tbuckley/cabot-search huggingface dataset:
Clinical outcomes in patients with BRAF<sup>V600</sup> mutant melanoma and undetectable circulating tumor DNA treated with dabrafenib and trametinib.
Authors: Alain Patrick Algazi, Megan Othus, Benjamin Newell Voorhies, Kari Lynn Kendra, Shaker R. Dakhil, Amy K. Harker-Murray, Christopher D. Lao, Bartosz Chmielowski, Roger Lo, Kenneth F. Grossmann, Antoni Ribas
Journal: Journal of Clinical Oncology (2020)

10059 Background: Circulating tumor DNA (ctDNA) analysis has been promoted as a less-invasive surrogate assay for tumor-tissue based tumor oncogene analysis. Here, we associate detection of BRAF mutant ctDNA with PFS and OS in patients with tissue-confirmed BRAF V600 mutant melanoma enrolled in S1320, a randomized phase 2 clinical trial of continuous versus intermittent dosing of dabrafenib and trametinib. Methods: Patients with BRAF V600 melanoma received continuous therapy with dabrafenib and trametinib for 8 weeks after which patients were randomized 1:1 to proceed with intermittent treatment on a 3-week-off, 5-week-on schedule or to continue with continuous therapy. Pre-treatment blood samples were interrogated using the Guardant 360 ctDNA assay for all exons of 30 known oncogenes including BRAF and for all exons with known oncogenic mutations in the COSMIC database in 40 additional oncogenes. Clinical responses were assessed at 8-week intervals by RECIST v1.1 and PFS and OS estimates were compared using log-rank test in patients with detectable versus undetectable BRAF V600 mutant ctDNA,. Results: Somatic BRAF V600E or BRAF V600K ctDNA was detected in 34 of 50 patients with baseline (before lead-in cycle 1) blood samples available for analysis including 16 of 23 (70%) patients randomized to continuous dosing, 15 of 21 (71%) randomized to intermittent dosing, and 3 of 6 (50%) who were not randomized due to disease progression at 8 weeks or other factors. Four additional patients had other detectable somatic mutations but no detectable BRAF V600 ctDNA at baseline, and 12 patients had no detectable somatic ctDNA mutations at baseline. Detection of BRAF V600 ctDNA was associated with baseline disease stage (p = 0.008). There was no difference in the overall response rate based on baseline ctDNA detection. Detection of ctDNA at baseline was associated with worse PFS (median BRAF V600 ctDNA positive = 5.8; 95% CI: 4.2-9.6 months, BRAF V600 ctDNA negative = 21.4 mos; 95% CI 10.4-NA; measured from registration to lead-in cycle 1, p = 0.001) and OS (BRAF V600 ctDNA positive = 17.8 mos; 95% CI 9.76-NA, BRAF V600 ctDNA negative = not reached; 95% CI NA-NA, p = 0.0021). Conclusions: The absence of detectable BRAF V600 ctDNA at baseline is associated with improved PFS and OS in patients receiving treatment with dabrafenib and trametinib. Clinical trial information: NCT02196181.
Clinicopathological features of patients with ovarian and breast cancer with BRCA mutation.
Authors: Metin Ozkan, Sedat Tarık Fırat, Ramazan Coşar, Oktay Bozkurt, Mevlude Inanc, Muhammet Ensar Dogan
Journal: Journal of Clinical Oncology (2020)

e13524 Background: Breast cancer is the most common cancer and the leading cause of cancer death in women. Ovarian cancer contributes significantly to mortality and morbidity rates. BRCA1 and BRCA2 are the best known genes associated with breast and ovarian cancer, which are important in DNA repair and transcriptional regulation. Methods: In this study, we retrospectively analyzed the clinicopathological features of breast and ovarian cancer patients who were found to have BRCA 1/2 mutations in Erciyes University Medical Oncology between 2009-2019. Results: BRCA mutation was detected in 14 patients with breast cancer and 10 patients with ovarian cancer. The median age of patients with breast cancer was 41 (25-67). Of 14 BRCA mutated patients, 9 (64 %) patients had BRCA2 mutations while 5 (36 %) patients had BRCA1 mutations. All patients had invasive ductal carcinoma. Of 14 patients, 7 patients were grade 3, 6 patients were grade 2, 1 patient was grade 1. At the time of diagnosis, 5 of 14 patients were stage 3 and 5 patients were stage 4. 4 (80%) of 5 patients with stage 4 had BRCA 2 mutation. 5 of 10 patients who received adjuvant therapy after surgery had 4 or more lymph node metastases. Hormone receptor positive / HER2 negative disease was the most common molecular subgroup (8/14, 57%). Five patients were triple negative histology. 4 (80%) of triple negative patients had BRCA1 mutation. Ovarian cancer developed in 2 of 14 patients who had breast cancer with BRCA mutation. Median age of patients with ovarian cancer with BRCA mutation was 52.5 (19-67). 2 of 10 patients with ovarian cancer had germ cell tumors and 8 had epithelial serous carcinoma. Of 10 BRCA mutated patients, 7 (70 %) patients had BRCA2 mutations while 3 (30 %) patients had BRCA1 mutations. Both patients with germ cell tumors were stage 1 at the time of diagnosis, 7 of the patients with epithelial serous carcinoma were stage 3, and 1 was stage 2. While patients with germ cell tumors were followed without recurrence, 6 patients with epithelial serous carcinoma developed recurrence, and all of these patients were platinum sensitive. Breast cancer developed in 1 patient with BRCA1 mutation at follow-up. All patients were alive according to the last control date. Median DFS was 29 months. Conclusions: BRCA-related breast cancer is characterized by a more aggressive phenotype than sporadic breast cancer, BRCA1-associated breast cancer is more frequently high-grade and triple negative histology. BRCA-related ovarian cancer is more sensitive to treatment, especially platinum-based chemotherapy, and is associated with improved prognosis.
老年人贫血110例的病因及临床特点分析
Authors: 梁勇, 井丽萍, 宋文秀, 付蓉, 瞿文, 李丽娟
Journal: BMJ (2005)

对110例老年贫血患者的临床资料进行回顾性分析.结果显示其中缺铁性贫血39例(35.5%),营养性巨幼细胞性贫血24例(21.8%),肾性贫血10例(9.1%),自身免疫性溶血性贫血8例(7.3%),骨髓增生异常综合征7例(6.4%),再生障碍性贫血5例(4.5%),混合性贫血6例(5.5%),慢性病性贫血5例(4.5%),急性白血病及阵发性睡眠性血红蛋白尿各2 例(各占1.8%),多发性骨髓瘤及原发性骨髓纤维化各1例.39例(35.5%)患者同时存在一种以上合并症,其中合并高血压18例、冠心病10例、糖尿病8例、慢性支气管炎5例、肝肾功能损害3例、老年痴呆2例.提示老年贫血患者病因复杂,合并症多,表现不典型.临床医师应开拓思路,避免漏诊或误诊。
Abstract 16650: The Relationship Between Post Deployment Balloon Dilation and Cerebrovascular Events During Transcatheter Aortic Valve Replacement
Authors: Kashish Goel, Vuyisile Nkomo, Scott Hoffman, Joshua P Slusser, Ryan Lennon, Robert D Brown, Rakesh Suri, Kevin Greason, David R Holmes
Journal: Circulation (2015)

Introduction: The risk of stroke or transient ischemic attack (TIA) remains increased after transcatheter aortic valve replacement (TAVR), especially in the first 30 days. Limited data is available regarding the impact of procedural characteristics on risk of stroke/TIA. Hypothesis: Post deployment balloon dilatation (PD) and total number of balloon dilatations (pre, valve and post insertion) may be associated with increased risk of stroke/TIA in patients undergoing TAVR. Methods: We included consecutive patients who underwent balloon-expandable TAVR until June 2014 at Mayo Clinic, Rochester. Patients who died in the operating room, converted to open surgery, or had valve-in-valve, or underwent self-expanding TAVR were excluded. Primary end-point was stroke or TIA at 30 days. Results: Mean age was 80.9±8 y, mean STS score was 8.3±5 and 50% underwent transfemoral access. The overall incidence of PD was 14% (n=53). Total number of dilations ranged from 2-7, with 5% (n=19) getting ≥ 4 total dilatations. Out of the 370 patients, 13 patients (3.5%) suffered stroke/TIA (9.4% in PD group vs. 2.2% in non-PD group) in the first 30 days after TAVR. Cox-proportional hazards regression analysis indicated that PD during TAVR was associated with a significantly increased risk of 30-day stroke/TIA (HR, 3.8; 95% CI, 1.2-11.6; p=0.02). There was a trend towards increased stroke/TIA with total number of dilations (HR, 1.5; 95% CI, 0.87-2.6; p=0.14), longer procedural time (HR per 30 minutes, 1.3; 95% CI, 0.96-1.7; p=0.09) and severity of atherosclerosis (moderate-severe - HR, 1.9; 95% CI 0.95- 3.8; p=0.07). PD was not significantly associated with the risk of 30 day death (HR, 1.1; 95% CI, 0.24-4.85; p=0.93). Conclusions: In patients undergoing PD after balloon-expandable TAVR, 9.4% suffered a stroke or TIA in the first 30 days. PD was associated with a four-fold increase in 30 day risk of stroke or TIA.
Finding a risk assessment model for thromboembolic events in hospitalized cancer patients: The Indicate Study.
Authors: Marco Platania, Federico Nichetti, Leonardo Provenzano, Giulia Montelatici, Andrea Franza, Luca Porcu, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2020)

e24108 Background: Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). Given the hemorrhagic risk associated with untailored thromboprophylaxis, the identification of patients at low TE risk who might not receive it during in-hospital stay would be clinically useful. Methods: The INDICATE study was a monocentric, observational study enrolling patients with active solid malignancy hospitalized for at least two nights for treatment administration, diagnostic procedures or acute medical illness (excluding TEs). The primary objective was to assess the Negative Predictive Value (NPV) of low-grade Khorana Score (e.g. KS = 0), evaluated at the time of patients’ in-hospital admission, for TEs prediction during and after (next 45 days) hospitalization. The primary analysis was conducted on patients with KS = 0. However, all-grade KS patients were enrolled for secondary outcomes analysis. Assuming a 7% of TEs as the unsatisfactory percentage and a 3% as the satisfactory percentage, expecting about 5% of collected data as incomplete, all consecutive patients who fulfil the inclusion criteria irrespective of the KS were enrolled, until a total of 149 patients with KS = 0 were included to detect the favorable NPV with one-sided alpha equal to 0.10 and power equal to 0.80. Results: Between November 2016 and May 2019, a total of 535 patients were enrolled. Among these, 153 (28.6%) had a KS = 0. The primary study endpoint was met: 29 (5.4%) patients received a diagnosis of TEs during or after hospitalization, with 7 (4.6%) cases in the KS = 0 group. However, patients with higher KS values did not show increasing TE incidence. Among the other evaluated risk assessment models, the ONKOTEV scoreshowed the best predictive potential, with significantly higher values in patients with TEs (p &lt; 0.001).Of note, TEs were associated with poorer overall survival (median, 6.7 vs 24.8 months, log rank p &lt; 0.001). Conclusions: The INDICATE study showed that hospitalized cancer patients with KS = 0 at admission have a low risk of TEs, and could thus be spared from routine thromboprophylaxis. Further studies are needed to better define a RAM in this population.
Homologous sclera implantation for treating eyelid cicatricial entropion after burns
Authors: Tao Chen, Dong-mei Li, Yi Oin, Jie Sun
Journal: BMJ (2010)

To explore effects of homologous sclera implantation for treating eyelid cicatricial entropion after burns.Fifteen patients (15 eyes) with cicatricial entropion after burns were operated under microscope with homologous sclera graft in the eyelid.The tarsus was separated fully from the palpebral margin of the musculus orbicularis oculi,with deleted area of the conjunctiva for implantation,and homologous sclera graft was taken on the implant bed and sutured together.The implant and the bed were well cured together during postoperative follow-up,with less than 10 percent of constriction of the implant,indicating obvious effect of homologous sclera graft for treating the eyelid cicatricial entropion after burns.

Key words: 
Entropion;  Tissue transplantation
Expression of p16 and Ki67 in cervical intraepithelial neoplasia and cervical carcinoma
Authors: Ju-ying Lu, Wan-ping Qin
Journal: BMJ (2011)

Two hundred and seventy four patients with suspicious cervical lesions underwent pelvic examination and biopsy. Tissue biopsy results revealed 153 cases of cervical intraepithelial neoplasia(CIN)and 10 cases of cervical carcinoma. p16 and Ki67 were detected by immunohistochemistry method in tissue specimens. The positive rates of p16 were 9.0%, 69. 9%, 93. 8%, 95. 5% and 10/10 in normal cervical mucosa, CIN Ⅰ , CIN Ⅱ , CIN Ⅲ and cervical carcinoma, respectively; while those of Ki67 were 76. 6%,89. 2%, 91.7%, 95.5% and 10/10, respectively. The expressions of p16 and Ki67 were significantly associated with cervical lesions ( P ＜ 0. 01 ). The study suggests that p16 and Ki67 may be used as supplemental diagnostic markers for cervical lesions.

Key words: 
Cervical intraepithelial neoplasia;  Proteins
Risks, Benefits, and Effects on Management for Biopsy of the Papilla in Patients With Familial Adenomatous Polyposis
Authors: Neal A. Mehta, Ravi S. Shah, Jiyoon Yoon, Margaret O'Malley, Lisa LaGuardia, Gautam Mankaney, Amit Bhatt, Carol A. Burke
Journal: Clinical Gastroenterology and Hepatology (2020)
A phase I, open-label, multicenter study to assess the safety, pharmacokinetics, and preliminary antitumor activity of AZD4635 both as monotherapy and in combination in patients with advanced solid malignancies: Results from prostate cancer patients (NCT02740985).
Authors: Emerson A. Lim, Todd Michael Bauer, Manish R. Patel, Gerald Steven Falchook, Janet L. Karlix, Jennifer Hsing Choe, Daniel J. George, Ganesh M. Mugundu, Elizabeth Pilling, Huifang Chen, Bolan Linghu, Lara McGrath, Wenlin Shao, Melinda S. Merchant, Ben Sidders, Kris F. Sachsenmeier, Gayle Pageau Pouliot, Charles G. Drake, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2020)

5518 Background: AZD4635 inhibits adenosine 2a receptor (A2aR) signaling and improves immune activation and anti-tumor activity in preclinical models. This phase I study assessed the safety, pharmacokinetics, pharmacodynamics and efficacy of AZD4635 monotherapy (mono) and in combination (combo) with durvalumab (durva) in patients (pts) with refractory solid tumors. Here we present data for immune checkpoint-naïve pts with metastatic castrate-resistant prostate cancer (mCRPC). Methods: Pts with refractory mCRPC received AZD4635 mono (75 mg or 100 mg QD oral nanosuspension [(RP2D]) or in combination (75 mg or 100mg QD) with durva 1.5g IV q4wk. Results: Between 30Aug16 and 20Jun19 (data cutoff [DCO]) 94 mCRPC pts were treated with mono (n = 49) or combo (n = 45): median age 70.5 yrs; ECOG 0-1 = 99%. The median number of prior treatment regimens was 5 (range = 1-10); 61% of pts (57/94) had prior chemotherapy, 90% had prior new hormonal therapy. PK data suggest AZD4635 concentrations at 75-100 mg QD are above the in vitro IC 50 for A2aR inhibition throughout the dosing interval. Modeling predicts 80-90% A2aR occupancy at steady state for doses at ≥75 mg QD. Most common treatment-related AEs ( &gt; 10%) were nausea, vomiting, fatigue, decreased appetite, dizziness, and diarrhea. At the DCO in this ongoing study, 70 pts were evaluable for response by RECIST v1.1 (mono = 33, combo = 37). Confirmed response occurred in 8 pts: mono = ORR 6.1% (2PRs) and combo = 16.2% (2CRs, 4PRs). The duration of response across cohorts ranged from 1-18.5 mo (5 pts ongoing). PSA response (defined as ≥50% decrease from baseline of ≥1ng/ml) was observed in 6.4% (3/47 pts; 95% CI, 1.3-17.5) of mono-treated patients and 20% (9/45 pts; 95% CI, 9.6-34.6) of combo-treated patients. Patients with high adenosine (ADO) gene expression signature (N = 46) in peripheral blood, showed a median PFS of 21 weeks v. 8.7 weeks in ADO signature low patients (N = 46) (HR 0.5, CI 0.3-0.9) (DCO 20Jun19). In addition, baseline TCR clonality and diversity were linked with response. Conclusions: In mCRPC pts, AZD4635 alone or in combination with durva was tolerable and associated with clinical benefit. A mCRPC phase II trial is ongoing with continued exploration of predictors of response to treatment. Clinical trial information: NCT02740985 .
Correlation of blood concentration with efficacy and safety of tacrolimus in treatment of myasthenia gravis patients
Authors: Di Chen, Shifang Hou, Ming Zhao, Xuelin Sun, Hua Zhang, Liping Yang
Journal: BMJ (2018)

Objective
To investigate the relationship of blood concentration of tacrolimus with efficacy and safety in treatment of patients with myasthenia gravis.


Methods
The clinical data of 74 patients with myasthenia gravis admitted in our hospital from January 2013 to December 2015 were analyzed retrospectively. The blood concentrations of tacrolimus were determined by chemiluminescence microparticle immunoassay. Treatment effects were evaluated with clinical relative scoring in China.


Results
There were 41 men and 33 women in 74 patients with the mean age of (56.7±15.8) years. According to the Osserman classification, there were 7 cases of type Ⅰ, 18 cases of type Ⅱb, 27 cases of type Ⅱa, 5 cases of type Ⅲ and 17 cases of type Ⅳ. Forty seven patients underwent thymectomy, including 9 cases of thymoma and 38 cases of hyperplasia. Patients were followed up for (28.1±14.5)days, and the effective rate was 74 %(55/74). There was no significant correlation between tacrolimus blood concentration and clinical efficacy. The incidence of adverse reaction of tacrolimus was 22%(16/74), and the incidence of adverse reactions increased with the increase of blood concentration.


Conclusion
Tacrolimus is effective in treatment of myasthenia gravis. The correlation of blood concentration of tacrolimus with the clinical efficacy needs to be further studied, but certainly, the monitoring of blood concentration can reduce the incidence of adverse reactions.


Key words: 
Myasthenia gravis; Tacrolimus; Drug monitoring; Adverse drug reaction
Lung cancer incidence in never smokers in the Southeast of Brazil: 10 years analysis.
Authors: Jose Zago Pulido, Sabina B. Aleixo, Narelle Parmanhane
Journal: Journal of Clinical Oncology (2020)

e13571 Background: Lung cancer is a leading cause of cancer death worldwide. In Brazil, the Ministry of Health estimated an absolute incidence of 30,200 cases of lung cancer in 2020. Eighty-five percent of diagnosed cases are associated with consumption of tobacco products. Although smoking remains the predominant cause, lung cancer in never smokers is an increasingly prominent public health problem. However, data on this topic, particularly lung cancer incidence rates in developing countries in never smokers are limited. Methods: The data presented in this work correspond to the period from 2007 to 2017 and were extracted from the database of the Hospital Cancer Registry of the Evangelical Hospital of Cachoeiro de Itapemirim (RHC / HECI) through SisRHC, a computerized database management tool for Hospital Cancer Records. Results: Of the 494 patients who were diagnosed with lung cancer aged 18 years or over, 395 (80%) had complete information on a history of tobacco use, of which 68 patients denied smoking. Based on data from 68 patients, the years 2011 and 2012 had the lowest incidence, 6%, of non-smokers with lung cancer. 2009 and 2007 were the years with the highest incidence, 24 and 33% respectively. In the remaining years, the percentage varied between 15 and 23%. Regarding gender, 47 (69%) of the cases were women and 21 (31%) were men. Adenocarcinoma without a specific origin (NOS) was the most frequent histological type in non-smoking patients, with 33 (48.5%) of the cases, followed by malignant neoplasia 10 (14.7%), squamous cell carcinoma NOS 8 (11, 8%) and NOS carcinoma 7 (10.3%), the types of NOS large cell carcinoma, NOS small cell carcinoma, NOS papillary carcinoma, NOS bronchioloalveolar adenocarcinoma and adenosquamous carcinoma account for 10 (14.7%) cases. Analyzing the clinical staging (CE) at the time of diagnosis, 1 (1.5%) had EC 1, 4 (5.9%) EC 2, 12 (17.6%) EC 3, 42 (61.8%) EC 4 and 9 (13.2%) had no reports of staging. The median incidence rate was 17%, confirming that smoking remains the biggest cause of lung cancer, and reinforcing the need for more comprehensive epidemiological analyzes for this population. As the data can reach even higher percentages, as the information is provided by patients, without an available reliability assessment method. Conclusions: Lung cancer in never smokers is a major public health problem and further exploration of its patterns of incidence, etiology and biology is needed.
Effect of long-term peripheral neuropathy induced on cisplatin-based chemotherapy or radiation to the retroperitoneum in testicular germ cell tumor survivors.
Authors: Michal Chovanec, Dominika Galikova, Lucia Vasilkova, Valentina De Angelis, Katarina Rejlekova, Jana Obertova, Zuzana Sycova-Mila, Patrik Palacka, Katarina Kalavska, Daniela Svetlovska, Beata Mladosievicova, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2020)

e17062 Background: Treatment for testicular germ cell tumors (GCTs) results in late chemotherapy-induced peripheral neuropathy (CIPN). This study aimed to evaluate impact of curative treatments on different subtypes of self-reported peripheral nerve damage. Methods: GCT survivors (N = 186) followed-up annually at National Cancer Institute in Slovakia have prospectively completed European Organisation for Research and Treatment of Cancer (EORTC) CIPN20 questionnaire at 10 years of median follow-up (range 4-25). EORTC CIPN20 scoring allowed to obtain subscales on sensory function, motor function and autonomy function as well as an overall score. Study groups consisted of survivors treated with chemotherapy (N = 141) and radiotherapy to the retroperitoneum (N = 15). The control group consisted of survivors cured with orchiectomy alone (N = 30) Results: GCT survivors cured with chemotherapy reported higher impairment in overall peripheral neurological function compared to controls (mean score ± SEM: 24.2 ± 0.5 vs. 22.3 ± 1.1, P = 0.03). CIPN20 subscales have shown greater impairment in motor function (P = 0.04), but not in sensory/autonomy functions (both P &gt; 0.05) in chemotherapy group versus controls. Survivors treated with BEPx3 or EPx4 reported similar CIPN in all subscales (all P &gt; 0.05). Motor function was worse in survivors who received ³400mg/m 2 of cisplatin compared to ones who received &lt; 400mg/m 2 (mean score ± SEM: 9.5 ± 0.2 vs. 8.9 ± 0.3, P = 0.04). Interestingly, patients treated with radiotherapy to the retroperitoneum (but not with chemotherapy) suffered from significantly more peripheral neuropathy in all measured domains compared to the controls (all P &lt; 0.02) Conclusions: Evaluation of long-term perceived peripheral neuropathy after treatment for GCT has shown primarily motor function impairment after chemotherapy. Moreover, significant peripheral neuropathy in all observed CIPN20 subscales after radiotherapy to the retroperitoneum suggests this symptom is not exclusive to cisplatin-based chemotherapy.