda
Journal: Journal of the National Comprehensive Cancer Network (2020)
Maintenance therapy in epithelial ovarian cancer (EOC): Could EGFR inhibitor- gefitinib be a candidate drug? A pilot study
Authors: R. Hariprasad, L. Kumar, R. Patnaik, A. Gupta, S. Kumar
Journal: Journal of Clinical Oncology (2006)

15046 Background: We aimed to evaluate the role of EGFR inhibitor, gefitinib among patients with advanced &amp; recurrent EOC to prolong progression-free survival (PFS). Methods: Between Nov. 2004 and Dec. 2005, 32 patients (median age 45 years, range 33 to 63) have been recruited. The study subjects were - (i) eleven patients with EOC stage IIIC-IV who had gross residual disease (≥1 cm) after primary debulking surgery and had achieved complete response (CR) following six cycles of paclitaxel and carboplatin (Group-I) (ii) Group II - includes 21 patients who achieved CR following salvage chemotherapy for relapsed EOC (1 st relapse- 8, 2 nd - 8, 3 rd -3 &amp; 4 th relapse in 2 patients). All Patients received gefitinib 250 mg once daily till evidence of relapse. Patients were examined every month and toxicity (CTC version II) was recorded. Serum CA-125 was done once in 2 months and CAT scan of abdomen &amp; pelvis at 6 monthly interval. The study was approved by Institute Ethics Committee and informed written consent was obtained from each patient before starting Gefitinib. Results: The mean duration of treatment is -5.6 months (Gp-I: 7.7 months, Gp-II: 4.5 months). Toxicity was mild, mainly in the form of skin rash &amp; diarrhoea. Skin rash occurred in 10 patients (31.3%); Group I - 8 patients (grade IV-2, III-2, I-4) &amp; in 2 patients in group II (grade III-1, II-1). Diarrhoea occurred in 7 patients (22%); Group I-1, group II-6) all grade I. No pulmonary or hematological toxicity was observed. Currently, 18/32 patients are on Gefitinib (mean duration of treatment 6.1 months); in 12 patients gefitinib has been discontinued due to relapse (group I- 4, Group II-10). Among 10 patients with skin toxicity (Gp I-8, Gp II-2), 6 continue to be disease-free (Group I- 5, Group II-1) compared to 12 of 22 without skin toxicity. Conclusions: Toxicity to gefitinib was mild, and limited to skin and GIT. Correlation between EGFR expression vs. response can help in identifying patients who possibly might benefit with gefitinib therapy. No significant financial relationships to disclose.
Low but Long-lasting Risk of Reversal of Seroconversion in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
Authors: Ming-Han Chen, Ming-Huang Chen, Chung-Tei Chou, Ming-Chih Hou, Chang-Youh Tsai, Yi-Hsiang Huang
Journal: Clinical Gastroenterology and Hepatology (2020)
A phase I study of the combination of sorafenib (Sor) and bortezomib (Bor) in patients (pts) with metastatic melanoma (MM).
Authors: Ryan J. Sullivan, Nageatte Ibrahim, Donald P. Lawrence, Julie Aldridge, F. Stephen Hodi, Keith Flaherty, Christine Conley, Sarah DeNoble, James Walter Mier, Daniel C. Cho, Michael B. Atkins, David F. McDermott
Journal: Journal of Clinical Oncology (2013)

9076 Background: Sor is a small molecule tyrosine kinase inhibitor that has many targets and previously was developed for the treatment of MM. Bor is a proteasome inhibitor widely used to treat multiple myeloma and other malignancies. In preclinical studies, the combination of Sor and Bor has been shown to modulate expression of BCL-family members and augment cytotoxicity in MM cell lines. Methods: Pts with MM were enrolled in cohorts of 3 during dose escalation to determine the maximum tolerated dose (MTD) of Sor twice daily (BID) in combination with Bor given days 1, 8, 15 of a 28 day cycle. The MTD was defined as the highest dose level at which less than 33% of pts exhibited a dose limiting toxicity (DLT). Efficacy, as measured by 6-month progression free survival (PFS) and response rate (RR) per RECIST, was documented. Results: Eleven pts were enrolled in 3 dose levels. DLTs (fatigue and rash respectively) were seen in 2 of 3 patients enrolled at the highest dose level (Sor 400 mg and Bor 1.3 mg/m 2 ). The next lowest dose level (Sor 400 BID and Bor 1.0) enrolled 5 pts and none had DLTs. Thus, this dose level was defined as the MTD. Toxicities seen in &gt;20% of pts included hypertension, pruritus, hand-foot syndrome, mucositis, nausea, vomiting, rash, constipation, abdominal pain, anorexia and fatigue. Of 9 response evaluable pts, none had radiographic evidence of tumor response. Two of 11 (18%) pts remained progression free for greater than 6 months. Conclusions: The combination of Sor and Bor is safe, but minimally active in pts with MM. In the absence of tumor response at or above the MTD, the study was closed with only 5 pts treated at the provisional MTD and enrollment to a planned dose expansion cohort will not occur. Clinical trial information: NCT01078961.
The Conference of Germs
Authors: Jack Coulehan
Journal: Annals of Internal Medicine (2020)

Ad Libitum17 March 2020The Conference of GermsJack Coulehan, MDJack Coulehan, MDCenter for Medical Humanities, Compassionate Care, and Bioethics at Stony Brook University, Stony Brook, New York (J.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0933 Audio Reading - “The Conference of Germs” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Conference of Germs” by Jack Coulehan, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In time the bacteria will convenea conference to consolidate their plansfor coping with the loss of humans.Those who colonized the humanswill be welcomed with respect and givenappropriate support, acknowledgingit was not their fault. The germs who livein volcanic cracks will offer workshopson the simple life. Others, on fixingnitrogen. The more scholarly germswill tackle the history of devastation;specifically, the ingenious methodshumans used to eradicate their species.Poet germs will sing of humans snippingwisdom from their reproductive strands.The principal theme will be the future.Every germ will vow to continuemolding the planet, as duty demands. Author, Article, and Disclosure InformationAffiliations: Center for Medical Humanities, Compassionate Care, and Bioethics at Stony Brook University, Stony Brook, New York (J.C.)Current Author Address: Jack Coulehan, MD; e-mail, john.[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Conference of Germs” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Conference of Germs” by Jack Coulehan, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 March 2020Volume 172, Issue 6Page: 443KeywordsBacteriaForecasting ePublished: 17 March 2020 Issue Published: 17 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The PARP inhibitor olaparib (AZD2281) as potent radiosensitizer of head and neck cancer cells.
Authors: Inge Tinhofer, Mariya Boyko-Fabian, Franziska Niehr, Ulrich Keilholz, Volker Budach
Journal: Journal of Clinical Oncology (2012)

e16018 Background: Current combined radiotherapy regimens for squamous cell carcinoma of the head and neck (SCCHN) are frequently not curative, necessitating novel therapeutic strategies. Inhibitors of poly(ADP-ribose) polymerases (PARPi), either alone or in combination with chemo- and radiotherapy have been shown to be highly active in tumor cells with intrinsic defects in DNA repair. Despite the frequent occurrence of genomic alterations in SCCHN cells also affecting their capacity of DNA repair the radiosensitizing potential of PARPi has not been addressed in detail so far. In this study, the efficacy of PARPi as radiosensitizer in SCCHN and possible mechanisms of cross-resistance between PARPi and cisplatin were evaluated. Methods: Usingthe clonogenic survival assay and a panel of 10 SCCHN cell lines the sensitivity of SCCHN cells to olaparib alone (0 to 500 nM) or in combination with irradiation (0 to 4 Gy) was determined. Survival fractions for given treatments were calculated on the basis of survival of untreated cells. In addition, the activity of cisplatin to inhibit clonogenic growth and its radiosensitizing potential was determined. From the dose-effect curves the IC50 values and the combinatory indices were calculated using the CalcuSyn Software. Results: In 9 of 10 cell lines, olaparib monotherapy showed significant inhibitory activity on clonogenic survival. Synergistic activity of olaparib in combination with irradiation was observed in all cell lines. No correlation between sensitivity of cells to olaparib and cisplatin (IC50 cisplatin vs IC50 olaparib: r 2 =0.042, p=.57; IC50 cisplatin vs CI [IR+olaparib]: r 2 =0.005, p=.95) was observed. Furthermore, the activity of olaparib was not dependent on the p53 genotype. Conclusions: The combination of PARPi with radiotherapy represents an active therapeutic regimen in SCCHN. The observed high activity of this combination even in cells with reduced sensitivity to cisplatin and p53 dysfunction suggests its clinical usefulness also in the group of patients with more aggressive disease and the second-line setting. Currently, detailed molecular characterization for identification of potential biomarker for tumor susceptibility to PARP inhibition is ongoing.
Identification of new liver tumor biomarkers using proteomics.
Authors: Peter J. Maimonis, Yoh Zen, David J. Britton, Andrew Brand, Malcolm Ward, Ian Pike, Alberto Quaglia
Journal: Journal of Clinical Oncology (2012)

e21091 Background: It is crucial to identify new biomarkers that help diagnose cancers at an early stage and contribute to the development of new anti-cancer drugs. Here, we identify new liver tumor biomarkers using proteomics. Methods: We evaluated 9 types of liver tissue from 55 patients: normal liver parenchyma (n=7), hepatocellular carcinoma (HCC) (n=7), normal bile duct (n=6), peripheral cholangiocarcinoma (CC) (n=7), hilar CC (n=7), CC associated with primary sclerosing cholangitis (PSC) (n=7), metastatic colorectal cancer (n=7), and mixed HCC/CC after trans-arterial chemoembolization (n=7; areas of HCC and areas of CC separately examined). Protein extracted from microdissected, formalin-fixed paraffin-embedded tissue (0.15 mm 3 in total) was reduced, alkylated and digested with trypsin in a stacking gel. Peptides were analyzed using nano-liquid chromatography-Mass spectrometry. The raw data were searched using Mascot. Normalized spectral counts for each protein among each tissue type were compared. For each comparison, an unrelated t-test was computed to obtain the p value. q values (adjusted p values) were computed using a direct False Discovery Rate approach (q &lt; 0.05 considered statistically significant). Results: The mean number of proteins identified per sample was 762 +/- 119 S.D, resulting in a total of 2643 proteins identified. Numbers of proteins with significantly different expression levels among different tissue types are shown below. Some of these proteins are being reported here for the first time in the context of liver carcinogenesis. Conclusions: This study revealed proteins that are significantly over/underexpressed in particular types of liver tumors. Clinically useful new biomarkers may be present among these proteins and are now undergoing validation using immunohistochemisty. [Table: see text]
CARVEDILOL FOR PREVENTION OF CHEMOTHERAPY-INDUCED CARDIOTOXICITY: FINAL RESULTS OF THE PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED CECCY TRIAL
Authors: Silvia M. Ayub-Ferreira, Monica Avila, Sara Brandão, Fatima D. Cruz, Mauro Wanderley, Vagner O.C. Rigaud, Ludhmila Hajjar, Roberto Kalil-Filho, Cecilia B.V. Cruz, Marco Stephan Alves, Guilherme V. Guimarães, Maria Abduch, Victor S. Issa, Marilia Santos, Marcio Bittencourt, Edimar Alcides Bocchi
Journal: Journal of the American College of Cardiology (2020)
Beginning with biology: “Aspects of cognition” exist in the service of the brain's overall function as a resource-regulator
Authors: Jordan E. Theriault, Matt Coleman, Mallory J. Feldman, Joseph D. Fridman, Eli Sennesh, Lisa Feldman Barrett, Karen S. Quigley
Journal: Behavioral and Brain Sciences (2020)

Abstract Lieder and Griffiths rightly urge that computational cognitive models be constrained by resource usage, but they should go further. The brain's primary function is to regulate resource usage. As a consequence, resource usage should not simply select among algorithmic models of “aspects of cognition.” Rather, “aspects of cognition” should be understood as existing in the service of resource management.
EFFICACY OF HYBRID EMERGENCY ROOM FOR OUT-OF-HOSPITAL CARDIAC ARREST PATIENTS UNDERGOING EXTRACORPOREAL CARDIOPULMONARY RESUSCITATION WITH VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION
Authors: Masafumi Mizusawa, Yoshiaki Ito, Keisuke Hirano, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Yasunari Sakamoto, Shinsuke Mori, Masakazu Tsutsumi, Yohsuke Honda, Kenji Makino, Shigemitsu Shirai, Takahide Nakano, Tomoya Fukagawa, Toshihiko Kishida, Yuki Kozai, Yusuke Setonaga, Shutaro Goda
Journal: Journal of the American College of Cardiology (2020)
MID-TERM FOLLOW UP OF BALLOON PULMONARY ANGIOPLASTY FOR INOPERABLE CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION: INITIAL MULTICENTER EXPERIENCE IN CHILE
Authors: Pablo Andrés Sepúlveda, René Hameau, Christian Backhouse, Gustavo Charme, Pablo Ramirez, Francisco Pacheco, Alberto Fuensalida, Jorge Quitral, Alejandro Martínez Sepúlveda, Gonzalo Martinez
Journal: Journal of the American College of Cardiology (2020)
Adjuvant dendritic cell (DC)-based vaccine therapy of melanoma patients.
Authors: Natalia N. Petenko, Irina N. Mikhaylova, George Z. Chkadua, Anatoly Y. Baryshnikov, Lev V. Demidov
Journal: Journal of Clinical Oncology (2012)

2524 Background: Earlier DC vaccine therapy demonstrated clinical benefit in some patients (pts) with advanced melanoma although the effect was seen only in pts with minimal tumor burden (ASCO2007 abstract No: 3077). As there is no effective treatment for high risk resected melanoma we conducted an exploratory trial to assess the effectiveness of DC vaccine in stage III and IV melanoma pts after radical surgery in comparison with observation. Methods: 108 stage III and IV melanoma pts were enrolled in two comparative arms. The arms were well balanced in respect with demographic and prognostic factors. The vaccine was based on mature autologous monocyte-derived DC primed with autologous tumor lysate, administered intradermally every 2-6 weeks until the disease progression. Disease free survival (DFS) and overall survival (OS) were evaluated with Kaplan-Meier method and compared between the two arms using the log rank test. Safety of DC vaccine was also monitored. Results: The vaccine arm included 56 pts (stage III – 46, stage IV – 10 pts) who were surgically rendered free of disease and treated with DC vaccine. 52 pts were enrolled in the control arm (stage III – 47, stage IV – 5 pts), they were treated surgically and observed afterwards. At a median follow-up of 22 months, the HR (DC vs observation) for DFS was 0.45 (p &lt; 0.05; 95%CI 0.29-0.69) and for OS was 0.71 (p=0.23; 95%CI 0.40-1.25). 60% of pts in the DC arm remained alive at this time point. Risk reduction significantly correlated with the strong delayed type hypersensitivity reaction induced by vaccine in 31 (55%) out of 56 vaccinated pts. The vaccine was safe and well tolerated although vitiligo was registered in 4 cases which was associated with more durable time to progression and OS. Conclusions: The immunotherapy with DC vaccine is safe and significantly improves DFS compared with observation in the adjuvant treatment of stage III and IV melanoma.