tbuckley/cabot-search huggingface dataset:
Using algorithms to standardize peripheral stem cell mobilization and collection.
Authors: Dawn Jourdan, Kim Schmit Pokorny
Journal: Journal of Clinical Oncology (2014)

233 Background: Review of peripheral stem cell (PSC) collection data showed a significant practice variation in the number of collections, minimum and target dose of PSC collected, and the use of plerixafor for mobilization of PSC. In addition, the peripheral blood CD34 test was not used to determine the start of collections. At this institution, approximately 100 adult patients collect PSC per year with a mean of 3 (range 1-10) collections per patient. Cost per patient varied from $9,800 to $74,600. Methods: Patients planned to undergo an autologous PSC transplant, 18 years and older, were included. Three years of historical data was analyzed and pilot algorithms developed. Algorithms identified when to start and stop collecting, if and when to start plerixafor, and when to re-evaluate the mobilization method. The use of the peripheral blood CD34 test was implemented. The minimum CD34 cell dose was standardized and the target dose was lowered. The entire collection process was reviewed and additional efficiencies were identified. Results: Analysis of 42 patients’ collections January 2013 through July 2013 revealed that the majority of patients (86%, n=36) were able to achieve the target CD34 dose in 3 or fewer collections (mean = 1.5, range = 1-4). The algorithms were followed in 41/42 patients. The patients’ engraftment and length of stay were similar to historical data suggesting that the minimum and target CD34 dose is acceptable. Work flow changes associated with the use of the peripheral CD34 test didn’t produce any negative impact on the departments involved. The initial collection cost decreased by approximately $2,000 and each additional collection decreased by approximately $800. The average cost savings per patient was $9,500. The actual total cost savings over a six month period was $303,204. The mean total number of collections per patient decreased from 3 to 1.5. Conclusions: Standardization of practice can result in significant cost savings. Using an expensive drug (plerixafor) in well-defined situations makes good clinical and economic sense. Reviewing processes also identifies additional opportunities in which to make positive changes.
<i>In vivo</i> confocal microscopy of multiple myeloma associated crystalline keratopathy
Authors: Caleb Busch, Shizuka Koh, Yoshinori Oie, Michiko Ichii, Yuzuru Kanakura, Kohji Nishida
Journal: American Journal of Hematology (2017)

An 81-year-old Japanese woman, who had been diagnosed 5 years previously with smoldering multiple myeloma, was referred to the ophthalmology department for blurry vision. She reported the visual change when new clinical symptoms associated with anemia and light chain deposition disease of the kidney were being evaluated. Serum IgG protein was 40.6 g/L. Bone-marrow biopsy demonstrated 21.8% involvement of myeloma cells. She had stage II disease according to the International Staging System. Her best-corrected visual acuity was 20/16 in both eyes. Examination with slit-lamp (Figure 1, upper left image) and anterior segment optical coherence tomography (Figure 1, upper right image) revealed small, white, crystalline deposits in both eyes throughout all layers of the cornea including the epithelium, stroma, and endothelium. In vivo confocal microscopy (Figure 1, bottom image) showed intracellular hyperreflective deposits in the epithelium, rod-like hyperreflective deposits in the stroma and hyperreflective deposits in the endothelium of both eyes. Crystalline keratopathy is reported to be observed in <1% of patients with multiple myeloma.1 It is thought that the crystals form due to immunoglobulin light chain deposition within the cornea, and originate from the tear film.2 Deposits can have various manifestations in the corneal epithelium and anterior stroma, but are rarely seen as deep as the endothelial layer.3 Our case highlights the possible formation of corneal crystalline deposits in the endothelial layer secondary to multiple myeloma and is consistent with recent findings which have also used in vivo confocal microscopy to demonstrate hyperreflective endothelial cells in a patient with multiple myeloma.4 In vivo confocal microscopy is capable of showing the nature and depth of corneal crystalline deposits in each corneal layer at the cellular level. Pathologic evaluation of corneal tissue using in vivo confocal microscopy can be invaluable in documenting immunoglobulin light chain deposits and in guiding systemic evaluation. Further investigation of endothelial involvement using in vivo confocal microscopy in a greater number of patients will contribute to understanding the pathophysiology of multiple myeloma associated crystalline deposits. Slit-lamp examination showing corneal crystalline deposits (Upper left). Optical coherence tomography of the cornea shows small, white deposits throughout all layers of the cornea (Upper right). In vivo confocal microscopy is able to visualize crystalline deposits in each layer of the cornea: Intracellular hyperreflecctive deposits in the epithelium, rod-like hyperreflective deposits in the stroma and hyperreflective deposits in the endothelium were observed (Bottom). All authors contributed to patient management and writing of the report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Prostate biopsies using both gray scale and 3D color flow power doppler ultrasound (3DCFPDU).
Authors: Michael J. Dattoli, Richard A Sorace, Stephen M Bravo, David G. Bostwick
Journal: Journal of Clinical Oncology (2015)

103 Background: Historically, prostate cancer (CAP) is identified through random biopsies. Experts usually recommend 10-12 core transrectal ultrasound guided biopsies (TRUS). This often leads to sampling errors with missed diagnosis, delayed and repeated biopsies, understaging and finding indolent CAP leading to over treatment. Advances in 3DCFPD imaging suggest that selective biopsies may be superior to standard TRUS biopsies. Methods: 192 consecutive patients were biopsied (Feb. 2012 – July 2014) in the dorso-lithotomy position with local anesthesia. Median number of biopsies per patient = 8; total number of cores = 1,520. Only 3 patients had not been previously biopsied (median previous biopsies = 2). We studied tumor detection rate using combined gray scale and 3DCFPD with direct sampling of specific regions using the transperineal brachytherapy template guided method as a simple outpatient procedure. Inclusion criteria were abnormal DRE, PSA kinetics 0.75ng/mg/yr, PSA &gt;10 and % free PSA &lt;17. PSA density 0.27. Cores were stratified into 4 risk groups: 1) hypoechoic lesion (72 patients, 648 cores); 2) hypervascular lesion (26 patients, 182 cores); 3) hypoechogenic with hypervascular pulsatile vessels synchronous and coinciding with normal cardiac pulse (32 patients, 256 cores); and 4) hypoechogenic with hypervascular non-pulsatile vessels suggesting independent vascular flow consistent with neoplasm (62 patients, 434 cores). Isoechoic regions were not biopsied. Subgroups were analyzed using chi-square, student t-test, and logistic regression. Results: The diagnostic yield associated with Group 4 was statistically significantly higher compared to: 1.) 20% biopsy positive (p &lt;0.5); 2.) 19% biopsy positive (p &lt;0.3); 3.) 55% biopsy positive (p &lt;0.1); 4.) 97% biopsy positive (p &lt;0.1). Only Group 4 revealed a greater number of Gleason 7-10 CAP (p &lt;0.1). Conclusions: Transperineal template guided biopsies with gray scale and 3DCFPD are highly effective and cost effective. This may lead to reducing the number of prostate biopsies performed, better staging and allowing for enhanced detection of serious CAP by targeting the most suspicious lesions. Additional research should study the diagnostic gain with 3DCFPD.
Regorafenib for previously treated metastatic colorectal cancer (mCRC): A subgroup analysis of 364 patients in the USA treated in the international, open-label phase IIIb CONSIGN study.
Authors: Udit Verma, Yull Edwin Arriaga, Heinz-Josef Lenz, Charles A. Henderson, Jyotsna Fuloria, Thomas H. Cartwright, Ali Khojasteh, Philip J. Stella, Marc Saltzman, Allen Lee Cohn, Philip Agop Philip, Christian Kappeler, Joachim Kalmus, Axel Grothey, Eric Van Cutsem, Howard S. Hochster, Francis P. Arena
Journal: Journal of Clinical Oncology (2016)

735 Background: In the phase III CORRECT study, regorafenib significantly improved overall survival and progression-free survival (PFS) vs placebo in patients with treatment-refractory mCRC. CONSIGN (NCT01538680) was a large phase IIIb study that included 2872 patients from 25 countries; it was designed to provide continued access to regorafenib for patients with mCRC who failed standard therapy and to further characterize the safety of regorafenib. In CONSIGN, adverse events (AEs) and PFS were consistent with those reported in phase III studies. We present a retrospective subgroup analysis of patients enrolled in CONSIGN in the USA. Methods: Patients with mCRC who progressed on standard therapies and had an ECOG PS 0─1 received regorafenib 160 mg QD for the first 3 weeks of each 4-week cycle. Treatment was continued until disease progression, death, or unacceptable toxicity. The primary endpoint was safety. PFS (per investigator) was the only efficacy variable assessed. Results: A total of 364 patients in the USA were assigned to treatment (all evaluable for safety). The median age was 60 years; 38% and 62% had ECOG PS 0 and 1, respectively. KRAS mutation was present in 59%, KRAS wt in 38%; 74% had ≥ 3 prior regimens for metastatic disease. Median duration of treatment was 2.3 months (range: 0–30). Median PFS (95% CI) was 2.3 (2.0–2.6) months (2.1 months KRAS wt; 2.3 months KRAS mutant). NCI-CTCAE v4.0 grade ≥ 3 AEs occurred in 81% of patients and were considered drug-related in 53% (Table). Grade ≥ 3 hepatobiliary disorders occurred in 2%. Grade ≥ 3 treatment-emergent laboratory toxicities included bilirubin (9%), AST (6%), and ALT (3%). Conclusions: In patients from the USA enrolled in CONSIGN, the safety profile of regorafenib was consistent with that of the overall population and the known safety profile of regorafenib in mCRC. Median PFS was in the range of that reported in phase III trials. Clinical trial information: NCT01538680. [Table: see text]
Are palliative patients less accepting to self-report symptom measures for clinical management than curative patients?
Authors: Samantha Sarabia, Andrea Perez Cosio, Catherine Brown, Yvonne Leung, Gursharan Gill, Mindy Liang, Sabrina Yeung, Aixin Liu, Lauren Wong, Geoffrey Liu, Doris Howell
Journal: Journal of Clinical Oncology (2015)

79 Background: Patient reported outcome measures (PROMs) are a tool used for collecting patient symptom data in the clinic, prior to the patient’s appointment. Patients being treated with a palliative intent are often assumed to find completing PROM surveys more burdensome than patients being treated with a curative intent. We compared patient acceptability of palliative versus curative patients to complete PROM surveys. Methods: 202 cancer out-patients (120 curative and 82 palliative) at the Princess Margaret Cancer Centre completed a PROM survey using a touchscreen tablet regarding their symptoms of pain. Ten questions assessed patient acceptance of completing PROM surveys. Results: The median age was 60 (range 21-86) and 48% were female. There were no clinically relevant demographic differences between the palliative and curative patients; however there were a higher proportion of palliative patients than curative patients with gynecological (8.3% palliative, 16% curative), lung (5.8% palliative, 10% curative), and gastrointestinal (14% palliative, 28% curative) cancers. There were no significant differences in acceptability between palliative and curative patients (p&gt;0.05, all 10 comparisons). Only 3.6% of palliative patients and 3.3% of curative patients reported that completing the survey made their clinic visit more difficult; 16% of palliative patients and 11% of curative patients found the survey to be time consuming; no palliative patients and only 0.83% of curative patients found the questions upsetting or distressful. 93% of palliative patients and 92% of curative patients were happy to complete the surveys on a touchscreen tablet. Overall 62% of patients surveyed were willing to complete surveys at every visit (56% palliative and 67% curative, p&gt;0.05). Conclusions: Palliative and curative patients appear to have an equally high level of acceptance of PROM surveys, though a significant minority would have problems with completing them at every visit. Further research using mixed-methods analysis will be done to better understand the factors limiting the overall willingness of both palliative and curative patients to complete the survey on a regular basis.
NBI-assisted cystoscopy to improve follow-up of patients with transitional cell carcinoma of the bladder.
Authors: Andreas Eisenhardt, Lucas Hirner, Herbert Ruebben
Journal: Journal of Clinical Oncology (2016)

400 Background: Narrow Band Imaging (NBI) is a new technique of urethrocystoscopy, in which only a certain bandwidths of illumination (415 (blue) and 540nm (green)) of the spectrum is used to detect urothelial carcinoma. The aim of the investigation was to analyse the potential benefit of NBI in the follow up of patients with transitional cell carcinoma of the bladder. Methods: In the time between August 2013 until August 2014, patients with history of transitional cell carcinoma of the bladder, who presented for follow-up cystoscopy , were either examined via flexible white light endoscopy [WLE] plus second look WLE (n = 317, controls) or second look NBI-cystoscopy alone (n = 308) in the same session. Results: Rates of recurrences were similiar in both groups (NBI 95 (25%); WLE 85 (26.8%)). NBI after WLE identified more tumours in 21 patients (6.1 vs. 3.81). In 9 patients NBI showed no vascularization in suspicious areas. In the control arm, in 9 cases more tumours (4,67 vs. 3.33) were identified in the second WLE. After macroscopical identification of a recurrence, the time since the last resection was measured (WLE 10,67 months, NBI 16,85 months). Conclusions: While the number of patients with recurrent bladder cancer is not influenced by the use of NBI, the additional use of NBI in the follow-up cystoscopy of patients after transurethral resection of superficial bladder cancer (TUR) leads to an increased number of detected tumors. A part of the additionally detected tumors can be explained by the double examination. In addition NBI appears to provide a hint in individual cases whether a TUR is necessary at all.
Association of CT antigen expression and survival in stage III melanoma.
Authors: N. H. Turner, T. John, S. Deb, A. M. Campbell, A. Azad, P. C. Boutros, Y. Chen, J. S. Cebon
Journal: Journal of Clinical Oncology (2011)

8556 Background: Patients with advanced (AJCC Stage III & IV) malignant melanoma (MM) have variable outcomes despite similar stage. Defining prognostic factors is important to identify patients most likely to benefit from novel therapies. Cancer Testis antigens (CTAg) are immunogenic molecules expressed in normal testis and some cancers including MM. CTAg expression increases with stage. We recently reported that CTAg expression conferred poorer progression free survival (PFS) but not overall survival (OS) in patients with Stage II MM. This may be due to emerging anti-cancer immunity, with antibodies to CTAg developing with disease progression. Here we investigate stage III and IV patients to determine the prognostic impact of CTAg expression in advanced MM. Methods: A paraffin embedded tissue microarray (TMA) was created from tumors of patients with MM undergoing lymphadenectomy or metastectomy from 2005 to 2007. The TMA was stained with a panel of antibodies against the following CTAg: MAGE-A1, MAGE-A3/4, NY-ESO-1, GAGE, SAGE1, NXF2/CT39, ACTL8/CT57, MAGEC1/CT7, MAGEC2/CT10 and CT45. Tumor infiltrating lymphocytes were characterized by CD8, CD4 and FoxP3 staining. T-regulatory (Treg) lymphocyte rates were assessed by CD8:CD4 and CD8:FoxP3 ratios. An experienced pathologist reviewed all samples, and results were correlated with clinical parameters. Results: 62 stage III and 94 stage IV MM were included. Frequencies of CTAg expression were similar between stage III and IV; e.g. MAGE A1 (42% vs 58%), 57B (39% vs 38%), NY-ESO-1 (55% vs 46%). In stage III tumors, higher rates of CTAg expression, compared with no expression, was significantly associated with both improved PFS (median: 69 vs 17mths) [p=0.02], and OS (100 vs 46 mths) [p=0.038]. Furthermore, a high CD8:Treg rate was associated with improved PFS (82 vs 21 mths). For stage IV patients no association was seen between CTAg expression and survival. Conclusions: In contrast to previously reported findings in stage II MM, CTAg expression was associated with improved PFS and OS in stage III disease. In addition, a high CD8:Treg ratio conferred better outcomes. The clinical impact of emergent spontaneous immunity against CTAg warrants further investigation in patients with advanced MM.
Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials: an assessment of CYP2D6 or BCRP inhibition by rolapitant
Authors: S. Barbour, T. Smit, X. Wang, D. Powers, S. Arora, V. Kansra, M. Aapro, J. Herrstedt
Journal: Annals of Oncology (2017)

Rolapitant, a long-acting neurokinin (NK)1 receptor antagonist (RA), has demonstrated efficacy in prevention of chemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlike other NK1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined adverse events (AEs) by use versus non-use of drug substrates of CYP2D6 or BCRP.
Combined Akt and MEK pathway blockade in pre-clinical models of enzalutamide-resistant prostate cancer.
Authors: Paul Toren, Soojin Kim, Ladan Fazli, Barry Davies, Martin Gleave, Amina Zoubeidi
Journal: Journal of Clinical Oncology (2016)

192 Background: Despite recent advances with newer androgen receptor(AR) pathway inhibitors, treatment resistance in castrate resistant prostate cancer continues to remain a clinical problem. Co-targeting approaches are of significant interest to slow the progression of disease and delay the onset of resistance. With both Akt and MEK pathways becoming activated as prostate cancer develops resistance to AR-targeted therapy, this study explores co-targeting these pathways in AR positive prostate cancer models. Methods: Using in vitro models of prostate cancer progression from androgen dependent to castrate resistant and ENZ-resistant disease, we evaluated the effect of Akt and/or MEK inhibition with AZD5363 and PD0325901, respectively, on cell proliferation, apoptosis and downstream signalling pathways. For in vivo models, we tested the combination of Akt and MEK inhibition castrated mice bearing MR49F and 22RV1 cells which are resistant to ENZ. Results: Inhibition of Akt reduced S6 phosphorylation, inhibited growth and induced apoptosis in LNCaP-derived cells; the addition of a MEK inhibitor increased apoptosis and cell cycle arrest, but did not further decrease cell proliferation. In contrast, PTEN wild-type 22RV1 cells demonstrated a greater sensitivity to MEK inhibition, but were generally insensitive to Akt inhibition. In vivo, combination of Akt and MEK inhibition resulted in more consistent tumour growth inhibition of MR49F xenografts and longer disease specific survival than Akt inhibitor monotherapy, with induction of pERK staining being evident in some AZD5363 monotherapy treated tumours. Conversely, 22RV1 xenografts had greater resistance to Akt inhibition and greater sensitivity to MEK inhibition. Conclusions: Our data suggest that combination of Akt and MEK inhibition may improve prostate cancer control in ENZ-resistant prostate cancer. Further, with the major effect in both MR49F and 22RV1 xenografts attributable to one inhibitor, our results also suggest the importance of characterizing the dominant oncogenic pathway in each patient’s tumour in order to select optimal therapy.
Using MRI/ultrasound fusion biopsy to detect clinically significant prostate cancer in the African American population.
Authors: Arvin George, Soroush Rais-Bahrami, Jason Rothwax, Minhaj Siddiqui, Lambros Stamatakis, Daniel Su, Chinonyerem Okoro, Dima Raskolnikov, Nabeel Shakir, Annerleim Walton-Diaz, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Maria Merino, Peter A. Pinto
Journal: Journal of Clinical Oncology (2014)

57 Background: African-American (AA) men are at greater risk for prostate cancer (CaP) and experience increased prostate cancer-specific mortality. We aimed to determine racial disparities in CaP incidence, pathology, and anatomy identified on MRI/US fusion biopsy. Methods: Patients who underwent MP-MRI with targeted MRI/US fusion biopsy at our institution between May 2007 and June 2013 were reviewed. AA patients undergoing fusion biopsy were matched by age and PSA with a Caucasian cohort at a 1:2 ratio. MRI and pathologic parameters including lesion location, number of lesions, and Gleason score. Bivariate comparisons were made with the Student’s t-test and Χ 2 analysis. Results: 822 patients had MRI/US fusion biopsy. 127 AA men were paired with a matched cohort of 254 Caucasians. Mean age was 60.2 and 61.4 years and mean PSA was 11.6 and 10.7ng/ml in AAs and Caucasians, respectively. We identified significantly more AA with CaP (49.6% vs 37.4%, p=0.03; Table). AAs also had higher grade disease (Gleason 7-10) versus white men (20.5% vs. 11.8%, p=0.04). Additionally, the diagnostic yield for the AA cohort was significantly higher per sampled lesion (37.5% vs 24.5%, p&lt;0.01), despite no significant differences in % core involvement of the highest risk lesion between the groups. While there was no significant difference in presence of anterior lesions between the groups (15.7% vs 12.9%, p=NS), anterior lesions equally represented the highest risk lesions in both cohorts. Conclusions: MRI/US Fusion-guided biopsy demonstrates increased diagonostic yield/incidence of CaP and higher risk disease in the AA population in an age and PSA matched cohort of Caucasian patients. [Table: see text]