tbuckley/cabot-search huggingface dataset:
Trends in the utilization of diagnositics for upper-tract urothelial carcinoma.
Authors: Goutham Vemana, Sam Bhayani, Jack Baty, Joel Vetter, Seth A. Strope
Journal: Journal of Clinical Oncology (2014)

348 Background: The evolution and adoption of better endoscopes and imaging allow for improved diagnostic capacity for upper tract urothelial cancer (UTUC). We evaluated the changes in diagnostic modalities used to establish a diagnosis of UTUC. Additionally, we assessed how these changes affected the stage of patients receiving definitive surgery. Methods: Using linked SEER-Medicare data from 1992-2009, we identified patients between the age of 66-90 who underwent surgical treatment for UTUC. Among this cohort we assessed the types of diagnostics: endoscopy, computed tomography urogram (CTU), magnetic resonance urography (MRU), intravenous pyelogram (IVP), and retrograde pyelogram (RGP), used to evaluate their disease. Additionally, we dichotomized the final stage at surgery as lower stage disease (Ta, CIS, or unknown stage) or higher-stage disease (T1 or greater). Tests for trend were calculated for the five diagnostic modalities. Logistic regression models were fit to determine the impact of diagnostic modalities on stage at surgery. Results: We found a downward trend in utilization of IVP and RPG over time (p &lt; 0.001, p = 0.011) with IVP having largest decline in use. Endoscopy, CTU and MRU all demonstrated increased utilization over time (p &lt;0.0001). The incidence of lower stage disease was not found to be changing over time (p = 0.123). Logistic regression analysis demonstrated that among modern use (2000-2009), only the use of endoscopy and IVP were associated with smaller tumors (CI 1.310-1.996, CI 1.150-1.720). Conclusions: Modern diagnostics (endoscopy, CTU, MRU) have supplanted traditional methods of establishing a diagnosis of UTUC. Although these newer adopted technologies have a greater sensitivity in diagnosis of UTUC, only the use of endoscopy prior to definitive management has been associated with the diagnosis of smaller tumors.
Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma (MEL).
Authors: F. Stephen Hodi, Mario Sznol, David F. McDermott, Richard D. Carvajal, Donald P. Lawrence, Suzanne Louise Topalian, Jon Wigginton, Dan McDonald, Georgia Kollia, Ashok Kumar Gupta, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2012)

8507 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. This study describes the activity and safety of BMS-936558 in patients (pts) with previously treated advanced MEL and underscores the importance of the PD-1/PD-L1 pathway in MEL therapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 95 MEL pts were treated with BMS-936558 at 0.1 (n=13), 0.3 (n=17), 1 (n=28), 3 (n=17), or 10 mg/kg (n=20). ECOG performance status was 0/1/2 in 56/36/3 pts. The majority of pts (60/95) had received prior immunotherapy (IT), primarily interferon-alpha or IL-2 (prior anti-CTLA-4 excluded). Prior B-raf inhibitor therapy was noted in 7/95 pts. The number of prior therapies was 1 (n=35), 2 (n=34), or ≥3 (n=26). Sites of metastatic disease included lymph node (n=60), liver (n=32), lung (n=55), and bone (n=10). Median duration of therapy was 15 wk (max 120 wk), with 40 pts still receiving treatment. The incidence of grade 3-4 related AEs was 19% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity was observed at all dose levels (Table). Of 20 pts with OR at the time of data lock, 12 had OR duration ≥1 yr and 6 pts were on study with OR duration between 1.9 and 11.3 mo. OR were seen in pts with visceral or bone metastases. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. Conclusions: BMS-936558 had durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Further development of BMS-936558 in MEL is ongoing. [Table: see text]
Survival trends in mantle cell lymphoma in the United States over 16 years, 1992-2007.
Authors: R. Chandran, S. K. Gardiner, M. Simon
Journal: Journal of Clinical Oncology (2011)

e18530 Background: Mantle cell lymphoma is a subtype of Non-Hodgkin’s lymphoma and constitutes six percent of cases. Prognosis is poor with median overall survival approximately 3-5 years. Several new treatment protocols have emerged over the last decade. The purpose of this study is to determine if newer protocols and regimens have translated into an overall survival benefit in the United States. Methods: Retrospective cohort analysis was done using the Surveillance, Epidemiology, and End-Results (SEER) database of the national cancer institute. A total of 5367 cases of mantle cell lymphoma were identified from 1992-2007 using the SEER database. Cases were split into three different cohorts. Group 1 included all cases of mantle cell lymphoma from 1992- 1999, Group 2 included cases from 2000-2003 and Group 3 was from 2004-2007. Overall Survival was analyzed using a Cox proportional hazards model to adjust for age, gender and disease stage and summarized using ANOVA. Results: The proportion of advanced cases compared to localized has increased over the years (Fisher’s exact test p= 0.0012). In a survival model, increased age (4.6%, p< 0.001) and male sex (19.2 %, p< 0.001) were both associated with a higher mortality. Compared to the cohort from 1992-1999 (group1), mortality was reduced in 2000-2003(group 2) by 9.5% (p=0.03) and in 2004-2007 (group 3) by 14.6% (p=0.0036). Patients with localized disease had a 38.8% better survival than those with advanced disease (p < 0.001), but there was no difference between the groups in survival in patients with localized disease. For patients with advanced disease, there is a 14.1% reduction in mortality in group 2 (p=0.0064) compared to group 1. Mortality in group 3 was 22.8 % lower than group 1 (p<0.001), and 8.7% lower than group 2. Conclusions: The survival for patients with mantle cell lymphoma with advanced stage has improved in the United States over the last sixteen years. However, the overall survival remains unchanged. This is most likely due to a significant increase in the proportion of patients with poor prognostic features- advanced age, male sex and advanced stage of disease. In a survival model predicted by disease stage,age, sex and year group, a significantly better survival was noted in women.
Transition of breast cancer (BC) survivors to primary care: Results of a Cancer Care Ontario (CCO) pilot project.
Authors: Jonathan Sussman, Maria Grant
Journal: Journal of Clinical Oncology (2014)

58 Background: Emerging evidence indicates that the transition of well breast cancer survivors to primary care is safe and effective. Methods: Prospective longitudinal cohort study across 14 health regions in Ontario, Canada. Each region received $100 000 (CAN) to develop and implement a sustainable new model of survivorship care for BC survivors that involved transition from medical oncology-led practice. Each region had a designated lead, and support from primary care. Funding could be used to develop any aspect of the model including personnel support, development of communication materials and outcome measurement. A minimal dataset reporting requirement included a description of the program, documentation of transitioned BC survivors as well as standardized patient and provider experience feedback once transition completed. Results: All 14 health regions in Ontario participated and all developed a survivorship care plan and patient educational materials. The models developed included direct transition to primary care in 6 regions, a nurse-led transition clinic in 4 and a GP-led transition clinic in 4. To date, 3,418 BC survivors have transitioned. Of 676 BC respondents to date, 83% felt there was a clear plan for follow up and 87% felt adequately prepared for transition. Feedback from primary care providers demonstrated that many feel informed about intent of transition and understand their role in on-going follow-up care. Process outcomes such as re-referral back to cancer center and adherence to follow-up guidelines are currently underway. Conclusions: The wide scale transition of appropriate BC survivors to a primary setting appears feasible with high acceptability by patients and providers.
Analysis of Surveillance, Epidemiology, and End Results Program (SEER) PSA coding error using primary data.
Authors: Timothy E. Schultheiss, Matthew David Hall, Ginamarie Farino, Jeffrey Y.C. Wong
Journal: Journal of Clinical Oncology (2016)

21 Background: SEER did not report PSA values for the 2014 submission because of inaccurate coding. This inaccuracy was a result of a confusing data entry guideline where PSA is coded in a 3-digit field with an implied decimal between digits 2 and 3. Our study uses original registry data to assess the magnitude and implications of these coding errors. Methods: The National Oncology Data Alliance is a database of more than 150 Commission-on-Cancer compliant tumor registries that use proprietary cancer registry software sold by Elekta AB (Stockholm, Sweden) and contains the same data sent to state tumor registries and SEER. De-identified data from all newly diagnosed prostate cancer cases from 2005-2013 were extracted (n = 89,379). PSA data were acquired from both the Collaborative Staging (CS) Site Specific Factor 1 (SSF1) for prostate cancer and from de-identified text fields. SSF1 contained the error prone datum that was transferred to SEER. The PSA data contained in the text fields, which are used to record lab results, etc. verbatim, were taken to be definitive. PSA values from both SSF1 and text fields were complete in 63,051 patients. AJCC Stage was determined using the clinical T stage field and the SSF fields that code for Gleason score. We calculated the error rates and their directions for PSA stratification into three levels (0 to &lt; 10, 10 to &lt; 20, and ≥ 20) and for the AJCC stage. Results: The measured error rate in PSA values in SSF1 caused by erroneous decimal placement was 9.0%. The resulting error rate in PSA stratification was 7.5%, with the SSF1 PSA value giving a higher PSA category in 4.8% of cases and lower in 2.7%. The consequent error rate in AJCC staging was 2.8% overall, with the PSA error resulting in a higher stage group in 1.9% and lower in 0.9%. Conclusions: Many factors can contribute to the overall error rate in PSA values in SEER data, but we are addressing only the errors associated with the implied decimal. The consequences of this error are modest despite a 9% error rate. However, SSF1 for prostate cancer is not the only confusing SSF introduced by the CS system. The current cancer registry database design is derived from outdated technology and needs restructuring to be a more effective surveillance and research tool.
Impacts of T and N factors on curability of pancreatic, gastric, and colonic cancers.
Authors: S. Maetani, Y. Segawa, H. Banja, H. Obayashi, M. Imamura, J. W. Gamel
Journal: Journal of Clinical Oncology (2011)

e21042 Background: As an increasing number of patients have been cured of their cancers, it has become necessary to predict whether treatment will achieve cure or merely prolong time to failure. This question cannot be answered by the Cox regression model, but is addressed by the Gamel-Boag regression model. Previously, using this model we evaluated curative impacts of T and N factors in locally invasive pancreatic cancer and found that involvement of pancreatic tissue beyond 2 cm in diameter is a more serious predictor of incurable (generalized) disease than lymphnode involvement. We study the effects of the same factors in gastric and colonic cancers. Methods: We analyzed follow-up data from 1410 advanced gastric cancer patients and 1753 advanced colonic cancer patients, who were operated on with curative intent. In each group, three regression analyses were performed, whose dependent variables include cure rate and failure time (the Boag parameters) while the explanatory variables studied included lymphnode status, depth of tumor invasion and tumor size; the first two were converted to dichotomous variables (presence or absence of nodal metastasis and serosal invasion). Thus, effects of these factors on curability and failure time were evaluated in each cancer. Since more than three variables were incorporated in this regression model, P<0.005 was used to denote statistical significance. Results: In colonic cancer, as opposed to the previous study of pancreatic cancer, the lymphnode metastasis significantly lowered the cure rate but neither the tumor size nor serosal invasion had significant impact on curability. In gastric cancer, the curability was significantly affected by lymphnode metastasis, tumor size and serosal invasion. Such varying findings may be explained by clinical observations that each cancer has different patterns of recurrence; e.g., the most common pattern of gastric cancer recurrence is peritoneal dissemination, for which serosal invasion is responsible, and hence a significant predictor of curability. Conclusions: T and N factors do not necessarily have similar impacts on curability of different cancers. Which factor is the major determinant of cure has yet to be studied.
Impact of a change of body mass index (BMI) on outcome following adjuvant endocrine therapy, chemotherapy, or trastuzumab for breast cancer.
Authors: R. Yerushalmi, B. Dong, J. W. Chapman, P. E. Goss, M. N. Pollak, M. J. Burnell, V. H. Bramwell, M. N. Levine, K. I. Pritchard, T. J. Whelan, J. N. Ingle, W. Parulekar, L. E. Shepherd, K. A. Gelmon
Journal: Journal of Clinical Oncology (2011)

513 Background: Pre-treatment BMI has been found to impact early breast cancer (EBC) outcomes and observational studies suggest that increasing BMI after diagnosis is detrimental. We hypothesize that changes in BMI after initial treatment of EBC are associated with breast cancer outcomes. Methods: We determined the effects of changes in BMI after initial treatment of EBC on disease outcomes in a series of NCIC CTG EBC clinical trials employing investigational therapies: chemotherapy (MA.5, MA.21), endocrine therapy (MA.12, MA.27), or biological therapy such as insulin-like growth factor pathway (MA.14) or trastuzumab therapy (MA24/HERA). Taking into account differing trial designs we created common operable definitions for investigative factors (BMI change at 1-, 3-, 5- years; age; ECOG performance status; menopausal status; race; T; nodal status; hormone receptor status; endocrine therapy; chemotherapy; anthracycline; trastuzumab) and STEEP endpoints. MA.14 and MA.27 results are provided here for breast cancer-free interval (BCFI), defined as the time from randomization until recurrence: first local invasive or DCIS; regional, or distant; contralateral invasive or DCIS; or death from breast cancer. Stratified Cox regression was used to assess the effect of continuous BMI changes on BCFI. Results: Preliminary results are as follows with a median FU of 9.8 years for MA14 and 4.1 years for MA27. There was no significant interaction between BMI changes and trial therapy (tamoxifen +/− octreotide LAR) in MA.14. Conclusions: In this analysis, increases in BMI at 1- and 5- years were associated with improved prognosis in MA14, with no difference based on treatment arm. BMI changes were not associated with BCFI in the MA.27 trial comparing aromatase inhibitors. At ASCO we will report results for all trials and endpoints. This data may impact our understanding of the role of BMI and breast cancer recurrence. Trial Year Number at risk Mean BMI % change BCFI (%) P value MA14 1 537 1.64 74.5 0.03 MA14 3 496 2.09 78.6 0.19 MA14 5 436 1.96 82.1 0.018 MA27 1 6,569 1.23 94.4 0.79 MA27 3 5,034 1.33 97.4 0.68 MA27 5 956 0.57 99.2 0.47
Effects of high-dose Asian ginseng (Panax ginseng) to improve cancer-related fatigue: Results of a double-blind, placebo-controlled randomized controlled trial.
Authors: Sriram Yennu, Nizar M. Tannir, Janet L. Williams, Kenneth R. Hess, Susan Frisbee-Hume, Helen L House, Frank V. Fossella, Zita Dubauskas Lim, Gabriel Lopez, Akhila Sunkepally Reddy, Ahsan Azhar, Angelique Wong, Sunil M. Patel, Ahmed Omar Kaseb, Wen-Jen Hwu, Zhanni Lu, Lorenzo Cohen, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

209 Background: Cancer related fatigue (CRF) is the most common and disabling symptom in cancer.Panax ginseng extract (PG) is frequently used as a nutraceutical treatment for fatigue. There are no well-powered placebo-controlled trials that used validated CRF outcome measures to investigate of PG effects in cancer patients. The primary objective of this trial was to evaluate the effects oral PG versus Placebo (PL) for CRF. Methods: Patients with cancer fatigue ≥ 4/10 on Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomized to either 400mg of standardized PG or matching PL orally twice a day for 28 days. The primary endpoint was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) fatigue subscale from baseline to Day 28. Secondary outcomes were Functional Assessment of Cancer Therapy-General (FACT-G), Hospital Anxiety and Depression Scale (HADS), and ESAS. Results: Total evaluable patients were 112 (56 for PG and PL groups). No significant differences in baseline characteristics between the two groups except cancer type (p = 0.002). There was significant improvement in FACIT fatigue and ESAS fatigue scores in PG and PL groups at Day 15 and Day 29. The mean (SD) of FACIT-F fatigue scores at baseline, Day 15, and Day 29 were 22.6 (10.4), 29.8(10.7), 30.1 (11.6) and 23.8 (9.1), 30.0 (10.1), 30.4 (11.6) for PG and PL respectively. Mean (SD) improvement in the FACIT-F subscale at Day 29 was not significantly different in PG than in the PL group [7.5 (12.7) vs 6.5 (9.9), P = 0.67]. Mean (SD) improvement in the ESAS fatigue, FACT-G, and HADS at Day 29 were also not significantly different in PG than in the PL group. In a multiple linear model analysis, the change in FACIT-F fatigue from Day 0 to Day 29 was negatively correlated with baseline FACIT-F fatigue (p = 0.0005), baseline HADS score (p = 0.032), and male gender (p = 0.023). There were a significantly higher number of any grade of toxicities in PL group than in PG group (33/62 vs. 28/64, p = 0.024). Conclusions: Both PG and Placebo result in a significant improvement in CRF at Day 15 and Day 29. PG was not significantly superior to placebo after 4 weeks of treatment. Further studies are needed. Clinical trial information: NCT01375114.
Factors influencing the number of retrieved lymph nodes (LNs) in patients with stage II colon cancer: LN size and areas of B cells and T cells.
Authors: Kazutake Okada, Sotaro Sadahiro, Gota Saito, Akira Tanaka, Toshiyuki Suzuki, Akemi Kamijo
Journal: Journal of Clinical Oncology (2015)

577 Background: In patients with stage II colon cancer, a high number of retrieved LNs has been reported to be associated with better outcomes. We examined the association between a high number of retrieved LNs and the presence of large mesenteric LNs and we evaluated the areas occupied by the T-cell and B-cell fields in LNs with large diameters. Methods: The study group comprised 320 patients with stage II colon cancer who underwent R0 resection from 1991 to 2003. The long- and short-axis diameters of 4,745 LNs were measured with a digitizer on specimens stained with hematoxylin and eosin. A LN with the largest long-axis diameter was selected for each patient and stained immunohistochemically using CD3 as a marker of T cells and CD20 as a marker of B cells. The CD3-positive and CD20-positive area ratios were evaluated, respectively. Results: The mean number of retrieved LNs was 15±10 per case. The correlation coefficients between the numbers and the long-axis diameters of LNs were as follows: mean 0.23, median 0.16, maximum 0.59, and minimum -0.29. The correlation coefficients between the numbers and short-axis diameters were 0.18, 0.13, 0.54, and -0.33, respectively. The correlation coefficient was highest for the maximum long-axis diameter. When the maximum diameter was divided at 5-mm intervals, the number of LNs significantly increased in parallel to an increase in the maximum long-axis diameter (p&lt;0.001). The median follow-up was 119 months. Fifty-six patients (18%) had recurrence, 110 (34%) died of all causes, and 48 (15%) died of colon cancer. On survival analysis, age, T stage, and maximum long axis diameter of LNs were independent prognostic factors. The CD20 area ratio was significantly higher in LNs with a long-axis diameter of 10 mm or greater (0.44±0.09) than in LNs with a long-axis diameter of less than 10 mm (0.41±0.10, p=0.018). There were no differences in the CD3 area ratio. Conclusions: In stage II colon cancer, the number of retrieved LNs correlated with the maximum long-axis diameter of LNs. The long-axis diameter as well as age and T stage were independent prognostic factors. LNs with a larger long-axis diameter had a significantly increased intranodal B-cell area ratio.
Polymorphisms of the aromatase gene (CYP19A1) and benefit of aromatase inhibitors (AIs) in metastatic breast cancer (mBC) patients.
Authors: M. Arnedos, R. Ferraldeschi, R. A'Hern, K. Hadfield, S. Roberts, S. Drury, A. Howell, D. G. Evans, A. M. Wardley, I. E. Smith, W. G. Newman, M. Dowsett
Journal: Journal of Clinical Oncology (2011)

608 Background: Germline genotypic polymorphisms in CYP19A1 have been associated with differential benefit from treatment with AIs in patients with mBC, but validation is lacking. Methods: We retrospectively identified patients with ER-positive mBC treated with a 3rd generation AI. DNA was obtained from archival paraffin-embedded tumors and genotyped for 74 polymorphisms in 20 candidate genes, including CYP19A1 using the Sequenom MassARRAY Platform. The CYP19A1 Arg264Cys (rs700519) variant was analyzed by Pyrosequencing. The CYP19A1 (TTTA)n(rs60271534) and TCT Ins/Del (rs11575899) variants were genotyped by fragment analysis.Primary endpoint was time to treatment failure (TTF), analyses being undertaken using Cox’s regression to estimate the hazard ratio for risk of failure per allele. Results: 308 patients were included. Mean TTF was 15 months (range 1 to 58). Two sets of analyses were undertaken. The first were confirmatory analyses for the CYP19A1 variants rs4646, rs10459592 and rs4775936, previously associated with letrozole efficacy in mBC.TTF was significantly improved in patients carrying the T allele of rs4775936 compared to homozygous wild-type patients [HR=0.79 (0.66-0.95); p=0.012]. However, this association lost significance when adjusted for other prognostic factors. When the analysis was limited to letrozole treated patients (n=165), the difference was no longer significant (p=0.068). None of the 60 other SNPs with MAF ≥5%, included as an exploratory set, showed significant association with TTF. Patients with >7 TTTA repeats on either allele of CYP19A1 had lower risk of failure than those without it [HR=0.84 (0.7-0.99); p=0.04]. This association also lost significance when adjusted for clinical factors. Conclusions: In this retrospective cohort of patients with mBC treated with a 3rd generation AI, carriage of the minor allele of the CYP19A1 variant rs4775936 and greater than seven repeats of the TTTA polymorphism within intron 4 of CYP19A1 were significantly associated with improved AI treatment efficacy in univariate analysis and require further study. There was no significant association of any other candidate SNP with efficacy of AIs.