tbuckley/cabot-search huggingface dataset:
Salivary miRNA-210 involvement in medication-related osteonecrosis of the jaws.
Authors: Antonio Picone, Antonia Marcianó, Rosanna Dimarco, Eleonora Miano, Alessandra Zacchia, Maria Vita Sanò, Alessia La Fauci, Maurizio Chiarenza, Marco Ali, Maria Grazia Di Leo, Rosa Anna Aiello, Eleonora Taibi, Giuseppa Fallica, Michele Caruso
Journal: Journal of Clinical Oncology (2017)

e23052 Background: Improved survival rates from cancer have increased the need to understand the health related problems of cancer treatment. Persistent oral health related problems significantly affect patient's quality of life. Medication-related osteonecrosis of the jaws (MR-ONJ) is an oral complication of antiresorptive medications, denosumab and other medications that target angiogenesis for the management of metastatic bone cancer. The purpose of this pilot study, is to investigate, for the first time, microRNAs expression in MR-ONJ. Recent studies reported the miRNA-210 (a specific angiogenic-related miRNA) demethylation in the Osteonecrosis of the Femoral Head. We hypothesized that MiRNA-210 could also be involved in MR-ONJ development. Primary objective of the study is to investigate the role of miRNA-210 in MR-ONJ pathogenesis. Secondary objective is to investigate the feasibility of salivary miRNAs detection as potential non invasive biomarkers for MR-ONJ. Methods: A case-and-control study has been designed. Inclusion criteria are malignant tumors with ongoing treatment or previous history of anti-resorptive or anti-angiogenic medications. The predictor variable is the presence or absence of MR-ONJ. Oral examination and dental x-ray examinations suggestive of MR-ONJ will be performed. Saliva sample will be collected according to the protocol by Navazesh. The methylation status of miRNA-210 will be investigated using quantitative PCR (Q-PCR). Values will be compared between case and control group. Results: The main expected results are to enroll approximatively twenty patients in case group and sixty patients in control group within a one year recruitment period, validate that saliva is a medium for the identification of biomarkers associated with MR-ONJ and confirm the hypothesis that miRNA-210 is involved in MR-ONJ development. Conclusions: Results acquired within this project would represent a contribute to the understanding of the molecular mechanisms driving to the development of MR-ONJ lesions. MiRNA-210 demethylation could serve as a potential therapeutic target for the treatment of MR-ONJ through stimulation of angiogenesis.
Prostate cancer (PCa) incidence and severity in hypogonadal men treated with testosterone compared to untreated controls: Experience from 6,500 patient-years from a controlled registry study.
Authors: Ahmad Haider, Karim Sultan Haider
Journal: Journal of Clinical Oncology (2018)

5066 Background: EAU Guidelines state that there is no evidence that testosterone (T) treatment in hypogonadal men increases PCa risk. Methods: 412 symptomatic men with T≤350 ng/dL received T undecanoate 1000 mg every 3 months following an initial 6-month interval for up to 12 years (T-group). 393 hypogonadal men (age range 51-74) decided against testosterone (CTRL). Total observation time covered approximately 6,500 patient-years. PCa was excluded by transrectal ultrasound, digital rectal examination and PSA measurement before treatment/observation initiation. Examinations were repeated between one and four times per year. Biopsies were performed when indicated according to EAU Guidelines. Results: In the T-group, 11 men (2.7%) were diagnosed with PCa. In CTRL, 35 (8.9%) were diagnosed with PCa. The mean baseline age of PCa patients was 65.3 years in the T-group and 63.7 in CTRL. In the T-group, the average time span between the day of first injection and positive biopsy was 386 days (range: 260-546). In CTRL, PCa was diagnosed at any time during the observation time. In the T-group, radical prostatectomy was performed in all men. All but 2 patients had a Gleason score (GS) ≤6, and all had a primary GS of 3. Tumor grade was G2 in all 11 (100%), tumor stage T2a in 7 (64%), T2b in 3 (27%), and T2c in 1 (9%) patient(s). In CTRL, radical prostatectomy (RP) was performed in all but 6 patients who received radiation therapy (RT). 7 patients received RP+RT. GS was ≤6 in 2 patients, 7 men had a GS of 7, 16 a GS of 8, and 10 a GS of 9. 4 men had a primary Gleason score of 3, 22 had 4, and 9 had 5. Tumor grade was G2 in 8 (22.9%) and G3 in 27 (77.1%) patients, tumor stage T2a in 2 (5.7%), T2c in 1 (2.0%), T3b in 13 (37.1%) and T3c in 19 (54.3%) patients. In CTRL, biochemical recurrence occurred in 10 (28.6%) patients. These patients received androgen deprivation therapy (ADT). 12 (34.3%) patients died of whom 7 were on ADT. In the T-group, no biochemical recurrences or deaths occurred during the observation time. Conclusions: PCa incidence and severity in testosterone-treated hypogonadal patients were less compared to untreated hypogonadal controls.
Association of risk of febrile neutropenia (FN) with docetaxel in prostate cancer (PC) patients: A meta-analysis of published phase II-III trials.
Authors: Blazquez Arroyo Maria, Antonio Merida Garcia, David Lora, Brandon David Bernard, Lorente David, Ray Manneh Kopp, Juan Manuel Sepúlveda, Daniel Castellano, Christopher Sweeney, Guillermo De Velasco
Journal: Journal of Clinical Oncology (2017)

e21683 Background: Reported rates of FN with docetaxel (DTX) in PC patients are variable. This creates uncertainty regard the use of granulocyte colony-stimulating factor primary prophylaxis (G-CSF) in this setting. We conducted a meta-analysis of randomized clinical trials to determine the relative risk (RR) of FN in patients receiving DTX. Methods: To perform this analysis we systematically searched in PUBMED and MEDLINE database the following terms: “DTX”, “randomized clinical trial” and “prostate cancer” only for articles published between January 1996 and August 2016. Phase II-III clinical studies comparing DTX to non-DTX control arms (best supportive care [BSC] including non-cytotoxic therapy or mitoxantrone) for PC were included. The meta-analyses were performed by computing RRs with 95% confidence intervals (CI) using fixed-effects model with the Mantel-Haenszel method. Results: Seven studies (N = 5088 patients) were included. The global incidence of FN in patients treated with DTX was 10.7%. The RR of FN was higher in patients receiving DTX compared to patients did not receive DTX (RR 16.8 [95% CI 10.7; 26.4] p &lt; 0.0001). 6.6% of patients with metastatic castration resistant prostate cancer (CRPC) treated with DTX developed FN, the RR of FN with DTX compared to mitoxantrone was 28.6 (95% CI 5.6; 145.1). 12.4% of patients with hormone-sensitive prostate cancer (HSPC) treated with DTX developed FN, the RR of FN was 15.3 (95% CI 9.6; 24.6) compared to BSC. There was no statistically significant differences in the rate of FN according to the hormone sensitivity (HSPC vs CRPC) (p = 0.7). In most studies the use of G-CSF was at the discretion of the investigator. Conclusions: This meta-analysis shows that DTX is associated with a significant increase in the relative risk of FN in patients with PC. The effectiveness of primary prophylactic G-CSF in this setting has not been fully established. The incidence reported here does not meet the threshold recommended by ESMO and ASCO guidelines for the use of prophylactic G-CSF. Special attention should be given to high risk groups for FN, including elderly patients and those with bone marrow involvement or previous radiotherapy/chemotherapy.
TCT-533 Predictors of High Hospital Cost After Transcatheter Aortic Valve Replacement in the United States: Analysis of Nationwide Inpatient Sample Database
Authors: Tomo Ando, Oluwole Adegbala, Pedro Villablanca, Emmanuel Akintoye, Said Ashraf, Alexandros Briasoulis, Tesfaye Telila, Hisato Takagi, Cindy Grines, Theodore Schreiber, Luis Afonso, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2018)
Primary melanoma histologic subtype (HS) impacts melanoma specific survival (MSS) and response to systemic therapy.
Authors: Michael Lattanzi, Yesung Lee, Eric Michael Robinson, Sarah A. Weiss, Una Moran, Danny Simpson, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Melissa Wilson, Tomas Kirchhoff, Judy Zhong, Iman Osman
Journal: Journal of Clinical Oncology (2017)

9577 Background: Unlike other solid tumors, the impact of primary HS on melanoma survival and response to systemic therapy is not well studied. Nodular melanoma (NM) has a worse prognosis than superficial spreading melanoma (SSM), which is usually attributed to thicker primary tumors. Herein, we examine the hypothesis that HS might have an impact on MSS independent of thickness and that NM and SSM exhibit different mutational landscapes that associate with response to checkpoint inhibitor immunotherapy (IT) and BRAF targeted therapy (TT) in the metastatic setting. Methods: Primary NM and SSM patients prospectively enrolled at NYU (2002 - 2016) were compared to the most recent SEER cohort (1973 - 2012) and analyzed with respect to MSS. Next-Generation Sequencing (NGS) was performed on a subset of matched tumor-germline pairs, allowing a comparison of the mutational landscape between NM and SSM. In the metastatic setting, survival analyses were used to compare outcomes and responses to treatment across HS. Results: The NYU cohort of 1,621 patients with either NM (n = 510) or SSM (n = 1,111) was representative of the analogous SEER cohort (21,339 NM, 97,169 SSM), with NM presenting as thicker, more ulcerated, and later stage (all p &lt; 0.001). Among the NYU cohort, NM was found to have lower rates of TIL (p = 0.047), higher mitotic index (p &lt; 0.001), and higher rates of NRAS mutation (p &lt; 0.001). In multivariate Cox models, NM was a significant predictor of worse MSS, independent of thickness and stage (p = 0.01). NM had a significantly lower mutational burden across the exome (p &lt; 0.001). Some of the most under-mutated genes noted in NM were NOTCH4, BCL2L12 and RPS6KA6 (all p &lt; 0.01). Among patients treated with TT (n = 56), NM remained a significant predictor of worse MSS (p = 0.004). However, there was no difference in response to IT. Conclusions: NM and SSM show divergent mutational patterns which may contribute to their different clinical behaviors and responses to BRAF targeted therapy. More studies are needed to better understand the key molecular and cellular processes driving such differences. Integration of HS data into prospective clinical trial reporting is needed to better assess its impact on response to treatment.
Immune-infiltrate characterization in localized osteosarcoma patients treated within protocol ISG-OS1.
Authors: Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano A Pileri, Pier-Luigi Lollini, Katia Scotlandi, Maria Serena Benassi, Teresa Marafioti, Stefano Ferrari
Journal: Journal of Clinical Oncology (2017)

11025 Background: We hypothesized that immune-infiltrates were associated with survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: Biopsies of patients (pts) treated from 04/2001 to 11/2006 were analyzed. TMAs from representative areas were assembled. Clinical and pathological characteristics at diagnosis, expression of CD8, CD4, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage), Tia-1 (cytotoxic T cell), CD303 (plamacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immuno-cells (IC), and PD-L1 both on tumor cells (TC) and IC were correlated with patients outcome. A TMA of surgical specimens of the same cases also was assembled, and chemotherapy-induced changes analysis is ongoing. Results: 86 pts identified. Median age: 16 (range 4-39); high LDH: 36/86; high serum alkaline phosphatase (SAP): 18/86. All pts underwent neoadjuvant chemotherapy and surgery. A good pathologic response (≥90% necrosis) was achieved by 45/86 pts. IHC results are displayed in the Table. With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-yr OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-yr OS for: a) good responders (good 89% vs poor 57%, p=0.0001); b) pts with CD8/Tia1 tumoral infiltrates (+/+ 81% vs +/- 60% vs -/- 45% p=0.002); c) pts with normal SAP (normal 85% vs high 44%, p=0.04). A numerically lower 5-yr OS was found in PD-L1 (IC) positive (+ 58% vs - 77%, p=0.14) and CD163 negative (+ 81% vs - 56%, p=0.17) cases. After multivariate analysis, poor histologic response (p=0.007) and lack of CD8/Tia1 infiltration (p=0.02) were independently correlated with poorer survival. In the subset of CD8+ patients, poorer (p= 0.02) OS was observed for PD-L1 (IC) + cases. Conclusions: Our findings support the hypothesis that CD8/Tia1 (cytotoxic T cells) infiltrate in tumor microenvironment at diagnosis is associated with superior survival for patients with localized osteosarcoma, while PD-L1 expression is associated with poorer survival. [Table: see text]
Effect of breastfeeding on the risk of breast cancer in Li-Fraumeni syndrome.
Authors: Payal Khincha, Ana F Best, Jennifer T. Loud, Sharon A. Savage, Maria Isabel Achatz
Journal: Journal of Clinical Oncology (2018)

1530 Background: Li-Fraumeni syndrome (LFS) is an autosomal dominant inherited cancer predisposition syndrome associated with germline pathogenic variants in TP53. It is characterized by early-onset cancer and a high lifetime risk for multiple cancers. Although women with LFS are at very high risk of pre-menopausal breast cancer some women will perhaps never develop the disease. This may be due to non-genetic factors that may modify the risk. Methods: The aim of this retrospective cohort study was to evaluate the impact of female reproductive factors such as age at menarche, parity, breastfeeding (BF) and use of oral hormonal contraceptives (OCP) on the risk of breast cancer (BC) in LFS patients. Results: We enrolled 154 TP53 mutation-positive women from the NCI’s LFS protocol, 86 of whom had at least one breast cancer. Median age at first breast cancer diagnosis was 32 years (range 20-54 years), 32 women had a second BC. Sixty percent of first breast cancers were ER/PR+; and 57% were HER2/neu+. Our data showed that breastfeeding (BF) reduced the risk of breast cancer in LFS, most notably reduced in patients with over 6 months of BF (Odds Ratio (OR) 0.36, p = 0.04, OR at 12 months of BF 0.32, p = 0.02). The association was strongest in ER+ BC versus BC-free women, but was not significant when comparing odds of developing ER+ to ER- BC. Controlling for age and parity, women with BF > 12 months had a lower risk of BC versus BF < 12 months (p = 0.02). Neither parity nor OCP independently altered BC risk significantly, a finding limited by limited sample size of the comparator group of OCP non-user LFS women. Conclusions: Our data show that while BF for any duration reduces risk of BC, the risk is significantly reduced with BF for at least 6 months, a protective effect similar to previous studies of BF and BC risk in the general population and BRCA1 cohorts. Neither parity nor OCP independently altered BC risk significantly. This is the first study to evaluate BC reproductive risk modifiers in LFS patients. Larger, prospective case-control studies are needed to validate these findings. If confirmed, women with LFS would warrant education regarding BF's protective effect to inform management decisions.
The hidden burden of anxiety and depression in ovarian cancer: A prospective longitudinal study from diagnosis.
Authors: Penelope M Webb, Vanessa Beesley, Anna deFazio, Andreas Obermair, Peter T. Grant, Christina M Nagle, Michael Friedlander
Journal: Journal of Clinical Oncology (2018)

10081 Background: Women with ovarian cancer (OC) report high rates of anxiety (A) and depression (D), but most studies have used a cross-sectional design at a single time-point, not considered prior history and not included women who are symptom-free due to medication. Our goals were to quantify the total burden of A/D among women newly diagnosed with OC; the proportions who experienced symptoms only after their OC diagnosis and those with persistent symptoms; and determine use of appropriate medication/services by those affected. Methods: The OPAL (Ovarian Cancer Prognosis & Lifestyle) Study is a prospective study of Australian women diagnosed with OC from 2012-15. At baseline, they were asked if they had ever been diagnosed with A or D and if they took medication for this in the year before their OC diagnosis. At follow-up (3, 6, 9, 12, 24, 36 & 48 months after diagnosis) they complete the Hospital Anxiety and Depression Scale (HADS) and are asked about current medication use. Results: Of 893 women with ≥1 follow-up questionnaire, 373 (42%) reported clinical levels of anxiety (HADS > 10, 18%) and/or depression (15%) and/or use of anxiolytic or antidepressant medications (A/D meds) (18%) on at least one occasion during the first 3 years after diagnosis. An additional 166 women (19%) reported subclinical A or D (HADS 8-10). Of those with clinical A/D or taking A/D meds, 159 (42%) reported this at ≥3 time-points, 218 (58%) reported no prior history of A or D and 274 (73%) reported no use of A/D meds in the year prior to diagnosis. When women reported clinical levels of A or D, only 45% reported taking medication (37%) and/or seeing a psychiatrist or psychologist (19%). Among those not already on A/D medication at diagnosis, a prior history and low levels of optimism were the strongest predictors of A/D onset. Conclusions: More than 40% of women with OC experienced clinical levels of A or D during treatment or the first 3 years of follow-up. For 42% of those affected this was their first experience of distress and > 50% did not receive appropriate medication or psychological support. The hidden burden of anxiety and depression in this population is much greater than previously reported but is amenable to effective intervention if recognized.
P04.20 Analysis of HORMAD1, FTHL17 and ADAM29 Cancer/testis specific genes expression in Glioblastoma
Authors: K Anvari, M Mojarrad, M Gholamin, M Fathi, A Tabatabaii, A Eslahi
Journal: Neuro-Oncology (2018)

Glioblastoma multiform (GBM, World Health Organization grade IV) is the most common and aggressive primary brain tumor.Immunotherapy is a promising therapeutic adjuvant in fighting against this cancer. Cancer/testis antigens (CTAs) are a group of tumor-associated antigens that are typically restricted to adult testis, but they are aberrantly expressed in several types of cancers, especially in advanced cancers with stem-like characteristics. These tumor-associated antigens are immunogenic in different cancers. Finding of frequently expressed CTAs in GBM can provide effective immunotherapeutic targets to use in translational researches on this cancer. The aim of this study was conduct an extensive expression analysis of ADAM29, HORMAD1, FTHL17 in GBM to determine whether these antigens can be appropriate target in immunotherapy of GBM. Fifty pathologically confirmed GBM paraffin embedded tissue sample were conducted into this experiment. Total RNA was extracted from these samples and TaqMan based RealTime PCR technology was used to evaluation of HORMAD, ADAM29 and FTHL17 gene expression according to our results HORMAD1 is the most frequent expressed gene in these tissue samples. Forty-four percent of samples (22 out of 50 samples) expressed HORMAD1 in various levels. Either FTHL17 and ADAM29 were expressed in only one of samples.On the other hand, according to statistical studies of patients’ demographic findings and the expression of genes, HORMAD1 has had a much higher level of expression in glioblastoma samples than other genes, which, based on these results, we can consider this gene as a therapeutic target in immunotherapy. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, A review of carcinoma showed that 31% of carcinomas express this antigen in high numbers. In 2006, the gene had a high expression in gastric cance. so far no precise and thorough study has been done on the existence (expression) of these gene in glioblastma samples,HORMAD1 can be a promising target in immunotherapy research targeting GBM.
Trametinib in pediatric patients with neurofibromatosis type 1 (NF-1)–associated plexiform neurofibroma: A phase I/IIa study.
Authors: Geoffrey Brian McCowage, Sabine Mueller, Christine A. Pratilas, Darren R Hargrave, Christopher L. Moertel, James Whitlock, Elizabeth Fox, Pooja Hingorani, Mark W. Russo, Kohinoor Dasgupta, Lillian Tseng, Bijoyesh Mookerjee, Birgit Geoerger
Journal: Journal of Clinical Oncology (2018)

10504 Background: NF-1 loss-of-function alterations are associated with development of plexiform neurofibromas (PNs). NF-1–associated PNs can arise early in life in different locations, with variable and significant morbidity. Many patients (pts) progress following surgery, and currently there are no approved systemic therapies. The MEK inhibitor trametinib is being evaluated in pediatric pts across a spectrum of tumor types in a dose-escalation cohort of a phase I/IIa study (NCT02124772) to determine a recommended dose; disease-expansion cohorts include pts with NF-1 PN. Here we present an interim analysis of safety and clinical benefit of trametinib in pediatric pts with NF-1–associated PN. Methods: Pts aged 1 mo to < 18 y with medically significant, unresectable NF-1–associated PN were treated with trametinib 0.025 to 0.040 mg/kg/d. The primary objective was safety, and secondary objectives included tumor response assessed by independent review (IR) using published MRI volumetric criteria. Results: Twenty-six pts received trametinib (0.025 mg/kg/d, n = 21; 0.032 mg/kg/d, n = 1; 0.040 mg/kg/d, n = 4). Presented here are results from the disease-expansion cohort (n = 10). Median duration of exposure was 408 d (range, 360-429 d), and 8 pts (80%) had treatment ongoing at the data cutoff (September 2017). Median age was 5.5 y (range, 1-16 y), and prior therapies included surgery (n = 5), biologics (n = 1), and targeted therapy (n = 1). Treatment-related AEs (TRAEs) were reported in 9 of 10 pts (90%), and 1 pt discontinued due to a TRAE. The most frequent TRAEs were paronychia (50%) and rash (40%). No deaths occurred on treatment. Analysis of the full NF-1 PN cohort (n = 26) is ongoing; across this cohort, 12 of 26 pts (46%) had a PR (≥ 20% volume reduction) by IR, and 10 of the 12 responses (83%) were ongoing. Conclusions: Trametinib demonstrated a manageable safety profile in pediatric pts with NF-1–associated PN. Using volumetric criteria for response determination, the objective responses observed with trametinib support continued investigation in this pt population. Clinical trial information: NCT02124772.
TCT-159 Endothelial Shear Stress and Local Viscosity Assessment of Coronary Bioresorbable Scaffold: A Five-Year Follow Up
Authors: Erhan Tenekecioglu, Vikas Thondapu, Eric Poon, Ryo Torii, Christos Bourantas, Yohei Sotomi, Jouke Dijkstra, Yuki Katagiri, Taku Asano, Rodrigo Modolo, Frank Gijsen, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)