tbuckley/cabot-search huggingface dataset:
P05.81 Neurocognitive assessment in cancer patients without central nervous system disease treated with bevacizumab at week 34: an observational transversal multi-centric pilot study
Authors: C Panciroli, G Lucente, O Cecilia, V Quiroga, E Carcereny, J Pardo, M Romeo, J Velarde, S Villa, C Balaña
Journal: Neuro-Oncology (2018)

Low performances in visuomotor processing speed and executive functions were found after 34 weeks of treatment with bevacizumab plus radiotherapy (XRT) and temozolomide (TMZ) in first line treated glioblastoma patients but not in patients treated with TMZ and XRT, suggesting that bevacizumab was the cause of those alterations. Our aim was to explore the neurocognitive effects of bevacizumab in non-brain cancer patients in order to assess if the use of this antiangiogenic therapy interfered with the results of the neuropsychological tests. Seventy-seven cancer patients distributed among four groups were enrolled. None of the subjects suffered from central nervous system (CNS) disorders or had previously diagnosed neurological diseases. The first group (n=20) was treated with bevacizumab and chemotherapy (BEV), the second one (n=19) with chemotherapy alone (ChT), the third group (n=19) received only non-brain radiotherapy (RxT), and the last group (n=19) were healthy people without cancer (HC). Verbal memory, visuomotor scanning speed, executive functions, and verbal fluency were evaluated with the next tests: Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Tests (TMTA, TMTB), Controlled Oral Word Association Test (COWAT). Assessments were administered to each patient after 34 weeks from the treatment’s start date (in BEV and ChT groups), or after having completed the radiotherapy sessions (in the RxT group). All patients with cancer (BEV, ChT and RxT) showed significant alterations of the HVLT-R total recall (HVLT-R TR) in front of the HC (p<0.05). Moreover only the RxT showed a lower performance than the HC in the delayed recall (DR) of the HVLT-R (p=0.011). No statistically significant differences were observed in any tests among cancer patients groups. Our results suggest that the use of bevacizumab during 34 weeks does not produce a neurocognitive decline in cancer patients without CNS disease, in front of the group treated with chemotherapy alone. This means that combining bevacizumab with chemotherapy does not impact on neurocognitive performance. The spontaneous recall resulted impaired in all cancer patients’ groups, and the words delay recall just in the RxT group, when compared to the HC. These are important outcomes to consider as it seems that that the oncologic disease itself could impair the neuro-cognitive functions, despite the treatment administered. Accordingly, other factors such as anxiety, depression, pain, or stress, could interfere with the neuro-psychological assessment.
Racial differences in patterns of treatment among men first diagnosed with advanced prostate cancer.
Authors: Jennifer Lynn Beebe-Dimmer, Julie J. Ruterbusch, Ann G. Schwartz, Kendra L. Schwartz, Andreana Holowatyj, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2017)

e16527 Background: A small proportion of men (~4%) are newly-diagnosed with advanced stage prostate cancer (PCa) and experience poorer survival compared to men diagnosed with local or regionally-advanced disease. Prostate cancer mortality is higher in African Americans (AA) than in non-Hispanic whites (NHW), with a marginally higher proportion of AA men first diagnosed with advanced disease. We sought to describe recent patterns of treatment among men diagnosed with de novo AJCC stage IV PCa. Methods: We used the Surveillance, Epidemiology and End Results database linked to Medicare Claims files to identify men diagnosed with advanced PCa between 2007 and 2011, with follow-up through 12/31/2013. We examined patterns of treatment (surgery, radiation, chemotherapy, and hormonal therapies) as well as rarer modalities and drugs included in Medicare Part D, both overall and by race. Results: Of the 6,906 men eligible for this study, 74.6% were NHW and 13.1% were AA with a median survival of 32 months among all patients. Survival was poorer among AA compared to NHW (p &lt; 0.0001). Among the significant predictors of mortality were TNM stage, age at diagnosis, race, Gleason grade, and the presence of comorbid conditions. Androgen Deprivation Therapy (ADT) was the most widely-used treatment (78.7%), followed by radiation therapy (31.2%) and chemotherapy (30.2%). AA patients were significantly more likely to go without treatment (p &lt; 0.0001) compared to NHW patients. This finding did not change after excluding men who died within 3 months of diagnosis or men without distant metastatic disease (T4 or N1 and M0/MX). The frequency of nearly all forms of treatment was lower among AA patients with two notable exceptions; orchiectomy was significantly higher (11.8% vs. 6.9%), and among Medicare Part D enrollees, use of the progesterone Megace (27.7% vs. 17.2%). Conclusions: ElderlyAA patients newly diagnosed with stage IV PCa have shorter overall and disease-specific survival compared with NHW. Results from this study suggest less aggressive treatment may contribute to poorer survival. Understanding drivers of treatment-related decisions are critical in reducing racial disparities in survival among men with advanced PCa.
Tumor suppressor gene and mismatch repair protein expression in uterine sarcomas and carcinosarcomas.
Authors: Sally Markee, Koah Vierkoetter, David Shimizu, Keith Y. Terada
Journal: Journal of Clinical Oncology (2018)

e13516 Background: Loss of expression of p53, ARID1a, MLH1, PMS2, MSH2, and MSH2 are commonly seen in endometrial adenocarcinomas. The objective of our study is to delineate the incidence of loss of expression of these genes in uterine sarcomas and carcinosarcomas. Methods: This is a retrospective descriptive study in which all cases of uterine sarcoma and carcinosarcoma diagnosed at Queen’s Medical Center from January 1, 2000 to December 31, 2014 were pooled and reviewed. Medical chart review was performed for clinical characteristics. Tissue microarrays were created and cases were evaluated for loss of nuclear staining following immunohistochemical analysis with antibodies against MLH1, PMS2, MSH2, MSH6, p53, and ARID1a. Results: Out of our sample size of 103 cases, 12 cases were identified to have loss of expression of these genes. We identified 2 cases with loss of MLH1 and PMS2, 1 case with PMS2 and ARID1a loss, 1 case with only ARID1a loss, 1 case with MSH6 loss, and 7 cases with p53 loss. Ten out of 51 carcinosarcomas (19%), 1 out of 23 leiomyosarcomas (4%), and 1 out of 3 of undifferentiated sarcomas (35%) showed loss of expression of at least one of these genes. Average survival in the cases with loss was 23.5 months compared to 36.3 months in the group with intact expression. There was no difference in ethnic group, BMI, or age at diagnosis between the group with loss of expression and the group with intact expression. Conclusions: Loss of expression of these 6 genes known to be commonly found in endometrial adenocarcinoma does not appear to be significant in uterine sarcomas. Loss of expression of these genes in carcinosarcomas may be significant, however further research is needed.
Serum microRNAs to predict the response to nivolumab in patients with esophageal squamous cell carcinoma.
Authors: Kazuki Sudo, Ken Kato, Juntaro Matsuzaki, Junpei Kawauchi, Satoko Takizawa, Takahiro Miyamoto, Hirokazu Shoji, Satoru Iwasa, Yoshitaka Honma, Atsuo Takashima, Tetsuya Hamaguchi, Fumitaka Takeshita, Hiromi Sakamoto, Narikazu Boku, Takahiro Ochiya
Journal: Journal of Clinical Oncology (2017)

e14511 Background: A phase II study demonstrated that nivolumab (Nivo), a PD-1 inhibitor, had a meaningful activity for patients with esophageal squamous cell carcinoma. Although several biomarkers, including PD-L1 expression levels in tumor tissue, are explored to predict the efficacy of Nivo, further investigation is needed. Here we evaluated whether serum levels of microRNA (miRNA) could be a candidate of predictive markers. Methods: Among 65 patients who participated in the phase II study (JapicCTINo.142422) and received Nivo 3 mg/kg IV Q2W, 19 patients were treated at our institution. Patients were classified into responder and non-responder by investigators based on modified ir-RECIST. Serum samples were stored before and during treatment in the National Cancer Center Biobank. Comprehensive miRNA microarray analyses were performed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.), which was designed to detect 2565 miRNA expression levels. miRNA were compared between responders and non-responders using Fisher’s linear discriminant analysis, and then we calculated the area under curve (AUC) values of receiver operating characteristic curve. We explored the miRNA that showed AUC values of more than 0.8 and difference by 0.5 in the average log2 value of miRNA levels (log2miRNA) between responders and non-responders, and investigated their relation to progression-free survival using Kaplan-Meier curves and log-rank tests. Results: Among 19 patients, 5 responded (CR/PR, 1/4) to Nivo. We identified 3 miRNAs in the serum before treatment that were related to response to Nivo with AUC of 0.84 (log2miRNA of non-responder/responder: 13.16/12.47), 0.90 (8.65/10.20) and 0.81 (7.18/6.57), respectively. In the serum after the first treatment, 5 miRNAs were related to response to Nivo with AUC of 0.93 (11.93/11.09), 0.93 (11.87/11.13), 0.85 (7.92/8.53), 0.92 (6.61/5.82) and 0.93 (7.77/ 7.09), respectively. Among these 8 miRNAs, 4 miRNAs were significantly associated with progression-free survival. Conclusions: We identified miRNA candidates that could predict the response to Nivo. Further validation is warranted to confirm the results of our explorative research.
Abstract 18300: Therapy With Sacubitril/Valsartan is Superior to Enalapril in Improving Left Ventricular Relaxation and Exercise Tolerance in Rats With Preexisting Dilated Cardiomyopathy
Authors: Mikhail Y Maslov, Stephan Foianini, Michael V Orlov, Mark A Lovich
Journal: Circulation (2017)

Background: Sacubitril/Valsartan is an angiotensin receptor neprilysin inhibitor used for heart failure (HF) therapy. Sacubitril/Valsartan aims to promote effects of natriuretic peptides by inhibit...
Differential expression of SRSF2 contribute to the splicing changes related to micropapillary variant histology in nonmuscle-invasive bladder cancer (NMIBC).
Authors: Adria Closa, Michaela Bowden, Anna Orsola, José Lloreta, Nuria Juanpere, Chensheng Willa Zhou, Joaquim Bellmunt, Eduardo Eyras
Journal: Journal of Clinical Oncology (2018)

e16520 Background: Bladder cancer is the fifth most common cancer type in both sexes but more frequent in men, with an estimate of 79,030 new cases and 16,870 deaths expected for 2017 in the US. Micropapillary bladder cancer (MPBC) is a variant histology of urothelial carcinoma that although rare, it is estimated to represent 0.01-2.2% of urothelial tumors, it is associated with poor outcomes. Methods: We have evaluated the differential gene expression and splicing at genome-scale of a cohort of micropapillary and non-micropapillary high-grade T1 bladder cancer samples of clinically annotated and prospectively followed patients. The FFPE samples were processed in the same way and RNA was sequenced with Illumina. Expression of transcripts and genes was quantified using SALMON and differential expression analysis of genes was analyzed with LIMMA. Analysis of alternative splicing events was performed with SUPPA, and enrichment analysis of binding sites for splicing factors with MOSEA. Results: 14 micropapillary and 54 non-micropapillary high-grade T1 bladder cancer were analyzed. We identified 11 splicing factors differentially expressed in MPBC samples compared to non-micropapillary samples, with SRSF2 being the most significant and showing upregulation in MPBC. Additionally, we detected a switch in the pattern of isoform expression in SRSF2 with 1 single isoform mainly expressed in MPBC, whereas 2 other isoforms were expressed in the non micropapillary. This isoform expression pattern was also different in normal bladder tissues from GTEX. Motif enrichment analysis identified a significant proportion of differentially spliced events associated with micropapillary with SRSF2 motifs. Conclusions: We have identified a deregulation of several splicing factors and alternative splicing events in association to micropapillary high-grade T1 bladder tumors. The largest expression change occured in SRSF2, which potentially explains the majority of skipping exon events of the splicing differences. Our analysis suggests a role for SRSF2 in determining the histological properties of bladder tumors at early stage, with potential clinical consequences.
Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory (R/R) mantle cell lymphoma (MCL).
Authors: Narendranath Epperla, Mehdi Hamadani, Kwang Woo Ahn, Eunhye Oak, Amanda F. Cashen, Abraham Sebastian Kanate, Oscar Calzada, Zachary Luke Farmer, Michael Tallarico, Chadi Nabhan, Luciano J Costa, Vaishalee Padgaonkar Kenkre, Nilanjan Ghosh, Jonathon Brett Cohen, Parameswaran Hari, Timothy S. Fenske
Journal: Journal of Clinical Oncology (2016)

7544 Background: Ibrutinib (IB) has shown significant activity in R/R MCL in prospective studies, but less is known about its “real world” activity. Moreover factors predicting IB failure, impact of prior transplantation (HCT) on IB’s efficacy and patient (pt) outcomes following IB failure warrant further investigation. Methods: We performed a multicenter retrospective study of R/R MCL pts receiving IB between Nov 2013 and Dec 2015. Pts achieving a CR or PR with IB were considered responders. The primary aim was to evaluate predictive factors for IB response, while the secondary aims were to examine predictors for OS & PFS following IB therapy, impact of prior HCT on IB therapy and assessment of pt outcomes post IB failure. Results: 97 pts met study inclusion criteria. 62 pts (64%) achieved a CR/PR with IB, with a median duration of response (DOR) of 9 mo. None of the tested variables (Table) were predictive of IB response. Achieving CR/PR with IB (HR = 0.1), low MIPI (HR = 0.28) and pts without primary refractory disease (HR = 0.15) were predictors of better PFS, while IB response (HR = 0.13) and ECOG PS ≤ 1 (HR = 0.14) were predictors of better OS. IB response rate (RR) in pts without prior HCT, with prior autoHCT and with prior alloHCT was 65%, 66% & 64% respectively. Their median PFS & OS (in mo) in similar order were 10 vs 6 vs 4, and 13 vs 9.5 vs 8 respectively. After IB failure, the median OS was 2 mo. The RR to bortezomib (n = 9), lenalidomide (n = 10) & bendamustine (n = 6) use after IB failure was 30%, 20% & 50% respectively. Median DOR (in mo) in similar order was 7.4, 5.5 and 3 respectively. Conclusions: No clinical factors including types of prior therapies predicted response to IB therapy. In this large real world analysis, durability of IB response (9 mo) is shorter than previously reported. Pts failing IB have poor outcome and this represents an area of urgent unmet need. IB Responders N = 62 (%) IB Non-responders N = 35 (%) Median age 62 63 ECOG PS 0-1 54 (87) 28 (80) Stage III-IV 54 (86) 34 (99) Blastoid variant 6 (10) 9 (26) Ki-67 > 30% 21 (34) 16 (46) Low MIPI 19 (31) 9 (26) Median prior therapy lines 2 2 Primary refractory disease 1 (2) 6 (17) Prior AutoHCT 25 (40) 13 (37) Prior AlloHCT 7 (11) 4 (11) Prior Bortezomib 22 (35) 8 (23) Prior Lenalidomide 10 (16) 3 (9)
A large 10-year series from a single-site institution in the United Kingdom of vulva carcinoma: An audit on adherence of United Kingdom guidelines and overall survival.
Authors: MayThit Lwin, Almurtadha MulaKh, Tobi Adeagbo, Yoodhvir S Nagar, Ghassan Khoury, Siavash Rahimi, Chukwumobi Ihezue, Chit Cheng Yeoh
Journal: Journal of Clinical Oncology (2018)

e17572 Background: We audited if our 10-year-series in our Institution's Vulva Carcinoma adhered with the Royal College of Obstretrician and Gynaecology (RCOG) Guidelines. In United Kingdom, from 2014, the guidelines states 1) Wide local excision of primary tumor with minimum 15mm of disease free tissue is often sufficient 2) Sentinel lymph node (LN) biopsy can be done in unilateral tumor of less than 4cm and if no clinical suspicion of LN involvement 3) In bilateral tumors, only ipsilateral groin node surgery needs to be done initially. Contralateral LN dissection may be required if ipsilateral nodes are positive 4) Groin node dissection should be omitted in stage Ia SCC, BCC, verrucous tumor and melanoma 5) Patient unfit for surgery can be treated with primary radiotherapy (RT) Methods: All Vulva Carcinoma Cancer coded from 2009-2017 were mined from database. Results: Total of 121 patients. Mean age 74 years old (36-104 years old). Squamous cell carcinoma = 105, Melanoma = 5, Adenoid cyst = 1, Paget's = 2, Verrucous = 2, Basal cell carcinoma = 2, Sarcoma = 1, Adenocarcinoma = 3. All stages of Vulva cancer were 100% compliant with RCOG guidelines, except for Stage 1C, which achieved 62.5% compliance. Out of 104 vulva cancer, 32 had no indications for surgical groin LN assessment (16 patients in 1a disease + 16 patients stage 4 disease) 72 had indications and were offered surgical groin LN assessment. However, 45 out of 72 (62.5%) had surgical groin LN assessment. 12 out of 72 (16.7%)were declined due to co morbidities. 15 out of 72 (20.8%) did not wish surgical groin node assessment. Conclusions: WLE were offered to all vulva patients. Clear margins were achieved in 97%. RT was offered to 2% of patients as there was not possible to achieve clear margin with re-excision. All eligible patients with indications for groin LN surgical assessment had offered nodal surgery. Patients with multiple comorbidity and not fit for surgery due to their advanced staging were treated with RT alone, chemo/RT and best supportive care. Overall survival was 205.7 weeks. Stage Surgery (Sx) Radiotherapy (RT) Sx+RT Sx+chemo RT+chemo BSC Ia 16 Ib 59 II 1 1 III 6 3 5 1 3 2 IV 1 3 2 SCC unknown staging 2 Non SCC 16
Therapeutic peptide vaccince therapy in combination with CpG-B for the patients with advanced esophageal squamous cell carcinoma.
Authors: Masahiro Katsuda, Makoto Iwahashi, Motoki Miyazawa, Mikihito Nakamori, Masaki Nakamura, Toshiyasu Ojima, Keiji Hayata, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

e14585 Background: Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A clinical trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-B. Methods: This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. In phase I trial, nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-B (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) . In phase II, eight patiens were vaccinaed the same pepides on the same schedule wih CpG-B (0.1ng/kg). Results: All were tolerated by this treatment. In phase I, LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-B increased and activated both plasmacytoid dentritic cells and natural killer cells, and increased the serum level of a-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). This vaccine protocol is therefore recommended to undergo further phase II trials. In phase II, there were no CR and PR. LY6K and TTK-specific T cell responses were observed wihin 8 weeks and the frequency of the antigens specific CTL was increased after continuous vaccination. The medican survival time (MST) of all vaccination patients was 194 days. Conclusions: Vaccination with LY6K-177 and TTK-567 in combination with CpG-B successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate imunity of patients with advanced esophageal squamous cell carcinoma. Clinical trial information: NCT00669292.
Pegilodecakin with nivolumab (nivo) or pembrolizumab (pembro) in patients (pts) with metastatic renal cell carcinoma (RCC).
Authors: Nizar M. Tannir, Aung Naing, Jeffrey R. Infante, Kyriakos P. Papadopoulos, Deborah J.L. Wong, Michael Korn, Raid Aljumaily, Karen A. Autio, Shubham Pant, Todd Michael Bauer, Alexandra Drakaki, Naval Guastad Daver, Annie Hung, Peter Van Vlasselaer, Joseph Leveque, Martin Oft
Journal: Journal of Clinical Oncology (2018)

4509 Background: Pegilodecakin (PEGylated hIL-10, AM0010) alone produced 25% partial responses (PR) in heavily pre-treated (median prior therapies 3) RCC pts. IL-10 receptors and PD1 are expressed on activated and exhausted CD8+ T cells. IL-10 stimulates the cytotoxicity and proliferation of CD8+ T cells. This provides a rationale for combining pegilodecakin with anti-PD-1. Methods: Between 2/20/2015 and 11/18/16, 38 pts with metastatic RCC (87% clear cell) were enrolled in a phase Ib trial and received pegilodecakin at 10 (n = 6) or 20 ug/kg (n = 32, QD SC) and nivo (n = 29; 3mg/kg, q2wk IV) or pembro (n = 9; 2mg/kg, q3wk IV). Pts had intermediate- or poor-risk disease by IMDC criteria (94%) and a median of 1 prior therapy (range: 1-3), including at least one VEGFR-TKI. Results: Pegilodecakin + nivo or pembro was well tolerated. TrAEs were reversible and transient. G3/4 TrAE in pts who received pegilodecakin (20 ug/kg) + nivo or pembro included anemia (10), thrombocytopenia (7), and hypertriglyceridemia (6). Two pts had a reversible cytokine release syndrome with splenomegaly and increased immune mediated red blood cell phagocytosis (HLH) most likely due to T-cell activation, as both pts had PRs. Pts on 10ug/kg pegilodecakin + nivo or pembro did not have G3/4 anemia or thrombocytopenia. As of 1/29/2018, response evaluation by irRC yielded 14 PRs of 34 evaluable pts (41%) including 3 complete response [CRs] (9%); 15 additional pts had stable disease (44%), 8 of whom had a tumor reduction of more than 30%. By RECIST, ORR and disease control rate (DCR) were 53% and 81%. Median progression-free survival (PFS) was 16.7 mos with pegilodecakin + pembro, and was not reached for pegilodecakin + nivo at a median follow up of 13.8 mos (range: 0.5-19.8). The 1y- overall survival for pegilodecakin + anti-PD-1 is 89%. Pegilodecakin strongly expanded previously undetectable T cell clones in the blood, which correlated with tumor response. Nanostring expression profiling separated pts with CR/PR from progressive disease. Conclusions: Pegilodecakin with nivo or pembro is well-tolerated in mRCC pts; the recommended phase 2 dose is 10ug/kg. The efficacy and the observed CD8+ T cell activation are very encouraging. Clinical trial information: NCT02009449.