tbuckley/cabot-search huggingface dataset:
Next-generation sequencing (NGS) in an advanced hepatocellular carcinoma (HCC) cohort: Analyses of TP53 and CTNNB1.
Authors: Robin Kate Kelley, John Dozier Gordan, Kimberley Evason, Paige M. Bracci, Nancy M. Joseph, Andrea Grace Bocobo, Blake K. Rosenthal, Halla Sayed Nimeiri, Alan P. Venook
Journal: Journal of Clinical Oncology (2016)

286 Background: Mutations in TP53 and CTNNB1 are common in early stage HCC resection samples. The frequency and prognostic impact of these mutations in advanced HCC is not known. We conducted this retrospective analysis using a large NGS panel to explore for association between tumor genetics, clinicopathologic features, and prognosis in an advanced HCC cohort. Methods: Eligible cases had diagnosis of unresectable HCC or mixed HCC-cholangiocarcinoma and were enrolled on NCT01008917 or NCT01687673 clinical trials of sorafenib plus temsirolimus with informed consent for specimen banking for future research including genetic testing. Paired tumor and germline (blood) DNA samples were sequenced using a capture-based NGS cancer panel to allow for determination of somatic variants. Analysis was based on the human reference sequence UCSC build hg19. Variants were called using GATK Unified Genotyper software. Somatic, non-synonymous, and exonic calls were curated using COSMIC, cBioPortal, and Pubmed. Results: Cases with HCC (n = 21) and mixed HCC-cholangiocarcinoma (n = 2) comprised the cohort (N = 23). Male/female: 83%/17%. Race: White 56%, Asian 39%. BCLC stage: B 35%, C 65%. Etiology: HBsAg+ 26%, HCV+ 39%. Immune infiltrates ( ≥ 1 on scale 0-3) were present in 7/12 (58%) evaluable tumor samples. TP53 mutations were present in 14/23 (61%, 95% CI: 38.5, 80.0). CTNNB1 mutations were present in 7/23 (30%, 95% CI: 13.2, 52.9). There was no significant difference between HBsAg+ and HCV+. Both TP53 and CTNNB1 mutation were present in 4/23 (17%). CTNNB1 mutation was present in 2/7 (29%) cases with immune infiltrate score ≥ 1, and 1/5 (20%) with score &lt; 1 (not significant). Other mutations and variants will be reported. Conclusions: NGS in this advanced HCC cohort suggests a higher incidence of TP53 and coexisting TP53 plus CTNNB1 mutations than has been reported in early stage HCC which requires confirmation in a larger cohort. There was no clear relationship between these mutations, HCC etiology, or tumor immune infiltrates though interpretation is limited by small sample sizes. Analyses are ongoing to explore for association between TP53 and CTNNB1 mutations and prognosis in this advanced HCC cohort.
Male breast cancer: Risk factors, treatment, and survival.
Authors: Salome Arobelidze, Abdo S. Haddad, Timothy Peter Spiro, Hamed Daw
Journal: Journal of Clinical Oncology (2015)

110 Background: We conducted a retrospective study to investigate male breast cancer risk factors, treatment and survival. Methods: All patients with male breast cancer diagnosed between 1985 and 2014 at the Cleveland Clinic were retrospectively reviewed. Results: 131 patients were enrolled in the study. The median age at diagnosis was 66. Most of the tumors were invasive ductal carcinomas (85%, 111/131) and most were intermediate grade (47%, 41/87). Most patients had localized disease – stage 0-1 (45%, 48/107); stage 2 (35%, 37/107). Among the patients with data, 93% (94/101) were ER+, 73% (74/101) were PR+, 12% (10/80) were HER2 positive, and 6% were triple negative. Estimated median survival was 20.2 years (95% C.I. 19.0-29.4), and estimated 2 and 5-year survival were 96% + 2% and 87% + 3%. Grade was associated with outcome (p=.07). Conclusions: In our study only age at diagnosis was associated with overall survival. Further research is required to understand the treatment outcomes of this rare cancer. [Table: see text]
Tumor size as a predictor of pathologic complete response (pCR) and survival in a prospective trial of chemoradiation for locally advanced rectal cancer
Authors: C. S. Kim, P. R. Anne, E. P. Mitchell, J. Palazzo, E. Pequignot, R. Fishel, S. D. Goldstein, G. A. Isenberg, W. Curran
Journal: Journal of Clinical Oncology (2005)

3672 Background: Preoperative chemoradiation (CRT) is becoming the standard therapy for locally advanced rectal cancer patients. Prognostic factors are important to determine response and outcome. We previously demonstrated that high microsatellite instability and p21 are predictive for pCR in patients treated with preoperative CRT (Charara et al. Anticancer Research, 2004). The aim of this study was to determine if tumor size is a predictive factor for pCR and survival. Methods: 67 patients with locally advanced rectal cancer (cT3/T4) were treated with preoperative CRT on PhaseI/II clinical trial. Patients received CPT-11 (30–50 mg/m2 on days 1,8,15,22) and 5-FU (protracted continuous infusion 300 mg/m2 initially, then 225 mg/m2/day on days 1–5 weekly during radiation therapy) and standard radiation therapy (45–54 Gy). Surgery was performed at 6–10 weeks following completion of therapy. A total of 58 patients were evaluable for tumor size. Patients were divided in 2 groups: tumors < 5 cm and ≥ 5 cm. Tumor size was determined by endoscopy, endorectal ultrasound, CT scans, and CT simulation for RT. Statistical analysis was performed using t-test, log scale, and logrank test. Results: Of 58 patients, 25 patients had tumor size < 5 cm and 33 had tumor size ≥ 5 cm. In the entire group, pCR rate was 16/58 (28%) of patients. In patients with tumors < 5 cm, pCR rate was 11/25 (44%) compared to 5/33 (15%) in those with tumors ≥ 5 cm. Pretreatment tumor size was predictive for pCR (p=0.022). Tumor size did not correlate with p21 marker status (p=0.23). 5-yr disease-free survival (DFS) was 80% in patients with small tumor size (< 5 cm) compared to 60% in those with larger tumor size (p=0.11). Difference in DFS was not statistically significant between the two groups. Conclusions: Tumor size is an independent predictor of pCR but not for DFS in locally advanced rectal cancer patients treated with preoperative CPT-11, 5-FU, and radiation therapy. No significant financial relationships to disclose.
Association of telomere length (TL) with clinical outcomes in patients with colorectal carcinoma (CRC).
Authors: Mahadi Ali Baig, Amartej Merla, Titto A Augustine, Gil Atzmon, Temuri Budagov, Sanjay Goel, Radhashree Maitra
Journal: Journal of Clinical Oncology (2013)

418 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem.” During aberrant cell proliferations the normal check points of cell cycle is compromised leading to unrestricted cell division with extremely short T and subsequent genomic instability. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 122 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (&gt;/&lt; median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs. 5295 p=0.04). There was a trend towards increased overall survival (&gt;/&lt; median) with longer TL (4934 vs. 4117; p=0.08). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. Conclusions: TL is a potential biomarker predictive of clinical outcome (PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.
The impact of screening mammography in women age 40-49 as a function of tumor biology.
Authors: John C. Ruckdeschel, William V. Rees, Brett T Parkinson, Thomas Belnap, Braden D. Rowley, Kenneth Pena
Journal: Journal of Clinical Oncology (2013)

113 Background: Mammographic screening for women 40-49 years of age remains controversial based on results from earlier large scale, controlled mammography trials. Methods: From 2002-2006, 871 women aged 40-49 were diagnosed with breast cancer at Intermountain. The charts of all patients without a record of a screening mammogram at Intermountain (n= 436) were reviewed to confirm that they had not had a screening mammogram in the prior two years at any facility (Interval Cancers) and their survival was compared to 435 women who had their cancer diagnosed on a screening exam (Screen Detected). All patients were followed for at least 5 years via the tumor registry. Results: Stage distribution for Screen Detected/Interval cancers was 25.3/6.4% stage 0, 36.8/24.8% stage I, 24.6/35.6% stage II, 6.9/20.4% stage III and 0.5/3.4% stage IV. Overall, 67 patients (7.7%) did not have complete staging data. Overall survival was significantly better (p&lt;.0001) for 40-49 year old women with Screen Detected compared to those with Interval cancers. 702 (79.6%) had ER/PR status recorded (83.5% ER/PR positive). Women with DCIS or LCIS did not have tissue sent for markers. 679 patients (76.9%) had HER2 status recorded (78.8% HER2 neg). Of the patients with both HER2 and ER/PR status recorded 10.4% were “triple negative.” Survival following screening mammography was significantly enhanced for women who were ER/PR positive (p&lt;0.0001), HER2 negative (p=0.0065), or HER2 positive (p=0.0013). Survival was not improved by screening mammography for women who were ER/PR negative (p=0.3818) or for women who were triple negative (p=0.416). Conclusions: A minority of women age 40-49 who develop breast cancer (13%) have biologic features suggestive of aggressive disease and, after 5 years of follow up, they are not benefitted by screening mammography. The remaining 87% are clearly benefitted by screening mammography. Our results suggest that the discrepancies noted in the screening mammography trials in 40-49 year old women may have resulted from population variations in the proportion of women with unfavorable biology. Based in part on these results, we continue to recommend regular screening in the 40-49 year old cohort.
Reactivating PP2A by FTY720-Loaded Lipid Nanoparticles, a Novel Therapeutic Strategy in Acute Myeloid Leukemia
Authors: Ander Estella-Hermoso de Mendoza, Remedios Castello-Cros, Cristina Cirauqui, Raffaella Pippa, Isabel Moreno, Maria J Blanco-Prieto, Maria D Odero
Journal: Blood (2012)
Pre-cystectomy serum levels of CA19-9, CA125, and CEA: Correlation with pathologic stage and oncologic outcome in urothelial carcinoma of bladder.
Authors: Hamed Ahmadi, Hooman Djaladat, Gus Miranda, Jie Cai, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2013)

303 Background: To evaluate the association between pre-cystectomy carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) levels and pathologic stage and oncological outcome of urothelial carcinoma of bladder (UCB). Methods: Preoperative stored serum samples of 186 patients with UCB who underwent radical cystectomy at USC between 2004 and 2009 were randomly selected to measure CA19-9, CA125, and CEA levels. Laboratory cut-off point values were used to define abnormal marker levels (CA 19-9&gt;35.5, CA125&gt;35.5, CEA&gt;3.8). Pathologic stage was categorized as organ confined (OC) (pT1,T2), extravesical (EV) (&gt;pT2), and lymph node positive (LN+) UCB. Cox regression model was used to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). Results: The mean age of patients were 70 years (ranges, 36-91) and the median follow-up was 4 years (ranges, 0.1–7). 94 (50.5%) patients had OC, 45 (24%) had EV, and 47 (25.5%) had LN+UCB. The mean CA 19-9, CA125, and CEA levels were14 (0.6–278) U/mL, 11.8 (3–79) U/mL, and 2.3 (0.3–30) ng/mL. 30/186 (16%) patients had at least one abnormal marker. Percentage of abnormal CA19-9 was significantly higher in locally advanced UCB (EV and/or LN+) compared to OC UCB (85.7% vs. 48%; P=0.03). The percentage of abnormal CA125 and CEA levels were comparable between locally advanced and OC UCB.4-year RFS and OS were 66% and 65%, respectively. After controlling for pathologic stage, age, and adjuvant chemotherapy; Abnormal CA19-9 and CEA were independent predictors of worse 4-year OS (HR:2.7; P=0.04 and HR:2; P=0.03). Abnormal CA 19-9 was also an independent predictor of worse 4-year RFS (HR: 2.8; P=0.05). Pre-cystectomy CA 125 level had no correlation with oncological outcome. Conclusions: In patients with UCB, abnormal precystectomyserumCA19-9 is correlated with advanced pathological stage and is an independent predictor of worse oncological outcome. Precystectomy CEA and CA 125 showed no significant correlation with pathological stage and oncological outcome. Prospective studies are encouraged to elucidate the clinical value of these serum markers.
2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease: Executive Summary
Authors: Thomas G. Brott, Jonathan L. Halperin, Suhny Abbara, J. Michael Bacharach, John D. Barr, Ruth L. Bush, Christopher U. Cates, Mark A. Creager, Susan B. Fowler, Gary Friday, Vicki S. Hertzberg, E. Bruce McIff, Wesley S. Moore, Peter D. Panagos, Thomas S. Riles, Robert H. Rosenwasser, Allen J. Taylor
Journal: Circulation (2011)
Prognostic significance of post-treatment standardized uptake value (pSUV) of positron emission tomography (PET) to predict overall survival (OS) and relapse-free survival (RFS) in patients with esophageal or gastroesophageal cancer treated with definitive chemoradiotherapy.
Authors: A. Suzuki, L. Xiao, Y. Hayashi, J. Welsh, S. H. Lin, D. Maru, W. L. Hofstetter, R. J. Mehran, J. H. Lee, M. S. Bhutani, H. A. Macapinlac, Z. X. Liao, J. A. Ajani
Journal: Journal of Clinical Oncology (2011)

4055 Background: The value of PET after definitive chemoradiotherapy is still unclear. We hypothesized that the post-treatment pSUV and the percentage decrease SUV from baseline (dSUV) would correlate with patient outcome. Methods: We performed retrospective study, selecting patients with advanced E-GEC who had pre- and post-treatment PET, endoscopic ultrasonography (EUS) and were treated with definitive chemoradiation at MD Anderson Cancer Center between 2002 to early 2008. Correlations were performed between clinical variables, pSUV, and dSUV. Results: We analyzed 209 consecutive E-GEC patients treated with definitive chemoradiation for outcome; of these 180 had baseline PET and 161 had post-treatment PET performed 5 to 6 weeks after the completion of definitive chemoradiotherapy for additional analyses. The median OS and relapse free survival (RFS) for all patients was 20.7 months (95% CI; 18.8 to 26.3) and 11.2 months (95% CI; 9.44 to 14.34). Patients with clinical complete response (cCR, 68.9%) which assessed by EUS, PET and clinical parameters lived longer than those not achieving a cCR (P < 0.001). The median pSUV and dSUV were 4.3 (range, 0 to 19.9) and 76.85% (range -177 to 100), respectively. In the univariate analysis, continuous pSUV and dichotomized pSUV cut off by median were associated with OS (Cox model, P = 0.01; log-rank test, P = 0.01) and RFS (Cox model P=0.0004, log-rank test, P = 0.0004). In the multivariate model, continuous pSUV was an independent prognosticator of OS (p = 0.003) and RFS (p < 0.001). dSUV were not associated with OS (P = 0.096) and RFS (P = 0.082) in the univariate analysis. Conclusions: The higher SUV after chemoradiotherapy, the poorer are OS and RFS of gastroesophageal cancer patients treated with definitive chemoradiotherapy. Post chemoradiation PET may become useful in guiding individualized therapy.
Epidemiology of basal cell carcinoma: scholarly review
Authors: J.A.C. Verkouteren, K.H.R. Ramdas, M. Wakkee, T. Nijsten
Journal: British Journal of Dermatology (2017)

Basal cell carcinoma (BCC) is the most common cancer in white‐skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability‐adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR‐sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision‐making and choose their treatments wisely.
Evaluation of pandemic H1N1(2009) influenza vaccine in adults with solid tumor malignancies on active systemic treatment.
Authors: J. D. McGee, A. M. Oza, L. M. Tinker, J. Gubbay, K. MacAlpine, L. Shi, D. Villa, J. Kuruvilla, L. Wang, H. Mackay
Journal: Journal of Clinical Oncology (2010)

9050 Background: Vaccination is the most effective way to prevent infection with influenza. Patients (pts) undergoing systemic therapy are at high risk of influenza-related complications. 90% of healthy individuals vaccinated with pandemic (pH1N1) vaccine will achieve seroprotective antibody levels. The aims of this study were to evaluate the safety and immunogenicity of pH1N1 vaccine in pts undergoing chemotherapy. Methods: This was a prospective, single center, cohort study. Eligibility criteria included: age >18 years, solid tumor malignancy receiving systemic therapy and undergoing pH1N1 vaccination. Pts with a hx of pH1N1 infection were excluded. Blood samples were taken prior to and ≥21 days post vaccination for serology and CBC. HAI antibody testing was performed for pH1N1 (A/California/7/2009 strain) and seasonal H1 (A/Brisbane/59/07 strain). Seroprotection was defined as a pH1N1 antibody titre ≥ 1:40 and seroconversion as a pH1N1 antibody titre ≥ 4x baseline. Pts completed a symptom diary card. Results: 18 pts (8 M:10F), median age 63 (range 50-76) years, ECOG PS ≤1 received p H1N1 vaccine, 17 received cytotoxic chemotherapy (Table) and 1pt a biological agent alone. The overall seroprotective rate post vaccination was 55% (10/18) and seroconversion rate 50% (9/18). Rates of seroprotection and seroconversion grouped according to timing of vaccination during the chemotherapy cycle are shown in table 1. The 3 pts mid cycle achieved the highest pH1N1 titres post vaccination. 16 pts completed symptom diaries. All reported toxicity was grade 1: localized pain (10 pts), cough/fever (1). 5 pts reported no toxicity. Conclusions: Although well tolerated, the rate of seroconversion and seroprotection following pH1N1 vaccination is lower than would be expected in the general population and is a cause for concern. Further investigation into the timing of vaccination in pts undergoing chemotherapy is warranted. Day in chemoptheray cycle N* ANCMedian (range) ×109/L Pre-pH1N1seroprotection rate No (%) Post-pH1N1seroprotection rate No (%) Seroconversion rate 0 to -4 14 3.2 (1.2-7.9) 2 (14%) 6 (43%) 5 (36%) Other: 9/10 and 14 3 0.6 (0.5-3.3) 0 (0%) 3 (100%) 3 (100%) * 1 pt on EGFR inhibitor seroconverted. No significant financial relationships to disclose.
Economic burden of advanced hepatocellular carcinoma (HCC) in Spain among patients discontinuing first-line sorafenib.
Authors: Astra M. Liepa, Sean D. Candrilli, Yulia D'yachkova, Kaisa Taipale, James A. Kaye
Journal: Journal of Clinical Oncology (2014)

324 Background: No treatments (Txs) are currently recommended after discontinuation (DC) of sorafenib (SOR) for advanced HCC and there are limited reports of Tx patterns. This study assessed Tx patterns, resource use, and associated costs for a select cohort of patients (pts) from Spain. Methods: Via an internet-based chart review, 50 physicians provided clinical and resource use data for 5 de-identified pts each. Medical records were eligible if the pt was ≥18 years old, was diagnosed with advanced HCC, initiated first-line SOR after 2008, subsequently discontinued SOR, survived ≥2 months post-SOR DC, and had ≥6 months of follow-up data (or had died). Unit costs for healthcare resources were obtained from publicly-available sources and applied to the number of each resource type to obtain cost estimates. All analyses were descriptive in nature. Results: From September to October 2012, physicians provided data for 250 pts. Mean pt age was 61 years and 73% were male. At SOR initiation, 35% were Barcelona Cancer Liver Clinic stage B and 63% C. From SOR initiation to DC, 43% declined in Child-Pugh status. Following SOR DC, inpatient hospitalization was reported for 45% and emergency room visits for 49%. For those reported as having received supportive care (n=209), 73% received pain interventions, 42% nutritional support, 33% antiemetics, and 17% transfusions. 28% received anti-cancer Tx (chemotherapy, procedures). For all pts, hospitalization represented about half of total costs. For pts who received further anti-cancer Tx, chemotherapy and procedures represented about one-third of costs and hospitalization less than one-third. Total costs per pt are summarized (Table). Conclusions: Following sorafenib DC, most advanced HCC pts who we studied did not receive further anti-cancer Tx. Those who received further anti-cancer Tx had greater total healthcare costs, but these costs accrued over a longer period of time. [Table: see text]