tbuckley/cabot-search huggingface dataset:
The development of a validated data linked tissue microarray of bladder cancer patients undergoing cystectomy.
Authors: Richard Robinson, Sarah Anderson, Gary Ashton, Chris Womack, Mick D. Brown, Noel W Clarke
Journal: Journal of Clinical Oncology (2013)

330 Background: Over the last 25-30 years there has been little or no advancement in the prognosis or treatment of high grade and muscle invasive bladder cancer, with 5 years survival rates following radical treatment of 40-50%. The aim of this project was to develop a validated, data linked tissue microarray (TMA) of cystectomy patients for the assessment putative biomarkers the provision of a developmental drug pre-screening tool. Methods: All cystectomy derived FFPE tissue blocks from The Christie tertiary cancer centre (1969-2006) were retrieved and independently reviewed. Representative 1mm tissue cores were extracted for TMA construction and associated DNA/RNA bank. The TMA quality was validated using standard H&amp;E histopathological assessment and immunohistochemistry for pan-cytokeratin and phospho-tyrosine. Results: Of 889 cases identified between 1969-2006, tissue of sufficient quality for inclusion was available from 605 patients, comprising 535 bladder cancer cases (85% TCC) and a normal cohort of 70 cases where cystectomy was performed for a non-bladder malignancy. All cases have been linked to a clinical database complete with follow up data up to 10 years post treatment or death. TMA construction has been validated by immunohistochemistry. General immuno-reactivity across the TMA was confirmed by pan-cytokeratin staining (100%). Preservation of phosphorylation, demonstrated by phosph-tyrosine staining, was confirmed in 80%. Notably there was no correlation between sample age and staining. Conclusions: We have successfully created a validated bladder cancer TMA linked to long term follow up data, which provides a powerful research tool for collaborative research into putative biomarkers and novel drug targets.
Updated analysis of a pilot study examining the role of circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer.
Authors: J. B. Aragon-Ching, S. J. Simmens, F. Hendricks, R. Andrawis, H. Frazier, M. Phillips, T. Jarrett, S. R. Patierno, R. S. Siegel
Journal: Journal of Clinical Oncology (2011)

e15023 Background: CTCs have been used as a prognostic factor in metastatic prostate cancer. Little data exists regarding the role of CTCs in BR of prostate cancer. The primary aim of this study was to determine whether there is a correlation between the number of CTCs with prostate specific antigen (PSA) levels and PSA doubling time (PSADT) in men with BR. In addition, we wished to explore the correlation of the CTCs with clinical and laboratory factors (Gleason scores, testosterone, hemoglobin, alkaline phosphatase, BMI, imaging results). Methods: BR was defined as patients (pts) who have undergone primary treatment with prostatectomy or radiation or both, with rise to ≥ 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy. The study was powered to detect a Pearson correlation of .46 with a sample size of 36. 16 of planned accrual of 36 pts were enrolled from May to December 2010. PSADT was obtained and correlated with the CTC values, categorized as PSADT of < 3 mos, 3-14.9 mos and > 15 mos. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: Median age for 16 patients was 71.5 (range: 57 – 91); median PSA of 1.6 ng/mL (range 0.2 – 65.8); testosterone levels of 304 ng/dL (range: 31 – 600). Gleason scores ranged from 5 to 8. Prostatectomy was the primary treatment in 9 pts, radiotherapy in 5 pts, Cyberknife in 1 pt and combined radiohormones in 1 pt. Median hemoglobin was 12.81 g/dL, BMI was 27.1 and alkaline phosphatase was 68 IU/L. PSADT varied between 2.27 to 55 months, with a median of 9.6 mos. All pts accrued had 0 CTC levels except one who had a CTC of 1 but found to have biopsy-proven isolated metastatic bony lesion, with the shortest PSADT of 2.27 and an absolute PSA level of 5.6 ng/ml. Conclusions: Most prostate cancer pts with BR have negative blood CTCs but the small sample precludes a formal assessment of the correlation of CTC levels with PSADT and PSA. However, the only pt with a positive CTC also had the most rapid PSADT out of 16 pts, raising the possibility that obtaining a positive CTC may herald onset of metastatic disease and may have utility for longitudinal follow-ups of pts with BR. Supported by IRG-08-091-01 from ACS to GWUCI.
IMPACT OF INCREASED BASAL TONICITY OF CORONARY ARTERY ON ACETYLCHOLINE PROVOCATION TEST RESULT IN KOREAN PATIENT WITH CHEST PAIN
Authors: Sunwon Kim, Seung-Woon Rha, Amro Elnagar, Byoung Geol Choi, sung il Im, Jin Oh Na, Seongwoo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Hong-Seog Seo, Chang Gyu Park, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2012)
Survival impact of neoadjuvant therapy in resected pancreatic cancer.
Authors: Katelin Anne Mirkin, Christopher S Hollenbeak, Joyce Wong
Journal: Journal of Clinical Oncology (2016)

367 Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. In recent years, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT on survival in patients with resected stage I-III pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was analyzed for patients with clinical stage I-III resected carcinoma of the pancreas who underwent NAT or surgery first +/- adjuvant therapy. Univariate statistics were used to compare characteristics between groups. Analysis of variance and Kaplan Meier analyses were used to compare median survival for each clinical stage of disease. Multivariate analyses were performed using a Cox proportional hazards model. Results: 16,122 patients who underwent NAT and 16,869 patients who underwent surgery-first were included. Patients who underwent NAT tended to be younger, covered by private insurance, have a higher median income, greater comorbidities, higher clinical stage disease, and undergo a whipple. Additionally, NAT patients had a greater number of positive regional lymph nodes (9 vs. 6, respectively), although a similar number of nodes retrieved, and higher pathological stage disease. In patients with clinical stage I disease, adjuvant therapy was associated with improved median survival than NAT and surgery-alone (24.8, 18.5, 17.9 months, p &lt; 0.0001, respectively). However, in stage II, adjuvant and NAT offered similar median survival, which was improved over surgery-alone (20.5, 20.1, and 12.4 months, p &lt; 0.0001, respectively). In stage III, NAT had improved median survival than the other groups (19.6, 14.2, 8.6 months, p &lt; 0.0001, respectively). In the multivariate survival analysis, patients who received NAT had a 22% lower hazard of mortality up to 5 years as compared to adjuvant therapy (p &lt; 0.0001). Conclusions: Neoadjuvant therapy in advanced stage pancreatic cancer confers a survival benefit and may allow more patients to undergo surgery; NAT appears to offer similar survival as adjuvant therapy in early stage pancreatic cancer.
Single-agent docetacel (D) versus docetaxel alternating with single-agent gemcitabine (G) as treatments of patients (pts) with advanced breast cancer (ABC): Final analysis of a randomized trial
Authors: H. Joensuu, L. Sailas, T. Alanko, K. Sunela, R. Huuhtanen, M. Utriainen, R. Kokko, P. Bono, M. Hahka-Kemppinen, P. Kellokumpu-Lehtinen
Journal: Journal of Clinical Oncology (2008)

1035 Background: Alternating use of single agents has not been compared with single-agent taxane as treatment of ABC. Methods: The key eligibility criteria for this open-label, prospective, randomized, multicenter, phase II trial were female gender, age <70, WHO performance status <2, and no prior chemotherapy for ABC. Pts were allocated to receive either D (80 or 100 mg/m2, d. 1 of a 3-wk cycle; D-D-D-D… Group A) or D alternating with G (1,000 mg/m2, d. 1 and 8 of a 3-wk cycle; D-G-D-G… Group B). G was scheduled to be given after treatment failure in Group A, in Group B second-line therapy was not defined. Trastuzumab was allowed for HER2+ disease. The primary endpoint was time to treatment failure (TTTF). Pts were stratified for performance status, prior taxane exposure and center at randomization. The planned sample size was 240 pts, α 0.05, 1-β 0.80, 2- sided log-rank test. Results: 240 pts were entered between Mar 2002 and Sep 2006, of whom 237 were assigned to treatment (Group A, 115; Group B, 122). The groups were balanced with main prognostic factors (ER+, A 71%, B 74%; HER2+, A 24%, B 19%). In May 2007 166 pts (70%) had failed treatment (A, 74%; B, 66%). The median TTTF was 5.6 months in Group A and 6.2 months in Group B (hazard ratio 0.85, 95% CI 0.63–1.16; P=0.31); a median of 8 cycles were given in both groups before failure. There was no statistical difference in time to progression (HR 1.05, P=0.72), survival (HR 1.11, P=0.60), response rate (76% in both groups) or response duration between the groups. When adverse events were evaluated per cycle using generalized estimating equations for repeated measurements, both hematologic (P=0.014) and nonhematologic (P=0.007) grade 3 or 4 events were less frequent in Group B than in Group A. Conclusions: D alternating with G is an effective and generally well tolerated treatment for ABC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly sanofi-aventis sanofi-aventis Eli Lilly, sanofi-aventis
Phase I/II study of preoperative intensity-modulated radiation therapy (IMRT) and docetaxel for high-risk prostate cancer: A platform for radiosensitizer development.
Authors: M. Garzotto, A. Hung, T. M. Beer, P. E. Farris
Journal: Journal of Clinical Oncology (2010)

TPS250 Background: Treatment results from both adjuvant and salvage radiation trials show that local recurrence after prostatectomy for high-risk cancer is common. Preoperative chemoradiation has the potential to reduce local recurrences and improve survival, but has not been studied in prostate cancer. The establishment of a pre-prostatectomy model that includes radiation would facilitate and promote the discovery of novel radio-sensitizers. Methods: The primary objectives of this trial are to define the MTD of the combination of IMRT and docetaxel and to determine the pathologic response rate at the phase II dose. Secondary objectives include PSA responses, relapse-free survival, surgical margin status, HRQOL, and tissue and serum biomarker effects. Eligible patients have: 1) cT2b or resectable cT3a tumors, 2) a serum PSA ≥ 15 ng/ml, or 3) a primary Gleason grade ≥4. All patients undergo pre-treatment placement of prostatic fiducial seed markers along with cryopreservation of study–designated tumor tissue. Patients receive 45 Gy IMRT over 25 fractions to the prostate and seminal vesicles. Prostatectomy is performed within 4 to 6 weeks after completion of chemo-radiation during which time additional tumor tissues is cryopreserved for biomarker analyses. Escalating doses of weekly docetaxel are given for 5 consecutive weeks during IMRT. A minimum of 3 patients are accrued at each dose levels of 0 mg/m2, 10 mg/m2, 20 mg/m2 and 30 mg/m2. The dose escalation continues to a planned dose of 30 mg/m2 or until one or more patients per cohort experienced a DLT, defined as greater than grade 3 nonhematological (excluding hyperglycemia) or grade 4 hematological toxicity. After definition of the MTD, a minimum of 15 additional patients are accrued at the phase II dose. Minimum accrual target is 27 patients, assuming no DLTs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Routine imaging to detect recurrences in high-risk melanoma patients.
Authors: T. S. Park, K. H. Lagisetty, R. M. Sherry, J. C. Yang, M. S. Hughes, K. Morton, D. E. White, Y. Klionsky, S. A. Rosenberg, G. Q. Phan
Journal: Journal of Clinical Oncology (2011)

8576 Background: Strategies for followup surveillance in melanoma patients are controversial and in general emphasize clinical exam as the primary screening method. We aim to determine the modalities that detected disease recurrence in high-risk melanoma patients being followed in adjuvant clinical trials. Methods: A retrospective analysis was performed on a prospective database containing 4 adjuvant melanoma immunotherapy trials from 1998-2009, the results of which have been published in part. Patients with ulcerated or ≥1.5mm primary melanomas or completely resected locoregional disease or distant metastases were eligible within 6 months of surgery. They were screened with physical exam, lab tests, brain MRI, and CT scan of chest, abdomen and pelvis. Depending on the protocol, they were followed with physical exam, imaging and lab tests every 3-6 months in the first year and every 6-12 months in subsequent years. We here evaluate the method of relapse detection based on the site of relapse. Results: Of 474 patients enrolled, 459 were evaluable, of which 109 (24%) had resected stage II disease, 327 (71%) had stage III and 23 (5%) had stage IV. 221 patients (48%) developed recurrent disease. Median time to relapse from enrollment date was 8 months. Recurrences were detected by the patient, physician exam or routine imaging in 25% (56/221), 13% (28/221) and 58% (128/221), respectively. 1% (3/221) was detected by abnormal blood tests. Site of relapse was locoregional in 38% and systemic in 62%. In those with locoregional relapse, 30% were detected by routine imaging, 43% by the patient, 23% by physician exam and 5% by either patient or physician exam. In those with systemic relapse, 75% were detected by routine imaging, 15% by the patient, 7% by physician exam and 2% by abnormal lab values. Conclusions: Routine imaging identified 58% of recurrences not found by the patient or physician exam in these high-risk melanoma patients. The addition of routine imaging found additional disease in 30% of those with locoregional relapses and 75% of those with systemic relapses not suspected by the patient or physician. This study could not determine whether aggressive radiologic followup detecting early recurrence translated into improved survival for these patients.
Framing the benefits of cancer treatment: How survival is described influences preferences for care.
Authors: P. Lin, T. W. Concannon, D. Greenberg, G. P. Rossi, J. Hille, C. Fang, H. R. Auerbach, P. J. Neumann
Journal: Journal of Clinical Oncology (2011)

6099 Background: To examine how the framing of survival benefit affects individuals’ preferences for cancer therapies. Methods: Through an internet-based survey of 2,050 U.S. adults (50% with a prior episode of cancer), respondents were randomized to one of two sets of scenarios, each of which described survival benefit of a new treatment as either increased median survival time (median survival), or increased probability of survival for a given length of time (landmark survival). Each respondent answered questions about their inclination for new treatment and their willingness to pay (WTP) out-of pocket in hypothetical scenarios. In this study, WTP was used as a methodological approach for determining patient preferences for framing of clinical benefits. Each respondent was presented with two randomly selected scenarios with different baseline and improvement in survival. We used a double-bounded, dichotomous-choice bidding game to elicit their preferences for care. We estimated mean WTP values across scenarios and assessed whether message framing predicted WTP, adjusting for respondent characteristics. Results: Most respondents (65%-91%, depending on the scenario) preferred (as determined by WTP) treatments that conferred additional survival benefit. The predicted probability of willing to pay some amount was 5% to 13% higher, and the predicted mean WTP values were 34% to 45% higher when treatment benefit was framed as improvements in landmark survival probability as opposed to median survival time. Conclusions: How survival benefits are described may strongly influence the perception of value of cancer treatment options. Our approach using WTP suggest that people may be more inclined to prefer therapy when the expected benefit is described as an increase in landmark survival probability, compared to an increase in median survival time. Further research is needed to better understand framing effects and to develop decision tools that help patients evaluate the risks and benefits of different treatment options and clarify their preferences for care.
Recommendations for designing comparative effectiveness studies in oncology.
Authors: R. Montgomery, C. D. Mullins, A. P. Abernethy, A. Hussain, S. R. Tunis
Journal: Journal of Clinical Oncology (2011)

e16550 Background: Substantial uncertainty exists about the benefits and harms of many oncology drugs in real-world settings, creating challenges for patients, providers, payers, and policymakers. Comparative effectiveness research (CER) can provide evidence to support this decision-making. However, oncology CER often lacks standards, making results difficult to cross-compare and interpret. Methods: The Center for Medical Technology Policy (CMTP) developed a guidance document with the goal of setting CER standards to improve the validity, relevance, and consistency of CER for anti-neoplastic agents. The recommendations are aimed at assisting trial designers in developing post-approval clinical studies for new indications of oncology drugs and were developed using expert input from semi-structured interviews and an in-person meeting. Results: Stakeholders included advocacy groups, medical oncologists, pharmaceutical companies, the Food and Drug Administration (FDA), the Centers for Medicare & Medicaid Services (CMS), the National Cancer Institute (NCI), ASCO, foreign health technology assessment agencies, payers, drug compendia, and statisticians. Recommendations are in four categories: trial design and data analysis; patient and site recruitment; comparators; and outcomes. Examples of the recommendations include: 1) Whenever feasible, actual survival rather than a surrogate for survival should be used as the primary outcome; however, when a surrogate is necessary, then evidence for the validity of the surrogate within the targeted indication should be provided; and 2) a clinically-relevant dosing regimen for the comparator drug that allows for evidence-based comparisons should be used. Conclusions: In contrast to FDA guidance for conducting trials for regulatory approval, this guidance is directed towards post-approval trials for decision makers, which may help maximize the generation of evidence that would be of relevance to decision makers.
Icotinib and whole brain radiotherapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.
Authors: Fan Yun, Zhiyu Huang, Lei Gong, Haifeng Yu, Haiyan Yang, Maio lu Lu, Weimin Mao
Journal: Journal of Clinical Oncology (2013)

e19073 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have shown efficacy in advanced NSCLC with brain metastases (BM). Icotinib is a new EGFR-TKI. A randomized, double blind phase III trial proved that icotinib was non-inferior to gefitinib in advanced NSCLC. We have conducted a phase II study to evaluate the efficacy and safety of icotinib in combination with WBRT in Chinese NSCLC patients with BM. Methods: From January 2012 to January 2013, 20 patients aged 18-75 years with ECOG PS 0-2 and BM from NSCLC,were recruited regardless of EGFR status. The treatment comprised icotinib 125mg, TID concurrently with WBRT (30Gy/10f/2w). CSF and plasma samples were collected at the same time from 10 patients at least 5 days after icotinib treatment. The concentrations of icotinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The primary end point was progression-free survival (PFS) . Additional end points were response rate, safety and CSF concentrations of icotinib. Results: The median PFS was 7.3 months [95% confidence interval (CI) 4. 2-9.8]. Patients with EGFR mutation-positive disease had significantly longer median PFS versus EGFR wild-type disease [NR versus 4.2 months (95% CI 2.9-5.1); P = 0.000]. The CNS response rates were 25% complete response (n=5), 55% partial response (n= 11), 15% stable disease (n=3), and 5% progressive disease (n =1). The overall CNS response rate was 80% (n = 16). The most common adverse events were rash (40.0%), diarrhea (15.0%),nausea (45.0%), vomiting (20.0%), headache (35.0%)and fatigue (45.0%). And no patient experienced grade ≥ 3 toxicity. The mean plasma and CSF concentrations of icotinib were 936.47 ± 503.80 and 8.93 ± 8.01 ng/ml, respectively, and the mean ratio of CSF-plasma concentration was 1.04% ± 0.95. Conclusions: Icotinib was well tolerated and showed promising activity in combination with WBRT in patients with BM from NSCLC. The concentrations of icotinib in CSF were low. Further randomized trials are warranted. Clinical trial information: NCT01514877.
Clinical significance of serum protein and mRNA level of insulin-like growth factor-1 (IGF-1) in patients with hepatocellular carcinoma.
Authors: Senem Karabulut, Nuri Faruk Aykan, Ibrahim Yildiz, Leyla Kilic, Fatma Sen, Sezai Vatansever
Journal: Journal of Clinical Oncology (2014)

203 Background: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. The aim of this study was to assess the usefulness of serum protein and circulating mRNA of insulin-likegrowth factor-1 (IGF-1) as a diagnostic and prognostic tool in HCC. Methods: Fifty-four HCC patients were enrolled into this study. Age and sex matched 20 healthy controls were also included in the study. Serum IGF-1 levels were determined by the solid-phase sandwich ELISA method. Serum IGF-1 mRNA levels were determined by quantitative RT-PCR. Results: The median age at diagnosis was 60 years, range 16–88 years; 48 patients were men. All of patients had cirrhotic history. Fourty-six percent (n=25) of patients had Child-Pugh Score A, 30% (n=16) had Score B or C. All of the patients were preformed with local therapies but none of them treated with sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p=0.04). while for IGF-1 protein no significant difference was observed (p=0.18). History of HBV infection and untreated patients for HCC had higher serum IGF-1 mRNA levels (p=0.03, and p=0.03, respectively). Poor performance status (p&lt;0.001), viral etiology of cirrhosis (p=0.03), large tumor size (p=0.01), lower serum hemogloblin levels (p=0.03), and not be treated for HCC (p=0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p=0.53, and p=0.42, respectively). Conclusions: Serum circulating IGF-1 mRNA had diagnostic value, both serum protein and mRNA levels of IGF-1 had no prognostic value in patients with HCC.