tbuckley/cabot-search huggingface dataset:
Prognostic value of loss of chromosome 10q in patients with localized renal cell carcinoma.
Authors: Cedric Michel Lebacle, Aydin Pooli, Nagesh Rao, Erika Louise Wood, Nils Kroeger, Sandy Liu, Izak Faiena, Karim Chamie, Arie S. Belldegrun, Brian Shuch, Alexandra Drakaki, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2019)

626 Background: Several tumor-suppressor genes have been mapped to chromosome 10q, including PTEN. While loss of 10q is a frequently seen cytogenetic abnormality noted to occur in patients with renal cell carcinoma (RCC), little is known about its prognostic significance. We investigated the association of loss of 10q with pathological features and disease-free survival (DFS) in patients with localized RCC. Methods: All patients from UCLA with primary localized RCC who had tumor cytogenetic analysis were included. Alterations in chromosome 10q was specifically reviewed for this study. Logistic regression analyses were used to assess association of loss of 10q with ISUP grading, and T-stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to assess the impact of loss of 10q on DFS and OS. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: A total of 886 patients were included in this study. Loss of 10q occurred in 68 (7.7%) patients and was more commonly seen in chromophobe subtype (24% vs. 6% in non-chromophobe RCC, p &lt; .0001). Loss of 10q was associated with greater tumor size (mean 6.3 vs 5.1 cm, OR = 1.085 [1.024-1.150], p = .008), T3-stage (37% vs 23%, OR = 1.99 [1.17-3.39], p = .011), and ISUP 3-4 (61% vs 37%, OR = 2.64 [1.58-4.40], p &lt; .0001). On survival analysis, after a mean follow-up of 55 months, these patients had a shorter time to recurrence (Log-rank p = .026) and a worse DFS (HR = 2.15 [1.32-3.50], p = .002) than those without loss of 10q. These findings were confirmed on clear-cell RCC subgroup with also a worse OS (HR = 2.00 [1.09-3.67], p = .026) with an estimated 34% risk of death at 5 years for patients with loss of 10q. Conclusions: Loss of chromosome 10q is a prognostic factor associated with larger tumor size, higher grade and T-stage, and worse survival in patients with localized RCC. Identifying patients with loss of 10q can provide additional prognostic information to clinicopathologic variables.
Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury
Authors: Yun Xie, Ghada Ankawi, Bo Yang, Francesco Garzotto, Alberto Passannante, Andrea Breglia, Kumar Digvijay, Fiorenza Ferrari, Alessandra Brendolan, Bonato Raffaele, Davide Giavarina, Dario Gregori, Claudio Ronco
Journal: Kidney International (2019)
The impact of a molecular tumor board on treatment decisions for 35 patients: The Dartmouth experience.
Authors: Laura J. Tafe, Ivan P Gorlov, Francine B Blumental de Abreu, Joel A Lefferts, Xiaoying Liu, Jason R Pettus, Katarzyna J Bloch, Jonathan D Marotti, Vincent A Memoli, Arief A Suriawinata, Jason D Peterson, Gregory J. Tsongalis, Britt Meredith Holderness, Clinton Roy Morgan, Todd W. Miller, Mary D. Chamberlin
Journal: Journal of Clinical Oncology (2015)

1550 Background: Genetic profiling of tumors is a powerful approach to predict drug sensitivity and resistance. However, oncologists are often unfamiliar with interpretation of genetic data. We established a Molecular Tumor Board (MTB) at our Cancer Center to interpret individual patients’ tumor genetic profiles and provide treatment recommendations. Methods: DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory to identify coding mutations in a 50-gene panel (n= 34), or a 255-gene panel (n= 1). Cases were evaluated by a MTB composed of molecular and anatomic pathologists, medical oncologists, basic research scientists, and genetic counselors. Results: Thirty-five cases were evaluated in one year by the MTB. The most common reason for MTB referral was a request for recommendations on targeted therapies (91.9%), and for potential germline mutations. Tumors exhibited a wide range of genetic heterogeneity: 71 different mutations were found across 30 genes, and 63 mutations were observed only once. In 56.3% of cases (18/32) of advanced/metastatic disease, MTB recommended non-standard therapy with a specific targeted agent (11 clinical trials; 7 off-label use) based on evaluation of tumor genetic profile, and disease and treatment histories. Four patients were subsequently treated with a MTB-recommended targeted therapy; 3 of these 4 patients remain on therapy, 2 of whom have experienced clinical benefit lasting > 10 months. The remaining 14 patients continued on current therapy because disease was stable (n= 4), were treated with non-MTB-recommended standard therapy (n= 4), declined conventional therapy (n= 5), or died prior to receiving further therapy (n= 1). Conclusions: Case evaluation by a multidisciplinary group of individuals in the context of a MTB frequently shapes treatment options and decisions. Importantly, anticipated obstacles to capitalizing on the benefits of a MTB such as access to drugs were rarely encountered. Instead, the most commonly encountered reasons that MTB-recommended therapy was not administered stemmed from patient preferences, and genetic profiling at a very late stage of disease.
Therapeutic p53 gene agent in the treatment of NPC cases: Preliminary results.
Authors: Xia He, Jianhua Xu, Wenjie Guo, Cheng Kong
Journal: Journal of Clinical Oncology (2015)

e13551 Background: To evaluate the feasibility of adding p53 gene agent to the current standard treatment of NPC cases. Methods: Gendicine was given intravenously at a dose of 2×1012VP/day on 5 consecutive days with routine anti-cancer treatment, and was repeated after an interval of 16 days. All patients were planned to receive two cycles of Gendicine. The inclusion criteria include: Pathologically confirmed NPC cases; Locoregionally advanced or disseminated or recurrent cases; With IMRT technique . The exclusion criteria include: with severe liver, kidney, heart or hematological disorders; pregnancy; without informed consent. Acute toxicities during the treatment were recorded according to NCI-CTCAE 3.0 version grading system. Efficacy was evaluated according to the results of contrast-enhanced MRI or CT which was performed three months after the completion of treatment. The trial was conducted in accordance with the ethical guidelines of the Declaration of Helsinki. Results: 30 patients were enrolled in the study with a median age 54, including 25 male and 5 female. Sixteen were new NPC cases ,other 14 were recurrent or disseminated NPC cases. The pathology were poorly-differentiated squamous cell carcinoma(26 cases), neuro-endocrine tumor(3 cases), or mucosal melanoma. All patients finished 2 cycles of Gendicine treatment and the planned chemoradiotherapy (22 cases), or chemotherapy (8 cases). All patients had chill and fever to some degree after injection of Gendicine. Preventive use of NSAIDs effectively relieved the symptoms. Other acute toxicities during the treatment included: vomiting (Grade 2 or above) 66.7%; thrombocytopenia (Grade 3/4) 3.3%; leucopenia (Grade 3/4) 36.7%; No ALT or Cr elevation was observed. The acute toxicities were controllable and reversible. The CR,PR,SD and PD were 40%, 36.7%, 20% and 3.3% respectively by the end of treatment while they were 60%, 26.7%, 10% and 3.3% respectively three months after treatment completion. Conclusions: The therapeutic p53 gene agent can be safely added to routine anti-cancer regimens with controllable and reversible acute toxicities. A randomized controlled phase II trail need make clear the role of the therapeutic p53 gene agent in the treatment of the NPC.
AUCtox: A new method to evaluate the safety of anticancer drugs in metastatic prostate cancer.
Authors: Vincent Launay-Vacher, Carole Helissey, Brigitte Laguerre, Dominique Spaeth, Thomas Lloret, Jerome Stevens, Paolo Bossi, Florian Scotte
Journal: Journal of Clinical Oncology (2019)

290 Background: The evaluation of anticancer drugs safety currently relies on the NCI-CTCAE classification. Most often in clinical trials, attention is focused on severe adverse events (AE) i.e.grade 3 or more. However, AE of lower grades can have a significant deleterious impact, especially when recurrent or permanent. We aimed at defining a new method to better describe the impact of treatment on quality of life (QoL). Methods: The oncology patient monitoring program OptiSoins prospectively records treatment, number of cycles, and toxicities (NCI-CTCAE). Patients with metastatic prostate cancer treated with either docetaxel (DOC) or cabazitaxel (CABA) were identified in the database. For each patient, toxicities and their grade reported in medical records were plotted against time under treatment, to calculate the area under the curve of toxicities (AUCtox) that takes into account both the intensity and duration of toxicities, and the number of events. AUCtox was calculated for any toxicity reported at least once. The association with QoL, evaluated by EQ-5D-3L. Results: In total, 146 patients were evaluable [DOC 85 (58%), CABA 61 (42%)]. Median age was 70.5 years (Q1-Q3: 64.7; 76.0). Median follow-up was 4.0 months. Patients underwent a median number of 6 cycles, with a median number of 15.0 evaluations (monitoring calls). At least one grade ≥3 AE was reported by 45.2% of patients, most frequently fatigue (20.6%) and pain (12.3%). A negative impact on global health status, assessed by the VAS of EQ-5D-3L, was identified for 3 AEs based on grade alone vs. 8 when considering AUCtox. Conclusions: Current evaluation of toxicity based on grade alone underestimates the impact of anticancer drugs on QoL. Our method, using AUCtox, can better detect this impact, allowing a more patient-oriented evaluation of drug safety. [Table: see text]
External beam radiation therapy and brachytherapy boost versus radical prostatectomy and adjuvant radiation therapy for high-risk prostate cancer.
Authors: Vinayak Muralidhar, Brandon Arvin Virgil Mahal, David Dewei Yang, Jonathan Eric Leeman, Anthony Victor D'Amico, Paul L. Nguyen, Peter F. Orio, Martin T. King
Journal: Journal of Clinical Oncology (2019)

21 Background: Previous studies have suggested that combination external beam radiation therapy (EBRT) with brachytherapy boost (BT) for high-risk prostate cancer is associated with equivalent overall survival (OS) compared with radical prostatectomy (RP). However, it is not known whether RP with post-operative radiation therapy (PORT) can offer improved OS compared with combination RT (EBRT + BT + androgen deprivation therapy [ADT]) for patients with Gleason 9-10 high-risk disease. Methods: We identified all patients diagnosed with clinical T1-T3, Gleason 9-10, prostate-specific antigen (PSA) 0-40 ng/mL, and clinically node negative disease between 2004 and 2014 from the National Cancer Database. We divided patients into 4 treatment groups: EBRT + ADT, combination RT (EBRT + BT + ADT), RP, and RP + PORT. Only patients who received PORT within 360 days of surgery were included within the RP + PORT group. We compared OS utilizing inverse probability of treatment-weighted multivariable Cox proportional hazards regression modeling after accounting for clinical and demographic factors, including Gleason grade (9 versus 10), T-stage (T1, T2, T3), age, Charlson-Deyo comorbidity score (0, 1, versus 2), education quartile, income quartile, geographic location within the US, insurance status, facility volume, and race. Results: Median follow-up in the entire cohort was 4.5 years. The numbers of patients treated with EBRT + ADT, EBRT + BT + ADT, RP, RP + PORT were 6778, 924, 7111, and 1929, respectively. There were no significant differences in 5-year OS when comparing combination RT to RP (85.0% vs 85.7%, adjusted hazard ratio (AHR) 0.92, 95% confidence interval [CI] 0.77-1.10, p = 0.36) or RP + PORT (85.0% vs 85.6%, AHR 0.89, 95% CI 0.71-1.12, p = 0.34). Combination RT was associated with superior 5-year OS compared to EBRT + ADT alone (without BT boost) (85.0% vs 79.4%, AHR 1.26, 95% CI 1.07-1.48, p &lt; 0.01). Conclusions: Our study suggests that for patients with Gleason 9-10 tumors, multi-modality surgical therapy is equivalent to combination RT.
Cascade testing of men with prostate cancer in families with a spectrum of inherited cancers: Importance of attention to race.
Authors: Veda N. Giri, Thenappan Chandrasekar, Sarah Hegarty, Laura Gross, Joon Yau Leong, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2019)

75 Background: Prostate cancer (PCa) is increasingly recognized as a part of hereditary cancer syndromes (HCS) with implications for cascade genetic testing (CGT) of men with PCa in these families. However, race-specific rates of HCS in probands presenting for inherited cancer assessment who report a family history (FHx) of PCa is not known has implications for CGT of men with PCa. Methods: A prospectively maintained genetic testing database at a tertiary care cancer genetics program was queried for all probands reporting a PCa FHx. Pedigrees were analyzed for three HCS linked with PCa: hereditary breast and ovarian syndrome (HBOC), classic Hereditary PCa (HPC), and Lynch syndrome (LS). Associations between HCS and race were evaluated using Fisher’s exact test. Each HCS was evaluated for potential genetic link to the male relative with PCa and associations with race were tested using Fisher’s exact test. Results: 345 probands met inclusion criteria: 53 African-American (AA), 292 Caucasian (Wh), 74.5% female. Proband cancer diagnoses included breast (43.2%), prostate (12.8%), pancreatic (3.8%), ovarian (3.2%), and colorectal (2.9%). Overall, 63.8% of probands met criteria for ≥ 1 HCS based on personal and FHx. Male relatives with PCa in these families with potential genetic link to HCS were found in 75.5% AA families and 61.6% Wh families. HBOC was identified in a higher percentage of AA families with a potentially-linked male relative with PCa compared to Wh families (69.8% vs. 52.4%, respectively; p=0.051). Among probands with HCS potentially linked to PCa (n = 169), 19.5% were found to carry a genetic mutation in a cancer risk gene (17.9% AA and 19.9% Wh). BRCA1/2 mutations accounted for all mutations identified in AA probands and 66.7% of Wh probands. Conclusions: A significant percentage of patients who present for inherited cancer assessment report a FHx of PCa potentially linked with a HCS. Importantly, AA probands with a PCa FHx have comparable rates of HCS as Wh probands, with potentially higher rates of HBOC in AA families accounted for by BRCA mutations. Cascade testing of men with PCa in families with HCS is crucial with a need to address any race-specific barriers.
Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma
Authors: Velina S. Atanasova, Celine Pourreyron, Mehdi Farshchian, Michael Lawler, Christian A. Brown, Stephen A. Watt, Sheila Wright, Michael Warkala, Christina Guttmann-Gruber, Josefina Piñón Hofbauer, Ignacia Fuentes, Marco Prisco, Elham Rashidghamat, Cristina Has, Julio C. Salas-Alanis, Francis Palisson, Alain Hovnanian, John A. McGrath, Jemima E. Mellerio, Johann W. Bauer, Andrew P. South
Journal: Clinical Cancer Research (2019)

Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.Experimental Design: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo.ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib.These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC.
Abstract P279: Marijuana Use, Multiple Sleep Characteristics, and Hypertension Among White, Black, and Hispanic Adults in the United States
Authors: Symielle A Gaston, Chandra L Jackson
Journal: Circulation (2019)

Introduction: Prior studies have found an association between marijuana use and hypertension. However, few consider the role of sleep as an explanatory factor or race/ethnicity as a moderator. Our objective was to investigate associations between marijuana use, sleep characteristics, and hypertension in a multiethnic population. Hypothesis: We hypothesized that the marijuana use and sleep association would vary by race/ethnicity and sleep would partially explain associations between marijuana use and hypertension. Methods: We used National Comorbidity Survey-Replication cross-sectional data (2001-2003) from white, black, and Hispanic participants aged ≥18 years who reported no current abuse of cocaine or prescription drugs. Participants self-reported marijuana use, multiple sleep characteristics (insomnia symptoms, early awakening, daytime sleepiness), and a physician’s diagnosis of hypertension (yes vs. no). Using Poisson regression with robust variance and sampling weights, we estimated the prevalence of poor sleep characteristics among participants who reported current or former use to never use adjusting for age, sex, and race/ethnicity. Sleep characteristics were added to adjusted models for associations between use and hypertension. Race/ethnicity*marijuana use interaction terms were tested for all models. Results: Among 3,928 participants, mean age±SE was 45±0.49 years, 79% were white, 11% black, and 10% Hispanic. Current users were younger (32±0.49 years), more likely to report black (17%) or Hispanic (13%) race/ethnicity and insomnia symptoms (31%), and less likely to report hypertension (12%) compared to former (40.6±0.45 years, 9.6% black, 9.9% Hispanic, 26% insomnia, 20% hypertension) and never (51.1±0.79 years, 10% black, 9.9% Hispanic, 22% insomnia, 29% hypertension) users. Estimates were similar across marijuana use categories for early awakening (16%) and daytime sleepiness (34%). Former and current marijuana use was associated with 22% (whites) to 38% (blacks) and 33% (Hispanics) to 85% (blacks, prevalence ratio (PR)=1.85 [95% confidence interval: 1.06-3.23]) higher prevalence of insomnia symptoms as well as 32% (blacks) to 49% (whites) and 46% (blacks) to 77% (whites, PR=1.77 [1.29-2.44]) higher prevalence of early awakening (p race/ethnicity*marijuana use &lt;0.05). Across all races/ethnicities, marijuana use was similarly associated with higher prevalence of daytime sleepiness (PR former =1.17 [1.03-1.33], PR current =1.20 [1.00-1.43]). Former marijuana use was associated with higher prevalence of hypertension only among blacks (PR=1.46 [1.04-2.05]) and sleep characteristics explained approximately 2% of this association on average. Conclusions: Marijuana use was associated with poor sleep and relationships varied by race/ethnicity, but relationships between marijuana use and hypertension were not explained by sleep.
HNC patient’s alcohol abuse and caregiver’s quality of life: What’s wrong?
Authors: Mario Airoldi, Luca Raimondo, Claudia Bartoli, Paolo Leombruni, Massimiliano Garzaro, Giancarlo Pecorari
Journal: Journal of Clinical Oncology (2015)

e17038 Background: Alcohol abuse affects 30-60% of head and neck cancer patients. It produces important effects on patient’s physical and psychological wellbeing and can influence the entire family’s functioning. Aim of this study is investigate and define how alcoholism can influence the psychological sphere of caregivers and their relationship with patients affected by Head and Neck cancer. Methods: Sixty couples of patients and caregivers were enrolled this observational cross sectional study on the base of the following inclusion criteria: age 18-80 years, Italian native language, stable patient-caregiver relationship established before cancer onset, oropharyngeal or hypopharyngeal SCC, advanced stage disease (stage III-IV of AJCC, 7th edition, 2010), completion of curative treatment and no evidence of disease at the enrolment. Patients and caregivers completed questionnaires that assessed demographic variables, anxiety and depression (STAI Y1-Y2, BDI and MDRS) and quality of life (EORTC-QLQ-C30 and Head and Neck-35 module for patients and CQOLC for caregivers). Results: The 43% of patients’ sample had a history of alcohol abuse. Alcohol abuse was defined according to criteria established by World Health Organization. Patient-caregiver dyads were divided according to patient’s alcohol abuse: 34 couple with abuse (43%) and 26 couples without abuse (57%). Caregivers of patients with a history of alcohol abuse have a statistically lower quality of life compared with caregivers of patients with no history of alcohol abuse (p < 0.0493). No differences were found in terms of caregivers’ anxiety and depression (p > 0.05). Moreover patients’ quality of life anxiety and depression doesn’t change depending on alcohol abuse (p = 0.9760). Conclusions: It’s necessary to detect patient’s with alcohol abuse not only to better target their treatment but to provide a particular attention to their cargiver. Caregiver’s wellbeing can influence patient’s compliance to treatments .
Tyrosine-kinase inhibitor sorafenib (S) in treatment of metastatic renal cell carcinoma cancer (mRCC) with lung metastases.
Authors: Irina L Popova, Liubov Yu Vladimirova, Natalya A Abramova
Journal: Journal of Clinical Oncology (2015)

e15611 Background: Lung metastases is one of the most often metastatic lesions from mRCC, nevertheless there is a few clinical evidence of vascular endothelial growth factor (VEGF) tyrosine-kinase inhibitors (TKIs) efficacy in treatment of these pts. This study was carried out to evaluate the efficacy and safety of S for mRCC with lung metastases. Methods: Elegibility criteria included measurable mRCC T2-4N0-2M0-1, ECOG ≤ 2, adequate hepatic, renal and bone marrow functions, no brain metastases. S was administrated 50 mg p.o. per day. The frequency of response rate (RR), OS, PFS and safety were evaluated. Results: 23 patients (15 men, 8 women), mean age 59,7±5,3 yrs were recruited. 52.1%(12) patients had mRCC initially and 47.8%(11) had progression after radical treatment. 7 (30.4%) pts had lung metastases, 16 (69.6%) had synchronous lung and bone metastases. RR was 78.3% (18) including 17.4% CR (4), 30.4% PR (7) and 30.4% SD(7). PD was 21.7% (5). OS was 18.3±2.8mos, PFS – 7.3±1.8mos. 19 patients (82.6%) are alive by the time of abstract submission. Common toxicities were: hand-foot syndrome 1/2Gr - 15(65.2%), 3Gr hypertension - 5(21.7%), leukopenia 1/2Gr - 8(34.8%), thrombocytopenia - 6 (26.0%) including 1Gr 4 pts and grade 3Gr – 2 pts, alopecia 2/3Gr - 16(69.5%). All toxicities were controlled by symptomatic medication if necessary, didn't require dose reduction and discontinuation. Conclusions: The study showed that VEGF TKI S could be an optimal method of treatment for mRCC with lung metastases.