tbuckley/cabot-search huggingface dataset:
Relationship of BRAF V600E and associated secondary mutations on survival rate and response to conventional therapies in childhood low-grade glioma.
Authors: Alvaro Lassaletta, Matthew Mistry, Anthony Arnoldo, Scott Ryall, Ana Sofia Guereirro Stucklin, Rahul Krishnatry, Cino Ling, Marion Honnorat, Nataliya Zhukova, Michal Zapotocky, Tara McKeown, Vijay Ramaswamy, Ute Katharina Bartels, Annie Huang, Nada Jabado, Eric Bouffet, Cynthia Hawkins, Uri Tabori
Journal: Journal of Clinical Oncology (2016)

10509 Background: Pediatric low-grade gliomas (PLGG) are the most common CNS neoplasm in children. PLGG are histologically and clinically diverse and molecular stratification is desperately needed. BRAF-V600E mutations are highly targetable for therapy but its biological relevance and impact on PLGG outcome is unknown. Methods: We determined RAS pathway and other secondary mutations in all patients diagnosed with PLGG since 1985 (n = 854), 506 had sufficient tissue. Tumors were tested for these alterations using the QX200 Droplet Digital PCR and nanostring technologies. Long term clinical data and imaging response to chemotherapy and radiation were collected on all patients. Results: BRAF-V600E mutation was observed in 19 % of PLGGs. Mutations were observed across a spectrum of histologies: pilocytic, pilomyxoid, ganglioglioma, PXA, DNET, and diffuse astrocytomas. Importantly, BRAFV600E positive cases were present in locations often not biopsied including spinal cord, brainstem and optic pathway. BRAF-mutated PLGG had poorer long-term outcome when compared with wild-type (WT) cases. For BRAF mutant vs. WT PLGG 15-year progression free (PFS) was 7±6% and 64±12%, respectively (p = 0.001) and 15-year overall survival (OS) was 57±16% and 94±6%, respectively (p = 0.0001). Progression in the V600E mutant cohort was also frequent after both chemotherapy and radiation with 10 year PFS of only 29.5±11% and 31.0±12% respectively. Specific quantitative imaging analysis revealed response to chemotherapy in only 20% of BRAF-mutant PLGG. Notably, V600E mutant PLGG had a significant worse PFS and OS when compared to NF-1 patients or those with the BRAF fusion. Secondary molecular alterations stratified BRAF mutant tumors into low and high-risk tumors (p = 0.004). Conclusions: BRAF-V600E mutations identify a unique group of PLGG with distinct biology and survival. Early detection, aggressive surgery, close monitoring and targeted therapies may transform the management and outcome of these children.
A survey on social media use and expectations in cancer patients.
Authors: Shamsher Ali, Mark W. Knestrick, Lori Aciavatti, Sijin Wen, Nilay Arvind Shah
Journal: Journal of Clinical Oncology (2017)

e18183 Background: Social media encompasses a wide variety of web based and mobile technologies. It has become increasingly popular, allowing for rapid communication and dissemination of information. Many believe that social media can be used as a platform for patient education and knowledge sharing. This survey intended to assess patient use of social media and patient expectations for its role at our cancer center. Methods: The study took place at West Virginia University (WVU) Hospital/Mary Babb Randolph Cancer Center, a tertiary care center. This IRB-approved, anonymous, and voluntary survey included twenty-five questions that abstracted patient data which included: age, gender, cancer type, level of education, internet use, information sources for given cancer, use of social media, and the use of WVU cancer website and social media. The survey was distributed by nursing staff to patients who were at least 18 years of age Results: 370 surveys were collected in total. 87.6 % of patients reported using social media, with Facebook as the most commonly used platform at 85.6 %. 70% reported to view or update social media sites daily. All patients reported at least monthly internet use with 61.1 % of patients reported using the internet daily. 32.7% of patients interact with WVU Cancer Centeron social media daily. When asked how patients search for background information or reviews about their provider, 57.8% of patients reported they used our institution’s website. 55.7% of patients believe it would beneficial to contact their cancer provider through social media. Only 22% of patients reported they use social media for medical information. Conclusions: With the increasing use of social media for medical information over the past several years, it is crucial for academic centers and providers to keep up with the growing demand to provide accurate and practical information for patients. Our data suggests our patient population would like to see an increased use of social media from the cancer center and its providers. The information can be used to update our cancer website and social media sites to provide patient-centered cancer information in hopes that patients will have one reliable source for all of their disease related questions and concerns.
Participation in clinical trials to improve outcomes of patients with relapsed lymphoma.
Authors: Grzegorz S. Nowakowski, Stephen Maxted Ansell, Thomas E. Witzig, William R Macon, Kay Ristow, Joseph Colgan, David James Inwards, Patrick B. Johnston, Robin Klebig, Yi Lin, Ivana N. M. Micallef, Svetomir Markovic, Luis F. Porrata, Carrie A. Thompson, Thomas Matthew Habermann
Journal: Journal of Clinical Oncology (2016)

7523 Background: Anumber of new agents with significant activity in lymphoma have been FDA-approved. These novel agents were typically first available to patients who enrolled in a clinical trial (CT). We investigated the impact of participation in a CT on the outcome in three histological subtypes of relapsed lymphoma considered to be largely incurable with standard subsequent therapies. Methods: Utilizing the prospective and actively maintained Mayo Clinic Lymphoma Database, we identified patients with i) relapsed Hodgkin lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL) and not candidates for or relapsed after high dose chemotherapy (HDC) or ii) relapsed mantle cell lymphoma (MCL). The characteristics and outcomes of these patients were compared based on whether they were enrolled on a clinical trial vs those pts who were eligible but not enrolled. Results: Between January 2001 and December 2014, 611 pts were identified: 340 pts with DLBCL; 156 pts with MCL and 115 pts with HL. During this time frame, 47 unique Phase 1-3 clinical trials were available, of which 17 involved a drug later approved by FDA for cancer therapy. 94 of 340 (27%) DLBCL, 63 of 159 (41%) MCL and 66 of 115 (57%) HL pts were enrolled on a CT at some point during therapy, with 38% of pts enrolled in more than 1 study (range 1 to 6). There were no major differences between patients enrolled in CT vs. others, including median age 62 (20-91) vs 64 (24-87) for DLBCL, 65 (38-89) vs 65 (36-90) for MCL and 28 (18-68) vs 34 (18-80) for HL. The median survival from the time of diagnosis of relapse in pts treated outside of clinical trial vs those treated on CTs was 7.5 vs 14 months (p < 0.001) in DLBCL, 20 vs 45 (p = 0.02) in MCL, and 32 vs 77 months (p = 0.02) in HL. Conclusions: In all three largely incurable lymphoma subgroups, participation in CTs was associated with significant prolongation of overall survival. While this is an observational study, and thus subject to potential selection bias limitations, the stdudy included all eligible patients utilized a prospective database. The degree of benefit is striking and such data should encourage patients to participate in clinical trials of novel agents in cancer therapy.
Abstract 20367: Interleukin-18 Mediates Left Ventricular Dysfunction Induced by Western Diet Independent of Metabolic Changes in the Mouse
Authors: Salvatore Carbone, Paul J Lee, Gabriele Adolfo Mauro, Eleonora Mezzaroma, Jessica A Regan, Donatas Kraskauskas, Raffaella Buzzetti, Benjamin W Van Tassell, Antonio Abbate, Stefano Toldo
Journal: Circulation (2016)

Background: Western diet (WD), rich in saturated fat and sugars, can induce cardiac dysfunction through unknown mechanisms. Saturated fat and sugars can prime and activate the NLRP3 inflammasome that produces the cardiodepressant pro-inflammatory cytokine interleukin-18 (IL-18). Hypothesis: We hypothesize that IL-18 mediates WD-induced cardiac dysfunction, independent on the effects on glucose metabolism. Methods: Adult C57BL/6J (WT)(N=7) and IL-18 knock out (KO)(N=9) mice were randomly assigned to either standard mouse diet (SD, saturated fat 0.8%, sucrose 0%) or WD (saturated fat 12.8%, sucrose 30%) for 8 weeks. Transthoracic echocardiography was performed at baseline and at 8 weeks to measure LV fractional shortening (LVFS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI). Food intake was measured daily, body weight weekly, and fasting glycemia at baseline and at 8 weeks. Results: After 8 weeks, WD-fed WT mice had significantly lower LVFS, higher IRT and MPI than WD-fed IL-18...
Acute‐on‐Chronic Liver Failure defined by NACSELD: The Impact on Prognosis and Futility of Care
Authors: Filipe S. Cardoso
Journal: Hepatology (2018)

TO THE EDITOR: O'Leary et al. should be congratulated for their manuscript on the validation of the NACSELD (North American Consortium for the Study of End‐Stage Liver Disease) acute‐on‐chronic liver failure (ACLF) score for the prognostication of 30‐day survival in hospitalized patients with cirrhosis.1 The definitions of extrahepatic organ failures proposed in this score are different from its European counterpart, the CLIF‐SOFA (chronic liver failure–sequential organ failure assessment) score, especially with regard to respiratory failure (RF).2 Although O'Leary et al. defined RF as the need for bilevel positive airway pressure or mechanical ventilation, Moreau et al. used a definition that is more in accordance with the intensive care literature: a ratio of arterial pressure of oxygen/inspired fraction of oxygen (PaO2/FiO2) of at least 200 mmHg.1 This difference may be relevant, as patients with grade III‐IV (West‐Haven criteria) hepatic encephalopathy (HE) often need to be intubated for airway protection rather than for actual RF. In fact, in the O'Leary et al. cohort, the 30‐day survival rates of patients with HE or RF were apparently similar (73% and 71%, respectively).1 Therefore, it would be important to clarify how many patients reported to be on mechanical ventilation were intubated due to actual RF. Despite the authors' claim that data on PaO2/FiO2 were not available, crossing patients with grade III‐IV HE and on mechanical ventilation could at least be informative.1 The definitions of organ failures used by O'Leary J.G. et al. may further affect their proposal of a criterion of futility of care in patients with ACLF: the presence of at least four organ failures.1 Out of 2,671 patients, 264 (10%) had NACSELD ACLF, and those with four or more organ failures had a 30‐day survival rate of 19%.1 Furthermore, liver transplantation, the potentially definitive treatment for ACLF, was performed in only 103 (4%) patients within 30 days of hospital discharge.1 Therefore, as discussed elsewhere, the concept of futility of care may be more complex than simply counting the number of organ failures present on admission to the hospital.4 Potential conflict of interest Nothing to report.
Predictive value of CD73 expression in <i>EGFR</i>-mutation positive non-small-cell lung cancer patients received immune checkpoint inhibitors.
Authors: Hidenobu Ishii, Koichi Azuma, Takashi Kinoshita, Norikazu Matsuo, Yoshiko Naito, Takaaki Tokito, Kazuhiko Yamada, Tomoaki Hoshino
Journal: Journal of Clinical Oncology (2018)

9065 Background: CD73 dephosphorylates and converts extracellular adenosine monophosphate to adenosine, leading to immune escape of malignancies. Although epidermal growth factor receptor (EGFR) mutation-positive NSCLC showed high expression of CD73, the predictive relevance of CD73 expression in patients with EGFR mutation received immune checkpoint inhibitors (ICIs) is unknown. Methods: We screened 67 patients with Stage I-III EGFR mutation-positive NSCLC received complete resection (cohort A), 17 patients with advanced or recurrent NSCLC received immune checkpoint inhibitors after resistance to EGFR-TKI treatment (cohort B), and 31 patients with EGFR mutation-negative NSCLC treated with ICIs. CD73 expression was evaluated by immunohistochemical analysis, and tumors with staining in over 50% of tumor cells were scored as high expression. Results: In cohort A, the high CD73 expression group showed relatively shorter disease-free survival and overall survival than the low CD73 group in patients with Stage I-III EGFR mutation-positive NSCLC received complete surgical resection. In cohort B, the overall response rate of ICIs was significantly higher in patients with high CD73 expression than those with low CD73 expression (66.7% versus 0%, p= 0.006), and the high CD73 expression group showed significantly longer progression-free survival (PFS) than low CD73 group (median 16.0 months versus 1.2 months, p= 0.024). Meanwhile, there was no significant difference in PFS of ICIs between in the high and low CD73 expression groups of EGFR mutation-negative NSCLC (median PFS; 2.8 months versus 2.8 months, p= 0.394). Conclusions: In patients with EGFR mutation-positive NSCLC, expression of CD73 may predicts a favorable outcome of ICIs treatment unlike in EGFR mutation-negative patients.
Performance of a 31-gene expression profile (GEP) test for metastatic risk prediction in cutaneous melanomas (CM) of the head and neck.
Authors: John T. Vetto, Sancy Ann Leachman, Brooke Middlebrook, Kyle R. Covington, Jeffrey D. Wayne, Pedram Gerami, Jonathan S. Zager
Journal: Journal of Clinical Oncology (2017)

9576 Background: Accurate prognostication of distant metastatic risk using sentinel lymph node (SLN) biopsy for CM can be challenging in melanomas of the head and neck due to a higher false negative rate compared to other anatomical areas. A GEP signature that predicts metastatic risk based on primary tumor biology, providing a binary outcome of Class 1 (low risk of metastasis) or Class 2 (high risk), was previously described. The prognostic capabilities of the GEP independently and in combination with SLN status in a cohort of patients with primary head and neck CM are assessed here. Methods: All samples and clinical data were collected under an IRB-approved multicenter protocol. qPCR analysis was used to assess expression of the gene signature (Class 1 vs. Class 2). Distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) were assessed. Results: 157 subjects with primary CMs in the head and neck region were identified. 110 of 157 subjects had a SLN biopsy performed. Median age was 65 years (range 25-89) and median Breslow depth was 1.6 mm (range 0.2-15.0 mm). In 71 SLN-negative patients, 18 of 27 (67%) distant metastatic events were GEP Class 2. Overall, 73% (47 of 64) distant metastases, and 88% (22 of 25) deaths due to CM were called Class 2. By comparison, sensitivities for DMFS and MSS were 41% (26 of 64) and 52% (13 of 25), respectively, using SLN biopsy alone, and increased to 80% (51 of 64) and 88% (22 of 25), respectively, when combining the SLN status and GEP class. Kaplan-Meier 5-year DMFS and MSS rates based on SLN status alone or in combination with GEP are shown in the table. Conclusions: These data support the ability of the GEP test to accurately identify low- and high-risk cases of head and neck melanoma. The results strongly support the role of GEP testing to enhance current staging by better predicting the risk of distant metastasis and death for patients with melanoma in an anatomic region that is associated with a higher SLN biopsy false negative rate. [Table: see text]
Abstract 15477: Endothelial Cells Overexpressing Interleukin-8 Receptors are Renoprotective in Rats With Acute Kidney Injury
Authors: Fadi G Hage, Dongqi Xing, Samantha Giordano, Yuanyuan Guo, Suzanne Oparil, Yiu-Fai Chen, Paul Sanders
Journal: Circulation (2015)

Introduction: In ischemia-reperfusion acute kidney injury (AKI) interleukin-8 (IL8) attracts neutrophils to the site of injury. Neutrophils interact with the damaged endothelium triggering the pro-inflammatory response that prolongs the underperfused state of the kidney and exacerbates injury. Hypothesis: We tested the hypothesis that intravenous transfusion of rat aortic endothelial cells (ECs) transduced with IL8 receptors (IL8RA/RB-ECs) ameliorates renal dysfunction and promotes structural recovery of the kidney post AKI. Methods and Results: Male Sprague-Dawley rats were subjected to sham surgery or AKI by clamping the left renal artery for 45 min and removing the right kidney. At time of reperfusion, 1.5x10 6 IL8RA/RB-ECs, ECs with empty adenoviral vector (AdNull-ECs), or vehicle were infused in the femoral vein. At 24 hrs after AKI, serum creatinine increased ~ 10 fold in the vehicle-treated group and then decreased towards baseline. IL8RA/RB-ECs but not AdNull-ECs significantly blunted the rise in serum creatinine (Fig) and decreased the local expression in the kidney and the circulating levels of inflammatory mediators at 24 hrs after AKI. At 6 wks after AKI, vehicle-treated rats had significant albuminuria compared to sham controls and EC treatment decreased albuminuria by ~65% (Fig). Stained kidney sections at 6 wks after AKI showed that vehicle-treated rats had increased interstitial collagen and decreased capillary density compared to sham controls. IL-8RA/RB-ECs were more effective at reducing interstitial collagen staining than AdNull-ECs. IL8RA/RB-ECs but not AdNull-ECs increased capillary density compared to vehicle (Fig). Conclusions: Following ischemia-reperfusion AKI, ECs equipped with IL8 receptors are attracted to the site of injury in order to inhibit inflammation, accelerate tissue repair, and preserve renal function. Our innovative cell-based strategy holds promise for improving outcomes after AKI.
Personalized neoadjuvant strategy in luminal A breast cancer to increase BCS rate (PLATO study)
Authors: W. Han
Journal: Annals of Oncology (2018)

Background: The most important and well-established benefit of neoadjuvant therapy for breast cancer patients is increased breast conservation rate. However, in luminal A type breast cancer, the response to neoadjuvant chemotherapy (NCT) is not as good as other subtype of breast cancer, such as HER-2 or triple-negative breast cancer. In addition, with the advancement of multi gene assay tools for this subtype, adjuvant chemotherapy is not needed at all in significant proportion of this luminal A subtype. Through a selective neoadjuvant therapy, either chemotherapy or endocrine therapy using histopathologic markers and 70-gene assay (Mammaprint. Agendia inc.), we hypothesize that we could increase the breast conservation rate in lumnal A type breast cancer. Trial design: This study is a non-randomized, phase II, prospective study. The main inclusion criteria is women with stage I-IIIA, ER-positive, HER-2 negative breast cancer that tumor size is measurable. Breast conserving surgery (BCS) is not feasible considering the turmor size, location, and patient's breast size. Two surgeons in each institution will judge the feasibility of BCS. Main exclusion criteria is diffuse malignant microcalcifiation or multicentrica breast cancer. The conversion rate from BCS-ineligible to BCS-eligible with NCT was 35.8% in luminal A breast cancer in our previous study. We assumed that with the study regimen, the rate will be increased to 50.8% (15% increase). Given these estimates, under 10% type I error rate and 70% power, 220 patients in total will be enrolled from nine tertiary hospitals in Korea. All the patients initially will be tested with Mammaprint assay. When the Mammprint result is high risk, the patients will receive NCT. When the Mammprint result is low risk, the patients will receive neoadjuvant endocrine therapy. Postmenopausal women receive letrozole 2.5mg per day for 16 weeks. Premenopausal women receive leuprorelin every 4 weeks with letrozole for 16 weeks. The primary endpoint is conversion rate from BCS-ineligible to BCS-eligible of more than 50%. The secondary endpoint is actual breast conservation rate. pathologic complete response. clinical response rate, and disease-free survival. Legal entity responsible for the study: Korean Breast Cancer Study Group (KBCSG). Funding: Agendia Takeda Kwandong Pharmaceutical Co Ltd. Korea Shin Poong Pharm, Co. Ltd. Disclosure: The author has declared no conflicts of interest.
The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institution.
Authors: Seung Tae Kim, Su Jin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park
Journal: Journal of Clinical Oncology (2016)

4091 Background: The clinicopathologic features of hindgut neuroendocrine tumor (NET) as well as the treatment outcomes are not well known. There are currently no published data on treatment outcomes for patients with metastatic hindgut NET. The aim of this study was to conduct a comprehensive analysis of clinicopathologic features, treatments and survival in hindgut NET patients. Methods: Among patients who were pathologically diagnosed with hindgut NET at Samsung Medical Center between March 2001 and February 2015, 607 were analyzed in this study. Hindgut NETs were defined as NETs that originated from the transverse and distal colon, rectum, and anus. Results: Primary sites included 81 colon (13.3%) and 526 rectum (86.7%). According to the WHO classification, 578 patients (95.2%) had grade 1 NETs, 17 (2.8%) grade 2 NETs, and 12 (2.0%) had neuroendocrine carcinoma (NEC). Forty-two patients (6.9%) had extensive disease, while the majority (93.1%, 565 patients) only exhibited localized disease. The five- and ten-year survival rates of 565 localized NET patients were 98.1% and 95.3%, respectively. The median OS in 42 patients with extensive disease was 24.8 months (95% CI, 10.7-38.8). Among 565 patients with localized disease, the majority (484 patients, 85.7%) were treated with endoscopic procedure by gastroenterologists. For 42 patients with extensive disease, 17 patients were managed by supportive care, 3 by concurrent chemoradiotherapy (CCRT), and 22 by systemic therapy. Among these 22 patients, 12 patients received only first-line therapy, 8 had second-line, and only 2 patients had third-line therapy. As first-line chemotherapy, the most commonly used regimens were etoposide plus cisplatin (N = 7) and long acting octreotide (N = 7). During treatment courses, the most commonly used regimen was long-acting octreotide. The median OS in 22 metastatic NET patients receiving systemic therapy was 19.3 months (95% CI, 3.2-35.3). Conclusions: This analysis provides useful information about the clinicopathologic features, treatments and survival outcomes for hindgut NET patients.