tbuckley/cabot-search huggingface dataset:
Detection of BRAF mutations in melanoma: Rate of mutation detection at codon 600 using Sanger sequencing as compared to the cobas 4800 method.
Authors: Kevin Z. Qu, Qiulu Pan, Xi Zhang, Luis Rodriguez, Jennifer Uyeji, Hairong Li, Albert Ho, Heather Sanders, Anthony Sferruzza, Daniel Jones, Frederic Waldman
Journal: Journal of Clinical Oncology (2012)

8596 Background: Detection of BRAF V600 mutations is currently a prerequisite for approved use of vemurafenib in patients with metastatic melanoma. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Diagnostics), a PCR-based assay approved to aid in selecting patients for vemurafenib therapy, primarily detects V600E. It is also reported to detect V600K, which has been associated with vemurafenib response as well. We compared the mutation detection rate of the cobas assay with that of Sanger sequencing. Methods: 125 de-identified FFPE tissues submitted for BRAF mutation analysis that all showed histologically-confirmed melanoma were tested. BRAF mutations were detected using both the cobas kit and bidirectional Sanger sequencing using BigDye kits (Applied Biosystems). DNA was extracted from 5-um sections without macrodissection using the cobas DNA extraction kit (for the cobas test) or from 5-10-um sections using Agencourt extraction kits (Beckman Coulter) following macrodissection. Results: The two methods showed agreement in 104/125 (83.2%) of cases (Table). Sanger sequencing detected V600 dinucleotide mutations in 9 samples that were negative by the cobas assay. Sanger sequencing produced no results in 10 cases owing to suboptimal PCR, including 2 that were positive by the cobas assay. The cobas assay produced 2 invalid results, including 1 that was positive for V600E by Sanger.The cobas assay detected 7/11 V600K mutations. Conclusions: Overall agreement between cobas and Sanger sequencing was 83.2%. The Sanger method had higher analytic sensitivity, resulting in nine additional V600 mutations not called by cobas compared to the two seen by cobas but not Sanger sequencing. Thus, 16% (9/57) more patients would be identified as candidates for vemurafenib therapy using the Sanger method. [Table: see text]
The role of F-18 FDG PET within randomized multicenter phase III trials for multi-modality treatment of non-small cell lung cancer stage III
Authors: M. Schmuecking, C. P. Schneider, M. Scheithauer, N. Presselt, J. Leonhardi, K. Hoeffken, R. P. Baum, T. G. Wendt, K. M. Mueller, R. Bonnet
Journal: Journal of Clinical Oncology (2006)

7213 Background: To evaluate the role of F-18 FDG PET within clinical trials for staging, therapy management, molecular radiation treatment planning (MRTP), early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 156 patients with NSCLC are analyzed prospectively in a randomized, open, multicenter phase III trial (LUCAS-MD). Methods: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. ECOG PS 0–1, adequate hematologic, renal, hepatic function. Primary end points: OS, DFS. Secondary end points: TTP, QoL, RR. Neoadjuvant treatment: 2–3 cycles of chemotherapy with paclitaxel/carboplatin and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant paclitaxel/carboplatin) followed by surgery. Randomization: early vs. late chemoradiation. Staging: PET in addition to CT and/or MRI after randomization. Second PET after completion of neoadjuvant therapy. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histological regression grade (RG) and correlation with PET for PT and each LN. Statistical analyses: Wilcoxon-, chi-square-, Mantel-Haenszel-test, Kaplan-Meier-method, multivariate Cox-regression. Results: Upstaging in 11 pts. due to distant metastases. Downstaging in 5 pts. Complete vs. incomplete metabolic remission after 48 months: 60% vs. 34% (p = 0.0058). RG III/IIb (no/less than 10% of vital tumor cells) vs. RGIIa/I (more than 10% vital tumor cells) after 48 months: 59% vs. 27% (p = 0.0006). Multivariate Cox-regression for SUV: p &gt; 0.05. Statistical power of the tests: 75% so far. Due to PET findings, the planning target volume for MRTP was reduced substantially in 23%, increased in 10%. Conclusions: Integration of PET in clinical trials enables a more accurate MRTP and therapy management (10% stage migration). Histological regression grade correlates well with metabolic remission as detected by PET. F-18 FDG PET may predict (long term) therapeutic outcome in stage III NSCLC. No significant financial relationships to disclose.
Attitude of Italian oncologists toward fertilty preservation in patients with early breast cancer.
Authors: Antonio Frassoldati, Sandro Barni, Domenico Amoroso, Elena Collovà
Journal: Journal of Clinical Oncology (2013)

e11547 Background: Patient’s desire for fertility preservation is a frequently underestimated problem in oncology clinical practice. Even if several different approaches have been suggested to maintain fertility in early stage breast cancer patients undergoing adjuvant chemotherapy, few women undergo to such procedures or are referred to a specialized team. Methods: Between April and July 2011, an electronic questionnaire regarding the treatment attitude in early breast cancer in premenopausal women was submitted to Italian oncologists, and 611 (female 52%, age range 25-65, 81% from general hospitals, 19% from research institute) filled in the questionnaire. Among the items, we explored also the issue of fertility preservation in women candidate for adjuvant chemotherapy and hormones. We compared the survey results (examined according to sex, age, working institution and geographic origin) with the recommendations available from guidelines of oncology and gynecology societies. Results: A pregnancy test before starting chemotherapy is considered mandatory only by 49.5% of oncologists, independently from age and type of treatment. In order to maintain fertility, several guidelines recommend eggs or embrio freezing, whereas the use of LHRH-analogs is recommended only in the contex of research trials. In our survey, the eggs freezing is considered the preferred method by 24,8% of Italian oncologists only, while 6% suggest cryopreservation of ovarian tissue. Embrio freezing is preferred by &lt;1% of oncologist. However, the majority of Italian oncologists considers the administration of LHRH-analog the treatment of choice to maintain fertility (independently from the hormone receptor status of the tumor in 83% of cases). No significant differences as by type of institution, geographic location, and physician’s age has been observed. Conclusions: The use of LHRH-analog is the preferred method by Italian oncologists for fertility preservation. A recent analysis of literature regarding the use of LHRH-analogs by Italian Society for Medical Oncology using the GRADE method suggest an important role of this drugs, even if not yet conclusive for their efficacy (level of evidence 1+, Recommendation “slightly positive”).
A report on treatment with rasburicase in 18 adult patients
Authors: D. M. Severson, S. M. Wills, M. Nguyen, J. H. Margolis
Journal: Journal of Clinical Oncology (2006)

16024 Background: Tumor lysis syndrome (TLS) is a life threatening complication occurring in highly proliferative malignancies. Chemotherapy often causes rapid tumor breakdown resulting in metabolic derangement, abnormal electrolytes and hyperuricemia. Untreated TLS can lead to renal failure and death. Rasburicase (recombinant urate oxidase) is a novel agent that reduces serum uric acid (SUA) levels in pediatric patients. Here we report on 18 adult patients treated with Rasburicase with highly proliferative malignancies. Methods: We retrospectively identified all adult TLS patients treated with Rasburicase at William Beaumont Hospital, Royal Oak, Michigan. We evaluated pre and post treatment SUA, electrolytes and renal function to determine the effect of a single dose of Rasburicase. Results: Twelve men and 6 women (mean age 56.5 years) received Rasburicase between July 2004 and November 2005. Thirteen patients had a diagnosis of TLS prior to treatment, 5 were treated prophylactically and did not develop TLS, 1 patient died of sepsis within 48 h of treatment and 1 patient died from cerebral hemorrhage within 72 h of treatment. Of the 12 assessable patients with TLS, the mean pretreatment SUA was 11.2 mg/dL and the mean 48 h post treatment SUA was 0.68 mg/dL. All SUA levels returned to normal (2.5–8 mg/dL) within 48 h. Ten patients had elevated pretreatment serum creatinine (Scr) levels (mean 2.5 mg/dL) and 2 patients had normal (0.7–1.5 mg/dL) levels. Within 72 h of treatment 7 of the 10 assessable patients showed improvement (mean reduction 0.6 mg/dL) in Scr. Conclusions: It is notable that while almost all patients had hematologic malignancies, 1 patient was diagnosed with an ovarian malignancy and showed great improvement in both SUA and Scr. Rasburicase reduced SUA levels in this patient group. Further studies on larger adult populations in or at high risk for TLS are necessary to determine statistical significance. No significant financial relationships to disclose.
Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia
Authors: Frederick J. Raal, David Kallend, Kausik K. Ray, Traci Turner, Wolfgang Koenig, R. Scott Wright, Peter L.J. Wijngaard, Danielle Curcio, Mark J. Jaros, Lawrence A. Leiter, John J.P. Kastelein
Journal: New England Journal of Medicine (2020)

Familial hypercholesterolemia is characterized by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. Monoclonal antibodies directed against proprotein convertase subtilisin-kexin type 9 (PCSK9) have been shown to reduce LDL cholesterol levels by more than 50% but require administration every 2 to 4 weeks. In a phase 2 trial, a twice-yearly injection of inclisiran, a small interfering RNA, was shown to inhibit hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholesterolemia.In this phase 3, double-blind trial, we randomly assigned, in a 1:1 ratio, 482 adults who had heterozygous familial hypercholesterolemia to receive subcutaneous injections of inclisiran sodium (at a dose of 300 mg) or matching placebo on days 1, 90, 270, and 450. The two primary end points were the percent change from baseline in the LDL cholesterol level on day 510 and the time-adjusted percent change from baseline in the LDL cholesterol level between day 90 and day 540.The median age of the patients was 56 years, and 47% were men; the mean baseline level of LDL cholesterol was 153 mg per deciliter. At day 510, the percent change in the LDL cholesterol level was a reduction of 39.7% (95% confidence interval [CI], -43.7 to -35.7) in the inclisiran group and an increase of 8.2% (95% CI, 4.3 to 12.2) in the placebo group, for a between-group difference of -47.9 percentage points (95% CI, -53.5 to -42.3; P<0.001). The time-averaged percent change in the LDL cholesterol level between day 90 and day 540 was a reduction of 38.1% (95% CI, -41.1 to -35.1) in the inclisiran group and an increase of 6.2% (95% CI, 3.3 to 9.2) in the placebo group, for a between-group difference of -44.3 percentage points (95% CI, -48.5 to -40.1; P<0.001). There were robust reductions in LDL cholesterol levels in all genotypes of familial hypercholesterolemia. Adverse events and serious adverse events were similar in the two groups.Among adults with heterozygous familial hypercholesterolemia, those who received inclisiran had significantly lower levels of LDL cholesterol than those who received placebo, with an infrequent dosing regimen and an acceptable safety profile. (Funded by the Medicines Company; ORION-9 ClinicalTrials.gov number, NCT03397121.).
Socio-demographic and psychological features in Moroccan patients with cancer: A prospective multicentric large cohort study.
Authors: Hassan Errihani, Mounia Amzerin, Saoussane Kharmoum, Ahmed Zidouh, Adellatif Benider, Abir El Kadi, Samira El Fakir, Hind Mrabti, Chakib Nejjari
Journal: Journal of Clinical Oncology (2013)

e20516 Background: To explore socio-demographic features and functional dimensions in patients included in a large Moroccan cohort study. Methods: This is the first Moroccan study which was designed to evaluate the quality of life in cancer patients. It is a prospective multicentric cohort study (the 10 existing centers). Patients with breast, cervical, lung or colorectal cancer were included during 2009. EORTC QLQ C30, BR23, CX24 and LC13 questionnaires were used after a transcultural validation. Results: Over 12 months, 2903 patients were included. Breast cancer was the most common (50.4%). Socio-demographic features: The average age at diagnosis was 52.7 years old. Most of them were women (75%). All of patients were Muslims. 75.1% were married. 60% were illiterate. 20% of patients were professionally active and 59.3% were housewives. 27.2% came from rural towns. The socioeconomic status was 65.8% low and 32.4% intermediate. 71.4% of patients had no social welfare. To get to the oncology centers, 77.8% of patients used public transportation while only 0.6% of total cases came in ambulances. The average distance was 150 kilometers. Psychosocial dimensions: For all types of cancer, functional dimensions were noticeably deteriorated with the stage. The lowest scores were observed in lung cancer, whereas the highest ones were for breast cancer. (Emotional function 62.54 vs. 53.05 professional function and leisure 74.14 vs. 42.22 cognitive activity 83.25 vs 26.93 social activity 86,17 vs. 77.69 p&lt;0.001). The financial problems score was higher in lung cancer (68.34). The future perspective was the most affected dimension in QLQ BR23 questionnaire (score40.51), while in QLQ CX24, the sexual enjoyment was the most impacted dimension (score 52.1). Conclusions: In the Moroccan culture, the social relationships the social relationships offset the negative impact of cancer on other functional dimensions. Social activity scores were the less affected. Financial issues are the major concern, resulting in a negative impact on the quality of life of our patients. Finally, over a period of one year, the scores of reported dimensions were significantly improved by the cancer treatment.
Chemotherapy in hormone-refractory prostate cancer: Docetaxel with and without VT122.
Authors: Gouri Shankar Bhattacharyya, Newell Bascomb, Hemant Malhotra, Ghanashyam Biswas, Shailesh Arjun Bondarde
Journal: Journal of Clinical Oncology (2013)

e16062 Background: Randomized study in metastatic castration resistant prostate cancer treated with docetaxel and the benefit of adding VT122. Methods: Castration resistant prostate cancer with bone metastasis, symptomatic were treated with docetaxel 75 mg/m2 every 3 week and prednisolone with continued androgen suppression, LHRH analogue and zoledronic acid, every 28 days with or without VT122. VT122 is a drug combination of etodolac, a COX-2 inhibitor and propranolol, a beta blocker with anti angiogenic properties; this combination has previously been shown to be anti cachectic, anti neoplastic.The dose of etodolac was titrated by C-reactive protein levels to a maximum of 800 mg/day. The dose of propranolol was titrated to keep heart rate at around 60 b/min to 70 b/min. GCSF was allowed, all patients were given Calcium and VitaminD. The primary end point was time to progression, a composite end point of objective progression by RECIST criteria, PSA progression or pain progression, whichever occurred first was applied.The McGill questionnaire was applied to patients. Number of patients 69; 34 in docetaxel arm; 35 in VT122 arm. Age between 50-65 years. Taken from 3 centers with PS ECOG &lt;2 controlled comorbidity with stable analgesic regime. All patients were planned for 6 cycles of docetaxel. Follow-up was for a period of two years. Results: Median age of 62 years with ECOG status 1 was seen in 88%. The median PSA value was seen as 138 ng/ml (10 - 600). 66% in both arms had measurable disease. Conclusions: Addition of VT122 improves response rates, duration of response and symptom scales along with 1-year survival which are statistically significant; toxicities are also significantly decreased and indicating increased efficacy and safety profile of docetaxel. The efficacy and control of toxicity and easy to administer makes this an attractive combination. [Table: see text]
BPI20-016: Comparative Study Between the Clinical Effect of Palonosetron and Granisetron as Antiemetic Therapy for Patients Receiving Highly Emetogenic Chemotherapy Regimens
Authors: Mohamed Ahmed Mahrous, Gamal Abd El Khalek El- Azab, Hisham Ahmed Tawfik
Journal: Journal of the National Comprehensive Cancer Network (2020)

"BPI20-016: Comparative Study Between the Clinical Effect of Palonosetron and Granisetron as Antiemetic Therapy for Patients Receiving Highly Emetogenic Chemotherapy Regimens" published on 20 Mar 2020 by National Comprehensive Cancer Network.
T2 Mapping Identifies Early Anthracycline-Induced Cardiotoxicity in Elderly Patients With Cancer
Authors: Ana Martin-Garcia, Elena Diaz-Pelaez, Lucia Lopez-Corral, Clara Sanchez-Pablo, Guillermo Macias de Plasencia, Carlos Galan-Arriola, Javier Sanchez-Gonzalez, Juan Jesus Cruz, Borja Ibanez, Pedro L. Sanchez
Journal: JACC. Cardiovascular imaging (2020)
APPLICATION OF MACHINE LEARNING IN SCREENING OF CONGENITAL HEART DISEASES USING FETAL ECHOCARDIOGRAPHY
Authors: Tuyen Kim Le, Vien Truong, Thanh-Hoang Nguyen-Vo, Binh P. Nguyen, Tam N.M. Ngo, Quoc V.P. Bui, Thanh K.N. Pham, Justin Tretter, Michael Taylor, Philip Levy, Eugene Chung, Wojciech Mazur, Huan Q. Do, Phuong T.N. Do, Vinh N. Pham, Hoa N. Chau
Journal: Journal of the American College of Cardiology (2020)
再生不良性貧血を持つ小児の免疫抑制療法への良好な反応が予測できないHLA-DR15、マイナーPNHクローンまたは再生不良性貧血関連自己抗体の存在
Authors: Yagasaki H, Yoshida N, Hirano N, Nishio N, Wang Y, Takahashi Y, Kojima S
Journal: Blood (2006)
Maximising the potential of HPV vaccines
Authors: Jos Luttjeboer, Abrham Wondimu, Jurjen Van der Schans, Maarten J Postma
Journal: The Lancet Global Health (2020)

In The Lancet Global Health, Kaja M Abbas and colleagues1 present revised estimates of the worldwide impact of human papillomavirus (HPV) vaccination on prevention of cervical cancer, using the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model. Their updated analysis uses population demography data from the UN World Population Prospects 2019 revision, disability weights from the Global Burden of Disease 2017 study, and cervical cancer burden from the Global Cancer Incidence, Mortality and Prevalence 2018 database.
Heart Failure Association of the European Society of Cardiology Quality of Care Centres Programme: design and accreditation document
Authors: Petar M. Seferović, Massimo F. Piepoli, Yuri Lopatin, Ewa Jankowska, Marija Polovina, Manuel Anguita‐Sanchez, Stefan Störk, Mitja Lainščak, Davor Miličić, Ivan Milinković, Gerasimos Filippatos, Andrew J.S. Coats
Journal: European Journal of Heart Failure (2020)
In memoriam: Norman K. Hollenberg, MD, PhD, 1936–2020
Authors: Murray Epstein
Journal: Kidney International (2020)

Norman K. Hollenberg, MD, PhD, renowned leader in cardiovascular medicine and hypertension, passed away on January 15, 2020, after a long illness. He spent his last days in the Brigham and Women's Hospital, the institution he loved and his academic home for 50 years. Dr. Hollenberg was professor of medicine and radiology and director of the physiologic research division in radiology at Brigham and Women's Hospital and Harvard Medical School. He leaves a remarkable, lasting legacy in nephrology, hypertension, and in medicine broadly.
INCIDENCE AND CLINICAL EVOLUTION OF LONG TERM ANTHRACYCLINE CARDIOTOXICITY
Authors: Jose Maria Serrano Antolin, Rebeca Mata Caballero, Carmen Cristobal, Iria Gonzalez, Carlos Gutierrez Landaluce, Silvia del Castillo, Rosa Maria Jimenez, Catherine Graupner, Pedro Talavera, Javier Alonso Bello, Juan Guerra, JOAQUIN ALONSO MARTIN, Alejandro Curcio
Journal: Journal of the American College of Cardiology (2020)
Noncoding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies
Authors: Kailong Li, Yuannyu Zhang, Xin Liu, Yuxuan Liu, Zhimin Gu, Hui Cao, Kathryn E. Dickerson, Mingyi Chen, Weina Chen, Zhen Shao, Min Ni, Jian Xu
Journal: Cancer Discovery (2020)

Mutations in protein-coding genes are well established as the basis for human cancer, yet how alterations within noncoding genome, a substantial fraction of which contain cis-regulatory elements (CRE), contribute to cancer pathophysiology remains elusive. Here, we developed an integrative approach to systematically identify and characterize noncoding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage-associated CREs and mutation discovery, we uncovered 1,836 recurrently mutated CREs containing leukemia-associated noncoding variants. By enhanced CRISPR/dCas9-based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor-suppressive CREs in human leukemia. Noncoding variants at KRAS and PER2 enhancers reside in proximity to nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently colocalize with noncoding variants across cancer types. Hence, recurrent noncoding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies. SIGNIFICANCE: We describe an integrative approach to identify noncoding variants in human leukemia, and reveal cohorts of variant-associated oncogenic and tumor-suppressive cis-regulatory elements including KRAS and PER2 enhancers. Our findings support a model in which noncoding regulatory variants connect enhancer dysregulation with nuclear receptor signaling to modulate gene programs in hematopoietic malignancies.See related commentary by van Galen, p. 646.This article is highlighted in the In This Issue feature, p. 627.
REFERRAL PATTERNS FOR PULMONARY EMBOLISM (PE) PATIENTS AT A TERTIARY ACADEMIC MEDICAL CENTER: INSIGHTS INTO PULMONARY EMBOLISM RESPONSE TEAM (PERT) UTILIZATION AND PATIENT OUTCOMES
Authors: Robert Zilinyi, Alexander Murphy, Danial Saleem, Mahesh Madhavan, Shayan Nabavi Nouri, Andrew Jeffrey Einstein, Sowmya Sreekanth, Hui Qing Su, John Capua, Nadira Hamid, Jay Leb, Daniel Brodie, Erika Berman Rosenzweig, Koji Takeda, Ajay Kirtane, Sahil Parikh, Philip Green, Sanjum S. Sethi
Journal: Journal of the American College of Cardiology (2020)