tbuckley/cabot-search huggingface dataset:
Prevalence and predictors of adherence to antiemesis prophylaxis in lung cancer: A population-based study.
Authors: Daniel Richard Gomez, Kai-Ping Eric Liao, Hoang Nguyen, Benjamin D. Smith, Linda S. Elting
Journal: Journal of Clinical Oncology (2012)

6124 Background: Nausea/vomiting is a significant toxicity in the treatment of lung cancer, but barriers exist to the delivery of prophylaxis. We studied compliance and predictors of prophylactic antiemetics with chemotherapy in this setting. Methods: We used a Texas state registry of clinical data linked with Medicare claims from 2001-2007. Our study population was incident lung cancers treated with platinum agents within 12 months of diagnosis. To define guideline-adherent care, we assessed compliance to the American Society of Clinical Oncology recommended prophylactic agents dexamethasone and a 5-HT3 antagonist. Adherence was scored as a binary variable and defined as administration within 24 hours of the first day of the first cycle of chemotherapy. We utilized a logistic regression model to evaluate the role of the following factors in predicting adherence: concurrent radiation therapy (RT), race (black vs. white), histology (small cell vs. non-small cell), rural location, Charlson Comorbidity Index (CCI), household income (by quartiles [Q]), education, and treatment year (binary). Results: Of 31,762 patients in the database, 5155 patients met the above criteria. The adherence rate to dexamethasone and 5-HT3 antagonists increased over time, from 51.5% in 2001 to 71.6% in 2007. Patients treated in the years 2005-2007 were 1.739 times more likely to be adherent to prophylaxis than were those from 2001-2004. Variables that predicted adherence (adjusted odds ratio [OR], 95% confidence interval [CI]) were: age (OR=1.013, CI [1.001, 1.026]), treatment year (OR=1.756, CI [1.548, 1.991]), race (black vs. white OR=0.684, CI [0.548,0.853]), median income (higher vs. lower OR=1.83 [Q2 vs. Q1]; OR=1.296 [Q3 vs. Q1]; OR=1.496 [Q4 vs. Q1]), CCI (1+ vs. 0, OR=0.613, CI [0.530,0.709]), and concurrent RT [yes vs. no OR=1.358, CI [1.197,1.541]). Conclusions: Compliance with guidelines for prophylactic antiemetics is suboptimal, but increasing over time. Several characteristics predict for improved adherence, including white race, median income, advanced age, and the receipt of concurrent RT. These findings highlight substantial economic disparities in supportive care of lung cancer in the state of Texas.
Patient-related factors influencing time between first signs of breast cancer (BC) and appointment for medical visit (AMV): An international survey.
Authors: Jacek Jassem, Florin Bacanu, Janis Eglitis, Jozef Mardiak, Tadeusz Pienkowski, Zsuzsanna Kahan, Vahit Ozmen, Monika Drobniene, Damir Vrbanec, Tatyana Semiglazova, Ljiljana Stamatovic, Constanta Timcheva, Suzana Vasovic, Piotr Zaborek
Journal: Journal of Clinical Oncology (2012)

9046 Background: Reducing diagnostic delays may improve treatment outcomes in BC. We investigated in various countries patient-related factors influencing time to seeking medical advice for signs of BC. Methods: A total of 4,816 female BC patients from 10 countries were surveyed using a uniform questionnaire translated into local languages. Time between first patient-detected signs of BC and AMV was measured using categorized time scales. Out of 14 original items on a multiple scale measuring BC-related attitudes and behaviors, 5 factors were extracted and used for further analysis: distrust in medical system and success of therapy, disregard of signs, fear of BC, practicing regular breast self-examination and support from friends and family. Results: In the subset of 2,870 patients with self-detected BC who provided complete answers to relevant variables, the mean time to AMV varied in particular countries from 3.4 to 6.2 weeks (grand mean of 4.7 weeks), with 39% of cases with a delay of &gt;4 weeks. Overall, patient attributes that significantly influenced time to AMV were: distrust (p&lt;1E-36), disregard (p=1.26E-30), fear (p=2.65E-16), self-examination (p=1.31E-21), place of living (p=3.5E-3) and education (p=2.73E-3). Multilevel analysis indicated that significant differences among particular countries were only due to slopes of distrust and disregard included in general regression model. The model enhanced with the two abovementioned random effects provided significant improvement in predicting time to AMV. Re-estimation of the model based solely on data from individual countries produced 10 significant equations with varied coefficients for distrust and disregard (see table). Conclusions: Patient-related factors contribute considerably to delay in the diagnosis of BC. Differences between particular countries call for country-specific approaches. [Table: see text]
Utility of iron oxide nanoparticles in the radiographic diagnosis of CNS lymphoma and inflammatory diseases.
Authors: Brian T. Farrell, Bronwyn E. Hamilton, Edit Dosa, Endre Rimely, Morad Nasseri, Seymur Gahramanov, Cindy Lacy, Eugene P. Frenkel, Nancy Diane Doolittle, Paula M. Jacobs, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2012)

2077 Background: Ferumoxytol, an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO), is approved for intravenous treatment of iron deficiency in chronic renal failure. The package insert warns of potential alterations of magnetic resonance imaging (MRI). Our initial animal studies provided evidence of USPIO uptake by macrophages and lymphoreticular cells suggesting its potential in CNS lymphoma (CNSL), post transplant lymphoproliferative disease, or CNS inflammation (i.e. multiple sclerosis). The mechanism of USPIO enhancement differs from gadolinium-based contrast agents (GBCA), which optimally image areas of increased vascular permeability. Methods: USPIO was administered as an MRI contrast agent to 20 patients with presumptive or de facto diagnosis of CNSL or CNS inflammation. Seventeen of 20 patients underwent both USPIO- and gadolinium-based MRI. Three patients received only USPIO due to risk of nephrogenic systemic fibrosis (NSF) with GBCA exposure. In the pilot phase of the study, patients were given the USPIO ferumoxtran-10 and subsequent patients were given a successor USPIO (ferumoxytol) which has improved pharmaceutical properties. All patients were monitored for adverse reactions. MRI scans were subsequently reviewed by a neuroradiologist. Results: No significant toxicities were seen. Thirteen of 17 patients who received both contrast agents showed equal numbers of enhancing lesions on postcontrast images. USPIO-based contrast revealed additional areas of enhancement in three of 17 patients that were not visible when GBCA was administered. In three patients more lesions were seen with GBCA. Examples of ferumoxytol utility include 1) improved targeting for surgical biopsy; 2) avoidance of NSF; 3) demonstrating enhancement related to macrophages within lesions; 4) correlating cerebral blood volume and CNS inflammation; 5) demonstrating pitfalls such as prolonged imaging changes (3 months) in one case due to intensive inflammation, which can simulate hemorrhage. Conclusions: These studies provide data about the utility and value of USPIO-based contrast imaging in CNSL and inflammatory CNS lesions that support a dual role for these agents beyond iron replacement.
Phase I trial of exogenous testosterone (T) for the treatment of castrate metastatic prostate cancer (PC)
Authors: M. J. Morris, W. K. Kelly, S. Slovin, N. Sauter, C. Eicher, K. Regan, T. Curley, A. Delacruz, V. Reuter, H. I. Scher
Journal: Journal of Clinical Oncology (2004)

4560 Background: Standard treatment for metastatic PC is androgen withdrawal. In preclinical studies, growth of selected PC cell lines and xenografts following prolonged androgen deprivation can be repressed with the re-introduction of high-dose androgens. We conducted a phase I trial to test the feasibility of this strategy in humans. Methods: Eligible patients (pts) had metastatic PC with progression on scans or PSA rises >25% over baseline, had T levels <30 mg/dl, were castrate for ≥1 year, and had failed anti-androgen withdrawal. Pts were treated with T-containing transdermal patches or gel. T was given at 3x standard dosing using three Testoderm TTS 5 mg patches or three Androgel 1% 5 G packets to maximize serum levels, while GnRH agonists were continued. Three cohorts of 3–6 pts each were defined by treatment duration: 1 week of T, 4 weeks of T, and treatment with T until progression. Antitumor effects were gauged by post-treatment PSA assays and imaging studies. Androgen receptor (AR) levels were assayed from bone marrow specimens to correlate with antitumor effects. Results: Twelve patients were treated; 3 in cohorts 1 and 2, and 6 in cohort 3. No pt was taken off study for tumor flare, defined as an increase in tumor-related symptoms within the first two weeks of therapy. Therapy was well tolerated. There were no grade 4 events, and only 1 grade 3 event (transaminitis) was felt to be possibly related to drug. The median total T level achieved by all pts during week 1 was 409 ng/dl (range 95 –908), median free T level was 78 ng/dl (range 11 –213), and median DHT level was 61 ng/dl (range 29 –135). Median treatment duration for cohort 3 was 59 days (range 27–124). AR assays are underway. 1 pt achieved a ≥50% post-treatment PSA decline; 2 pts had stable PSAs; no pts had a radiographic response. Conclusions: Administration of T to patients with advanced PC for 1 week, 4 weeks, or until disease progression is safe, and not limited by tumor flare. PSA declines were seen, but were rare and short-lived. Combinations of T with other agents that modulate AR may be a more productive strategy than continuous monotherapy. Support: Prostate Cancer Foundation, PepsiCo, Sacerdote Fund, NIH CA102544 No significant financial relationships to disclose.
Association of high expression of Hsp90-beta and GRP 94 with poor survival in resected non-small cell lung cancer patients.
Authors: Seok-Hyun Kim, Gyeong-won Lee, Jong-Sil Lee, Yu Ji Cho, Yi Yeong Jeong, Ho-Cheol Kim, Jong Duk Lee, Ji Hyun Lee, Eun hee Lee, Hyoun Wook Lee
Journal: Journal of Clinical Oncology (2014)

e22183 Background: Heat Shock Protein 90 (Hsp90) is an ATP-dependent molecular chaperone that was required for the stability and function of more than 200 signaling proteins that promote cancer cell growth and/or survival. It exists as multiple isoforms that includes Hsp90-alpha and Hsp90-beta in the cytoplasm and GRP94 and TRAP1 localized to the ER and mitochondria, respectively. We investigated the relationship with clinical outcome and the expression of Hsp90-beta, GRP94 in the resected non-small cell lung cancer (NSCLC) patient. Methods: We obtained surgical tissue specimens from 208 patients with NSCLC (stage IA, 40; stage IB, 57; stage IIA, 22; stage IIB, 50; stage IIIA, 27; stage IIIB, 12) who underwent surgical resection of their tumors for immunohistochemical analyses of Hsp90-beta, GRP94. Clinical characteristics, survival were analyzed according to immunohistochemical expression of Hsp90-beta, GRP94 using the χ2 test, Kaplan–Meier method, and Cox proportional hazard model. Results: No correlations were observed between the expression of Hsp90-beta, GRP94 and several clincopathological factors. In a survival analysis, the expression of Hsp90-beta was significantly related to overall survival (OS, log-rank test, p=0.021). The OS was 95.97 months (95% confidence interval[CI], 48.31~143.63) with the low expression group of Hsp90-beta, as compared with 31.6 months (95% CI, 10.58~52.62) with high expression group (hazard ratio[HR], 1.95; 95% CI, 1.08~3.48). The expression of GRP94 was also significantly related to OS(log-rank test, p=0.036). The OS was 72.43 months (95% CI, 47.58~97.29) with the low expression group of GRP94, as compared with 32.27 months (95% CI, 18.48~46.06) with high expression group (HR, 1.64; 95% CI, 1.03~2.63). Conclusions: We found that the immunohistochemically high expression of Hsp90-beta, GRP94 were independent prognostic factors for reduced survival, although further large prospective studies are needed to validate our findings.
High-grade endometrial cancer: Revisiting tumor size and the lower uterine segment.
Authors: Kemi M. Doll, Sheri Denslow, Jill Tseng, Paola A. Gehrig, Amanda Nickles Fader
Journal: Journal of Clinical Oncology (2013)

5589 Background: Tumor size is an independent poor prognostic factor in endometrial cancer, while tumor location has shown mixed results, with few studies addressing high-grade disease. We aim to determine if tumor size (TS) or lower uterine segment involvement (LUS) is associated with nodal disease and recurrence in high-grade endometrial cancer. Methods: In an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer (grade 3 and all non-endometrioid histologies), records were reviewed for demographic, pathologic, and treatment data. Recurrence as a function of tumor size and location were analyzed using logistic regression and exact tests for significance. Hazard ratios were calculated. Results: 208 patients with high-grade histology were identified from Jan 2005 to Jan 2012 with 188 patients having tumor location identified and 183 having tumor size reported. Both pelvic and para-aortic lymphadenectomy were completed in 100% of patients. There were 75 endometrioid (36.1%), 35 papillary serous (16.8%), 12 clear cell (5.8%), 26 carcinosarcoma (12.5%), and 60 (28.8%) with undifferentiated or mixed histology. Median follow up time was 17.2 months (0.2 – 67.6 mo) with 55 recurrences. LUS tumors were more likely to have pelvic and para-aortic nodal disease (OR 3.83, 95%CI 1.70 – 8.60, OR 5.13, 95% CI 1.96 – 13.45) and increased recurrence rates (HR 2.21, 95% CI 1.16-4.20) on univariate analysis. Tumors size ≥2cm was associated with pelvic nodal disease (27.4% vs. 0%, p = 0.01; OR 10.00, p = 0.01). TS was not independently associated with recurrence and patterns of failure did not significantly differ with LUS involvement. Conclusions: In patients with clinically early stage, high-grade endometrial cancers, TS and LUS tumor location are significantly associated with lymph node metastasis and advanced stage disease at the time of comprehensive surgical staging. Tumor location in particular is strongly associated with distant nodal disease and is a poor prognostic indicator for recurrence. Studies evaluating the role of adjuvant therapy based on tumor size and tumor location would be helpful in improving patient related outcomes.
Hepatitis B virus screening before adjuvant chemotherapy in patients with early stage breast cancer: A cost-effectiveness analysis.
Authors: William W. L. Wong, Lisa K. Hicks, Hong-Anh Tu, Murray Krahn, Kathleen I. Pritchard, Jordan J. Feld, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2015)

6617 Background: The seroprevalence of Hepatitis B virus (HBV) infection among Canadian was 0.4%, and 1.6% among immigrants. Most infected individuals have clinically silent disease. Cytotoxic chemotherapy causes reactivation in 30% of the HBV infected patients. This can be severe and fatal, may also lead to interruption of chemotherapy. HBV screening before adjuvant chemotherapy (ADJ) for breast cancer (BC) seems to be a plausible strategy. Our objective is to estimate the health and economic effects of HBV screening strategies. Methods: We developed a state transition microsimulation model to examine the cost effectiveness of 3 strategies for 55 year old BC patients undergoing ADJ: (1) No screen; (2) Screen Imm: Screen immigrant only and treat; (3) Screen all: Screen all and treat; with antiviral therapies. In the model, health states were constructed to reflect the natural history of BC and HBV. Model data were obtained from published literature. We used a payer perspective, a lifetime time horizon, and used a 5% discount rate. Results: Screen all would prevent 38 severe reactivations (SR), 9 deaths from reactivation (DR), 21 chemotherapy interruptions (CI), 32 decompensated cirrhosis (DC), 38 HCCs, and 56 HBV deaths per 100,000 persons screened over the lifetime of the cohort. Screen Imm would prevent 29 SR, 7 DR, 16 CI, 23 DC, 27 HCCs, and 41 HBV deaths. Screen all was associated with an increase of at least 0.0034 quality adjusted life years (QALY) and cost C$164 more per person, translating to an incremental cost effectiveness ratio (ICER) of C$47,808-76,527/QALY gained compared with No screen, depends on different antiviral therapies. Screen all was the most cost effective, while Screen Imm was ruled out due to extended dominance (ED) by No Screen and Screen all. Conclusions: HBV screening before ADJ for BC patients would prevent a significant number of reactivations, and is likely be cost effective. Strategy Cost($) QALYs VS no screen Sequential ICER($) DCost($) DQALYs ICER($) No screen 53,986 10.4345 - - - - Screen Imm 54,120-54,203 10.4361-10.4361 134-217 0.0016-0.0017 82,188-130,084 ED Screen all 54,150-54,252 10.4379-10.4379 164-266 0.0034-0.0035 47,808-76,527
Next generation sequencing of stool specimens from patients with metastatic renal cell carcinoma (mRCC) defines a bacterial profile associated with treatment-related diarrhea.
Authors: Sumanta Kumar Pal, Sierra Mi Li, Yulan Lin, Manasvi Pinnamaneni, JoAnn Hsu, Hanjun Qin, Xiwei Wu, Paul Henry Frankel
Journal: Journal of Clinical Oncology (2015)

e15580 Background: In patients with mRCC receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), diarrhea can be problematic. All grade diarrhea and grade 3-4 diarrhea occurs in roughly 50% and 10-15% of patients receiving VEGF-TKIs, respectively, but the etiology remains unknown. Methods: Eligible patients had mRCC and were receiving an FDA approved VEGF-TKI. Stool was collected via a standardized protocol and total genomic DNA was isolated using the PowerSoil DNA isolation kit (Mo Bio, USA). A standard PCR protocol was used to amplify bacterial 16S rRNA genes from all samples and PCR primers were then used to amplify the V4 and V5 regions of the 16S rRNA. Paired-end sequencing 2X100bp was performed by Illumina HiSeq 2000, sequences were clustered at 97% similarity with USEARCH algorithm, and a close-reference approach was used for OTU picking against Greengene database. Non-clustered analyses were also performed, comparing bacteria abundance between patients with diarrhea to those without at the time of stool collection. Results: Preliminary spike-in experiments using increasing proportions of Salmonella typhimurium were used to validate our methodology; these data will be presented. Of the 26 patients consented, 23 patients submitted stool specimens and 20 had sufficient data for the current analysis. Amongst these 20 patients, the median age was 63 and the majority of patients (60%) were intermediate risk by Heng criteria. Eight patients (40%) were receiving VEGF-TKI therapy in the first-line setting. Across all lines of therapy, the most commonly used VEGF-TKI was sunitinib (44%). A total of 247 genera and 346 bacterial species were identified. Clustering based on incurred toxicity suggested that Prevotella spp and Bacterioides spp were negatively and positively associated with the risk of diarrhea, respectively (P < 0.05). Conclusions: While Prevotella spp may have a protective effect, Bacteroides spp may be associated with a higher risk of VEGF-TKI-related diarrhea. Funding has been obtained to perform a validation study in an expanded cohort with sequential specimen collection.
Randomized phase 2 study to assess the safety and efficacy of CRLX101 in combination with bevacizumab in patients (pts.) with metastatic renal cell carcinoma (RCC) versus standard of care (SOC).
Authors: Martin Henner Voss, Andrea Coates, Edward Graeme Garmey, Naomi B. Haas, Thomas Hutson, Stephen Michael Keefe, Robert Motzer, Anthony Piscitelli, Nicholas J. Vogelzang, Robert A. Figlin
Journal: Journal of Clinical Oncology (2015)

TPS4579 Background: Up to 30% of pts. with RCC present with metastatic disease and 5-year survival among these pts. is less than 10%. VEGF-targeted and mTOR inhibiting drugs constitute SOC in this setting but anti-tumor effects are generally short-lived and there exists a pressing need for new therapeutic strategies. Among pts. with tumors progressing through multiple prior lines of therapy, the GOLD trial (Motzer et al., Lancet Oncology 2014) reported that sorafenib and the comparator agent dovitinib achieved PFS of approx. 4 mos. CRLX101 is a novel camptothecin (CPT)-containing nanoparticle drug conjugate that delivers sustained levels of active CPT into cancer cells while reducing systemic exposure and toxicity. In addition to its topo-1 effect, CRLX101 durably inhibits HIF-1α, a hypoxia-induced transcription factor implicated in tumor angiogenesis, metastasis, and resistance to VEGF inhibitors. Clear cell RCC (ccRCC) accounts for approx. 80% of RCC and is characterized by high levels of HIF-1α, providing an ideal clinical setting in which to evaluate potential synergy between CRLX101 and the VEGF inhibitor bevacizumab (BEV). Phase 2 data presented separately at this conference highlight notable signals of RCC activity for this combination with objective response rate (ORR) and median progression free survival (mPFS) exceeding 20% and 9 mos., respectively. Methods: This randomized clinical trial is being conducted at approx. 40 U.S. cancer centers and will enroll 110 pts. with advanced, unresectable metastatic RCC who have completed 2 or 3 prior regimens of therapy. The primary endpoint will compare PFS among 90 ccRCC pts. treated with concurrently administered CRLX101 + BEV vs. SOC (any approved agent per investigator choice not previously used in the same patient). Statistical power is set at 80% to detect an increase in mPFS from 3.5 mos. to 5.8 mos. (HR~0.6). Secondary/exploratory endpoints incl. OS, ORR, safety, PK, and plasma biomarkers of efficacy. Additionally, 20 pts. with non-ccRCC histology will be evaluated independently. Enrollment is ongoing and is expected to be complete by the end of 2015. Clinical trial information: NCT02187302.
Cervicovaginal Bacteria May Influence HIV Risk
Authors: M.J. Friedrich
Journal: JAMA (2017)

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