tbuckley/cabot-search huggingface dataset:
Nonmyeloablative Allogeneic Transplantation Using TLI-ATG Conditioning for Lymphoid and Myeloid Malignancies: Mature Follow-up from a Large, Single Institution Cohort
Authors: Michael A Spinner, Vanessa E Kennedy, John S Tamaresis, Philip W Lavori, Linda V Elder, Sally Arai, Laura J Johnston, Everett H Meyer, David B. Miklos, Lori S Muffly, Robert S. Negrin, Andrew R Rezvani, Judith A Shizuru, Wen-Kai Weng, Richard T Hoppe, Samuel Strober, Robert Lowsky
Journal: Blood (2018)
Incidence of incidental and symptomatic venous thromboembolism (VTE) and Khorana’s score in ambulatory pancreatic cancer patients receiving chemotherapy.
Authors: Andres Jesus Muñoz Martin, Silvia Garcia Adrian, Luisa Sánchez Lorenzo, Eva Martinez De Castro, Purificación Martinez, Vanessa Pachon, Joaquina Martínez-Galán, Jose David Cumplido Buron, Ana Isabel Ferrer Perez, Sara Perez Ramirez, Maitane Mugica, Cynthia S. González Rivas, Paula Jiménez-Fonseca
Journal: Journal of Clinical Oncology (2014)

e15187 Background: VTE is a common complication in exocrine pancreatic cancer (EPC), however it´s true incidence remains uncertain. Khorana’s score is the only validated predictive model to gauge cancer patients’ risk for developing VTE. Methods: The aim of this study is to analyze the incidence of symptomatic and incidental VTE and Khorana score in ambulatory patients (pts) with EPC receiving chemotherapy. We performed a retrospective review in nine hospitals of the Cancer&Thrombosis Working Group-Spanish Society of Medical Oncology (SEOM). A total of 571 consecutive patients from Jan 2008 through Dec 20011 were included in the analysis. Results: VTE was identified in 22.6% of pts. Median follow-up: 9.3 months. Median time to diagnosis: 3.1 months (range 0-50 months). Median age: 64.3 (range 31-88). Stage I-III/IV: 39.9%/59.9% Previous VTE: 3.5%. Previous arterial thromboembolism: 8.1%.31 events (24%) were identified during the diagnostic workup of EPC and 67.2% of the events occurred during the first 6 months after EPC diagnosis. In 1.9% of pts VTE was the leading cause of diagnosis. Type of first VTE: 30.2% pulmonary embolism (PE), 39.6% deep vein thrombosis (DVT), 38.0% visceral vein thrombosis (VVT) and 14.0% of the pts experienced 2 simultaneous different events. 50% of events were incidentally discovered (48.7% PE, 11.8% DVT and 91% VVT). Khorana’s score (Table 1). Recurrent rate: 5%. Conclusions: The high incidence of VTE observed in this study is consistent with prior reports. Hence primary thromboprophylaxis in patients with low bleeding risk should be assessed. Khorana´s score had no predictive value in incidental VTE. Khorana’s predictive model Risk category/pts(%) Number of pts (%) VTE+ (pts/%) VTE- (pts/%) Intermediate (2 points) 331 (58.0%) 73 (22.1%) 258 (77.9%) High risk (≥ 3) 218 (38.1%) 53 (24.3%) 165 (75.7%) Unknown 22 (3.9%) 3 (13.6%) 19 (86.4%)
Age-related genomic demethylation in non-small cell lung cancer.
Authors: Lela Buckingham, William Barbanera, Thomas Nichols, Philip Bonomi, Mary J. Fidler
Journal: Journal of Clinical Oncology (2014)

e22068 Background: Little information about biological indicators of tumor metabolism associated with non small cell lung cancer (NSCLC) in younger patients (<50 years) exists. We have previously observed epigenetic differences in patients older (>60) compared to younger (<60) at diagnosis. To further explore age-related epigenetic and potential metabolic influences, global demethylation and isocitrate dehydrogenase (IDH1) mutation status were measured in early stage NSCLC patients ranging in age from 30 to 87 years at diagnosis. Demethylation of 5-methyl cytosine, the major product of DNA methyltransferase in humans, is catalyzed by the ten-eleven translocation genes, TET1, TET2 and TET3. These enzymes are inhibited by products of mutated isocitrate dehydrogenase (IDH1). The latter activity is of interest as it connects epigenetic mechanisms to tumor cell metabolism. Methods: Analysis was performed on formalin-fixed tumor tissue DNA from 59 surgically treated stage Ib-II NSCLC patients (training group 30 >50 years, 29 ≤50 years). Demethylation was measured by ELISA quantifying global genomic 5-hydroxymethyl cytosine (5hmC) relative to input DNA and expressed as percent internal control. IDH1 mutations were analyzed by pyrosequencing. Results: There was no significant difference in stage, gender, nor smoking status by age group 5hmC levels were significantly less in NSCLC than that in non-malignant tissue. (5hmC%=3.53; p=0.008). Genomic demethylation decreased with age. Patients >50 had significantly less 5hmC than younger patients <50 years (5hmC%=0.42 vs. 1.02; p=0.005). In a smaller validation group of 37 patients, 5hmC was again lower in the older group than in the younger group (Rel 5hmC%=0.41 vs. 0.84, p=0.061). One IDH1 mutation (R132M) was found in group >50 and no mutations were found in the <50 group. Conclusions: Lung cancer arising in younger patients may occur through a different tumorigenic pathway than in older patients. These data are consistent with age-related genomic differences in methylation/demethylation status. Additional data are required to define the role of IDH and metabolic defects affecting hypermethylation.
Ethnic belief differences in the incidence and mortality of prostate cancer.
Authors: Patrick Guinan, Kiana Ongbueco, Marvin Rubenstein
Journal: Journal of Clinical Oncology (2014)

e16108 Background: One of the leading causes of male death worldwide is prostate cancer. Although many databases evaluate disease incidence, mortality and diverse contributory influences, few evaluate the combined role of geographic location and dominant ethnic beliefs, particularly in Northern Africa. Methods: Although published incidence rates in predominantly Muslim countries are not available, the GLOBOCAN database was carefully scrutinized for certain regions. These included Northern Europe as well as Northern and Western Africa. These regions were chosen as surrogates for populations dominated by Christians, Muslims and blacks, respectively. We evaluated incidence and mortality rates for prostate cancer within these groups, as well as correlations to ethnic beliefs. There are 95% Confidence Intervals and none of the incident rates are overlapping. Gathering religion percentages in various countries using different databases clarified that Western Europe, Northern Africa, and Western Africa are predominated by Christians, Muslims and blacks, respectively. Results: Evaluating prostate cancer incidence within the 95% confidence limit, we found no significant differences between groups. However, we did find a significant negative correlation (-0.8) between the practice of Islam and prostate cancer incidence, and a positive correlation (0.9) with Christians. Insignificant correlations were found for mortality. Conclusions: From the geographic GLOBOCAN areas, Western Europe, Northern Africa, and Western Africa, and assuming they are surrogates for Christian, Muslims and blacks, it is likely that the diminished incidence of proven prostate cancer in some countries is due to many factors including age differences, access to medical care, awareness, as well as the paucity of obtaining confirmatory biopsies. Also in African countries, many die of malaria or HIV prior to reaching the age at which prostate cancer produces clinical symptoms.
Possible survival markers in cancer patients undergoing chemotherapy.
Authors: Jan Filipiak, Magdalena Wisniewska, Krzysztof Roszkowski
Journal: Journal of Clinical Oncology (2014)

e13524 Background: Due to the importance of the identification of chemotherapy outcome prognostic factors, we attempted to establish the potential of oxidative stress / DNA damage parameters as such prognostic markers. The aim of the study was to determine whether platinum derivative-based chemotherapy in cancer patients (n=66) is responsible for systemic oxidative DNA damage and whether damage biomarkers, such as 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxo-dG) and the modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua), in urine and DNA may be used as a prognostic factor for the outcome of chemotherapy. Methods: All the aforementioned modifications were analyzed using techniques involving high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectroscopy (GC-MS). Results: Among all the analyzed parameters, the significantly decreased levels of 8-oxo-Gua in urine collected from a subgroup of patients 24 hours after the first infusion of the drug, as compared with the baseline levels, correlated with a significantly longer overall survival (60 months after therapy) than in the subgroup without any decrease of this parameter after therapy (median OS =24 mo., p=0.007). Moreover, a significantly longer overall survival was also observed in a group with increased urine levels of 8-oxo-dG after chemotherapy (38.6 vs. 20.5 mo., p=0.03). Conclusions: The results of our study suggest that patients with decreased 8-oxo-Gua levels and increased 8-oxo-dG levels in urine 24 hrs after the first dose should be considered as better responders to the administered chemotherapy, with a lower risk of death. Impact: The conclusion may permit the use of these parameters as markers for predicting the clinical outcome of platinum derivative-based chemotherapy.
Utilization patterns of abiraterone acetate before and after chemotherapy in patients with metastatic castration-resistant prostate cancer in the Veterans Health Administration System.
Authors: Diana I. Brixner, Ravinder Dhawan, Raymond Miao, Jennifer Sung, Li Wang, Onur Baser, Jyotsna Mehta
Journal: Journal of Clinical Oncology (2014)

e16014 Background: In April 2011, the FDA approved abiraterone acetate (AA) for the treatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy (ctx), and in December 2012 for ctx-naive pts. Prior retrospective US studies have shown high AA discontinuation (D/C) rates in pts with mCRPC. Using data from the Veterans Health Administration (VHA) Medical Dataset, this study retrospectively assessed pt characteristics and treatment patterns relating to AA therapy in veterans. Methods: Observational data were obtained from adult VHA pts with mCRPC with ≥1 pharmacy claim for AA between May 2011 and Mar 2012 and continuous health plan enrollment for ≥36 months (mo.) before the index date (ID; date of first AA claim). Pts initiated AA between May 2011 and Mar 2012 and were followed through Sep 2012. Pts with a gap of ≥2 mo. after last AA dose were considered discontinued. Descriptive analyses were performed (n and % for non-continuous variables and mean and SD for continuous variables). Results: Of 881 mCRPC pts receiving AA, 337 (38%) received AA pre-ctx (PRE) and 544 (62%) post-ctx (POST). PRE pts were older than POST pts (median age 79 vs. 71 years, respectively), which may reflect ineligibility for ctx in PRE pts. Only 76% of PRE pts received androgen deprivation therapy in the pre-ID period vs. 96% of POST pts. Baseline PSA was higher in POST than PRE pts (393 vs. 206 ng/mL, respectively). In total, 280/337 (83%) PRE pts and 440/544 (81%) POST pts had ≥6 mo. of follow-up. Among these pts, AA D/C rates were similar in PRE and POST pts at 3 mo. (17% vs. 16%, respectively; p = 0.6076) but slightly higher in POST than in PRE pts at 6 mo. (39% vs. 35%, respectively; p = 0.2509). POST pts received post-AA ctx more frequently than PRE pts (17% vs. 3%, respectively; p<0.0001). Conclusions: Consistent with prior studies, this retrospective analysis using a VHA pt population showed that AA D/C rates were high in both PRE (35% at 6 mo.) and POST (39% at 6 mo.) pts. These data will require validation in studies in wider pt populations. Future studies should also seek to identify the reasons for D/C and predictors of compliance and response.
Observations of a 5-year survivor of metastatic pancreas cancer on the current state of treatment.
Authors: Mark Stuart Vandersluis
Journal: Journal of Clinical Oncology (2014)

e20615 Background: The author is a 5 year survivor of metastatic pancreatic adenocarcinoma and has been treated with multiple modalities including surgery, radiation, chemotherapy, and immunotherapy, using both approved and investigational agents. This paper presents some of his observations over the 5 years of his treatment. Methods: The author has been treated for 5 years at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD. Results: Over the course of his treatment, the author has benefitted from ongoing treatment advances while also struggling against problems in the treatment system. Conclusions: (1) An aggressive, “fight-to-win” approach can benefit the patient both physically and psychologically. (2) Participation in clinical trials, by moving the patient from a known unfavorable statistical distribution to an unknown distribution, provides the possibility of tangible benefits as well as a rational basis for hope. (3) Current statistical methods drive study design that negatively impacts the patient in the clinic, both by excluding patients and by forcing sub-optimum treatment. Better methods may be applicable, for example Bayesian influence networks. (4) The lack of a widely proliferated and reliable surrogate for disease progress also drives exclusionary study design and sub-optimum treatment. Tumor size is too late, and CA19-9 is too unreliable; circulating cancer stem cells may be “just right,” but mostly unavailable. (5) The drug approval process is too slow; our community needs to learn from the successes of the HIV community. (6) We need to look for treatments, not drugs; this impacts study design and is enabled by improved statistical methods. (7) Better methods are required to enable smooth transition between treatment modalities and to ensure that the patient is presented with a treatment team, not a disconnected group of doctors.
Primary Diffuse Large B-Cell CNS Lymphoma over 80 Years: An Analysis of 110 Patients from the French Oculo-Cerebral Lymphoma (LOC) Network
Authors: Alizee Maarek, Delphine Maucort-Boulch, Caroline Houillier, Olivier Chinot, Fontanet Bijou, Luc Taillandier, Philippe Agape, Roch Houot, Eileen Boyle, Cecile Molucon-Chabrot, Philippe Rey, Sylvain Choquet, Jerome Tamburini Bonnefoy, Arnaud Jaccard, Guido Ahle, Michel Fabbro, Anne-Claire Gac, Jean-Come Meniane, Marie Francoise Le Coz, Emmanuel Gyan, Khe Hoang-Xuan, Carole Soussain, Herv Ghesquieres
Journal: Blood (2018)
Understanding structure-activity relationships of pH-sensitive cationic lipids facilitates the rational identification of promising lipid nanoparticles for delivering siRNAs in vivo
Authors: Yusuke Sato, Kazuki Hashiba, Kosuke Sasaki, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Journal: Journal of Controlled Release (2019)

Lipid nanoparticles (LNPs) are one of the more promising technologies for efficiently delivering short interfering RNA (siRNA) in vivo. A pH-sensitive cationic lipid that facilitates the targeting of hepatocytes and endosomal escape, strongly influences the availability of siRNA, thus making it a key material for efficient siRNA delivery. A systematic knowledge regarding lipid structure-activity relationships would greatly facilitate the development of sophisticated pH-sensitive cationic lipids for use in siRNA-based therapeutics. The systemic derivatization of a hydrophilic head group and hydrophobic tails of YSK12-C4, a pH-sensitive cationic lipid that was developed in our laboratory, revealed that hydrophilic head significantly affected the apparent pKa of the final product, a key factor in both intrahepatic distribution and endosomal escape. The clogP value of a hydrophilic head group was found to be associated with the apparent pKa of the product. In contrast, the hydrophobic tail structure strongly affected intrahepatic distribution without depending on apparent pKa. A structure-activity relationship study enabled the selection of an adequate combination of a hydrophilic head group and hydrophobic tails and permitted a potent LNP composed of a pH-sensitive cationic lipid CL4H6 (CL4H6-LNPs) to be developed that showed efficient gene silencing activity (50% effective dose: 0.0025 mg/kg), biodegradability and was tolerated. In vivo experiments revealed that the CL4H6-LNPs showed a superior efficiency for endosomal escape, cytosolic release and the RNA-induced silencing for the complex-loading of siRNAs compared to the previously developed LNPs.
Prognostic factors for squamous cell anal canal cancer.
Authors: Zainul Abedin Kapacee, Shabbir Susnerwala+, Marcus Wise+, Ashoke Biswas+, Nigel Scott+
Journal: Journal of Clinical Oncology (2014)

e15000 Background: Tumour size, nodal involvement and sex are recognized prognostic factors in squamous cell anal cancer. Our study aims to evaluate survival and potential prognostic factors amongst a large cohort of anal cancer patients. Methods: Between October 2000 to January 2013, 148 patients treated with definitive chemoradiation for non-metastatic squamous cell anal cancer were retrospectively analysed. Kaplan Meier, univariate and multivariate Cox Regression methods were used to assess prognostic value of age, sex, tumour size, anal canal circumference involved, nodal disease, tumour location, white cell count and pre-treatment haemoglobin. Results: The mean age was 63 with 95 females and 53 males. The estimated overall five-year survival and cancer specific survival were 84% and 86% respectively. On univariate analysis prognostic factors predicting poorer overall survival were: tumour size greater than 5 cm (HR 2.89; 95%CI: 1.28-6.52; p=0.01), node positive disease (HR 2.90; 95%CI: 1.07-5.34; p=0.03), over 2/3s anal canal circumference involvement (HR 3.28; 95%CI: 1.35-7.98; p=0.01) and pre-treatment haemoglobin less than 13.0g/dl (HR 2.32; 95%CI: 1.20-5.35; p=0.04). Multivariate analysis demonstrates large tumour size as the most significant prognostic factor (HR: 2.686; 95% CI 1.18-6.13; p=0.02). Increasing age, male sex, palpable lymph nodes, tumour location within the anal canal and high pre-treatment white cell counts did not show statistical significance as prognostic factors. Conclusions: Our study suggests that large tumour size, nodal disease and low haemoglobin confer poorer prognostic and survival outcomes. Use of alternative chemotherapy agents and intensity modulated radiation therapy may improve prognostic and morbidity outcomes for anal cancer patients.
Home Modifications to Reduce Disability in Older Adults With Functional Disability
Authors: Marlon J. R. Aliberti, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2019)

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Adjuvant chemotherapy with two cycles of cisplatin in stage I seminomas.
Authors: Luis Garcia-Aceituno, Hugo Raul Castro, Cesar Hernandez-Monroy, Noe V. Castro
Journal: Journal of Clinical Oncology (2014)

e15532 Background: Radiotherapy or chemotherapy with one cycle of carboplatin are widely accepted as adjuvant treatments in stage I seminomas, however a lot of patients in our country can not afford these treatments. Strict surveillance is also and option, but is highly difficult to achieve it in a proper way. We design this phase II study to evaluate if two cycles of cisplatin are a viable and much affordable adjuvant option in patients with stage I seminomas. Methods: Patients with stage I seminomas were assigned to receive two adjuvant cycles of cisplatin at a dose of 75 mg/m2 every 21 days. Variables analyzed were relapse free survival, overall survival, age, tumor size, rete testis invasion and adverse events. Results: 24 patients were enrolled in the study. Median age at diagnosis was 30 years. 14 patients (58.3%) had tumors <4 cm and 41.7%% of the patients (10) had tumors >4 cm. Rete testis invasion was present in 9 patients (37.5%). With a median follow-up of 31 months (12-63 months), only one patient relapsed (4.16% relapse rate). At the time of the analysis relapse free survival was 95.8% and an overall survival of 100%. The most common adverse event was nausea followed by neutropenia in 64% and 29% of the patients respectively. There were no grade 3 or 4 adverse events. Conclusions: Two cycles of cisplatin as adjuvant treatment for stage I seminomas seems to be an effective and affordable strategy, with a low relapse rate and manageable adverse events.
Venetoclax Synergistically Enhances the Antileukemic Activity of Imipridone ONC213, a Novel Imipridone ONC201 Analog, in Acute Myeloid Leukemia
Authors: Yongwei Su, Xinyu Li, Holly Edwards, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Katie Hege, Yu Fukuda, John D. Schuetz, Joshua E. Allen, Martin Stogniew, Varun Vijay Prabhu, Jeffrey W. Taub, Hai Lin, Yubin Ge
Journal: Blood (2018)