tbuckley/cabot-search huggingface dataset:
Continued Endemic Wild Poliovirus Transmission in Security-Compromised Areas — Nigeria, 2016
Authors: Chimeremma Nnadi, Eunice Damisa, Lisa Esapa, Fiona Braka, Ndadilnasiya Waziri, Anisur Siddique, Jaume Jorba, Gatei wa, None Nganda, Chima Ohuabunwo, Omotayo Bolu, Eric Wiesen, Usman Adamu
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On August 10, 2016, 2 years after the most recent wild poliovirus (WPV) case was reported in Nigeria (in July 2014) (1), two WPV cases were reported in the northeastern state of Borno, which has been severely affected by insurgency-related insecurity since 2013. On September 9 and 26, 2016, two additional WPV cases were reported in Borno in children whose families migrated from security-compromised, inaccessible areas of the state. All four cases were WPV serotype 1 (WPV1), with genetic differences indicating prolonged undetected transmission. A large-scale emergency response plan was developed and implemented. The plan initially called for vaccination of 815,791 children during August 15-18 in five local government areas (LGAs) in the immediate vicinity of the first two WPV cases. Subsequently, the plan was expanded to regionally synchronized supplementary immunization activities (SIAs), conducted during August 27-December 6 in five Lake Chad basin countries at increased risk for national and regional WPV1 transmission (Cameroon, Central African Republic, Chad, Niger, and Nigeria). In addition, retrospective searches for missed cases of acute flaccid paralysis (AFP), enhanced environmental surveillance for polioviruses, and polio surveillance system reviews were conducted. Prolonged undetected WPV1 transmission in Borno State is a consequence of low population immunity and severe surveillance limitations associated with insurgency-related insecurity and highlights the risk for local and international WPV spread (2). Increasing polio vaccination coverage and implementing high-quality polio surveillance, especially among populations in newly secured and difficult-to-access areas in Borno and other Lake Chad basin areas are urgently needed.
Estimating the economic burden of gastric cancer in the United States.
Authors: K. B. Knopf, D. B. Smith, J. F. Doan, J. Munakata
Journal: Journal of Clinical Oncology (2011)

e16589 Background: Gastric cancer is a worldwide problem; however, there is little information regarding its economic burden in the US. Our primary objective was to estimate real-world resource use and cost associated with gastric cancer in a US managed care setting. Methods: Retrospective cohort analysis of direct costs and healthcare services use in gastric cancer patients and controls was conducted using IMS LifeLink Health Plan Claims (US) Database. Cases were patients ≥ 18 years of age and newly-diagnosed with gastric cancer in 2007-2009 (date of first gastric cancer diagnosis considered index date). Cases were excluded if they had evidence of any cancer in the 360 days prior to index or evidence of cancer other than gastric in the 4 weeks after index. Controls were individuals without gastric cancer and matched 1:1 with cases (98.4%) on age, gender, region, health plan and payer type, and length of follow-up. Health resource utilization and costs were reported as monthly means. Results: A total of 303 cases were identified and matched to a control. In both groups, mean age was 58, 55% were male and median follow-up was 364 days. Mean monthly costs for hospitalizations, emergency room visits, physician office visits, laboratory and radiology procedures, and pharmacy services were all significantly higher for cases than controls (p<0.0001). Total mean monthly costs were $10,653 for cases and $571 for controls. 75% of cases were hospitalized during follow-up vs. 9% of controls (p<0.0001) and mean monthly cost of hospitalizations was 35 times higher for cases than controls ($6,511 vs. $182). 92% of cases incurred a radiology procedure vs. 53% of controls (p<0.0001) and mean monthly cost of radiology procedures was 24 times higher for cases than controls ($997 vs. $41). Mean monthly drug cost for cases was $1,083 vs. $115 for controls. Conclusions: The mean total monthly healthcare cost for newly-diagnosed gastric cancer patients was 18 times higher than that of similar plan enrollees without gastric cancer. The largest difference was in inpatient costs, followed by drug and radiology costs. Although gastric cancer is less prevalent in the US, on a per patient basis, this disease appears to be associated with significant costs.
Neutropenic risk, use of colony-stimulating factors, and impact on the relative dose intensity of administered chemotherapy.
Authors: W. B. Webb, Y. Wu, H. Head, S. Singh, G. H. Lyman
Journal: Journal of Clinical Oncology (2010)

6088 Background: Relative dose intensity (RDI) is an important prognosticator of therapy outcome, but also increases the risk of febrile neutropenia (FN). ASCO and NCCN guidelines recognize this tradeoff and recommend targeted prophylactic use of colony stimulating factors (CSFs) to limit the risk of FN while maximizing the benefit of chemotherapy. This study sought to define current practice concerning these issues. Methods: Data were extracted from the records of 947 adult cancer subjects treated between 1/2007 and 2/2009 at a 29 center community oncology practice. Subjects >18 years with a primary tumor type of breast, ovary, colorectum, lung, or lymphoma were included. RDI was calculated by dividing the delivered dose intensity by that reported in the NCCN guideline regimens. FN risk was determined using the reported NCCN guideline regimen risk and the logistic regression FN model of Lyman et al. Results: The Table shows no significant difference between the mean RDI for subjects receiving or not receiving CSFs when stratified by NCCN regimen risk for low (p=0.871), intermediate (p=0.288), and high (p=0.106) risk subjects. When mean RDI was stratified by CSF use and Lyman model score, there was no significant difference between the RDI for low risk subjects (p=0.195); however, intermediate (p<0.001) and high (p<0.001) risk patients receiving CSFs had significantly higher mean RDIs than those who did not receive a CSF. Conclusions: These results suggest the delivered RDI is influenced by more than regimen risk and that CSF use leads to higher RDI in high-risk patients. However, despite guideline recommendations, the majority of patients in this study had their FN risk managed by dose reduction rather than by CSF use. The findings suggest that a model-guided strategy could allow clinicians to more consistently optimize RDI by using targeted CSF prophylaxis (though this needs further study to be verified). Mean RDI by risk and use of CSF Regimen risk Model risk Low Intermediate High Low Intermediate High No CSF n 338 254 24 330 137 149 Mean RDI 87.76% 84.42% 85.49% 81.24% 92.86% 91.43% CSF n 149 130 50 227 51 51 Mean RDI 87.45% 86.86% 94.66% 83.75% 97.82% 99.12% p value 0.871 0.288 0.106 0.195 <0.001 <0.001 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proventys, Inc. Proventys, Inc. Proventys, Inc.
Prognosis and recurrence pattern of patients with cervical carcinoma and pelvic lymph node metastasis
Authors: E. Shrestha
Journal: Journal of Clinical Oncology (2008)

16585 Background: To investigate the prognostic risk factor(s) and pattern of disease relapse of patients with cervical carcinoma and pelvic node metastasis. Methods: 124 cases of FIGOIB1∼IIA cervical carcinoma with pelvic node metastasis treated from January 1991 to December 2001 were selected for this study. Prognosis and recurrence were retrospectively analyzed using the clinico-pathological data. Results: The over all 5 year survival and disease-free survival (DFS) was 63.3% and 61.4% respectively. Overall recurrence rate was 39.5% (49/124). Intra-pelvic relapse (25/41, 61.0%) was significantly more frequent than extra-pelvic relapse (13/41, 1.7%, P=0.008).Multivariate analysis identified involvement of common iliac node as independent prognostic factor (P=0.035). According to this factor, node-positive patients could be divided into low risk group (without common iliac node involvement, 104 cases) and high risk group (with common iliac node involvement, 20 cases). The DFS were 69.4% and 24.5% respectively which is significantly different (P=0.003). Intra-pelvic relapse was observed in 22.1% of low risk and 25.0% of high risk group respectively, the difference was not significant (P>0.05), however extra-pelvic relapse was seen in 7.7% of low risk and 40.0% of high risk group, and the difference was significant (P<0.001). Conclusions: Common iliac node involvement is the significant factor that influences the prognosis of patients with cervical carcinoma and pelvic node metastasis. According to this factor, survival and recurrence pattern differs significantly. These findings provide important reference for individualized modification and investigation of treatment mode. No significant financial relationships to disclose.
Yoga in a palliative care suite: Promoting self-care amongst nurses and practitioners.
Authors: Cheryl Gancio, Bridget Earle
Journal: Journal of Clinical Oncology (2015)

169 Background: North Shore University Hospital (NSUH) in Manhasset, NY has a thriving in-patient palliative medicine consult service and a 10 bed palliative care suite (PCS). The PCS specializes in managing and treating symptoms as well as the psycho-social, interpersonal and emotional needs of our patients and families. Approximately 80% of the admitted patients expire on the unit. This high rate of patient expiration presents a unique challenge for staff working in this setting. In order to promote self-care and prevent burnout we implemented a yoga program for the nurses and practitioners in the PCS. Our goal was to assess the effectiveness of the yoga program on staff well-being and perceptions on the unit. Methods: We started with an evidence based literature search to validate the high amount of burnout in the clinical setting amongst staff and the benefits of yoga on reducing stress and promoting self-care. A fellow nurse certified yoga instructor was identified to run each session. Participation waivers were obtained from all staff. The yoga program started in June 2013 once to twice weekly in the PCS. All participants were surveyed to evaluate compassion fatigue, burnout and perception of organizational involvement using the professional quality of life scale (ProQOL). Results: There were a total of 23 subjects; 13 (56.52%) participated in yoga and 10 (43.48%) did not. Most of the participants were female and registered nurses. Results of the ProQOL showed no significant difference in compassion fatigue but the majority of subjects reported high perception of organizational involvement from their managers after the program was implemented. Conclusions: The program was feasible, of low cost and sustainable although we did face some challenges. It further identified the value of support from management to improve practitioner self-care and burnout. Our future plans include, assessing effectiveness on a larger scale, offering yoga to patients and family and continuing to implement the project on a more structured basis in the PCS.
A drug-drug interaction (DDI) study to assess the effect of oral galeterone on the pharmacokinetics (PK) of oral midazolam.
Authors: Karen J. Ferrante, Douglas B Jacoby, Daryl Sonnichsen
Journal: Journal of Clinical Oncology (2016)

316 Background: Galeterone (gal) is a semisynthetic steroid that targets androgen receptor (AR) signaling via increased AR protein degradation, inhibition of CYP17 activity, and inhibition of androgen binding to AR. Gal is a novel potential treatment for prostate cancer. In vitro, gal competitively inhibits CYP3A4 (IC 50 = 5.5 μM; midazolam as substrate). This clinical study evaluated whether multiple daily doses of gal alter the single-dose PK of midazolam, a sensitive probe substrate for functional CYP3A4 intestinal and hepatic activity. Methods: In an open-label, fixed sequence, DDI study, 18 healthy male volunteers received midazolam 2 mg Day 1 and Day 5 and gal 2550 mg Days 2-5. Midazolam plasma PK was determined on Days 1 and 5. The effect of gal on the natural log-transformed C max , AUC 0-inf , and AUC 0-t of midazolam was assessed with a linear mixed-effects model; point estimates for geometric means, geometric mean ratios with 90% confidence intervals were determined. Safety was also monitored. Results: The T max of midazolam was not altered by gal coadministration. The &lt; 2-fold increases in midazolam C max and AUCs were statistically significant. For C max , the point estimate of the geometric least squares (LS) mean ratio between the 2 treatments was 1.25 (90% CI: 1.05, 1.48). Higher ratios were observed for the AUC ratios, with LS mean ratio for AUC 0-t of 1.57 (90% CI: 1.43, 1.73) and for AUC 0-inf of 1.58 (90% CI: 1.42, 1.75). The mean midazolam t 1/2 was approximately 76% higher with gal coadministration. Multiple doses of gal were well tolerated with no apparent effect on the safety of midazolam. Conclusions: Per FDA guidance, &lt; 2-fold increases in midazolam C max and AUCs observed with gal coadministration support its classification as a weak inhibitor of CYP3A4. Given the similar or higher in vitro IC 50 ’s for CYP2C8 and CYP2C19, respectively, a comparable or lesser degree of enzyme inhibition is expected for gal 2550 mg daily. Based on these results, concurrent CYP3A4, CYP2C8, and CYP2C19 substrates are not contraindicated in patients taking gal; caution is advised in patients receiving or initiating sensitive CYP3A4, CYP2C8, and CYP2C19 substrates, especially those with a narrow therapeutic range.
The tumor-stromal interaction between the intratumoral Wnt1 and the stromal VEGF-A is associated with angiogenesis in squamous cell carcinomas of the lung
Authors: S. Ishikawa, D. Liu, J. Nakano, T. Nakashima, D. Masuya, K. Kontani, H. Yokomise, C.-L. Huang
Journal: Journal of Clinical Oncology (2005)

7192 Background: Recent studies have reported that the tumor-stromal interaction plays an important role in the tumor progression. The Wnt signaling pathway is also considered to be implicated in the tumor progression through its target proteins. Therefore, we studied on intratumoral expression of Wnt1 in relation to expression of VEGF-A, one of the Wnt-target proteins, among patients with non-small cell lung cancer (NSCLC). Methods: We studied 199 NSCLC patients who underwent at the Second Department of Surgery, Kagawa University from 1996 to 2003. By immunohistochemstry, we evaluated the intratumoral expression of Wnt1, the intratumoral expression of VEGF-A, and the stromal expression of VEGF-A, respectively. Furthermore, we evaluated the intratumoral microvessel density (IMD) using the anti-CD34 antibody. Results: (1) 73.3% of carcinomas had positive expression of Wnt1. There was no difference of intratumoral expression of Wnt1 in relation to tumor histology. The intratumoral expression of VEGF-A was significantly higher in adenocarcinomas than in squamous cell carcinomas (p=0.038). In contrast, the stromal expression of VEGF-A was significantly higher in squamous cell carcinomas than in adenocarcinomas (p<0.001). (2) Among squamous cell carcinomas, the intratumoral VEGF-A expression was likely to be higher in Wnt1-positive tumors than in Wnt1-negative tumors (p=0.053). Furthermore, the stromal VEGF-A expression was significantly higher in Wnt1-positive squamous cell carcinomas than in Wnt1-negative squamous cell carcinomas (p<0.001). In addition, the IMD was significantly higher in squamous cell carcinomas with positive expression of stromal VEGF-A than in those with negative expression of stromal VEGF-A (p=0.008). However, there was no significant correlation between the intratumoral Wnt1 expression and VEGF-A expression in adenocarcinomas. Conclusions: The stromal VEGF-A expression induced by intratumoral Wnt1 was associated with tumor angiogenesis in squamous cell carcinomas of the lung. The Wnt signaling pathway plays an role in the tumor-stromal interaction. No significant financial relationships to disclose.
An international consortium study in chemorefractory metastatic colorectal cancer (mCRC) patients (pts) to assess the impact of FCGR polymorphisms on cetuximab efficacy.
Authors: R. Geva, B. V. Jensen, G. Fountzilas, T. Yoshino, D. Paez, C. Montagut, I. Sougklakos, F. Cappuzzo, A. Cervantes-Ruiperez, D. Papamichael, M. Frattini, B. Vincenzi, T. Macarulla, F. Loupakis, K. G. Spindler, C. Qvortrup, F. Ciardiello, S. Tejpar
Journal: Journal of Clinical Oncology (2011)

3528 Background: Germline variants FCGRIIA-H131R and FCGRIIIA-V158F have been suggested to influence efficacy of IgG1 antibodies trastuzumab and rituximab, primarily with VV or HH SNP (Wen-Kai W et al JCO 21, 2003: 3940-3947, Musolino A et al JCO 28, 2008: 1789-1796). Their role in cetuximab efficacy in mCRC pts is unclear with conflicting publications. A large cohort is needed to provide the statistical power to test this issue. Methods: Tumor and normal tissue/DNA from approximately 900 unselected Chemorefractory mCRC pts treated with cetuximab alone or in combination were collected in an international consortium. We report the results on the first 472 pts, all KRAS WT. A PCR based Taqman assay was used to determine the FCGR SNP. All the samples were analyzed centrally except the Japanese series that was performed locally. Results: Pts included 60.4% males and 39.6% females and received a median of 2 chemotherapy lines prior to cetuximab (range, 1-6). In 90% of pts cetuximab was administered with irinotecan, 10% received oxaliplatin, 5FU or single agent based. Objective response rate (ORR) was 32.2%. Median progression free survival (PFS) was 24.0 weeks (95% CI, 21.3-26.7) and median overall survival (OS) was 58.0w (95% CI, 53.1-62.9). FCGR IIA was obtained in 470 pts (99.6%) and included HR (45.7%), HH (35.5%), and RR (18.7%). FCGR IIIA was obtained in 443 (93.9%) with VF (40.9%), VV (12.6%) and FF (46.5%). Primary analysis included HH vs. the rest for FCGRIIA and VV vs. the rest for FCGR IIIA. ORR were, HH (28.5%) and non-HH (35.0%; P=0.091), VV (39.3%) vs. non-VV (31.8%; P=0.165). Median PFS was, HH (23.8w), non-HH (24.0w; P=0.925), VV (20.0w), non-VV (24.0w) (P=0.948). Median OS was, HH (59.0w), non HH (56.4w; P=0.454), VV (60.6w), non-VV (58.0w; p=0.990). No associations were seen for other SNPs and efficacy. The extended analysis on all pts will be updated for ASCO. Conclusions: Previously reported FCGR polymorphism associations to IgG1 efficacy showed no correlation with cetuximab in KRAS WT mCRC chemorefractory pts in a large international consortium cohort. Cetuximab efficacy reaffirmed results reported in the previous consortium.
Spironolactone: A selective androgen receptor modulator in castration-resistant prostate cancer.
Authors: Philippe Barthelemy, Eva Erdmann, Brigitte Duclos, Jean Pierre Bergerat, Jean-Emmanuel Kurtz, Jocelyn Ceraline
Journal: Journal of Clinical Oncology (2014)

212 Background: Spironolactone is an effective drug to treat arterial hypertension as well as fluid retention and hypokalemia. Recently, some data suggested that spironolactone might induce progression in castration-resistant prostate cancer (CRPC) patients treated by abiraterone acetate, a recently approved selective CYP17 inhibitor. Nevertheless, no biological data are available to explain these clinical observations. The purpose of this study was to identify the potential underlying molecular mechanism. Methods: Effect of spironolactone with or without Abiraterone acetate (AA) on androgen receptor (AR) was assessed on LNCaP cells in this study. We performed a yeast-based functional assay with different levels of spironolactone with and without AA. The nuclear localization and activation of androgen receptor (AR) were detected by immunofluorescence and luciferase assays. Results: Results from the yeast-based functional assay show that the wild type androgen receptor is activated by high concentrations of spironolactone in an androgen-depleted environment. Moreover, spironolactone-induced AR transcriptional activity is downregulated by different AR antagonists as well as high concentrations of AA. These results suggest that spironolactone is possibly a potential AR modulator. Luciferase reporter assays showed that AR transcriptional activity in LNCaP cells was upregulated by spironolactone as well. Finally, AR immunoreactivity was almost nuclear in spironolactone-exposed cells. Taken together, these results suggest that spironolactone is a selective androgen receptor modulator. Conclusions: Spironolactone is a selective androgen receptor modulator and should be used with caution in routine practice in patient with metastatic prostate cancer treated by hormonotherapy especially AA.
Safety and efficacy of addition of VEGFR and EGFR-family small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: A meta-analysis.
Authors: Tomohiro Funakoshi, Asma Latif, Matt D. Galsky
Journal: Journal of Clinical Oncology (2014)

415 Background: The approach of combining cytotoxic chemotherapy with small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a diverse range of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. Methods: PubMed and the ASCO databases were searched up to March 2013. Eligible studies included randomized trials in which the FDA approved TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR), with corresponding 95% confidence intervals (CI) were calculated. Results: A total of 16,011 patients from 43 trials were included. Among the 43 trials, ten met their primary efficacy endpoints. Among the 21 phase III trials, two led to Food and Drug Administration approval for the combination. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). Compared with chemotherapy alone, the addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). Chemotherapy plus TKI was also associated with a significant higher risk of seven of the 11 evaluated individual AEs: neutropenia (RR, 1.18; P =.004), thrombocytopenia (RR, 1.70; P &lt;.001), febrile neutropenia (RR, 1.48; P &lt;.001), hypertension (RR, 3.01; P &lt;.001), skin toxicities (RR, 6.38; P &lt;.001), diarrhea (RR, 2.57; P =.002) and fatigue (RR, 1.35; P &lt;.001). Conclusions: The addition of a VEGFR or EGFR-family TKI to chemotherapy in solid cancers increases the risk of severe toxicities and treatment discontinuations. These findings might explain the general lack of a survival benefit with these regimens.