tbuckley/cabot-search huggingface dataset:
Accuracy of computerized tomography (CT) imaging in predicting pathologic stage for patients undergoing surgery for transitional cell carcinoma (TCC) of the bladder.
Authors: A. Kumar, G. R. Pond, S. D. Mukherjee, M. N. Levine
Journal: Journal of Clinical Oncology (2010)

e15111 Background: Accurate pretreatment staging in bladder cancer patients is important to help determine which patients should be offered systemic therapy prior to surgery. At present, most patients are staged with a combination of CT imaging and cystoscopy to determine the tumor, nodal, and metastatic (TNM) stage. Despite significant advances in CT technology over the past 10-15 years, there has been very little published recently on the accuracy of CT in bladder cancer staging. We performed a study to determine the accuracy of preoperative CT imaging in bladder cancer patients with TCC histology that had undergone surgery. Methods: A retrospective study of all patients with bladder TCC undergoing cystectomy at the Henderson Hospital in Hamilton, Ontario between 2002 and 2009 was performed. Patients receiving neoadjuvant chemotherapy were excluded from this analysis. The primary outcome was the ability of preoperative CT to predict the tumor, nodal, and metastatic (TNM) stage compared to pathology. Results: 50 patients (mean age=69) met the inclusion criteria for the study. Pathologic T stage of patients were pT1 - 10%, pT2 - 20%, pT3 - 42%, and pT4 - 10%, and for N stage pN0 - 70%, pN1 - 10%, pN2 - 18%, and pN3 - 2%. CT correctly identified T stage in 23 of 50 patients (46%, weighted kappa statistic=0.38, 95% CI 0.19-0.57). Of the 27 patients with incorrectly identified T stage, CT indicated less invasive disease in 17 patients and more invasive disease in 10 patients. The sensitivity of CT in detecting nodal disease (N1,N2,N3) was 6/15 (40%). Only 1 additional patient with metastatic disease was identified with preoperative CT. Conclusions: Our study suggests that CT imaging is not very accurate for determining T stage in bladder cancer patients, and does not identify nodal disease in a substantial proportion of patients. Prospective studies to evaluate the predictive ability of CT imaging using modern CT techniques in patients with bladder carcinoma are warranted. No significant financial relationships to disclose.
Association of magnitude of cancer of the prostate risk assessment score change following biopsy gleason upgrade during prostate cancer active surveillance with adverse pathology at prostatectomy.
Authors: Michael S. Leapman, Niloufar Ameli, Carissa Chu, Christopher J. Welty, Ahmed Hussein, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2015)

76 Background: The occurrence of pathologic upgrading in men with prostate cancer (PCa) managed with active surveillance (AS) is a cause for concern and may prompt treatment; however the degree to which upgrading impacts further risk status is unclear. We evaluated the association between the Cancer of the Prostate Risk Assessment (CAPRA) score and adverse pathological outcomes following biopsy Gleason upgrading in men with PCa on AS. Methods: We retrospectively evaluated men with low and intermediate risk PCa managed with AS at our institution between 1993 and 2013 who received a minimum of two biopsies. We assessed change in CAPRA score between initial diagnosis and Gleason upgrade at repeat biopsy. Among patients proceeding to radical prostatectomy, multivariate models incorporating CAPRA change and reclassified CAPRA score were constructed to evaluate factors associated with adverse pathology and time to treatment. Results: We identified 312 men with PCa on AS who experienced pathologic upgrade on surveillance biopsy at a median of 24 months (IQR 12-47) and at a median age of 65.7 years (IQR 61-71). The median CAPRA score at diagnosis was 1 (IQR 1-2), and median change at upgrade was +2 (IQR 1-3). 196 patients (63.0%) were reclassified to higher CAPRA scores at upgrade, while 108 (34.7%) had CAPRA classification that remained unchanged. Seven (2.3%) patients had a decrease in CAPRA risk category after biopsy upgrade. In a multivariate logistic regression model, reclassification to high CAPRA risk category at upgrade was significantly associated with adverse pathology at RP (OR=21.34, 95% CI 2.58-176.57, p=0.0097). Conclusions: Recalculated CAPRA score following biopsy Gleason upgrade during AS is a strongly associated with adverse surgical pathology among treated patients. This finding supports the role of refined risk reassessment in men with PCa on AS, particularly in those experiencing upgrading on subsequent biopsy.
FOLFOX and nab-paclitaxel (nab-P) for advanced pancreatic cancer: A phase I study.
Authors: Howard Safran, Kevin Charpentier, Kimberly Perez, Kalyan Mantripragada, Trevor Clark Austin, Omar Nadeem, Alise Lombardo, Lindsay Houlihan, Lucia Fontes-Borts, Irene Kolberg, Kristen Mitchell, Kayla Rosati
Journal: Journal of Clinical Oncology (2014)

258 Background: FOLFIRINOX improves survival in advanced pancreatic cancer, however the contribution of irinotecan is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in pancreatic cancer, however nab-P demonstrates a survival benefit. This phase I study was designed to evaluate the maximum tolerated dose (MTD) of the addition of nab-P to fluorouracil, leucovorin, oxaliplatin (FOLFOX-A). Methods: Patients with metastatic or locally advanced pancreatic adenocarcinoma without prior treatment received oxaliplatin, 85 mg/m 2 , leucovorin 400 mg/m 2 and 5-FU 2400 mg/m 2 with 3 dose levels of nab-P (125, 150 and 175 mg/m 2 ) every 2 weeks. Pegfilgrastim was required during the first 2 cycles. Dose limiting toxicities (DLTs) were defined in the first 2 cycles of treatment. Results: Fifteen patients were entered: Dose level 1 (n=6), dose level 2 (N=6), dose level 3 (N=3). The median age was 64 (35-81). Ten patients had metastatic and 5 had locally advanced disease. DLTs of nausea and fatigue occurred in 2 of 3 patients at dose level 3. Two patients developed grade 3 neuropathy after &gt;= 10 cycles of treatment. One patient had grade 3/4 neutropenia. Eight of fifteen patients (53%) had a partial response. Conclusions: The MTD of nab-P is 150mg/m 2 every 2 weeks with FOLFOX. Cumulative peripheral neuropathy, similar to other FOLFOX regimens, is the most significant toxicity generally occurring after &gt;= 10 cycles of treatment. FOLFOX-A has substantial activity and may represent a promising regimen in pancreatic cancer. Patients are currently being accrued to an expansion phase utilizing dose level 2. Supported by the Davis and Browning families and LIFEcycle. Clinical trial information: NCT01744353.
Exploring the effects of abiraterone/enzalutamide failure prior to the initiation of radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.
Authors: Patrick Cotogno, Elisa M. Ledet, Allie E. Steinberger, Rajasree Pia Chowdry, Michael Stolten, Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

214 Background: FDA approval of three life-prolonging agents for metastatic castrate resistant prostate cancer (mCRPC) has occurred since April 2011. Two agents, abiraterone (abi) and enzalutamide (enza), disrupt androgen signaling. The third, radium-223 dichloride (Ra-223), targets bone metastases via alpha radiation. We sought to explore associations between prior abi/enza progression, number of Ra-223 cycles, prognostic factors, and overall survival (OS). Methods: Forty-two mCRPC patients (pts) treated with Ra-223 were identified. The sample was stratified based on progression (or not) on abi or enza prior to starting Ra-223. Number of Ra-223 doses administered, prognostic variables before Ra-223 treatment, and Kaplan-Meier estimates of overall survival (OS) were compared. Results: A strong association (p = 0.016) was demonstrated between prior abi/enza failure and number of Ra-223 doses administered. Patients without prior abi/enza failure were more likely to receive ≥ 4 doses of Ra-223 (94.12% vs 60.0%; odds ratio [OR] = 10.667; 95% CI, 1.214 – 93.699; p = 0.033). In comparison, those not receiving at least 4 doses of Ra-223 had a negative predictor in OS (p = .001) with a median survival of 89 days (n = 10; 95% CI, 44.064 – 133.936) compared to 303 days (n=15; 95% CI, 170.452 – 435.548). Patients initiating Ra-223 treatment after abi/enza progression had a higher median PSA (207.5 vs 49.2 ng/mL, p = 0.001), LDH (315 vs 253.5 U/L, p = 0.007) and alkaline phosphatase (ALP) (191 vs 106 U/L, p = 0.004). Conclusions: Our retrospective single institution analysis indicates that mCPRC patients who previously failed abi/enza are significantly less likely to complete 4 or more Ra-223 doses. These patients had significantly worse prostate cancer by a variety of standard prognostic variables. More information is needed from larger data sets to better understand this patient population and to best determine the optimal timing of Ra-223 administration.
Active surveillance outcomes among a cohort of county hospital patients.
Authors: Erika L. Wood, Steven Canfield
Journal: Journal of Clinical Oncology (2015)

136 Background: The standard of care for managing localized prostate cancer includes offering patients active surveillance. With the 10-year prostate cancer specific survival between 96-100% for both low and low-intermediate risk patients, active surveillance has proven to be a safe and effective option. Most studies have examined cohorts of patients within a tertiary referral center but data is sparse on county hospital patients, where health insurance coverage among other concerns pose barriers for patients to receive consistent medical care. We were interested in how active surveillance was performing amongst a cohort of county hospital based patients. Methods: A retrospective chart review was conducted on fifty patients placed on active surveillance for low and low-intermediate risk prostate cancer (by D’Amico criteria) between July 1, 2007 and August 1, 2013. Overall and cause-specific survival were the main outcome measures. Data was also collected on loss to follow-up rates. Results: In the cohort, the mean age at diagnosis was 62.2, mean body mass index was 28.0, most were African American or Hispanic (50% and 46%, respectively) and the majority had low-risk disease (84%). The median length of follow-up after diagnosis was 22 months. Nearly half of patients stopped active surveillance (44%), the most common reason being reclassification of their disease after second biopsy. All patients who were reclassified received definitive treatment with the exception of one patient who was lost to follow-up. Cause-specific and overall mortality were both 100% in this cohort. Nearly a quarter of patients (22%) were lost to follow-up (either had less than 12 months of surveillance following diagnosis or had not presented to clinic within the last 12 months). Conclusions: High rates of loss to follow-up present a significant challenge to managing localized prostate cancer with active surveillance in a county hospital population. In this small cohort, active surveillance appears to be a safe and effective management option for localized prostate cancer, yet undetected disease progression remains a significant concern.
Molecular prediction of biologic aggressiveness in pancreatic cysts.
Authors: W. Spence, D. M. Smith, E. M. Ellsworth, S. D. Finkelstein
Journal: Journal of Clinical Oncology (2010)

e21033 Background: Pancreatic adenocarcinomas (PA) which arise in pancreatic cysts (PC), in contrast to solid mass lesions, offer the potential to diagnose the cancer at an early, treatable stage. However, benign neoplasms and non-neoplastic cysts (pseudocysts) make the diagnosis of cystic PA difficult. We studied the integration of molecular analyses with the results of imaging, fluid chemistry, and cytology for early detection of PA and differentiation from non-cancerous lesions. Methods: A continuous series of 299 patients underwent endoscopic ultrasound fine needle aspiration of PC. Patients with clear evidence of malignancy who met guidelines for surgery were excluded; all remaining pts with clinically indeterminate PC underwent molecular analyses of DNA from cyst fluid to detect 17 oncogene and tumor suppressor gene mutations. Molecular features of aggressive biology (high grade dysplasia and PA) include Group 1 (highly elevated concentrations of intact DNA in the cyst fluid), Group 2 (three or more clonally expanded mutations), and Group 3 (elevated DNA and mutational change). Molecular features were correlated with patient survival. Results: 25 patients had PC fluid with aggressive molecular features. Survival with up to 4 years follow up showed: Group 1, 89% alive (11 total, 9 alive); Group 2, 50% alive (6 total, 3 alive); Group 3, none alive (8 total, 0 alive). Correlating DNA concentration with cytology suggested DNA elevation could result from increased inflammatory cells, addition of blood during aspiration, and active proliferation of the mucinous lining cells. The number and clonality of mutations help to discriminate among the different causes for DNA elevation. PC with high concentrations of good quality DNA showing clonally expanded mutations were invariably malignant, irrespective of all other findings. Conclusions: Improving detection of early cancers must be accompanied by improvements in distinguishing between neoplasia with aggressive biological potential and benign disease. Integrating molecular analyses with existing diagnostic parameters can address this need. High DNA concentration alone cannot affirm malignancy but, when combined with mutational analyses, can identify cancer and precancerous lesions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration RedPath Integrated Pathology RedPath Integrated Pathology
Functional impairment (FI) after hematopoietic cell transplantation (HCT) and impact on quality of life (QOL).
Authors: A. Bosworth, F. L. Wong, H. Kim, R. Ferrer Danao, J. Gyorffy, S. Patel, S. J. Forman, S. Bhatia
Journal: Journal of Clinical Oncology (2011)

9100 Background: HCT survivors may be at risk for FI, or experience difficulty performing activities of daily living, due to the high prevalence of morbidity (including fatigue) during the first year. Furthermore, FI may have a significant impact on survivors’ QOL. Little information exists regarding this aspect of HCT patients’ lives, making it difficult to anticipate their needs. Methods: Adult patients undergoing HCT for hematologic malignancies and healthy controls completed questionnaires examining FI (Pfeffer Functional Activities Questionnaire [PFAQ]), QOL (RAND-36), and fatigue (Fatigue Symptom Inventory), and underwent cognitive assessments (memory, processing speed, working memory, executive function, IQ estimate) at pre-HCT, 6 mo, and 1 yr post-HCT (with corresponding time points for healthy controls). Longitudinal analyses were conducted to examine: i) magnitude of FI compared with healthy controls; ii) time trends and risk factors for FI among HCT survivors; and iii) impact of FI on QOL. Results: Participants included 221 patients (61% males, 62% allogeneic HCT, 68% Caucasians, median age 52 yr) and 38 age-matched healthy controls. Adjusted for income, marital status, and IQ, the severity of FI was worse in HCT patients than healthy controls (p=0.001) at all time points. Patients classified as functionally impaired (PFAQ score >5) tended to have lower IQ (p=0.009), higher fatigue (p<0.0001), and poorer memory (p=0.0003). At 1 yr post-HCT, 47% of patients scoring in the lowest quartile in at least 2 of 3 areas (IQ, memory, fatigue) reported FI. Compared with pre-HCT, patients were more likely to experience FI at 6 mo (OR=2.4, p=0.01) but not at 1 yr (OR=1.2 p=0.6) post-HCT. FI was associated with poorer QOL in the domains of energy/fatigue (p<0.0001), physical function (p=0.001), social function (p=0.01), role limitations due to emotional problems (p=0.01), and general health (p=0.03). Conclusions: HCT patients demonstrate significantly greater FI compared with healthy controls. FI peaks at 6 mo after HCT, but recovers by 1 yr. Vulnerable subgroups include patients with lower IQ, greater fatigue, and worse memory, necessitating a multidisciplinary approach for management.
Associations between biomarkers and outcomes of first-line chemotherapy in advanced non-small cell lung cancer (NSCLC).
Authors: B. H. Grønberg, M. Lund-Iversen, E. H. Strøm, O. T. Brustugun, H. Scott
Journal: Journal of Clinical Oncology (2011)

7535 Background: Pemetrexed has demonstrated efficacy in the treatment of NSCLC, primarily in non-squamous cell carcinomas. One explanation may be that squamous cell carcinomas have a higher level of thymidylate synthase (TS); TS-inhibition is a key mechanism of action for pemetrexed. We conducted a phase III trial comparing pemetrexed/carboplatin (PC) with gemcitabine/carboplatin (GC) as 1st-line treatment in advanced NSCLC (Grønberg et al., JCO 2009). The aim of the present study was to investigate whether biomarkers characterize those patients who benefit the most from either regimen. Methods: Formalin-fixed, paraffin-embedded biopsies were collected. Levels of TTF1, TS, folate receptor (FR), FPGS, estrogen receptor (ER), RRM1, EGFR and PTEN were assessed using immunohistochemistry assays from Ventana Medical Systems. The percentages of positive/highly positive tumor cells and H-scores (range: 0-200) were assessed. A central pathology review was performed. Results: Biopsies from 370/436 pts enrolled onto the trial were collected - of which 239 were analyzable (PC: n=115, GC: n=124). Patient characteristics were well balanced between the treatment arms in this cohort. To date, we have assessed TTF1, TS, FR and FPGS. So far, no associations between these markers or histology (original and revised histological diagnoses) and outcomes of any of the two regimens have been revealed. TTF1 (Pos: 10.4 mo, Neg: 6.0 mo; p<.001), TS H-score (<100: 11.9 mo, >100: 6.3 mo; p<.001), but none of the FR- or FPGS-scores were prognostic factors. In multivariate analyses adjusting for other prognostic characteristics (gender, stage, performance status), TS but not TTF1 was a significant prognostic factor (p<.001). Conclusions: So far, no associations between TTF1, TS, FR or FPGS and outcomes of the PC- or GC-regimen have been detected. TTF1 and TS were significant prognostic factors for survival. Complete analyses including ER, EGFR, PTEN and RRM1 status will be presented at the meeting.
Standardized Patient Encounters
Authors: Michael A. Ainsworth
Journal: JAMA (1991)

The primary goal of medical education is to foster development of clinical competence in trainees at all levels. Variable clinical experience, inconsistent methods of instruction, and ambiguous evaluation criteria undermine this goal. Standardized patients, trained to consistently portray a wide variety of clinical cases, can help overcome many of these educational problems. This article describes the development and application of standardized patients throughout medical training at The University of Texas Medical Branch, Galveston, in the freshman interviewing course, the second-year physical diagnosis course, third-year clerkships, a fourth-year final exercise, and residency training. Development of this program is discussed in the context of a broader literature in medical education, and investigation of variables affecting standardized patient and student performance is reported. Future directions for use of standardized patients in monitoring and promoting the development of clinical competence are discussed. (<i>JAMA</i>. 1991;266:1390-1396)
A multicenter study assessing 12-weekly intravenous bisphosphonate therapy in women with low-risk bone metastases from breast cancer: The TRIUMPH trial.
Authors: N. Bouganim, J. F. Hilton, L. Vandermeer, S. Hopkins, D. Robbins, E. Amir, S. Dent, C. Milano, O. C. Freedman, R. A. Dent, G. Dranitsaris, M. J. Clemons
Journal: Journal of Clinical Oncology (2011)

TPS242 Background: Metastatic bone disease is a major cause of morbidity and mortality for breast cancer patients (pts). Bisphosphonates (BP) have been shown to significantly delay the onset and frequency of skeletal related events (SREs), improve pain control and overall quality of life. Most pts receive intravenous BP every 3-4 weeks regardless of their individual risk for a SRE. This “one size fits all” strategy exposes those pts at a relatively low risk of SREs to the financial and quality of life burden of multiple visits to the cancer centre for treatments as well as an increased risk of drug toxicity. This study aimed to assess whether IV BP can be safely given at reduced frequency. Methods: The primary objective of this study is to demonstrate in women with biochemically defined low-risk bone metastases that the administration of IV BP every 12 weeks is sufficient to maintain biochemical stability for one year. Eligibility criteria include; bone metastases from breast cancer, have received at least three months of regular 3-4 weekly IV BP, satisfactory renal function, adequate dental health, no systemic treatment change or SRE within 4 weeks of study entry. Low risk disease will be defined as serum CTx levels <600 ng/L Biochemical failure defined as CTx levels >600 ng/L measured at predefined time points. Secondary objectives are to evaluate the palliative benefit of 12-weekly IV BP therapy as reflected by occurrence of SREs, analgesic use, self-reported pain using the validated BPI and FACT-BP questionnaires. Sample size was calculated at 68 pts. Given the small sample size, nonparametric Bootstrapping will be employed to calculate point estimates, standard deviations and 95% confidence intervals. An exploratory multivariable analysis will also be undertaken to determine baseline factors that were associated with pt’s maintaining their telopeptide levels in the low risk range. Conclusion: TRIUMPH opened Oct. 2010 has quickly accrued 20/68 pts. This trial has the potential to allow lower risk women to receive less frequent dosing of BP, thus improving their quality of life with less cancer center visits and reducing their chance of drug induced adverse events.