tbuckley/cabot-search huggingface dataset:
Allo-immunity and graft rejection after checkpoint inhibitor therapy (CPI) in solid organ transplant (SOT) recipients.
Authors: Noha Abdel-Wahab, Ala Abudayyeh, Mohsin Shah, Daniel H. Johnson, VanAnh Trinh, Maen Abdelrahim, A.Osama Gaber, Maria E. Suarez-Almazor, Adi Diab
Journal: Journal of Clinical Oncology (2018)

3082 Background: The safety of CPI in patients (pts) with prior SOT was never fully assessed because they were always excluded from clinical trials due to the risk of allo-immunity and organ rejection, and being on immunosupresive therapy (IST). Methods: We identified from pharmacy records pts who had received CPI between January 2004 and June 2017 at our institution (n = 4,406). Claims data were obtained for all pts from 6 months prior to first infusion to last follow-up or death. ICD 9 & 10 diagnostic codes were used to identify pts with organ transplant (n = 173). Medical records were reviewed to identify SOT pts. We systematically reviewed the literature databases through September 2017 to identify similar pts. Results: A total of 24 pts were retrieved, 6 from institutional databases and 18 from literature. Median age was 61.5 (14-79) years; 75% were male; 67% had metastatic melanoma. Other cancer types included cutaneous squamous cell, non-small cell lung, hepatocellular, and duodenal carcinomas. Renal transplant was reported in 67%. Other SOT included liver and heart. Median time to initiation of CPI after SOT was 8 (1-25) years. Most received anti-PD1 agents (79%). At CPI initiation, all pts were kept on prednisone (≤ 10 mg), mTOR inhibitors, or other IST to maintain graft tolerance. Graft rejection occured in 50% of pts (8/16 kidney, 3/6 liver, and 1/2 heart transplants); 92% received anti-PD1 therapy. Median time to rejection was 21 (5-60) days. In 8 pts with biopsies, 6 had a T-cell mediated rejection, and 2 had mixed cellular and antibody infiltrates. Management of rejection included appropriate IST, and 29% remained dependent on dialysis. CPI was discontinued in all pts. Among all rejected cases, only one pt with cardiac transplant recovered. Interestingly, other irAEs occurred mainly in non rejected cases. They all improved with appropriate IST. In melanoma pts, 27% (4/15) responded to CPI. In all pts, death was reported in 35% (n = 8), in 4 pts was due to organ rejection (2 liver and 2 kidney). Conclusions: High rejection rate was evident in SOT pts shortly after CPI and was associated with high mortality rate. Further studies are needed to establish the risk-benefit profile in this population.
Landscape of <i>BRCA1</i> and <i>BRCA2</i> germline, somatic, and reversion alterations detectable by cell-free DNA testing among patients with metastatic breast, ovarian, pancreatic, or prostate cancer.
Authors: Aditya Bardia, Thereasa A. Rich, Victoria M. Raymond, Stephen R Fairclough, A. Oliver Sartor, Michael B. Lilly, Mohammad Nezami, Sandip Pravin Patel, Benedito A. Carneiro, Alice C. Fan, Adam Brufsky, Barbara A. Parker, Benjamin B. Bridges, Neeraj Agarwal, Benjamin Louis Maughan, Richard B. Lanman, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2018)

12097 Background: PARP inhibitors (PARPi) have shown efficacy in breast (BC), ovarian (OC), pancreatic (PaC), and prostate (PrC) cancers harboring deleterious germline or somatic alterations (alts) in BRCA1 or BRCA2 (gBRCA, sBRCA). Additional acquired reversion alts (rBRCA) which restore the open reading frame (ORF) have been reported in the setting of resistance to PARPi or platinum-based chemotherapy. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) provides a platform to evaluate the relative frequency of all three of these types of BRCA alts in pts with advanced cancers. Methods: BRCA alts were identified among 1,122 samples from 828 pts with metastatic BC, OC, PaC, or PrC with tumor DNA detected on a clinical 73-gene cfDNA NGS assay (tests run between 11/2016-10/2017, Guardant360). This assay evaluates single nucleotide variants and indels in BRCA1/2 and tracks individual DNA molecules allowing for phasing. BRCA alts were classified as gBRCA, sBRCA, or rBRCA based the variant allele fraction (VAF), AFs of neighboring germline SNPs, and relative positions of all alts in a sample. Treatment history was obtained from test request forms. Results: At least one deleterious BRCA alt was detected in 67 pts (8.1%), including 35/472 pts with BC, 6/47 OC, 5/85 PaC, and 21/223 PrC. 36 of these patients had putative gBRCA alts, 8 of whom had additional alts consistent with rBRCA (5 had BC, 3 had PrC). The remaining 31 BRCA+ pts had only sBRCA, 1 of whom had BC and multiple somatic alts consistent with rBRCA. Treatment history was available for 29/67 BRCA+ pts. Among the 7 who were indicated as having exposure to a PARPi, 2 had a rBRCA. Conclusions: Rates of cfDNA-detected gBRCA and sBRCA alts in pts with advanced BC, OC, or PaC are comparable to that reported by TCGA, and higher among men with PrC. Approximately half of the BRCA+ pts had gBRCA and half only had sBRCA, highlighting the value of cfDNA NGS testing to identify both types of targetable BRCA alts. Moreover, rBRCA were identified in a significant percentage (13%) of BRCA+ pts without foreknowledge of germline- or tissue-based testing, and may identify pts unlikely to respond to PARPi.
Bevacizumab, eribulin, and oxaliplatin in patients with platinum-resistant ovarian carcinomas: A phase II study with biomarker analysis.
Authors: Masashi Takano, Hiroko Kouta, Kazuya Kudoh, Tsunekazu Kita, Tomoyuki Yoshikawa, Ryoko Kikuchi, Hiroko Matsuura, Morikazu Miyamoto, Tomoko Goto, Kenichi Furuya, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2017)

5550 Background: Eribulin is a candidate for paclitaxel-refractory breast cancers, and Bevacizumab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A phase II study to evaluate weekly administration of B with eribulin and oxaliplatin (EriOX) in patients with platinum-resistant and refractory ovarian carcinomas (PR-ROC) was performed. Methods: Eligible patients were as follows: (a) ECOG PS = 0~2 (b) histologically confirmed epithelial ovarian cancer (c) diagnosed as platinum-resistant ovarian cancer (d) written informed consent. Patients were treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m 2 ) and oxaliplatin (30mg/m 2 ), three weeks on and on week off, q4weeks. The study was conducted using two-stage design of Simon (type I error = 0.05, power = 0.9, true response rate = 25%). Biomarker analyses including serum VEGF, BNP, p53, IL-6, and Her-2 were also conducted. Results: A total of 34 patients were enrolled in the present study: 13 cases in the first-stage, and additional 21 cases in the second-stage. There were 3 responders (≧2) in the first-stage, and the protocol was proceeded to the second-stage. Median age of the patient was 58.5 years (range: 35-76), and median number of previous regimen was 4 (range: 2-9). Overall, two patients (6%) had a complete response (CR), 8 patients (24%) had a partial remission (PR) and 16 patients (47%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 29% and 76%, respectively. Median progression-free survival was 4 months (range: 1-27+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (11%). Non-hematological AE greater than grade2 was observed in one case: hypo albuminemia and edema, which were manageable and tolerable. As there were 10 responders (≧6), the protocol was considered for additional investigation. The Patients with elevated serum mutated p53 / IL-6 showed lower response and worse prognoses. Conclusions: Weekly B and EriOX administration was considered for additional investigation for patients with PR-ROC. Serum mutated p53 protein and/or IL-6 could be biomarkers in PR-ROC patients treated with weekly B and EriOX.
DEVEC metronomic schedule for aggressive B and T-cell lymphomas.
Authors: Maria Christina COX, Roberta Battistini, Sabrina Pelliccia, Annalisa Arcari, Paola Anticoli Borza, Ivana Casaroli, Valerio Zoli, Francesca Di Landro, Francesca Fabbri, Giulia Galassi, Anna Paola Leporace, Monica Piedimonte, Marco Di Girolamo, Daniela Prosperi, Alessia Campagna, Arianna Di Napoli, Agostino Tafuri, Guido Bocci, Gerardo Musuraca
Journal: Journal of Clinical Oncology (2018)

7563 Background: Metronomic chemotherapy (MC) is an emerging approach in solid tumours. Since MC has been poorly investigated in aggressive lymphomas in 2011, we formulated a new oral MC regimen termed DEVEC (Deltacortene, Etoposide, Navelbine, Cyclophosphamide). Methods: The DEVEC foresees an induction and a deescalated maintenance phase both consisting in 6 cycles. Rituximab is administered in CD20+ cases. Patients with aggressive B and T cell lymphomas, unsuitable for standard-chemotherapies, were enrolled in 6 Italian institutions. HIV+ and CNS involvement were excluded. Data were retrieved as of 31th January 2018 (EC approval n° 4640). Results: 58 patients started DEVEC between October 2011 and October 2017: the median follow-up time is 23 months. Median age was 79 years (26–93): 22 (37.9%) were refractory and 20 (34.5%) relapsed after previous treatments; 16 (27.62%) were treatment-naïve. Histology: DLBCL = 41(70.7%); PTCL = 15 (25.9%) and MCL = 2 (3.4%). By comprehensive geriatric assessment, patients scored as FIT = 7 (12%), UNFIT = 16 (27.6%), FRAIL = 23 (39.6%); Super-Frail (SF) = 10 (17.2%). In 53 evaluable cases the overall hematologic toxicity was mild and manageable with growth factors. Extra-hematologic toxicity of grade ≥3 was reported in 12/53 patients (22.6%) and were all classified as SAE: 6/12 cases occurred in SF. 5/12 patients discontinued DEVEC and died respectively 0, 1, 4, 4 and 5 months after treatment stop. In 50/53 patients, evaluable for outcome, the ORR was 68% and CR rate 44%. In the Naïve subset (n = 14) ORR = 92.8% and CR+CRu = 64%; in the Relapsed subset (n = 16): ORR = 93.7%; CR = 62.5%; in the Refractory subset (n = 20) ORR = 30%; CR = 10%. The estimated median OS and PFS were 15 (95%CI = 9.17-20.83) and 13 (CI 95% = 2.07-23.93) months, respectively. No significant differences in OS and PFS were observed in DLBCL vs PTCL. The direct cost of drugs of the oral DEVEC schedule was estimated 930 and 817 Euro (year 2016) for a single induction and maintenance cycle, respectively. Conclusions: To our knowledge this is the largest series of aggressive lymphoma treated with MC. DEVEC induced sustained CR in a substantial proportion of patients with very poor outlook and deserves further studies in aggressive lymphomas.
Abstract 16199: Hemodynamic Effect of CoreValve Size and Position for Valve-in-valve Implantation in Small Surgical Bioprostheses: An in vitro Study
Authors: Anne-Sophie Zenses, Viktoria Stanova, Morgane Evin, Jean-François Obadia, Josep Rodés-Cabau, Philippe Pibarot, Régis Rieu
Journal: Circulation (2016)

Introduction: Valve-in-Valve (ViV) has emerged as a valuable alternative to treat failed surgical bioprostheses (BP) in patients at high surgical-risk. However, this procedure is often associated w...
Real world of infusion related reactions in an oncology outpatient clinic.
Authors: Beatriz Bernardez, Borja Franco, Nieves Mayo, Juan Cueva, Mar Lale, Goretti Duran, Manuel Touris, Elena Lopez, Alicia Mosquera, Sara Blanco, Bibiana Sanchez, Alba Garcia, Rafael Lopez, Maria Lamas
Journal: Journal of Clinical Oncology (2018)

e18872 Background: Most data on infusion related reactions (IRR) come from clinical trials. Its severity and management are issues addressed in many studies, however, the impact in real life in terms of receiving a suboptimal treatment has not been quantified. Our center is certificied with Spanish standard UNE 179003:2013, which provides healthcare organizations with a framework and a systematic protocol for managing patient (pt) safety. In this context, we established the standardized IRR document (SID), involving the cancer care team (CCT) in the follow-up of the IRR. Methods: CCT prospectively collected and analyzed all IRRs of cancer pts treated with chemotherapy during 2017. Oncology nurses collect pt data, date, reaction and constants. Medical oncologists assessed the severity and outcome of the reaction. Oncology pharmacists, at least one month later, reviewed the electronic health record data and assessed the impact and communication to the SPS. The percentages of IRR described in the literatura (PDL) were derived from the Micromedex database or label information. Frequency assessment is based on the CIOMS criteria. Results: 16059 treatments were administered to 1604 pts during 2017. The number of IRR collected was 85 (0.53%) affecting 75 pts. IRR by drug are recorded in Table 1. There have been no life-threatening consequences or death (grade 4 or 5) by IRR; 48.2% were moderate or severe (Grade 2 or 3). 61.2% of IRR were notified to the SSP. Of the 85 IRR reported, only 28 continued same infusion (24%). On 52 times, the IRR caused a change of treatment (69.3%), meaning 3% of all treated pts have not been able to receive their full treatment (common > 1%). Conclusions: A multi-disciplinary CCT collect, evaluate, and communicate all RRIs during 2017, improving the quality of care. SID provides useful information about our real world data and how IRR can cause treatment losses with a common frequency. DRUG IRR PREPARATIONS REAL WORLD(%) PDL (%) CARBOPLATIN 23 1468 1.6 12 OXALIPLATIN 21 1597 1.3 0.5-25 DOCETAXEL 11 754 1.5 21 CETUXIMAB 8 667 1.2 22 PACLITAXEL 8 2136 0.4 2-45 TRASTUZUMAB 4 986 0.4 0.6-8 IRINOTECAN 3 1283 0.2 NR* EPIRRUBICIN 2 510 0.4 NR* CISPLATIN 2 983 0.2 NR* PEGYLATED LIPOSOMAL DOXORUBICIN 2 129 1.6 7-11 NIVOLUMAB 1 686 0.1 NR* *NR = NOT REPORTED
Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Authors: Zobair Younossi, Frank Tacke, Marco Arrese, Barjesh Chander Sharma, Ibrahim Mostafa, Elisabetta Bugianesi, Vincent Wai‐Sun Wong, Yusuf Yilmaz, Jacob George, Jiangao Fan, Miriam B. Vos
Journal: Hepatology (2018)

Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world’s population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death. NAFLD and NASH are not only found in adults—there is also a high prevalence of these diseases in children and adolescents. Because of the close association of NAFLD with type 2 diabetes (T2DM) and obesity, the latest models predict that the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient‐reported outcomes. Nonetheless, there is no accurate noninvasive method to detect NASH, and treatment of this disease is limited to lifestyle modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during the 2017 American Association for the Study of Liver Diseases Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide.
OS3.1 IDH-wild type grade II gliomas: a retrospective series of AINO (Italian Association of Neuro-Oncology)
Authors: F Bruno, A Silvani, T Ius, L Bello, G Minniti, A Pace, G Lombardi, R Soffietti, R Rudà
Journal: Neuro-Oncology (2018)

Information regarding clinical characteristics and response to treatments of IDH-wild type grade II gliomas is still lacking. This national retrospective study aimed to investigate natural history, management, and factors affecting response to treatments and outcome of a cohort of WHO grade II IDH-wild type glioma patients. We collected all clinical data of patients diagnosed with WHO grade II IDH-wild type glioma from 1999 to 2017 in six major Italian Institutions. IDH mutation was assessed by either immunohistochemistry or sequencing (in cases with negative immunohistochemistry). Exclusion criteria were the presence of minimal anaplastic foci or radiological features of HGGs. Kaplan-Meier curves and Cox-regression models were used for univariate and multivariate analysis. Overall, 194 patients were collected and ultimately 122 met the inclusion criteria. Median age was 45 years. Seizures were the presenting symptoms in 74 cases (60.7%), while focal deficits were present in 25 cases (20.5%), and 5 patients (4.1%) had an incidental radiological diagnosis. Non-enhancing tumours on MRI accounted for 74% while 26% had minimal/mild contrast enhancement. Surgery consisted in gross total resection in 29%, partial/subtotal in 45%, biopsy in 24%, and unknown in 2%. According to WHO 2007 astrocytomas were 44%, oligodendrogliomas 35%, and mixed gliomas 21%. MGMT methylation was available in 68% of patients, and in 40% of them was methylated. Post-surgical management consisted in watch and wait in 42%, chemoradiation in 21%, chemotherapy alone in 21%, radiotherapy alone in 5%, radiotherapy followed by chemotherapy in 5%, and 6% unknown. Radiological response to first line treatment was available according to RANO criteria in 47 cases: stable disease was observed in 23 patients (48.9%), progressive disease in 16 (34.0%), partial response in 7 (14.9%), and complete response in 1 (2.1%). Median time of follow-up was 31 months. Median PFS at first recurrence from diagnosis was 24.0 months (1.2 - 147.0). Treatments at the recurrence were second line chemotherapy in 33 cases (42.3%), second surgery in 18 cases (23.1%), radiotherapy in 10 cases (10.4%), and palliative care in 13 cases (16.7%) - we miss information about 4 patients. Median OS was 45.3 months (1.0 - 225.6). Factors positively associated with PFS and OS in univariate analysis were younger age, absence of contrast enhancement, and gross total resection. Age and extent of surgery retained a statistically significant importance in multivariate analysis. WHO grade II IDH-wild type gliomas have a worse outcome as compared with IDH-mutant tumours. This is the first study that details clinical and radiological presentation of this rare subgroup of tumours and suggests that gross total resection is critical in improving survival.
Does moderate alcohol consumption really have health benefits?
Authors: Mark Wilson, Alain Braillon
Journal: BMJ (2018)

The public might be confused by The BMJ ’s editorial on the relation between alcohol consumption and Alzheimer’s disease, which was based on an observational study.1 The editorial’s salient message was that moderate alcohol consumption can ward off Alzheimer’s disease. But the view that moderate drinking has health benefits has been criticised as a bias favouring the alcohol industry.

Observational studies have been touting …
Evaluation of the safety of continuing trastuzumab despite overt left ventricular dysfunction.
Authors: Carly Barron, Umangjot Kaur, Muhammad Mustafa Al-Hussein, Mark Brown, Tammy Cosman, Som Mukherjee, Peter Michael Ellis, Sukhbinder K. Dhesy-Thind, Darryl Leong
Journal: Journal of Clinical Oncology (2018)

e18548 Background: Trastuzumab therapy is limited by cardiotoxicity. Current guidelines recommend withholding trastuzumab treatment for falls in left ventricular ejection fraction (LVEF); however, < 12 months’ trastuzumab leads to suboptimal cancer outcomes. We evaluated the safety of continuing adjuvant trastuzumab in patients with breast cancer despite mild, asymptomatic left ventricular impairment. Methods: In this retrospective study, charts of consecutive patients referred to cardio-oncology clinic for reduction in LVEF (defined as a fall ≥10% or a value < 50%) during adjuvant trastuzumab therapy were reviewed. Patients choosing to continue with trastuzumab therapy were treated with angiotensin converting enzyme inhibitors (ACE-I) and/or beta-blockers under cardiologist oversight. Patients were followed for a median of 9 months. The primary outcome was LVEF, which was measured before and during trastuzumab exposure, and up to 3 times after the initiation of cardiac medications. Results: Eighteen patients were included in the study (Table 1). Seventeen (94%) patients had previous anthracycline treatment or previous radiation therapy. After initiation of cardiac medications, LVEF increased over time by 4.64% (CI 1.92-7.36) approaching baseline values, and 17/18 patients were asymptomatic (NYHA Class I) at all future visits. All patients except one completed trastuzumab treatment successfully. One patient developed pulmonary edema related to mitral regurgitation. There were no deaths in the 18 patients. Conclusions: Our results suggest that some patients with mildly reduced LVEF and minimal heart failure symptoms may be able to continue trastuzumab without further decreases in LVEF, adverse cardiac events, or death. Future studies optimizing trastuzumab use while maintaining cardiovascular safety are warranted. Table 1. Baseline Characteristics Mean ± Std Dev Age (yrs) 57.4 ± 10.5 LVEF (%) 50.4 ± 5.2 N (%) Female 18 (100%) Cancer Stage: I 4 (22%) II 10 (56%) III 2 (11%) IV 2 (11%)
Radar-guided vs. wire localization for non-palpable breast lesions.
Authors: Timothy Borjas, Jennifer Chun, Mark Saraceni, Deborah M. Axelrod, Amber Guth, Karen Hiotis, Richard L. Shapiro, Daniel F. Roses, Freya Ruth Schnabel
Journal: Journal of Clinical Oncology (2018)

e18525 Background: Wire localization (WL) has been the standard for intraoperative localization for non-palpable breast lesions for many years. Wires must be placed on the same day as surgery, which may result in scheduling conflicts, and increases the total time that patients spend in the hospital system. We examined the effect of a newly developed wire-free localization technology on the surgical process at our institution. Methods: Our institutional databases were queried for patients who had breast surgery with WL from 1/17-3/17, and wire-free technique using the SAVI SCOUT® system (Cianna Medical) from 7/16-1/17. Data was accumulated including total time per patient in the hospital system, as determined from event times related to their surgery, type of procedure, and first cases. Descriptive statistics and Student’s T-test were performed. Results: A total of 169 patients underwent breast surgery with WL and 73 patients underwent SAVI SCOUT in the study periods. All wire-free localization cases had the SAVI SCOUT reflector implanted prior to the day of surgery and all WL procedures were done on the day of surgery. WL patients spent on average 8 hours and 45 minutes in the hospital system on the day of surgery, compared to SAVI SCOUT patients who spent 4 hours and 23 minutes (p < 0.0001) (Table). On average, 2 hours and 34 minutes elapsed between patient discharge from breast imaging after WL to their preoperative anesthesia consultation. 26 (25%) of SAVI SCOUT patients were first cases in the operating room (OR) on the day of surgery compared to 0 for the WL group. Conclusions: Our data shows that patients undergoing surgery with WL procedures spend double the amount of time in the hospital system compared with those undergoing surgery with wire-free techniques. Wire-free techniques lead to improved OR efficiency by allowing for first case scheduling for these patients, and uncoupling the surgical procedure from the required localization. As a result, wire-free localization techniques contribute to improved patient experience and efficiency. Table: WL vs. SAVI SCOUT WL (N = 169) SS (N = 73) Median Age (yrs, range) 59 (26-88) 59 (29-86) Sentinel Dissections 51 (30%) 29 (40%) General Anesthesia 63 (37%) 29 (40%) Total time in Hospital 8 hrs 45 mins 4 hrs 23 mins
TCT-268 Five-year clinical outcomes of patients with OCT-detected features of vulnerable plaque in intermediate grade coronary stenoses proven insignificant by FFR
Authors: Mariusz Tomaniak, Dorota Ochijewicz, Lukasz Koltowski, Adam Rdzanek, Arkadiusz Pietrasik, Jacek Jakala, Krzysztof Malinowski, Klaudia Proniewska, None Zenon huczek, Tomasz Mazurek, Jakub Maksym, Martyna Zaleska, Krzysztof Filipiak, Grzegorz Opolski, Janusz Kochman
Journal: Journal of the American College of Cardiology (2018)