tbuckley/cabot-search huggingface dataset:
Impact of pharmacy channel on prescription abandonment and adherence to oral oncolytics.
Authors: Michael Edward Stokes, Hans-Peter Goertz, Veronica Alas, Carolina Reyes, Elyse Gatt, Luke Boulanger
Journal: Journal of Clinical Oncology (2013)

6546 Background: Oral chemotherapy is increasingly prescribed to treat cancer. Despite benefits such as convenience of use, concerns have been raised regarding adherence to therapy. The objective was to compare and measure rates of adherence and abandonment in patients filling prescriptions in traditional retail versus specialty pharmacy channels. Methods: Using a retrospective cohort design, we selected patients aged ≥18 years with a prescription for erlotinib, capecitabine, or imatinib during 2007-2011 from a Medco population of both U.S. commercial and Medicare health plans. Patients were classified according to the initial oral oncolytic received and the pharmacy channel providing the medication. Abandonment was defined as a reversal following the initial approval of the prescription claim with no additional paid claims for the agent within 90 days of reversal. Adherence was defined as the proportion of days covered between the date of the first and last oral prescription. Patients were classified as adherent if the proportion of days covered was ≥80%. Unadjusted comparisons of adherence and abandonment measures were assessed using chi-square tests. Logistic regression models adjusted for baseline characteristics were used to examine the impact of pharmacy channel on abandonment and adherence. Results: Among patients treated with an oral oncolytic, 15,071 were prescribed erlotinib, 20,062 were prescribed capecitabine and 7,233 were prescribed imatinib. For all study cohorts, Medco specialty channel had the highest proportion of adherent patients compared with traditional retail (erlotinib 84% vs. 80%, capecitabine 63% vs. 35%, and imatinib 72% vs. 67%, P&lt;.001 all comparisons). Abandonment of the initial prescription was low with overall rates of 1.9%, 1.6%, and 1.2% for erlotinib, capecitabine, and imatinib, respectively. In multivariate models, specialty channel was significantly associated with lower abandonment and increased adherence for each cohort. Conclusions: Pharmacy channel appears to be influential on abandonment and adherence. Lower rates of abandonment and higher rates of adherence were observed among specialty pharmacy patients compared with traditional retail.
Prospective comparison of subcutaneous to intravenous administration of bortezomib in patients with multiple myeloma: Pharmacokinetics, efficacy and toxicity
Authors: P. Moreau, V. Coiteux, C. Hulin, T. Facon, H. van de Velde, M. Acharya, J. Harousseau
Journal: Journal of Clinical Oncology (2007)

8046 Bortezomib (Bz) is a novel proteasome inhibitor that is registered for treatment of relapsed or refractory MM as an IV bolus injection. Animal toxicology studies have indicated good local tolerability and an acceptable PK profile of SC injection of Bz supporting together with preliminary clinical data the exploration of this route of administration in humans. We conducted a randomized trial to compare pharmacokinetics/pharmacodynamics (PK/PD), toxicity and efficacy of SC and IV injections of Bz, both at standard dose of 1.3 mg/m 2 twice weekly for 2 wks (day 1–4-8–11), with 1 wk rest, for up to 8 cycles. From 01/06 to 10/06, 24 pts with relapsed/refractory MM were randomized to receive Bz either IV (arm A, n = 12) or SC (arm B, n = 12); Patients received a median number of 5 cycles in both groups. The local tolerance of SC injections was good. Response rates were similar in both groups (CR+VGPR/PR/MR: 3/2/1 in arm A, vs 3/2/2 patients in arm B. Grade 3 / 4 adverse events occurred in 7 cases in arm A, vs 5 in arm B, leading to study discontinuation in 5 and 3 cases, respectively. PK analysis: average plasma Cmax values were lower for SC as compared to IV (15 ng/mL at day 1, and 23 at day 11, vs 130 and 127, p &lt; .001), but overall systemic availability as measured by plasma AUC values were comparable between SC and IV administration for both day 1 &amp; 11 (145 and 388 ng.h/mL, vs 133 and 386, p =.7 &amp; .98, respectively). Average Tmax values were less than 1 hour for both routes. PD analysis (20S proteasome inhibition): average area under the curve for effect (AUE) values were comparable between SC and IV administration both for day 1 &amp; 11 (761 and 1,324 %.h, vs 1,089 and 1,110, p = .29 &amp; .54, respectively), while average Emax values were lower for SC administration (Emax day 1 &amp; day 11 SC, 58 and 56%, vs 72 and 69% IV, p =.003 &amp; .01 respectively). The overall systemic availability of Bz was comparable between SC and IV administration for both day 1 and 11. Similarly, the average AUE results were comparable between SC and IV, while average Emax was lower for SC administration. Response rates were identical in the 2 groups of patients, with similar toxicity profile. Given the good local tolerance of SC injection, this route of administration could be an alternative option to IV injection. [Table: see text]
Ki67 as a prognostic biomarker for patients with vertical growth phase (VGP) melanomas
Authors: P. Gimotty, D. Guerry, P. VanBelle, K. Montone, M. Guerra, W. Hwang, L. Schuchter, X. Xu, D. Elder
Journal: Journal of Clinical Oncology (2009)

9043 Background: In VGP melanomas proliferation is reflected in dermal mitotic figures (“mitogenic” VGP) and/or tumor cell nests larger than any epidermal nest. An alternative to mitotic rate (MR) to characterize cell proliferation is the expression of Ki67 protein. Since Ki67 is expressed in all phases of the cell cycle except G0, it is potentially a more robust biomarker for proliferation and prognosis than mitoses. Methods: To test the hypothesis that Ki67 would replace MR as a prognostic factor, we did a retrospective cohort study of 432 patients with Stage I/II primary VGP melanomas who had at least 10 years of follow up. Tissue sections were stained using the monoclonal antibody MIB-1 to Ki67 and the % of positive melanoma cells were evaluated by two readers. ROC curves for Ki67 and MR were computed. Predicted probabilities (PP) of 10-year melanoma-specific death were computed from 3 multivariate logistic regression models, one for each biomarker (Models 1 and 2) and one with both (Model 3), controlling for established melanoma prognostic factors (thickness, gender, anatomic site, ulceration, regression and tumor infiltrating lymphocytes), and compared. Cross-validation was used to assess differences between using Ki67 and using MR including the differences in PP, Brier scores and the misclassification rates. A decision curve analysis was done to assess the clinical net benefit of the two. Results: The areas under the ROC curve (AUCs) for Ki67 and MR, both continuous factors, were 0.69 and 0.79, respectively. In the multivariate analysis, Ki67 expression was significant in Model 1 (OR=1.03, 95% CI: 1.01–1.05), mitotic rate was not significant in Model 2 (1.05, 0.99–1.1), and only Ki67 was significant in Model 3 (1.03, 1.01–1.05). The AUCs for the three models were 0.84, 0.84, and 0.85, respectively. Based on cross-validation, there was no difference between the two biomarkers in PP, Brier scores, or misclassification rates. The decision cost analysis demonstrated the same net benefit for the two. Conclusions: A prospective study needs to be conducted to confirm that Ki67 and MR are equivalent. No significant financial relationships to disclose.
Indications for Hematopoietic Stem Cell Transplantation in Patients with Waldenstrom's Macroglobulinemia: A Consensus Project of the EBMT Lymphoma Working Party (LWP)/ European Consortium for Waldenstrom's Macroglobulinemia (ECWM)/International Waldenstrom's Macroglobulinemia Foundation (IWMF)
Authors: Charalampia Kyriakou, Ranjana H. Advani, Stephen M Ansell, Christian Buske, Jorge J. Castillo, Peter Dreger, Morie A. Gertz, Sergio A. Giralt, Veronique Leblond, David G. Maloney, Olivier Tournilhac, Silvia Montoto
Journal: Blood (2017)
Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model
Authors: Kim Anthony-Gonda, Ariola Bardhi, Alex Ray, Nina Flerin, Mengyan Li, Weizao Chen, Christina Ochsenbauer, John C. Kappes, Winfried Krueger, Andrew Worden, Dina Schneider, Zhongyu Zhu, Rimas Orentas, Dimiter S. Dimitrov, Harris Goldstein, Boro Dropulić
Journal: Science Translational Medicine (2019)

Multispecific duoCAR-T cells potently suppress HIV infection in a humanized mouse model.
Ebola in Sierra Leone and DRC: lessons learnt
Authors: Mara Kardas-Nelson
Journal: BMJ (2019)

Sierra Leone experienced an Ebola outbreak from 2013 to 2016. The current outbreak in the Democratic Republic of the Congo just hit the one year mark.1 Doctors Ian Crozier and Eugene Richardson worked in both places. They told <b>Mara Kardas-Nelson</b> about the differences and similarities in the response in the two countries
Characteristics of stage III and IV M0 prostate cancer (PCa) patients in SEER-Medicare who develop bone metastasis (BM) following diagnosis.
Authors: Arif Hussain, Ebere Onukwugha, Jinani Jayasekera, Diane L. McNally, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2012)

e15146 Background: BM is diagnosed in 70-80% of men with metastatic PCa. Less is known about the timing of BM diagnosis following incident non-metastatic PCa and associated patient characteristics. In this study, we determined the incidence and timing of post-diagnosis BM (BMpd) among PCa patients (pts) by incident stage, age, race and year of diagnosis using a large observational dataset. Methods: We analyzed pts aged 66 or older from the linked Surveillance, Epidemiology, and End Results and Medicare (SEER-Medicare) database. Pts with PCa were identified between 2000 and 2007 and were followed until death, Medicare disenrollment, HMO enrollment, or end of the study (December 31, 2009). The cohort included incident stage III and IV(M0) PCa in SEER, and identified BM occurring either within (i.e., +/-) 1 month of the SEER diagnosis month (BM90) or beyond the initial 90-day window (BMgt90) based on the presence of at least one inpatient or one outpatient claim with a diagnosis code of 198.5. We calculated summary and chi-square statistics to examine BMpd, BM90, and BMgt90 by incident stage, age, race and year of PCa diagnosis. Results: Among 9,188 Stage III (72%) and IV(M0) (28%) PCa pts who met inclusion/exclusion criteria, 14.6% (n=1,345) had BMpd: 2.3% (n= 217) had BM90 and 12.3% (n=1,128) had BMgt90. Average age was 72 years and 9% were African American (AA). Incidence of BMpd varied by stage (stage III: 11%; stage IV/M0: 25%; p&lt;0.001) and by age group (66-74 years: 13%; 75-84 years: 19%; &gt;85 years: 22%; p&lt;0.001) but not by race (White: 15%; AA: 16%; Other: 13%; p=0.49). The diagnosis BM90 and BMgt90 varied with stage (stage III: 2% and 9%; stage IV(M0): 4% and 21%; p&lt;0.0001) and age (66-74 years: 2% and 11%; 75-84 years: 3% and 16%; &gt;85 years: 5% and 17%; p&lt;0.001). The incidence of BM decreased over time whether considering BMpd (19% in 2000 to 9% in 2007; p&lt;0.001), BM90 (4% in 2000 to 2% in 2007; p=0.03) or BMgt90 (16% in 2000 to 6% in 2007; p&lt;0.001). Conclusions: BM occurred in only 2% of incident stage III/IV(M0) PCa pts within 1 month of diagnosis, but nearly 15% were diagnosed with BM during a median follow-up of 57 months. Prevalence of BM was highest in stage IV(M0) and older pts.
Factors Associated With Brain Heterogeneity in Schizophrenia
Authors: Luca De Peri, Antonio Vita
Journal: JAMA Psychiatry (2019)

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Innate lymphoid cells link gut microbes with mucosal T cell immunity
Authors: Jim G. Castellanos, Randy S. Longman
Journal: Gut Microbes (2019)

Despite continuous exposure to trillions of microbes, the intestinal immune system protects the mucosa by balancing barrier protection, tolerance, and immunity. As both sentinel and effector, the mucosal innate immune system plays a central role in coordinating these responses. By integrating signals from the intestinal microbiota, mononuclear phagocytes (MNPs) serve as a critical link in regulating effector functions of group 3 innate lymphoid cells (ILC3s). Our recent work identified the role for MNP production of the IBD-linked protein TNF-like ligand 1A (TL1A) in modulating microbial regulation of ILC3 barrier immunity. These findings highlight a broader role for ILC3s in local control of T cell immunity and their potential role in the pathogenesis and treatment of inflammatory disease.
Immunologic changes in patients with metastatic melanoma on bevacizumab and chemotherapy versus chemotherapy alone.
Authors: Aaron Scott Mansfield, Wendy Kay Nevala, Svetomir Markovic
Journal: Journal of Clinical Oncology (2012)

e21112 Background: Metastatic malignant melanoma is difficult to treat and has a poor prognosis. Systemic therapy for metastatic melanoma has had limited success and novel drug combinations need to be tested. To that end, we have combined anti-angiogenic therapy (bevacizumab) with chemotherapy in clinical trials and have shown some clinical efficacy. Vascular endothelial growth factor (VEGF) is increasingly seen as an immunosuppressive factor that hampers dendritic cell maturation and reduces antigen presentation. We have recently shown that tumor-derived VEGF plays a role in Th-2 driven systemic chronic inflammation seen in advanced melanoma patients. Therefore, our data suggest that blocking tumor derived VEGF with the monoclonal antibody bevacizumab may impact immunity in such a way that augments anti-tumor immunity enhancing clinical efficacy. Methods: In order to understand the immune status in metastatic melanoma patients on chemotherapy (n=55) or chemotherapy plus bevacizumab (n=73), we measured levels of 42 cytokines, chemokines and growth factors in plasma by a mulit-plex bead assay. Matched pairs analysis was performed to determine if the average responses of the measured cytokines were different between the patients that received chemotherapy with bevacizumab or chemotherapy alone. The pre-treatment levels were compared with levels drawn four weeks after the first treatment. Results: There were significant differences in IL-1a, IL-1ra, IL-6, IL-8 and IP-10 between patients treated with chemotherapy alone relative to patients treated with chemotherapy plus bevacizumab. In all cases of patients treated with chemotherapy plus bevacizumab, the levels of these cytokines all decreased relative to pre-treatment samples. In patients treated with chemotherapy alone the levels of these cytokines increased relative to pre-treatment samples. Conclusions: Our data suggest that treating patients with the anti-angiogenic drug bevacizumab may affect the plasma cytokine milieu by reducing the level of many key inflammatory cytokines. Therefore, the use of bevacizumab in combination with chemotherapy may augment host immunity and elicit a more effective anti-tumor immune response.
Essential tremor: diagnosis and management
Authors: Vicki Shanker
Journal: BMJ (2019)

ABSTRACT Essential tremor is one of the most common movement disorders in adults and can affect both children and adults. An updated consensus statement in 2018 redefined essential tremor as an isolated action tremor present in bilateral upper extremities for at least three years. Tremor may also be present in other locations, commonly the neck or the vocal cords. Patients with additional neurologic symptoms are now categorized as “essential tremor plus.” Additional clinical features associated with the condition include but are not limited to cognitive impairment, psychiatric disorders, and hearing loss. When treatment is needed, propranolol and primidone are considered first line treatments. Patients who are severely affected are often offered deep brain stimulation. Although the ventral intermediate nucleus of the thalamus is the traditional surgical target, the caudal zona incerta is also being studied as a possible superior alternative. Magnetic resonance imaging guided high intensity focused ultrasound is a newer surgical alternative that may be ideal for patients with substantial medical comorbidities. Current research explores novel oral treatments, chemodenervation, and noninvasive neuromodulation for treatment of essential tremor.
Cancer control in small island nations: from local challenges to global action
Authors: Diana Sarfati, Rachel Dyer, Paula Vivili, Josephine Herman, Dingle Spence, Richard Sullivan, David Weller, Freddie Bray, Sarah Hill, Christopher Bates, Sunia Foliaki, Neal Palafox, Silvana Luciani, Alec Ekeroma, James Hospedales
Journal: The Lancet Oncology (2019)
FDG-PET predicts disease burden in multiple myeloma
Authors: L. Kostakoglu, R. Niesvizky, M. Liu, S. J. Goldsmith, P. Christos, D. S. Jayabalan, M. Coleman
Journal: Journal of Clinical Oncology (2006)

7619 Background: Because of the clinical and biologic heterogeneity of multiple myeloma, staging systems have been developed based on recognition of various prognostic factors. The recent integration of FDG-PET into the diagnostic algorithm may also have prognostic implications. Our aim was to evaluate the value of FDG-PET in determining the extent of disease as a staging tool in MM and to compare PET results with the established staging systems and laboratory data. Methods: Thirty seven patients with MM (mean age: 62±12) underwent a whole body FDG-PET scan at initial staging prior to therapy. FDG uptake was qualitatively scored in the following patterns: minimally diffuse (score 1), focal (score 2), multifocal (score 3), diffuse (score 4) and extramedullary (score 5). Standardized uptake values (SUVmax) were obtained in 780 osseous and extramedullary sites for quantitative evaluation. Additionally, mean SUVmax was calculated in 14 representative anatomic sites in the axial and appendicular skeleton in 20 age-matched control patients with no osseous malignancy. Ratios of the mean lesion SUVmax to the mean SUVmax of corresponding osseous sections from the control group were calculated. A score was obtained for each patient to reflect disease severity by adding the ratio for each lesion. Qualitative and quantitative results were correlated with the tumor burden (paraproteins, free light chains in the serum) and staging scores of Durie-Salmon (D-S) and the international staging systems (ISS). Results: There was good correlation between the quantitative score and both D-S staging and the ISS. However, correlation was stronger with the D-S system compared to that with ISS (r=0.44, p=0.007 vs. r=0.33, p=0.06). There was also good correlation between the quantitative score and the tumor burden (r=0.37, p&lt;0.05). The qualitative scoring system produced a good correlation with the tumor burden (r=0.35, p&lt;0.05). There was no correlation between the qualitative scoring system and D-S staging or ISS (P&gt;0.05). Conclusions: FDG-PET is useful in assessing the extent of disease as a staging tool at initial diagnosis in MM. The scoring system we have developed appears to correlate with the established staging systems and the level of free light chains which may contribute to the prognostic evaluation of patients with MM. No significant financial relationships to disclose.
Effect of obesity on PSA density (PSAD): A new clinical predictor of prostate cancer
Authors: M. Garzotto, S. Mongoue-Tchokote, J. Shannon, L. Peters, M. H. Sokoloff, T. M. Beer, M. Mori
Journal: Journal of Clinical Oncology (2006)

4617 Background: The escalating rate of obesity in the Western world presents a diagnostic challenge when screening for prostate cancer. Increased body-mass index (BMI) disrupts the ability to effectively screen this population due to an associated decrease in serum prostate-specific antigen (PSA) levels and an increase in prostate volume. We therefore sought to understand how BMI impacts the probability of harboring prostate cancer. Methods: Data were collected on 647 referred men with a serum PSA of ≤ 10 ng/ml who underwent an ultrasound-guided prostate biopsy. Variables analyzed included: age, BMI, digital rectal exam (DRE), PSA, PSAD (i.e. PSA ÷ prostate volume), prostate volume, hypoechoic lesions on ultrasound and cancer on biopsy. A one-way ANOVA was performed to determine differences in log 2 (PSAD) among BMI groups (&lt;25 kg/m 2 vs. 25–30 kg/m 2 vs. &gt;30 kg/m 2 ). Multivariate logistic regression analysis was performed to estimate the odds-ratio (OR) and 95% confidence intervals (CI). Results: Prostate cancer was detected in 19.2 % of patients. ANOVA showed the mean PSAD to be significantly different in the three BMI groups (F value = 7.1, p = .0009). The mean PSAD significantly decreased as the BMI level increased (p = .0002). Independent pre-biopsy predictors of prostate cancer were tabulated (see below). Conclusions: Obesity was associated with a decrease in PSA density. The multivariate logistic regression revealed that the effect of PSAD on cancer detection was significantly modified by BMI. Specifically, the OR associated with a doubling of PSAD was 1.7 when BMI was &lt;25 kg/m 2 vs. 2.1 when BMI was ≥25 kg/m 2 ). This interaction was an independent predictor of prostate cancer risk, along with DRE and ultrasound findings. These data underscore the need to consider BMI as a potential effect modifier of traditional clinical risk factors for prostate cancer. The dramatic rise in obesity in the United States makes this effect modification particularly relevant. [Table: see text] No significant financial relationships to disclose.