tbuckley/cabot-search huggingface dataset:
Application of abiraterone acetate (AA) in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients who did not fulfil the patient inclusion criteria in the COU-AA-302 study.
Authors: Darren M. C. Poon, Chan Kuen, S.H. Lee, T.W. Chan, Chun-Kin Sze, Ka Chai Lee, Daisy Lam, Chan Fong Ting
Journal: Journal of Clinical Oncology (2016)

317 Background: Visceral metastases or poor performance status (ECOG 2 or above) were the major exclusion criteria in the COU-AA-302 study, and hence the efficacy of abiraterone acetate (AA) in chemo-naïve mCRPC patients with these characteristics remain undetermined. Our study compares the clinical efficacy of AA in chemo-naïve mCRPC patients with or without the aforementioned characteristics. Methods: The clinical records of chemo-naïve mCRPC patients from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. Patients with visceral disease who were medically unfit for, or who declined, chemotherapy, were allowed for AA in the study period. The median overall survival (OS), progression-free survival (PFS), patient and disease characteristics were compared between groups which satisfied, and did not satisfy, the inclusion criteria of COU-AA-302 study. Results: Fifty-eight consecutive chemo-naïve mCRPC patients had received AA in the review period, of which 29 fulfilled the inclusion criteria for the COU-AA-302 study (Group Eligible). All the remaining patients (Group Ineligible) had ECOG 2 or above, including 3 who had non-nodal visceral metastases. Group Ineligible had higher baseline PSA, haemoglobin and alkaline phosphatase level than Group Eligible, but otherwise there was no significant difference in the baseline characteristics between the groups for age, Gleason score, and co-morbidities. Group Ineligible had significantly shorter OS than Group Eligible (7.7 vs 25.0 months, p = 0.0095) and also a shorter PFS that did not reach statistical significance (5.3 vs 9.8 months, p = 0.2936). The duration of use of AA, and frequency of employment of post-AA treatment were comparable between the groups. Conclusions: Our study demonstrated a poor efficacy of AA in chemo-naïve patients who did not fulfil the inclusion criteria for COU-AA-302 study, by virtue of poor performance status or presence of visceral metastases. The impact of AA in this group of patients warrants further examination in clinical trials before its routine clinical use in this subgroup.
Prevalence of bowel dysfunction in colorectal cancer survivors.
Authors: Karanvir Sall, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

638 Background: There is limited research on the long-term bowel health outcomes of colorectal cancer (CRC) survivors even though colorectal surgery, radiation, and chemotherapy can pose significant morbidity for patients. Our aims were to characterize the prevalence of specific bowel complications in CRC survivors and to compare their outcomes with those of non-CRC survivors and non-cancer controls. Methods: Using population-based data from the 2009 U.S. National Health and Nutrition Examination Survey, we identified 3 different groups of adult patients: CRC survivors, non-CRC survivors, and non-cancer controls. Weighted multivariate logistic regression models were constructed to determine the relationship between survivor status and bowel health outcomes, while controlling for patient and disease characteristics. Main outcomes included leakage of gas, mucus, liquid stool, and solid stool. Stratified analyses were subsequently conducted to assess for effect modification based on gender (men vs. women), age (≤ 60 vs. &gt;60), and ethnicity (white vs. non-white). Results: In total, 10,894 subjects were included: 75 CRC survivors, 910 non-CRC survivors, and 9909 non-cancer controls. Baseline characteristics were similar among all 3 patient groups. In univariate analyses, more CRC survivors reported bowel dysfunction, including leakage of: gas (15 vs. 12 vs. 10%, p=0.01), liquid stool (8 vs. 7 vs. 4%, p&lt;0.001), and solid stool (2 vs. 0 vs. 0%, p&lt;0.001) than non-CRC survivors and non-cancer controls. In multivariate analyses, CRC survivors continued to have significantly higher odds of solid stool incontinence (OR 2.09, 95% CI 1.24-3.53, p&lt;0.05) when compared to the other groups. The association between surviving CRC and presence of bowel dysfunction was not modified by ethnicity, but specific outcomes, such as solid stool leakage, were more prominent in women (p=0.003) and those who were aged &gt;60 years (p=0.002). Conclusions: Bowel problems are significantly more frequent among CRC survivors than non-CRC survivors and non-cancer patients, especially for women and the elderly. Studies to develop interventions that minimize these bowel complications are needed in order to improve the long-term health and quality of life for CRC survivors.
Chemoradiation or standard radiation followed by adjuvant temozolomide (TMZ) and 13-cis-retinoic acid (CRA) for high grade glioma in adults - a regional cancer centre study
Authors: D. D. Eisenstat, C. Mihalcioiu, A. Demers, S. Huszar, G. Schroeder, K. Vijay, K. D. Jones
Journal: Journal of Clinical Oncology (2005)

1557 Background: A recent phase II study reported activity of TMZ and cRA for recurrent/progressive malignant gliomas with 43% 6 month progression-free survival (PFS); 32% for glioblastoma multiforme (GBM) patients (Jaeckle KA et al, 2003). Methods: From 2000–2003, we retrospectively analyzed adults with malignant glioma who received, following surgery and radiation therapy (RT) ± low dose TMZ (75 mg/m2/d x 42d), TMZ (150–200mg/m2/d, d1–5) and cRA (100 mg/m2/d, d1–21) every 28d for up to 24 cycles or until progression on neuroimaging. Time to progression (TTP) was the primary end-point and overall survival (OS) was the secondary end-point. Results: Of 33 patients (29 GBM, 2 anaplastic astrocytoma, AA, 2 malignant glioma, MG), 18 remain alive. The 33 patients received 308 cycles of TMZ/cRA (mean 9.3 cycles); 9 patients received greater than 10 cycles, but only 2 completed more than 15 cycles. Responses to TMZ/cRA were documented in 15/33 (45%) patients (10 partial responses/5 stable disease). For all patients, median TTP was 38.6 weeks, 50.5 weeks for chemoradiation patients and 27.1 weeks for those who received RT alone prior to TMZ/cRA, NS). Median OS was 103.2 for all 33 patients, 55.3 weeks for RT alone and median time not yet reached for RT/low dose TMZ, p=0.01). 6, 12 and 24 month TTP was 63%/39%/39% (53%/27%/27% for RT alone and 72%/49%/49% for RT/low dose TMZ). OS at 6, 12 and 24 months was 94%, 69% and 43%, respectively, for all 33 patients (86%/50%/25% for RT alone and 100%/86%/75% for RT/low dose TMZ). Conclusions: Our data for malignant glioma patients who received concurrent low dose temozolomide with RT prior to adjuvant temozolomide/cRA compares favourably with the results of the recently completed EORTC/NCIC trial (Stupp R et al, ASCO 2004). The chemoradiation strategy using concurrent low dose temozolomide provides a significant survival advantage when compared to radiation alone. Our study demonstrates that TMZ/cRA prolongs TTP for patients with malignant gliomas when compared to historical controls and supports use of this regimen in a Phase III clinical trial. No significant financial relationships to disclose.
Loss of PTEN Is Associated with Resistance to Anti-PD-1 Checkpoint Blockade Therapy in Metastatic Uterine Leiomyosarcoma
Authors: Suzanne George, Diana Miao, George D. Demetri, Dennis Adeegbe, Scott J. Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P. Raut, Scott L. Carter, Peter Hammerman, Gordon J. Freeman, Catherine J. Wu, Patrick A. Ott, Kwok-Kin Wong, Eliezer M. Van Allen
Journal: Immunity (2017)
Glioblastoma in the elderly: The Cleveland Clinic experience (1992-2010).
Authors: H. S. Bawa, N. Hashemi-Sadraei, J. H. Suh, G. Stevens, G. Rahmathulla, S. T. Chao, T. M. Tekautz, P. Elson, D. M. Peereboom, L. Angelov, R. Weil, M. A. Vogelbaum, G. Barnett, M. S. Ahluwalia
Journal: Journal of Clinical Oncology (2011)

2066 Background: Glioblastoma (GBM) is the most common malignant primary brain tumor. About 50% of cases occur in patients aged ≥65 years, however there is limited data on specific prognostic factors in these patients. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with histologically confirmed GBM who were ≥65 years at the time of diagnosis. Multivariable analysis was conducted to identify independent predictors of survival using a Cox proportional hazards model and a stepwise selection algorithm with p=.05 as criteria for entry and retention. Results: 420 GBM patients with a median age of 73 years (range 65-91, 56% male) were included. 40% of patients had biopsy only, 30% had gross total resection (GTR), 7% had near total resection (NTR), and 23% had subtotal resection (STR). 73% of patients underwent radiation, 37% had concurrent chemotherapy (CT), and 28% had adjuvant CT. Overall 93% of patients had died at the time of analysis. Median overall survival was 5.9 months (95% C.I.: 5.1-6.7); 1-year survival was 25% ± 2%.On multivariable analysis, five factors were identified as independent predictors of overall survival: age at diagnosis (p<.0001), extent of resection (p<.0001), multifocal disease (p=.003), seizure at presentation (p=.01), and Karnofsky Performance Status (p<.0001). Conclusions: As seen in previous studies in younger GBM patients, advancing age, performance status and extent of tumor resection were found to be independent prognostic factors in the current report. In addition seizure at presentation was associated with better outcome and multifocal disease had worse prognosis. Table 1: Patient Characteristics and Overall Survival Factor N (%) Overall Survival (months) Gender Female 183 (44%) 5.4 Male 237 (56%) 6.6 Race Caucasian 378 (93%) 6.2 Non-Caucasian 30 (7%) 3.4 Age at Diagnosis <70 132 (31%) 8.8 70-79 217 (52%) 5.7 >80 71 (17%) 3.1 KPS at Presentation 90-100 72 (22%) 9.7 70-80 159 (47%) 7.9 <70 104 (31%) 3.1 Seizure at Presentation No 315 (77%) 5.0 Yes 96 (23%) 10.1 Degree of Resection GTR, NTR, STR 245 (60%) 9.3 Biopsy Only 162 (40%) 3.1 Lesion Unifocal 353 (86%) 6.6 Multifocal 58 (14%) 3.3 Motor Symptoms No 194 (46%) 6.5 Yes 226 (54%) 5.4
Clinical characteristics of affected <i>BRCA1</i> and <i>BRCA2</i> mutation carriers in an underserved population.
Authors: M. El-Masry, C. Ricker, D. V. Spicer, D. Tripathy
Journal: Journal of Clinical Oncology (2011)

1532 Background: Genetic counseling and testing for breast cancer predisposition has not been integrated extensively into the underserved, clinical setting. Consequently, little data are available regarding demographic and clinical characteristics in this setting. Methods: Since 2007, 369 patients with cancer or a cancer family history have been evaluated for hereditary breast cancer risk at Los Angeles County and University of Southern California Medical Center (LAC+USC) using established guidelines. Of these, 261 underwent genetic counseling and BRCAtesting. Results: We report on 46 patients, from 45 apparently unrelated families, found to be carriers of known deleterious mutations. Of these families, thirty-eight (84.4%) reported Hispanic ancestry (n=31, Mexico; n=6, Central America; n=1, South America); two (4.4%) African-American ancestry; 4 (8.88%) Asian ancestry (n=2, Korea and n=2, the Philippines), and one Middle-Eastern ancestry. Of these families, 25 (55.6%) were found to have a BRCA1 mutation and 20 (44.4%) a BRCA2 mutation. Clinical characteristics are summarized in the table below. Amongst the BRCA-associated breast cancers, the majority had infiltrating ductal carcinoma the (BRCA1 = 89.5%, BRCA2=77.8%). One BRCA1 carrier had medullary breast cancer and another had squamous cell carcinoma of the breast. Two BRCA2 carriers presented with DCIS and one with lobular carcinoma. All the BRCA-associated ovarian cancers were epithelial tumors (n=9), and the majority were papillary serous (n=5), 2 were endometrioid, 1 transitional cell, and 1 was mixed papillary/clear cell carcinoma. Conclusions: Clinical, histological and biomarker characteristics of the BRCA mutation carriers in our underserved, ethnic minority population are consistent with previously reported, mostly insured cohorts. N BC Age at BC diagnosis Median (range) Triple negative ER or PR+ HER2 – HER2+ OC Age at OC diagnosis Median (range) BC and OC BRCA1 26 19 42 (28-55) 16 2 2 5 46 (43-55) 2 BRCA2 20 18 49 (32-59) 2 14 2 1 53 (48-57) 1
Independent validation of a prognostic classifier (Predictor-C) in a set of 292 patients with colorectal cancer of UICC stage II.
Authors: H. Adams, T. Mayr, B. Hinzmann, A. Rosenthal
Journal: Journal of Clinical Oncology (2011)

3558 Background: Adjuvant chemotherapy in stage II colorectal cancer (CRC) is generally not recommended. Patients (pts) with T4 tumors, performations, < than 12 lymph nodes assessed, or positive vessel / lymphatic invasion may receive adjuvant chemotherapy. Following these guidelines 15-20% of the true high-risk pts remain undetected, undertreated and will suffer from progression of disease. We previously reported on the validation of a prognostic 32-gene signature (Predictor-C) in a cohort of 164 pts with CRC of stage II and III (J Clin Oncol 28:15s, 2010 (suppl; abstr 3612). Methods: For this study 292 pts with stage II disease underwent curative resection (R0) between 1990-2000 in medical centers of Denmark, Finland, Germany, Austria, Netherlands and Canada. From all pts frozen CRC tissue, clinical data and a follow-up data of five years were available. Gene expression data were obtained using U133 Plus 2.0 arrays from Affymetrix. Results: In this cohort 49/292 pts suffered from a progression of disease, while 243/292 pts had no progression. Applying Predictor-C to this set of 292 UICC stage II pts we observed the following performance chararacteristics: sensitivity of 0.55 (95% CI: 0.402-0.693), specificity of 0.76 (95% CI: 0.706-0.816), positive predictive value (PPV) of 0.32 (95% CI: 0.224 -0.432), negative predictive value (NPV) of 0.89 (95% CI: 0.844-0.932). The point estimate for progression-free survival at 5 years after surgery for pts classified as low-risk is 0.91 (95% CI: 0.772-0.962), and for pts classified as high-risk this estimate is 0.73 (95% CI: 0.630-0.825). The hazard ratio is 3.289 (95% CI: 1.839-5.881), log-rank test and Wilcoxon test of survival times result in p-values < 0.001. The baseline characteristics of these 292 pts were representative for the whole population of CRC patients diagnosed with UICC stage II, in almost all aspects. Conclusions: Predictor-C was successfully evaluated in an independent set of 292 pts with CRC of UICC stage II. Our genomic risk classifier improves the management of pts with stage II after surgery. Low-risk pts identified by Predictor-C may not need adjuvant chemotherapy while high-risk pts may benefit from additional chemotherapy.
Effects of “Primary Prophylaxis” and “On-Demand” Therapy on the Clinical Expression of Severe Hemophilia A in Children - Results of a Multicenter Study.
Authors: Rosemarie Schobess, Karin Kurnik, Wolfhart Kreuz, Frauke Friedrichs, Anne Krumpel, Christoph Bidlingmaier, Carmen Escuriola Ettingshausen, Ulrike Nowak-Gottl
Journal: Blood (2007)
Antitumor activity of SS1P with pemetrexed and cisplatin for front-line treatment of pleural mesothelioma and utility of serum mesothelin as a marker of tumor response.
Authors: R. Hassan, E. Sharon, B. Schuler, Y. Mallory, J. Zhang, A. Ling, I. Pastan
Journal: Journal of Clinical Oncology (2011)

7026 Background: SS1P is an immunotoxin targeting mesothelin, a tumor antigen highly expressed in malignant mesothelioma (MM). Preclinical studies showed marked synergy between SS1P and chemotherapy, leading to this frontline trial in pleural MM. Methods: Patients with no prior treatment, advanced disease, ECOG 0-2, and good organ function received pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 every 3 weeks for 6 cycles. SS1P dose escalation was: 25 µg/kg; 35 µg/kg; 45 µg/kg and 55 µg/kg on days 1, 3 and 5 of cycles 1 and 2. CT scans were performed every 2 cycles. Results: Nineteen patients (16 males, 3 females) have been treated, with median age of 68 y (51 to 78 y). One patient at 55 µg/kg had Grade 3 fatigue, considered dose-limiting. The maximum tolerated dose (MTD) of SS1P with chemotherapy was 45 µg/kg. Adverse events possibly or probably related to SS1P included Grade 3 hypoalbuminemia (n=6), pain (n=3), and hypotension (n=2); and Grade 2 hypoalbuminemia (n=11), fatigue (n=9), edema (n=6), hypotension (n=5), and pain (n=5). One patient died from neutropenic sepsis during cycle 1. Of the 14 evaluable patients treated at all dose levels, 7 had partial response (PR), 3 stable disease (SD) and 4 progressive disease (PD). Of 7 patients treated at MTD, 5 had PR, 1 SD and 1 PD. Of the 10 patients whose serum mesothelin levels were evaluated before and at completion of treatment all 5 patients with PR had significant decrease in serum mesothelin (63-83%). Two of 3 patients with PD had increased mesothelin levels (16%-34%), while 1 pt had a slight decrease (7%). Two patients with SD had discordant responses (17% increase and 60% decrease). Conclusions: SS1P with pemetrexed and cisplatin is well tolerated and results in significant anti-tumor activity with 5 PRs, and 1 SD among the 7 patients treated at MTD. Serum mesothelin responses correlate with the radiological response with all patients who obtained a PR having significant decrease in serum mesothelin levels.
Clinical assay development program.
Authors: Barbara A. Conley, Margaret M. Cavenagh, JoyAnn Phillips Rohan, Tracy G. Lively, Chih-Jian Lih, P. Mickey Williams
Journal: Journal of Clinical Oncology (2012)

98 Background: Discoverers of predictive or prognostic molecular features often do not have the resources to analytically validate findings into a “locked down” assay. Methods: The Clinical Assay Development Program (CADP) was created to provide resources to transition promising markers/signatures into validated assays for use in clinical trials. The CADP is composed of the Clinical Assay Development Network of 8 contracted CLIA-accredited labs and research lab soon to be CLIA accredited (at Frederick National Laboratory for Clinical Research), and Tissue Resources. Applicants from industry, academia, and government are eligible to apply. Applicants must specify one intended clinical use, a prototype assay that performs in human tissues, and relevant prevalence information. Applicants must also describe the clinical need, the current state of the assay and future plans for assay development (such as use in clinical trial) and request the services required for analytical validation (e.g. platform migration, etc.). The applications are evaluated by outside experts. Recommended applications are reviewed internally to ensure availability of appropriate resources and consistency of the application with NCI strategic directions. The successful application is then overseen by a project management team: project manager, subject matter experts from NCI, expertise from contracted resources, and the assay submitter. Intellectual Property remains with the submitter. After validation, the specifics of assay performance and standard operating procedures are returned to the assay submitter. Results: Of 16 applications in year 1, 2 projects are near completion and 2 are beginning. Common problems of the applications were lack of definition of single intended use, specimen availability, and marker still in discovery. Several applicants have used the advice of the CADP team to improve development strategy. Conclusions: Continued education on assay development strategy, particularly intended use and clinical context, is necessary to encourage development of potential molecular assays from the research lab into clinical use. Creativity is needed in finding appropriate specimens. Initial results of CADP are promising; interest from potential applicants is increasing. http://cadp.cancer.gov .
The Role of HOXA4 in Chronic Lymphocytic Leukaemia Progression and Response to Therapy
Authors: Timothy M Barrow, Laura Woodhouse, Gesa Junge, Susan J Tudhope, Charlotte Behardien, Jonathan P Wallis, Helen J Marr, Scott R Marshall, Nick Bown, Elaine Willmore, Gordon Strathdee
Journal: Blood (2016)
A phase II therapeutic, open label, multi-center clinical trial of NPC-1C, a chimeric monoclonal antibody(mAb), in adults with chemotherapy refractory metastatic colorectal cancer (mCRC), initial results.
Authors: Richard D. Kim, Nilofer Saba Azad, Michael Morse, Benjamin R. Tan, Elizabeth Poplin, Melony A. Beatson, Sharon Mavroukakis, Philip M. Arlen, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2016)

500 Background: NEO-102 is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer. Its mechanism of action is through antibody dependent cellular cytotoxicity (ADCC). An earlier, phase I study, established the maximum tolerated dose at 3.0 mg/kg IV every 2 weeks with encouraging early signs of clinical activity. We report initial results of the subsequent phase II study. Methods: This is a single arm, open label multi-center clinical trial of NEO-102 in adults with mCRC pts who failed at least two lines of standard chemotherapy (C). An immunohistochemistry (IHC) based companion diagnostic assay was used to select eligible pts whose tumors express the target in &gt; 20% of tumor cells. NEO-102 at 3.0 mg/kg IV was administered q 2 weeks until disease progression. The primary endpoint was OS. A minimum of 43 pts were needed assuming that treatment with NEO-102 will improve OS by 40% (7.0 months) using a one-sided significance level of 10% and 80% power for this study compared to historical control of 5 months. Additional objectives were to evaluate response rate as measured by RECIST criteria and analyze patient PBMCs for ADCC and immune cytokine profiling. Results: A total of 47 pts enrolled were evaluable. 26 pts were male and 35 pts were white. Twenty-four out of 47 pts (51%) remain alive as of September 2015 with an ongoing median OS of 7.0 months (Range 2-22 months). Of these heavily pre-treated pts, 42 were evaluable for response, 13 (31%) demonstrated stable disease by RECIST. Seven pts had more than 4 doses of treatment, maximum 13 doses. Grade 3 adverse events were anemia 1/47 (2%), hyperbilirubinemia 1/47 (2%), diarrhea 1/47 (2%), fatigue 1/47 (2%), headache 1/47 (2%), nausea 1/47 (2%) and vomiting 1/47 (2%). No grade 4 toxicities were reported. Conclusions: In the monotherapy phase 2 study of NEO 102 in patients with refractory mCRC preliminary results demonstrate excellent tolerability and encouraging OS. Updated OS and Progression Free Survival data will be presented at the ASCO 2016 GI Cancers symposium. Additional combination trials with NEO-102 and C are underway. Clinical trial information: NCT01040000.