tbuckley/cabot-search huggingface dataset:
Activity of cabazitaxel following docetaxel and abiraterone acetate in patients with castration-resistant prostate cancer.
Authors: Avishay Sella, Tal Sella, Avivit Peer, Raanan Berger, Stephen Jay Frank, Eliahu Gez, David Sharid, Henry Hayat, Eli Rosenbaum, Victoria Neiman, Daniel Keizman, Svetlana Kovel
Journal: Journal of Clinical Oncology (2013)

e16023 Background: Cabazitaxel (CAB) and Abiraterone-acetate (AA) have been approved after Docetaxel in castration resistant prostate cancer (CRPC). Both exhibit hormonal effects. AA depletes androgen in microenvironment; taxanes affect the microtubule-dependent trafficking of the androgen receptor. Recently, clinical cross-resistance has been suggested between AA and taxanes. This prompted evaluation of CAB following Docetaxel and AA in CRPC. Methods: Over 13 months until December 2011, 130 CRPC patients received AA after Docetaxel in compassionate programs. Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their data (PCWG2/RECIST and NCI toxicity criteria). Results: Fourteen (58.3%) received CAB/prednisone at 20 mg/m 2 and 10 patients 25 mg/m2 , overall a median of 4 (1-13) cycles. Nineteen (79.1%) received primary G-CSF support. Patient characteristics (median, range in parenthesis): Age 65 (57-85) years, Gleason- 8 (6-10), K.S- 80 (50-90) %. Metastatic sites: liver- 5 (20.8%), visceral- 8 (33.3%), osseous- 22 (91.6%), No. sites involved- 2 (1-4). Lab-work: PSA- 128.1 (0.01-1700) ng/ml, PSA Doubling time- 2.16 (0.64-7.41) months, alkaline phosphatase 129 (35-1200) u/L. Castration sensitive period - 16.2 (2.0-92.1) months. Using Cox univariate analysis, only K.S was near-significant for prediction of survival after initiating CAB, p=0.075, OR=0.315, 95% C.I (0.88-1.125). A PSA response of 30%, 95% C.I (11,8-54,2)% was observed after CAB with non progression occurring in 6 (26%) out of 23 evaluable patients, 95% CI (10.2-48.4)%. At analysis 11 patients are alive. Median survival from initiation of CAB was 8.2 (95% C.I 3.34-13.05) months, from AA 16.1 (95 C.I 11.56-20.64) and from Docetaxel 32.0 (95% C.I 11.56-39.69). Non-progression with Docetaxel (but not AA) was associated with longer survival with CAB, p=0.049, 43.1 v.s 17.4 months. Four (16.6%) patients developed infectious complications, including one death due to septic shock. Conclusions: Limited number of patients with CRPC received CAB following Docetaxel and AA. In this selected population CAB was active. Response to prior Docetaxel was associated with prolonged survival to CAB therapy.
Effect of androgen deprivation therapy on intraductal carcinoma of the prostate (IDC-P), a prognostic factor for prostate cancer.
Authors: Masashi Kato
Journal: Journal of Clinical Oncology (2016)

146 Background: The presence of intraductal carcinoma of the prostate (IDC-P) is reported to be an adverse prognostic factor for cancer-specific survival (CSS) in localized and metastatic prostate cancer patients. However, there is no data indicating whether the presence of IDC-P can be affected by ADT (androgen deprivation therapy). Methods: We retrospectively evaluated 152 high risk prostate cancer patients who underwent radical prostatectomy with neoadjuvant ADT. They were diagnosed and treated at author-affiliated hospitals between 1991 and 2005. All patient data was made available from slides prepared from prostate needle biopsy samples and prostatectomy specimens and each patient received ADT before operation. Slides were re-reviewed by a single genitourinary pathologist (T.T.) according to the 2005 International Society of Urological Pathology (ISUP) grading system and presence of IDC-P was defined using previously published diagnostic criteria. Results: Patient median age was 68 years (range 46-80 years). The median iPSA was 32.7 ng/ml (range 2.4-296). The median follow-up period was 109 months (range 11-257). Sixty-one patients (40%) were ≥cT3 and 113 cases (74%) had biopsy Gleason score ≥8. Preoperative median ADT period was 4 months (range 1–20 ). IDC-P component was detected in 54 patients (36%) in needle biopsy and 69 (45%) in prostatectomy. There were 28 patients who died of the disease and 12 patients who died of other causes during follow-up. They were divided in 4 groups according to with or without IDC-P in biopsy/prostatectomy (-/- 68cases ,-/+ 30, +/- 15, +/+ 39). Twenty eight per cent of IDC-P positive cases in biopsy showed disappearance of IDC-P in prostatectomy specimen. Prognosis was the worst in +/+ group and IDC-P disappearance cases (+/-) tended to have better survival than IDC-P existing cases (+/+) in CSS (p = 0.04). Conclusions: In a number of IDC-P-positive cases determined by needle biopsy, the disappearance of IDC-P in prostatectomy specimens after ADT indicates the possibility that part of IDC-P positive patients can occasionally respond to ADT.
Are circulating tumor cells (CTCs) a feasible tool for predicting disease recurrence and survival in nonmetastatic (M0) colorectal cancer (CRC)?
Authors: Francesca Bergamo, Elisabetta Rossi, Salvatore Pucciarelli, Giovanna Rossi, Antonella Facchinetti, Francesca Battaglin, Paola Toppan, Pasquale Fiduccia, Alberto Amadori, Sara Lonardi, Rita Zamarchi, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2015)

650 Background: Based on the correlation between CTCs and clinical outcome of metastatic breast, prostatic and CRC cancer, CTCs might be an ideal model to investigate the individual risk to develop metastasis. On the other way, data on their significance in M0 CRC are still limited. In a previous study we investigated CRC cell death in the circulating compartment, finding high value of apoptotic CTCs (M30-positive) independently from the disease stage. Our aim was to evaluate the prognostic role of total and M30-positive CTCs in M0 CRC patients (pts). Methods: From January 2009 to December 2011, we prospectively enrolled 192 stage 0-III CRC pts (stage 0 identified rectal cancer pts with Tis or complete pathological response after neoadjuvant therapy). We used CellSearch assay to quantify total and M30-positive CTCs in peripheral blood of CRC pts candidate to curative resection at diagnosis, time of surgery and four months later. Multivariate survival analyses were conducted using a Cox-regression. Results: At baseline 81 out of 192 pts (43.3%) had at least 1 CTC/7.5 mL of peripheral blood, 40 pts (22.2%) had &gt;2 cells and 20 pts (11.6%) had &gt;3 cells. We found a weak association between OS and total CTCs number (p=0.069), a significant association with M30-positive CTCs (p=0.022) and no association between RFS and CTC status. Limiting the analysis to stage I-III (n=151), we found a strong association between OS and both CTCs number (p=0.021) and M30-positive cells (p=0.007). The multivariate analyses demonstrated a significant improvement of survival prediction adding baseline CTCs count to clinical and pathological characteristics (HR=1.51, 95% CI 1.16-1.96). Conclusions: We first demonstrated a significant association between OS and CTCs status in stage I-III CRC pts. This result is consistent with previous report in metastatic CRC. It highlights a potential advantage of CTCs count in stratifying CRC pts and identifying a subset of pts with a high metastatic risk that could benefit from an adjuvant therapy. Further studies are needed to explore this aspect, which might be particularly significant in stage II CRC where the indication for adjuvant therapy is still under debate.
Updated analysis of radium-223 dichloride (Ra-223) impact on skeletal-related events (SRE) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase III randomized trial (ALSYMPCA).
Authors: Nicholas J. Vogelzang, Chris Parker, Sten Nilsson, Robert Edward Coleman, C. Gillies O'Bryan-Tear, Minghua Shan, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2013)

11 Background: Ra-223 is a first-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy, short-range (&lt; 100 μm) alpha-particles. In the phase 3, double-blind, randomized, multinational ALSYMPCA study, Ra-223 significantly improved OS in CRPC patients (pts) with bone mets by a median increase of 3.6 months compared with placebo (median OS: 14.9 vs 11.3 mo; P &lt; 0.001; HR = 0.69; 95% CI: 0.58-0.83). An updated analysis of the SRE secondary endpoint is presented. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving best standard of care (BSoC); and either previously received docetaxel, or did not because they were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‑223 (50 kBq/kg IV) q4wk or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. Results: 921 pts were randomized (Ra-223, n = 614; placebo, n = 307); 40% had &gt;20 mets. Ra-223 significantly delayed time to first SRE versus placebo by a median increase of 5.8 months (median time to SRE: 15.6 vs 9.8 mo; P &lt; 0.001; HR = 0.66; 95% CI: 0.52-0.83). Ra-223 also reduced the risk of time to first event for all 4 SRE components versus placebo. Conclusions: Ra-223 significantly delayed time to first SRE with a reduction in risk observed for all 4 SRE components. Despite the longer time at risk, Ra-223 patients had an approximately 50% reduction in risk for SCC. Ra-223 is an effective therapy with a highly favorable safety profile and may provide a new standard of care for treatment of CRPC pts with bone mets. Clinical trial information: NCT00699751. [Table: see text]
How effective is telephonic case management of patients with cancer?
Authors: Charlotte Wu, Wade M. Bannister, Michael W. Rosen, Pam Schumacker, Arthur H. Rossof
Journal: Journal of Clinical Oncology (2013)

254 Background: Case management offers the opportunity to improve quality of cancer care but the financial impact is largely unknown. Optum’s Cancer Support Program (CSP) provides patients and their caregivers with telephonic case management services which are focused on reducing emergency department visits and hospitalizations, and helping patients comply with treatments and more effectively manage symptoms related to their disease or to its treatment. This study evaluates the effectiveness of CSP primarily from financial perspectives. Methods: The study used a case control approach to compare participants and non-participants of the Optum CSP program. The propensity score method was applied to adjust for baseline differences between the two groups. The study population consisted of cancer patients (N=8,833) enrolled in commercial health plans through self-insured employers. The patients were referred to CSP between July 2009 and June 2011. Analyses were conducted for survivors and decedents separately to account for mortality bias. Outcomes of cost and hospice days were estimated with generalized linear models. Results: For program participants who were under active treatment and survived at least 6 months after referral, cancer-related medical cost per patient per month during the six months of follow up was reduced by 9.8% (95% confidence interval [3.7%, 15.6%], p-value 0.002), and almost 60% of the cost savings were from inpatient admissions. The decedent’s cost during the last 3 months of the life was reduced by 19.9% (95% confidence interval [2.8%, 34.1%], p-value 0.025), and more than 80% of the cost savings were from inpatient admissions. The average hospice days of all deceased CSP participants increased by 42.3%, (95% confidence interval [13.9%, 77.8%], p-value 0.002). Conclusions: We conclude the Optum CSP program is effective in reducing medical cost among both cancer survivors under active treatment and those who did not survive, while promoting hospice utilization during end-of-life.
Evaluation of hand-foot syndrome (HFS) as a potential biomarker of sunitinib (SU) efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumor (GIST).
Authors: I. Puzanov, M. D. Michaelson, D. P. Cohen, S. Li, P. Burnett, J. Desai
Journal: Journal of Clinical Oncology (2011)

e21113 Background: Common side effects of tyrosine kinase inhibitors (TKIs) such as SU include HFS and related skin toxicities. SU is a multitargeted inhibitor of VEGFR, PDGFR and KIT, and is standard of care for the treatment of advanced RCC and imatinib-resistant/intolerant GIST. In this retrospective analysis, correlations between SU-associated HFS and efficacy endpoints were investigated in mRCC and GIST pts from 5 and 4 clinical trials, respectively. Methods: Analyses included data from 1,186 pts with mRCC (n=770) or GIST (n=416) who received single-agent SU at 25, 50, or 75 mg/d on an intermittent schedule (4 weeks (wk) on/2 wk off, 2 wk on/2 wk off, or 2 wk on/1 wk off: n=869; 73%) or at 37.5 mg continuous daily dosing (n=317; 27%). Median progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods and compared between pts with vs. without HFS by log-rank test. ORR was compared by Pearson's chi-square test. Tumor response was assessed by investigators and adverse events were recorded regularly. Multivariate, time-dependent covariate, and landmark analyses were performed. Results: Of 1,186 pts, 260 (22%) developed any-grade HFS, compared with 926 (78%) who did not. Pts with mRCC who developed HFS had significantly better ORR (66.5% vs. 31.8%), PFS (14.3 vs. 8.3 mo), and OS (38.3 vs. 18.9 mo) than pts who did not (P<0.0001). Pts with GIST who developed HFS also had significantly better ORR (22.2% vs. 10.7%), PFS (11.0 vs. 5.5 mo), and OS (35.7 vs. 16.6 mo) than pts who did not (P<0.01). SU-associated HFS remained a significant predictor of both PFS and OS in a multivariate analysis (and of OS by time-dependent covariate analysis) in both mRCC and GIST pts. In 6- and 12-wk landmark analyses, pts with mRCC but not GIST who developed HFS had significantly longer OS, with a trend toward longer PFS, than pts who did not. Conclusions: SU-associated HFS was associated with improved PFS and OS in both mRCC and GIST pts, although the landmark analysis suggests that HFS may not be a reliable biomarker of SU efficacy at early time points.
Twenty‐Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results From the Norfolk Arthritis Register
Authors: James M. Gwinnutt, Deborah P. M. Symmons, Alexander J. MacGregor, Jacqueline R. Chipping, Tarnya Marshall, Mark Lunt, Suzanne M. M. Verstappen
Journal: Arthritis & Rheumatology (2017)

To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up.Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring.This study included 602 patients with RA (median age 56 years [interquartile range 44-68 years]; 65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3 swollen joints and 3-6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow-up period (β = 0.03, 95% confidence interval [95% CI] -0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17]).The results of this study indicate the importance of early treatment with regard to the long-term outcomes in patients with RA.
Evaluation of venous thromboembolism (VTE) risk among ambulatory patients with pancreatic cancer in a real-world setting.
Authors: Jay Lin, Mehul R. Dalal, Gregory Clayton Connolly, Alok A. Khorana
Journal: Journal of Clinical Oncology (2012)

273 Background: Patients with cancer are at high risk for VTE, and risk varies by cancer type, patient demographics/history, chemotherapy regimen, and hospitalization status. This retrospective cohort analysis examined the incidence of and risk factors for VTE in a cohort of ambulatory cancer patients with primary pancreatic tumors who were starting chemotherapy. Methods: Data were extracted from the IMS Patient-Centric Database, a large administrative database of real-world US healthcare claims. Demographics/clinical characteristics of cancer patients with pancreatic and other solid tumors and a matched control cohort of patients without cancer were evaluated. The incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and DVT+PE was recorded during a follow-up period of 3-12 months after chemotherapy initiation in the group with pancreatic cancer. Results: Women composed 47% (632/1,336) of the pancreatic cancer and 51% (8,831/17,284) of the control cohort; mean age was 63 years in the pancreatic cancer cohort and 64 years in the control cohort. Mean Charlson Comorbidity Index scores were 6.8 and 0.6 respectively. VTE occurred in 19.2% of the pancreatic cancer cohort (odds ratio [OR], 5.39; 95% confidence interval [CI], 4.26, 6.80) compared with 1.4% in the control cohort (P&lt;0.0001). The incidence of DVT, PE, and DVT+PE was 12.6%, 2.3%, and 4.4%, respectively, in the group with pancreatic cancer vs 1.0%, 0.2%, and 0.2% in the control cohort (P&lt;0.0001 for all comparisons). The use of erythropoiesis-stimulating agents (ESAs) was associated with an increased incidence of VTE (OR, 1.71; 95% CI, 1.27, 2.31; P=0.0004 vs no ESA). Bleeding occurred in 23.4% of the pancreatic cancer cohort and 7.0% of the control cohort (P&lt;0.0001). Conclusions: In a real-world setting, nearly 20% of this cohort of ambulatory cancer patients receiving chemotherapy experienced VTE. The presence of primary pancreatic cancer was associated with a 5-fold increase in VTE risk compared with controls. Use of ESA was associated with significant incremental risk of VTE.
Prognostic significance of natural killer expression in Egyptian pediatric acute myeloid leukemia
Authors: I. Sidhom, A. Kamel, N. El-Sharkawy, D. Yassin, K. Shaaban, H. Hussein, S. Aboul Naga, H. Moussa, G. Mosallam, Y. El-Nahass
Journal: Journal of Clinical Oncology (2005)

8542 Background and Objectives: Expression of CD56 and CD16, Natural Killer (NK) associated antigens, has been reported in several hematopoietic malignancies including acute myeloid leukemia (AML). It has been claimed to be a bad prognostic parameter in adult AML; no data is available for pediatrics. The aim of this study is to evaluate the significance of CD56 and/or CD16 expression in pediatric AML. Methods: 305 consecutive de novo pediatric AML patients presented to the National Cancer Institute, Egypt, were evaluated for the expression of CD56 and/or CD16 using multicolor flow cytometry (coulter X) at a cutoff of 20% (as reported in literature). Complete clinical data were available for 163 cases. All patients received the same treatment protocol: induction therapy consisting of Cytarabine 100 mg/m2/d 24 hrs infusion d1–2; 100 mg/m2 IV q12 hrs d3–8, Daunorubicin 25 mg/m2 d3–5, Etoposide 100 mg/m2 d6–8 followed by another course as consolidation, then four courses of MIDAC as continuation therapy (Mitoxantrone 10 mg/m2 d1–3 and intermediate dose Cytarabine 1g/m2 q12 hrs d1–3). NK expression was correlated to clinical, hematological and immunophenotypic parameters as well as to treatment outcome. Results: The frequency of CD56 and/or CD16 expression was found to be 20.7%. Among the studied group NK antigen (CD56 and/or CD16) was positive in 48/163 cases; 19 were +ve for CD56, 10 for CD16 and 20 were not separately tested for CD56 or CD16. Neither the expression of NK antigens in the whole group nor CD56 positivity alone had any significant association with age, sex, white blood cell count, FAB or phenotypic markers including CD2, CD7, CD34, HLA-DR and P-gp expression. CD16 was significantly associated with M4-M5 subtypes (P=0.04, chi square). For the whole group, NK expression had no significant impact on complete remission rate (p=0.19) or duration (3-year DFS 23.6% vs 36.7% for +ve and -ve cases respectively, log rank p=0.32). CD56 had no impact on clinical outcome, while CD16 had significant impact on failure to achieve induction remission (55.6% for CD16+ vs 22.9% for CD16- cases; p=0.03 chi square). Conclusion: CD16 rather than CD56 might have prognostic impact in pediatric AML. Further study on a larger scale is recommended. No significant financial relationships to disclose.
Randomized trial of a short course of erlotinib 150 to 300 mg daily prior to surgery for squamous cell carcinomas of the head and neck (SCCHN) in current, former, and never smokers: Objective responses and clinical outcomes.
Authors: W. N. William Junior, R. S. Weber, J. J. Lee, J. Myers, L. E. Ginsberg, A. K. El-Naggar, E. M. Sturgis, A. L. Sabichi, M. S. Kies, E. Y. Hanna, A. C. Hessel, C. Lu, S. Y. Lai, R. Ayuste, S. M. Lippman, E. S. Kim
Journal: Journal of Clinical Oncology (2011)

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