tbuckley/cabot-search huggingface dataset:
TAK-243 Is a Selective UBA1 Inhibitor That Displays Preclinical Activity in Acute Myeloid Leukemia (AML)
Authors: Samir H. Barghout, Parasvi Patel, Xiaoming Wang, G. Wei Xu, Simon Kavanagh, Marcela Gronda, Rose Hurren, Danny V. Jeyaraju, Neil MacLean, Marc Hyer, Allison Berger, Tary Traore, Michael Sintchak, Michael Milhollen, Mark D. Minden, Razq Hakem, Aaron D. Schimmer
Journal: Blood (2017)
Abstract P087: Youth Tobacco Users Perceive Less E-Cig Harm
Authors: Delvon T Mattingly, Lindsay K Tompkins, Clara G Sears, Kandi L Walker, Joy L Hart
Journal: Circulation (2018)

Introduction: In Appalachia, youth tobacco use rates exceed the national average, and youth in these rural areas are increasingly aware of new and emerging tobacco products, such as e-cigarettes. G...
Predictors of missed appointments by international patients (IntlPts) in the International Assessment Center (IAC) at MD Anderson Cancer Center (MDACC).
Authors: Renato Lenzi, Gehan Botrus, Manal Hassan
Journal: Journal of Clinical Oncology (2015)

e17506 Background: Missed outpatient appointments adversely impact medical outcomes and result in loss of revenue. We studied multiple variables for correlation with no shows (NSh) among IntlPts referred to the IAC at MDACC. Methods: We conducted a retrospective analysis of 350 IntlPts referred to the IAC at MDACC during fiscal year 2010. Thirty variables potentially correlated with NSh were evaluated. X2test was performed for significance between categorical distribution and logistic regression analysis was performed to estimate odds ratio (OR) and 95% confidence interval (CI) after controlling for potential confounding factors. Results: of 350 IntlPts requesting to be seen 265 (75.5 %) were accepted; 134 (50.6%) were from the Middle East, 61 (23.0%) from South and Central America, 37 (14.0%) from Europe, 17 (6.4%) from Asia, Others 16(6%). Of these, 187 (70.6%) arrived for their appointment, 78 (29.4%) failed to show. Mean age was 53 ± 14 years and male to female ratio approximately 2 to 1. Most patients (164 or 61.9%) were self-referred. We found no significant impact of country of origin, visa issues, age, sex, marital status, type of primary cancer, stage. Payer, history of weight loss, bleeding, advanced liver disease, appointment over 14 days beyond patient requested date predicted NSh. Conclusions: This study was conducted to identify predictors of IntlPts NSh as a first step towards decreasing its frequency. Analysis of additional time periods is ongoing to confirm the impact of co-modifiers. Appointment after patient requested date Payer Disease related symptoms Show N (113)≤ 2 weeks(67) 59.3% > 2 weeks(46) 40.7% Self (85) 45.5% Embassy (66)35.3% Insurance (36)19.3% BleedingNone (182) 97.3% Yes (4) 2.1% Weight lossNone (169) 90.4% Yes (18) 9.6% Advanced liver diseaseNone (183) 97.9% Yes (3) 1.6% No show N (47) ≤ 2 weeks(16) 34.0% > 2 weeks(31) 66.0% Self (57) 73.1% Embassy (17) 21.8% Insurance (4) 5.1% None (41) 82.0% Yes (9) 18.0 % None (38) 76.0% Yes (12) 24% None (45) 90.0% Yes (5 ) 10% P-value 0.005 < 0.001 < 0.001 0.007 0.013
Metabolic syndrome and upper tract urothelial carcinoma: A retrospective analysis from a large Chinese cohort.
Authors: Hang Xu, Ping Tan, Lu Yang, Qiang Wei
Journal: Journal of Clinical Oncology (2019)

452 Background: Metabolic syndrome (MetS) has been reported to be associated with poor survival outcomes in cancer patients. However, the role of MetS in upper tract urothelial carcinoma (UTUC) has yet to be explored. We aim to investigate the prognostic value of MetS in UTUC after radical nephroureterectomy (RNU). Methods: A total of 644 patients with UTUC after RNU were identified at West China Hospital from May 2003 to December 2016. MetS was defined as the co-existence of three or more of five components (obesity, hypertension, elevated fasting glucose, decreased high-density lipoprotein-cholesterol and hypertriglyceridemia). Logistic and Cox regression analyses was performed to evaluate the associations of MetS with pathological features and survival outcomes. Decision curve analysis was performed to determine the clinical utility of the prediction models. Results: Of 644 patients, 157 (24.4%) had MetS. Over a median follow-up of 39 months, 269 (41.8%) experienced disease recurrence, 233 (36.2%) died and 185 (28.7%) died of UTUC. MetS was independently associated with high-grade disease (odds ratio [OR]: 2.01, P = 0.005), advanced pT stage (≥ pT3, OR: 1.54, P = 0.027) and lymphovascular invasion (OR: 1.71, P = 0.03). Multivariate Cox regression analysis showed that MetS was an independent factor for decreased cancer-specific survival (CSS, HR: 1.38, 95% CI: 1.01-1.89, P = 0.042) but not for RFS (HR: 1.27, 95% CI: 0.97-1.67, P = 0.078) and OS (HR: 1.24, 95% CI: 0.95-1.62, P = 0.121). The estimated c-index of the multivariate models for CSS was 0.763 compared with 0.769 when MetS added. Conclusions: MetS is a negative prognostic factor in UTUC. Further studies of MetS in UTUC are demanded.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Chronic Lymphocytic Leukemia (CLL) Driver Genes: Risk of CLL and Monoclonal B-Cell Lymphocytosis (MBL)
Authors: Nicholas J Boddicker, Daniel R O'Brien, Esteban Braggio, Sara J. Achenbach, Kari G. Chaffee, Aaron D. Norman, Celine M. Vachon, Brian Kabat, Timothy G. Call, Sameer A. Parikh, Jose F. Leis, Wei Ding, Eli Muchtar, James R. Cerhan, Tait D. Shanafelt, Neil E. Kay, Neil E Caporaso, Susan L. Slager
Journal: Blood (2018)
A phase II open-label study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pretreated with one immune-checkpoint inhibitor: The BREAKPOINT trial.
Authors: Elena Verzoni, Alessandra Bearz, Ugo De Giorgi, Franco Nole, Camillo Porta, Raffaele Ratta, Melanie Claps, Filippo Pagani, Antonia Martinetti, Agata Cova, Licia Rivoltini, Filippo G. De Braud, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2019)

TPS685 Background: First-line treatment landscape of metastatic renal cell carcinoma (mRCC) is evolving with strong evidence in favour of PD-1/PD-L1 combinations over tyrosine kinase inhibitors (TKIs). No prospective data about efficacy of TKIs post immune-checkpoint inhibitor (CPI) combinations are available. Among TKIs, cabozantinib has demonstrated progression-free survival (PFS) and overall survival (OS) benefit over everolimus in pre-treated mRCC patients (pts). Methods: Overall 49 mRCC pts who received a previous CPI (anti PD-1/PD-L1) will be treated with cabozantinib. Pts will be stratified according to Heng prognostic group, duration of first-line and type of previous therapy received (CPI+CPI or CPI+TKI or CPI+anti-VEGF or CPI monotherapy). Key inclusion criteria include: one previous treatment with a PD-1/PD-L1 inhibitor in first-line and histological diagnosis of clear-cell RCC. The primary endpoint is to assess the efficacy of cabozantinib based on PFS. Secondary endpoints include evaluation of OS, objective response rate and safety profile of the drug. Exploratory endpoints include evaluation of PD-L1 levels by immunohistochemistry in tumor samples; the analysis of the immunological signature/profile of tumor cells; the state of circulating immune cells, as well as the modulating activity of cabozantinib on systemic tumor immunity; the evaluation of bone formation and reabsorption markers in pts with or without bone involvement. Cabozantinib will be administered orally at a dose of 60 mg/day continuously until evidence of disease progression or onset of unacceptable toxicity. Statistical design: By the methodology of Brookmeyer and Crowley, assuming an accrual period of 18 months and a minimum follow-up of 10 months (mos), 49 pts are necessary to detect an increment of the median PFS time from 3.8 mos to 7.4 mos with a power of 90% and one-sided alpha of 5%. The large sample critical value detecting the increment of the PFS median survival time will be 5.54 mos. To date, 2 pts have been enrolled. Clinical trial information: NCT03463681.
A randomized, double‐blind trial comparing 5‐aminolaevulinic acid nanoemulsion with methyl 5‐aminolaevulinate in daylight photodynamic therapy for actinic keratosis
Authors: R.M. Szeimies, P. Calzavara‐Pinton
Journal: British Journal of Dermatology (2019)

Linked Article: Räsänen et al. Br J Dermatol 2019; https://doi.org/10.1111/bjd.17311
<i>HER-2</i> mutations in Chinese lung adenocarcinoma patients with negative <i>EGFR</i> mutations.
Authors: Caicun Zhou, Xuefei Li, Chao Zhao, ChunXia Su, Shengxiang Ren
Journal: Journal of Clinical Oncology (2015)

e12649 Background: To determine the prevalence and clinicopathological features of epidermal growth factor receptor 2 (HER-2) mutations in Chinese lung adenocarcinoma patients with negative EGFR mutations. Methods: Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 398 lung adenocarcinoma patients with wild-type EGFR were screened for HER-2 mutations by amplification refractory mutation system (ARMS) assay and all HER-2 mutations were validated by direct sequencing. The protein expression of HER-2 was evaluated by immunohistochemistry (IHC). Of the 398 samples, 331 were also detected ALK and ROS1 fusions by multiplex RT-PCR, and all fusions positive were verified by direct sequencing. The relationship between HER-2 mutations and clincopathological features and the prognostic effect of its status on disease free survival (DFS) were analyzed. Results: 21 of 398 (5.3%) harbored HER-2 mutations; 7.6% of 278 samples with triple-negative lung adenocarcinoma ( EGFR-, ALK-, ROS1-) were found to have HER-2 mutations. 17 samples (81.0%) were A775_G776insYVMA, two with G776 > VC, one with V777_G778insGSP and the last one with 2340_2341ins12 in-frame insertions of exon 20. 59 of 398 (14.8%) were positive of HER-2 expression. No association was found between HER-2 mutations and expression, only two patients coexisted the positive in mutation and expression. There was no statistically significant difference in age, sex, smoking history, and pathological stage between patients with HER-2 mutations and those with negative patients. The DFS of patients with HER-2 mutations have no significant difference compared with those patients with negative mutations. Conclusions: 5.3% of Chinese lung adenocarcinoma with wild-type EGFR harbored HER-2 mutations. The HER-2 mutations had no association with HER-2 expression. Clinical trial information: ChiCTR-OCH-13003507.
Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC).
Authors: Jonathan E. Rosenberg, Srikala S. Sridhar, Jingsong Zhang, David C. Smith, Joseph D. Ruether, Thomas W. Flaig, Joaquina Celebre Baranda, Joshua Michael Lang, Elizabeth R. Plimack, Randeep S. Sangha, Elisabeth I. Heath, Jaime R. Merchan, David I. Quinn, Sandy Srinivas, Matthew I. Milowsky, Chunzhang Wu, Elaina M Gartner, Amal Melhem-Bertrandt, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2019)

377 Background: Enfortumab vedotin (EV) is an antibodydrug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable. Methods: Patients with mUC treated with ≥1 prior chemotherapy, or those ineligible for cisplatin, received EV 1.25 mg/kg on Day 1, 8, and 15 every 28 day cycle. The primary objective was tolerability; antitumor activity (ORR per RECIST v1.1), assessed every 8 wk, was a secondary objective. Results: As of14 Sept 2018,112 pts with mUC received EV with a median follow up of 13.4 mo. Bladder was the primary tumor site in 86 pts (77%) and 33 (29.5%) had liver metastases (LM). Nearly all pts received prior platinum chemotherapy; 89 (79.5%) received prior anti-PD(L)1. EV was well tolerated; fatigue (53%), alopecia (46%), and decreased appetite (42%) were the most commonly reported treatment-related AEs (TRAEs). Anemia (8%), hyponatremia (7%), UTI (7%), and hyperglycemia (6%) were the grade ≥3 AEs reported in ≥5% of pts regardless of attribution; 4 fatal TRAEs were reported (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure). Confirmed ORR was 42% (CR, n = 5; PR, n = 42). Among responders, median duration of response was 7.7 mo (95% CI 5.6, 9.6) and 23.4% of responses were ongoing with a median follow up of 11.3 mo. Estimated median PFS and OS were 5.4 mo (95% CI 5.1, 6.3) and 12.5 mo (95% CI 9.3, 16.1), respectively; OS at 1 yr was 51.8%. Similar results were seen in pts with prior anti-PD(L)1 and with LM (Table). Conclusions: Single-agent EV was generally well tolerated and provided encouraging response and survival data in a population with an unmet medical need including pts with LM, which is associated with poor prognosis. Phase 2 and 3 monotherapy studies as well as evaluation of combination therapies are ongoing. Clinical trial information: NCT02091999. [Table: see text]
The mutational burden of targeted genes significantly correlated with overall survival after targeted therapy in metastatic renal cell carcinoma.
Authors: Jae Young Joung, Taek Sang Kim, Sang Hyun Park, Sung Han Kim, Weon Seo Park, Jinsoo Chung
Journal: Journal of Clinical Oncology (2019)

643 Background: This study aimed to find the correlation between tumor mutation burden and systemic first line therapeutic response in metastatic tissue samples from patients with metastatic renal cell carcinoma (mRCC). Methods: Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS) using the 88 targeted genes from the National Cancer Center, Korea (NCC) kidney cancer panel. The patients’ medical records, including therapeutic responsive profiles with overall survival (OS) to first-line targeted therapy, were evaluated with the mutational burden of triplet tissue samples using 88 TGS. A few significant target genes associated with therapeutic response towards targeted therapy were identified after comparing the mutational burden of positive for all three blocks and one or two positive blocks (p-value &lt; 0.05). Results: The median PFS for the first-line targeted therapy and OS were 8.7 and 42 months, respectively. MSKCC and Heng risk criteria showed 28.9/65.8/5.3% and 26,3/57.9/15.8% for favorable, intermediate, and poor risk groups, respectively. Also, 55.3% and 52.6% patients received metastatectomy and nephrectomy, respectively. Eighteen (32.1%) patients had all triplet blocks passed for quality check, whereas 21 (37.5%) and 17 (30.4%) patients had two or one passed tissue blocks, respectively. Among the 18 patients with triplet-block, TP53, URB4, PTK2, and SGO2 genes had significant discrimination power for OS on comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 11) (p &lt; 0.05). Among the 39 patients with either doublet or triplet blocks passed for quality check, TP53, URB1, PTK2, SGO2, BRAF, NEDD4, PDXDC1, CDH1, FGFR2, RET, RUNX1, and SDHB genes had significant discrimination power for DFS when comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 14) (p &lt; 0.01). Conclusions: The study showed the tumor mutational burden of many vital targeted genes to be significantly correlated with OS from metastatic tissues in mRCC.
Antitumor activity of PBI-1737 in xenograft human prostate PC-3 cancer by inhibition of cell adhesion and migration
Authors: Mouna Lagraoui, Brigitte Grouix, Marie-Eve Fafard, Dannyck Gaudreau, Natalie St-Amant, Lilianne Geerts, Francois Sarra-Bournet, Valerie Perron, Jean-Simon Duceppe, Boulos Zacharie, Christopher Penney, Lyne Gagnon
Journal: Cancer Research (2008)

1167  Cell adhesion, proteolytic degradation of extracellular matrix and cell migration are interrelated processes responsible for the invasion and metastasis of cancer. In prostate cancer, androgen-independence and bone metastasis are lethal complications in patients. PBI-1737 is a low molecular weight, orally active molecule that inhibits invasion and adhesion of androgen-independent human PC-3 cells. PBI-1737 demonstrated an inhibition of the EGF-induced PC-3 invasion in a two-dimension cell mobility assay. Furthermore, the addition of different concentrations of PBI-1737 induces in a dose dependent manner an inhibition of PC-3 cells adhesion to laminin, matrigel and collagen. The antitumor efficacy of oral administration of PBI-1737 with or without combination of cyclophosphamide on xenograft human prostate PC-3 tumor was also studied. Oral administration of PBI-1737 (50 mg/kg) induces a significant (p
Phase II study of metronomic cyclophosphamide and temozolomide in platinum resistance ovarian cancer.
Authors: Gouri Shankar Bhattacharyya, Hemant Malhotra, Purvish M. Parikh, Kanaka Setty Govindbabu, Anantbhushan Ranade, Ghanashyam Biswas, Shailesh Arjun Bondarde
Journal: Journal of Clinical Oncology (2015)

e16575 Background: Ovarian Cancer isangiogenically driven cancer; use of anti-angiogenic drugs in Platinum Resistance Ovarian Cancer can inhibit growth of Ovarian cell line as well as in vivo improves survival. Anti-angiogenesis is accepted method of therapy for Ovarian Cancer. Temozolomide in continuous low dose administration, targets tumor associated endothelial cells, thereby causing shrinkage of tumor. The metronomic dose also has a higher safety profile than normal dosing. Cyclophosphamide in a metronomic dose is also known to be a strong anti-angiogenic drug and is accepted as an Option in Care of Ovarian Cancer. Methods: Platinum Resistance Ovarian Cancer patients with histologically proven were eligible for this study. Metronomic Cyclophosphamide was administered at a dose of mg daily at 10am, and Temozolomide at a dose of 20 mg twice daily from days 1 to 14, repeated every 3 weeks. Results: A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one cycle of Metronomic Cyclophosphamide and Temozolomide. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9–58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1–6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5–10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3–4 toxicities were neutropenia (20%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥ Grade 3. Conclusions: Metronomic Cyclophosphamide and Temozolomide produced a high response rate with good survival in patients with Platinum Resistance Ovarian cancer. There is a good pharmacoeconomic outcome and a viable alternative.
Four-year outcomes of hypofractionated proton therapy for localized prostate cancer.
Authors: Amardeep S. Grewal, Caitlin Schonewolf, Stefan Both, Sarah Lam, Susan Mazzoni, Justin E. Bekelman, John Paul Christodouleas, Neha Vapiwala
Journal: Journal of Clinical Oncology (2019)

80 Background: Hypofractionated radiation therapy (HFRT) is an effective treatment for localized prostate cancer (LPC). This study was performed to determine the toxicity profile and biochemical-clinical failure (BCF) rates for patients with LPC treated with hypofractionated proton therapy (HFPT). Methods: Between 2010 and 2017, 184 men were enrolled on a trial of 70Gy in 28 fractions of HFPT for low to intermediate-risk LPC. Androgen suppression (AS) was allowed. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Urinary and erectile quality of life changes were captured using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) Questionnaire, respectively. Results: Median follow-up was 49.2 months. Enrolled patients had low-risk [LR] (n = 18), favorable intermediate-risk [FIR] (n = 78), and unfavorable intermediate-risk [UIR] (n = 88) disease. Twenty-six percent of patients received neoadjuvant and concurrent AS, with a median duration of 6 months. Four-year rates of BCF free survival were 95.7%, 94.4%, 98.7%, and 93.2% in the overall group and the LR, FIR, and UIR cohorts, respectively (p = .21). Overall survival at 4 years was 97.3%. No deaths were attributable to prostate cancer. Median IPSS before and 1 year post-HFPT were 6 and 7 for LR patients, 6 and 6 for FIR patients, and 8 and 7 for UIR patients. Median IIEF-5 before and 1 year post-HFPT were 21 and 18 for LR patients, 18 and 16.5 for FIR patients, and 15 and 10.5 for UIR patients. The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic (GU) toxicities were 3.8% and 12.5%, respectively. One acute grade 3 GI toxicity was reported. The 4-year incidence of late grade 2 or higher GU and GI toxicity was 7.6% and 13.6%, respectively. One late grade 3 GI toxicity was reported. The predominant late grade 2 GI and GU toxicities were rectal bleeding and urinary frequency, respectively, accounting for 79% and 57% events. All late toxicities were transient. Conclusions: HFPT is associated with low rates of toxicity in the treatment of prostate cancer. Further analyses are warranted to assess long term toxicity and understand differences between proton and photon HFRT. Clinical trial information: NCT01352429.
Correlation between plasmatic levels of vitamin D and testicular cancer.
Authors: Lucia Nappi, Vincenzo Damiano, Margaret Ottaviano, Pasquale Rescigno, Caterina Condello, Claudio Curci, Ciro Candido, Giovannella Palmieri
Journal: Journal of Clinical Oncology (2015)

e15561 Background: Testicular Germ cell Tumor (TGT) is the most common cancer in young male. Multidisciplinary integrated therapeutic strategies have been showed to be very efficient with excellent cure rate and a long life expectancy. Unfortunately treatment-related long-term sequelas can affect the quality and the length of life of these patients. Vitamin D deficiency was already described after orchiectomy but its severity and correlation with clinical features in TGT patients remains unknown. Methods: ELISA assay was used to evaluate the plasmatic levels of 25-OH vitamin D. A total of 78 patients affected by TGT, between 18 and 43 years old, 3 - 96 months after the orchiectomy, were enrolled. Patients were divided in two groups according to histology: Seminomas (S), presenting pure seminomas, and Non-Seminomas (NS), presenting mixed (seminomas and non-seminomas) or pure non-seminomas. T-and χ2 tests were used to compare serum levels of 25-OH vitamin D, calcium, FSH, LH, testosterone, progesterone and 17-β-estradiol in the two groups. Linear regression test was used to correlate serum 25-OH vitamin D to clinical stage, histology and treatment received. The results were normalized for the age of patients and light exposure at the moment of blood withdrawal (low season and high season). P < 0.05 was considered statistical significant. Results: 83% of analyzed patients presented insufficient ( < 30ng/ml) 25-OH vitamin D levels and 43% of them showed deficient ( < 20 ng/ml) 25-OH vitamin D levels . The deficiency was not influenced by time from diagnosis, treatment received and ligh exposure at the time of blood withdrawal. Among patients with NS the deficiency of vitamin D positively correlated with aggressive embrional carcinoma (EC) histology subtype (O.R. 13.2000 (2.9571 - 58.9223, p 0.0007) and advanced stage of disease (stage III-IV vs I-II: O.R. 4.8810 (1.3663 - 17.4371), p 0.0147) . In patients with EC vitamin D levels also correlated with high ( > 15 ng/ml) α-FPT levels (O.R. 22.0000 (1.8568 - 260.6595), p 0.0143). Conclusions: Our study showed high prevalence of 25-OH vitamin D deficiency in patients affected by TGT. Moreover in TGT patients vitamin D deficiency correlated with EC histology and advanced clinical stages.