tbuckley/cabot-search huggingface dataset:
P01.100 Tumour treating fields: Acceptable, tolerable, and can we reduce cost?
Authors: A Brodbelt, M Williams, A Thorpe, S Mills, S Price, E Lekka, C Watts, C Davies, M Jenkinson
Journal: Neuro-Oncology (2018)

Tumour treating fields (TTF) are a novel anticancer treatment that uses alternate electrical fields to disrupt cell division. In a randomized controlled trial, TTF significantly improved survival in patients with Glioblastoma. Use of the device is intensive for patients, with almost constant electrode application and battery use. Treatment currently costs €21,000 per month. Methods were explored to reduce cost and to examine acceptance and tolerability in a social health care setting. Three UK centres were offered support for trialing the treatment. Patients with proven MGMT unmethylated glioblastoma, had completed radical chemoradiotherapy, had a performance score >70, and had social support (for placing the electrodes), where approached. Monthly assessments of compliance and quality of life (QOL) (EORTC BT 20), and quarterly MRIs and tolerability questionnaires were completed. Reductions in company support were explored to reduce device costs. Oncologists in one centre declined to support any use of the device, so no patients were approached in that centre. 8 patients were approached in the other two centres, 5 accepted, and 1 further patient had treatment started elsewhere. Company home visits were not offered and clinicians were trained in the use and interface with the equipment. All patients tolerated the treatment. The main reason for patient refusal was monthly travelling for compliance checks. The main adverse comments related to the weight of the mobile battery. Two patients had skin irritation, and two patients found that the only aspect of life affected was showering. Four patients have progressed, but maintained stable QOL scores. Two patients have since died. Tumour treating fields is a well tolerated but intensive treatment, and acceptable to a UK population. At present monthly company support on site is still required, but future improvements in software may allow further reductions in on site support leading to cost reduction. A significant reduction in cost is required to allow routine UK use in a social care setting.
Randomized clinical trial of telephoned-based physical activity intervention in onco-geriatric patients.
Authors: Haritz Arrieta, Cyril Astrugue, Sophie Regueme, Jessica Durrieu, Aline Maillard, Yves Becouarn, Eric Terrebonne, Christophe Laurent, Brigitte Maget, Véronique Servent, Sandrine Lavau-Denès, Jérôme Dauba, Marianne Fonck, Rodolphe Thiébaut, Isabelle Bourdel-Marchasson
Journal: Journal of Clinical Oncology (2018)

10031 Background: Cancer in older patient favors the loose of physical function. Physical activity could be a key factor to diminish the age and cancer-related decline. Methods: We conducted a multicenter open-label 12-month randomized clinical trial with two parallel arms. Onco-geriatric patients with histological confirmation for lymphoma or carcinoma requiring curative treatment were included. Participants were randomly assigned to an intervention (IG) or usual care group (UCG). The IG received individualized phoned physical activity advice. Subjects in the UCG received a booklet with the current national recommendations in physical activity. Results: 301 participants were eligible and randomized. The loose of physical function measured by the Short Physical Performance Battery (SPPB) was experienced likewise in both the IG and the UCG at one year. However, after two years significantly less participants within the IG than the UCG declined in the SPPB score among breast cancer participants (P = .006), females (P = .019), and those with normal nutritional status (P = .040). Linear mixed models showed similar results in both the IG and the UCG in the SPPB, gait speed, the level of physical activity measured using the self-reported International Physical Activity Questionnaire, and verbal fluency at baseline and after three, six, twelve, eighteen and twenty four months (NS). Both the IG and the UCG showed similar results for falls, hospitalization, institutionalization, and death at one and two years (NS). Conclusions: Telephone-based physical activity intervention were not effective to reduce the functional decline at one year, but significant differences in favor of the IG were observed over two years among females with breast cancer and good nutrition subgroups. Clinical trial information: NCT01432067.
TCT-115 Long-Term Follow-up of the PADI Trial: Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia
Authors: Marlon Spreen, Thijs Wakkie, Lukas van Dijk, Jean-Paul de Vries, Evert-Jan Vonken, Jan Wever, Randolph van Eps, Willem Mali, Hans van Overhagen
Journal: Journal of the American College of Cardiology (2018)
Mohs micrographic surgery volume and payment patterns among dermatologists in the Medicare population, 2013.
Authors: Cameron Johnstone, Keith M Joiner, Robert S. Krouse
Journal: Journal of Clinical Oncology (2017)

e21078 Background: Mohs Micrographic Surgery (MSS) has expanded markedly in recent years but there is limited information on volume, practice patterns, compensation or comparative effectiveness data to support preferential use. This study examines patterns of MSS utilization in the Medicare population. Methods: We obtained the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013dataset from CMS.gov. This contains comprehensive payment and utilization data for physician/supplier Medicare Part B Fee For Service final-action non-institutional claims in 2013. For dermatologists as a whole and the subset of dermatologist MSS surgeons, we analyzed provider service volume and reimbursement for all services as well as for malignant skin cancer procedures (destructions, excisions or MSS) in SAS 9.3. Results: Total Medicare funded MSS procedures increased 25 percent from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MSS had significantly more average services per provider (5,419.4 vs. 3,627.1, r = 0.16, p &lt; 0.0001), earned significantly more in average total procedure-related compensation ($475,883.64 vs. $144,564.74, r = 0.49, p &lt; 0.0001) than dermatologists who did not perform MSS, and made up 71.3 percent of the top decile of dermatologists ranked by total payment received from Medicare. Total MSS service volume and compensation was concentrated among a subset of providers: the top quintile in this group (513 – 3,759 procedures) in annual procedure volume performed over 50 percent of total MSS surgeries. MSS providers with higher annual service volumes performed a greater percentage of their total MMS procedure annual totals on lesions located on the trunk, arms or legs versus the head, neck, hands, feet or genitals (r = 0.27, p &lt; 0.001). Conclusions: Mohs Micrographic Surgery is expanding among Medicare beneficiaries. A subset of dermatologists performing MSS accounts for most services and earnings, and performs surgeries more frequently on the trunk or extremities. Further studies are needed incorporating clinical data not available in Medicare billing information to explore implications of these findings for clinical practice.
Patient specific characteristics associated with T-cell expansion for HER2/neu vaccine-primed autologous adoptive T-cell therapy.
Authors: Lisa May Ling Tachiki, Yushe Dang, Jennifer Childs, Doreen Higgins, Kelsey K. Baker, Ted Gooley, Mary L. Disis, William Rayford Gwin
Journal: Journal of Clinical Oncology (2018)

e15041 Background: Adoptive T-cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has shown significant response rates for metastatic melanoma. The need to harvest TIL from a visceral metastatic source for ACT has prevented its further application to other types of cancers. Two prior Phase I/II trials from our group demonstrated the feasibility of expanding and infusing autologous HER2 specific T cells from peripheral blood into advanced HER2+ breast cancer patients who received HER2 vaccination. Given the resource-intensive nature of ex-vivo T cell culture, determining patient specific characteristics predictive of favorable T-cell expansion would allow more optimal patient selection for ACT clinical trials. Methods: Under IRB approved protocols, we collected patient demographics, prior cancer therapies, baseline cell counts, and pathology data from our prior ACT trials in advanced HER2+ breast cancer. Cell expansion was calculated by comparing fold expansion after 24 days of culture from baseline T-cell counts. Pearson’s correlation test, t-test, and ANOVA were used for statistical analysis. GraphPad 7.04 was used for graphing. Results: Retrospective analysis of 26 HER2+ metastatic breast cancer patients who received ACT revealed a median age of 53 years (range 32 – 71). Most patients (16/26) had hormone receptor positive disease. The median cell fold expansion achieved was 7.4 (0.03 – 17.4). Age is negatively correlated with cell fold expansion (*p = 0.003) with a correlation coefficient of -0.56. Baseline lymphocyte count is correlated with cell fold expansion (*p = 0.04) with a correlation coefficient of +0.4. Neither HER2 (p = 0.61) nor hormone receptor status (p = 0.30) have significant correlation with cell fold expansion. Our group previously reported that magnitude of HER2-specific immunity after active immunization influences ex-vivo expansion, though current analysis showed no statistically significant association between timing of vaccine administration and cell fold expansion (p = 0.68). Conclusions: Criteria including age and baseline lymphocyte count may help guide patient selection and treatment prioritization for future ACT clinical trials.
Offer histopathology trainees “golden hellos” to bolster numbers, says college
Authors: Abi Rimmer
Journal: BMJ (2018)

Just 3% of NHS histopathology departments have enough staff to meet clinical demand, a workforce census by the Royal College of Pathologists has found.1

In a report on the census findings, the college proposed a number of solutions to tackle the shortage of histopathologists, including “golden hellos” for specialist trainees in hard to recruit areas.

Almost three quarters (103) of the …
Iron attenuates erythropoietin production by decreasing hypoxia-inducible transcription factor 2α concentrations in renal interstitial fibroblasts
Authors: Norio Suzuki, Yukari Matsuo-Tezuka, Yusuke Sasaki, Koji Sato, Kenichiro Miyauchi, Koichiro Kato, Sakae Saito, Yasushi Shimonaka, Michinori Hirata, Masayuki Yamamoto
Journal: Kidney International (2018)
No improvement in metastatic bladder cancer health disparity over the last two decades.
Authors: Kevin Pan, Amy Klapheke, Rosemary Cress, Stanley Yap
Journal: Journal of Clinical Oncology (2017)

e18076 Background: Bladder cancer (BCa) is one of the top ten most common cancers in the world. However, very few studies have reported on health disparities involving advanced BCa. Methods: Patients with metastatic BCa diagnosed between 1991 and 2014 were identified through the California Cancer Registry. Included in the analysis were age at diagnosis, sex, race/ethnicity, area-based socioeconomic status (SES), first course of treatment, and survival time. Predictors of treatment were identified using logistic regression, and cause-specific survival was analyzed using Cox regression. Results: A total of 3,073 cases of metastatic BCa were identified. Among these cases, 67.39% were male, and 32.61% were female. The race distribution was 74.78% non-Hispanic white (NHW), 6.25% non-Hispanic black (NHB), 12.46% Hispanic and 5.96% NH Asian/Pacific Islander (Asian/PI). A Cox proportional hazards model analysis showed that NHB were more likely to die from BCa. After adjustment for sex, age, and SES quintile, the hazard ratio of overall survival for NHB over NHW was 1.18 (p=0.214) during 1991-2002, but it increased to 1.24 (p=0.041) during 2003-2014. A smaller proportion of NH black patients survived two years after diagnosis (6.5% versus 14.4% NH white, 18.3% Hispanic, and 15.4% Asian/PI). Patients over age 65, female patients and those residing in all but the wealthiest census tracts were less likely to receive chemotherapy with or without local treatment. Patients diagnosed between 2003 and 2014 were 32% more likely to receive chemotherapy than those diagnosed between 1991 and 2002 (p&lt;.001). There was no improvement of overall survival in the most recent time period. Conclusions: There had been no improvement in this heath disparity or in overall survival over the last two decades. Non-Hispanic blacks and patients who were not treated with chemotherapy experienced poorer survival than other groups. [Table: see text]
Functional characterization of VUS mutations found in patients' cell-free circulating tumor DNA (ctDNA) using Precision Cancer Analysis System (PCAS).
Authors: Gabi Tarcic, Daniel A. Simon, Mark Jacobstein, Richard Burnham Lanman, Michael Vidne, Zohar Barbash, Oded Edelheit, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2016)

11576 Background: A major advancement in patient diagnosis and monitoring is the use of ctDNA analysis using next-generation sequencing. Sequencing of patient samples using Guardant Health’s 70-gene panel identifies Variants of Unknown Significance (VUS). Here, we investigate the functional significance of these variants by utilizing the NovellusDx PCAS, which monitors the activity level of signaling pathways by means of a transfected cell-based assay. As a functional platform, PCAS reveals activated pathways regardless of the type of mutation, i.e., whether it is a known mutation or a VUS Methods: We investigated the VUS mutations that appear most frequently in a cohort of 10,168 patients that were tested with the Guardant360 ctDNA panel at its CLIA-certified, CAP-accredited clinical laboratory. The test is sensitive to a single DNA fragment of mutated ctDNA in a 10 ml blood sample (analytic specificity for SNVs of > 99.999 %). We synthesized the mutated genes’ and mapped them to their major signaling pathways. Using the PCAS platform we monitored the functional significance of the chosen mutations within these pathways and compared them to mutations of known significance Results: Using the Guardant360 test we found 14 frequent VUS mutations in EGFR, ERBB2, MET, KIT, FGFR1 and FGFR2 that occurred a total of 402 times in the cohort. Frequency of occurrence ranged from 10-80 patients, with a mean of 28 in 342 tests on 328 patients (3.2% prevalence). Of patients with one of the frequent VUS mutations, 27% did not have another actionable mutation. The PCAS platform was able to analyze all the frequent VUS mutations, identifying varying degrees of activity levels, as well as unique pathway specific patterns Conclusions: The high prevalence of VUS mutations in the patient population highlights the need to characterize their functional relevance. Using the PCAS platform offers a way to interpret novel mutations and identify actionable mutations. The findings expand our understanding of deleterious mutations, and creates targeted therapy treatment opportunities for patients who previously would not have had such treatment options
Abstract 14128: Association Between Prehospital First Defibrillation to Administration of Epinephrine Interval and Outcome After Out-of-hospital Cardiac Arrest
Authors: Shoji Kawakami, Yoshio Tahara, Teruo Noguchi, Satoshi Yasuda, Sunao Kojima, Naohiro Yonemoto, Keijiro Saku, Hiroshi Nonogi, Ken Nagao
Journal: Circulation (2016)

Background: In out-of-hospital cardiac arrest (OHCA) patients, although the epinephrine administration after second defibrillation is currently recommended by the AHA guidelines during shockable rh...
The estimated financial impact of diagnostic accuracy on melanoma diagnosis in 2018.
Authors: Kelly Nelson, Susan M. Swetter, Suephy Chen, Clara Curiel-Lewandrowski
Journal: Journal of Clinical Oncology (2018)

e18903 Background: Early melanoma diagnosis improves survival; provider diagnostic accuracy for melanoma varies significantly with potential financial implications. Methods: A systematic literature review was performed for publications citing provider melanoma diagnostic accuracy, with NNB (number needed to biopsy) ranging from 3 to 30, and a weighted average NNB of 15. For this estimation, we considered NNB from 10-25. The American Cancer Society’s estimated 2018 melanoma incidence data was adjusted by 50% for estimated underreporting. An estimated individual lesion diagnostic cost (EILDC) was calculated using the Current Procedural Terminology (CPT) Medicare 2018 physician fee schedule: $75 evaluation and management (CPT99202, CPT99213) + 108 procedural (CPT11100) + 76 pathology fees (CPT88305 + 1:40 CPT88342), with total EILDC = 259. The estimated total diagnostic cost (ETDC) was calculated as adjusted melanoma incidence * range of NNB * EILDC. The estimated melanoma diagnostic cost (EMDC) was calculated as the adjusted melanoma incidence * EILDC. The estimated benign biopsy diagnostic cost (EBBDC) cost was calculated by subtracting EMDC from ETDC. Results: Given the range of explored NNB, the estimated cost of biopsied benign tumors in 2018 ranges from $624 million to $1.7 billion. Conclusions: Removal of benign skin lesions is expected (perfect accuracy in melanoma diagnosis has not been demonstrated) and appropriate (no provider wishes to miss subtle melanoma). A more thorough and focused analysis on NNB is appropriate; the financial impact of providers with low diagnostic accuracy may be underappreciated and highlight an educational opportunity. 25:1 20:1 15:1 10:1 estimated invasive melanoma incidence 91270 91270 91270 91270 estimated in situ melanoma incidence 87290 87290 87290 87290 underreporting adjustment 1.5 1.5 1.5 1.5 number needed to biopsy (NNB) 25 20 15 10 estimated individual lesion diagnostic cost, EILDC (US$) 259 259 259 259 estimated total diagnostic cost, ETDC (millions) 1734.3 1387.4 1040.6 693.7 estimated melanoma diagnostic cost, EMDC (millions) 69.4 69.4 69.4 69.4 estimated benign biopsy diagnostic cost, EBBDC (millions) 1664.9 1318.0 971.2 624.3
‘Real world data’ of genomic sequencing for personalised therapy
Authors: M.S. Bergamino, A. Vethencourt, A. Stradella, S. Recalde, C. Fabregat, S. Vázquez, C. Falo, A. Fernández-Ortega, R. Villanueva Vazquez, M.E. Ferrer Cardona, S. Rubio, M. Gil-Gil
Journal: Annals of Oncology (2018)

Background: AMPLICON deep sequencing to determine gene mutations (mut) and copy number alterations (CNA) helps to understand tumors' molecular biology and to personalize therapy. At Institut Català d’Oncologia l’Hospitalet it is used to find the best treatment options. We aim to analyze its efficiency. Methods: We use AMPLICON sequencing to analyze genomic profile and CNA of unresectable or metastatic breast cancer tumors from selected patients (pts) with eligible criteria for clinical trials: 18-75 years, Performance Status (PS) ≤1, non-relevant comorbidity, organ preserved function and not heavily pretreated. We obtained the informed consent from all pts. An observational prospective analysis was carried out to evaluate pts and tumor characteristics, mut and CNA, target therapy (TT) and survival. Results: Since December 2017, 45 pts were tested. Median age at diagnosis of metastatic disease was 51 years (29-70) and at molecular screening 55 (29-72). Most patients had PS 0. In the metastatic setting, 32 pts (71%) had luminal breast tumors, 8 (18%) triple-negative and 5 (11%) HER2+. Median number of hormonotherapy lines at screening was 1 (0-5) and 1 chemotherapy line (0-5). Median follow up was 4.5 months. Only 2 pts died during this analysis. Overall, 30 mut were found. 23 pts (51%) had at least one mut. Almost 60% pts had 1 mut. Median number of mut was 1 (1-3). 49% pts had Wild Type (WT) tumors. The most prevalent mut were: 30% in PI3K, followed by 23% in ESR1, 13% in TP53, 7% in PTEN, 7% in FGRF4, and 3% in APC and in NOTCH. CNA was reported in 16 pts (35%). Pts with mut or CNA that could potentially benefit from TT were estimated in 13 pts (28%). 2 pts are currently under TT with PI3K inhibitors (inh) and 5 will be consider at progression for personalized treatment (PI3K inh and TAS 120). Conclusions: Personalized therapy by sequencing tumors is an option for pts who could benefit from TT in clinical trials. In our analysis we found less mut or CNA than those described in literature, may be due to the different population. Potential benefit from TT was only considered in less than half of pts with any genomic alteration maybe because some mut are not targetable as ESR1 or p53 and lack of follow-up. Genomic sequencing can be a useful tool to achieve personalized therapy if used in selected pts but further evidence is needed. Legal entity responsible for the study: Institut Català d'Oncologia L'Hospitalet. Funding: Institut Català d'Oncologia i Vall d'Hebron Institut d'Oncologia. Disclosure: All authors have declared no conflicts of interest.
Abstract 20149: Effect of Mitral Valve Area Following Surgical Repair for Degenerative Mitral Regurgitation on Exercise Hemodynamics and Functional Consequences
Authors: Kwan Chan, Thierry Mesana, Buu-Khanh Lam
Journal: Circulation (2014)

Introduction: Mitral valve (MV) area is the key measure of mitral stenosis (MS) in rheumatic MV disease, but its role in the follow-up of patients who had MV repair for degenerative mitral regurgitation (MR) remains uncertain. Our objective is to evaluate the relationships of MV area with hemodynamic effects at rest and during exercise, and with functional measures in patients following MV repair for degenerative MR. Methods: We prospectively assessed 110 patients who had MV repair for degenerative MR and no more than mild residual MR. Patients with aortic valve disease and ventricular dysfunction were excluded. The patients underwent comprehensive echo assessment at rest and during supine bicycle exercise. Brain natriuretic peptide (BNP) levels and SF36 questionnaires were also performed. MV area was calculated using the continuity equation. The patients were divided into 2 groups for comparison (MV area &lt; 1.5 cm 2 vs &gt; 1.5 cm 2 ). Results: 22 patients (20%) had MV area &lt; 1.5 cm 2 . The 2 groups were similar in age. Patients with MVR &lt; 1.5 cm 2 had worse resting and exercise hemodynamics, more limited exercise capacity and higher BNP levels compared to those with larger MV area (Table). These patients also had lower scores in physical functioning, vitality (p=0.01) and social function (p=0.04), based on the SF36 questionnaires. Multivariate analysis showed that MV area is an independent predictor of exercise capacity (p=0.003). Conclusion: In patients following MV repair for degenerative MR, MV area is a useful measure of MS severity because it is associated with resting and exercise hemodynamics and functional consequences. MV area should be routinely measured in this clinical setting, and refinement in MV repair techniques is needed to optimize MV area in addition to eliminate MR.
Resurrection of PARP Inhibitors in Breast Cancer
Authors: Tomas G. Lyons, Mark E. Robson
Journal: Journal of the National Comprehensive Cancer Network (2018)

PARP enzymes are essential for DNA damage repair. Cancers with defective homologous recombination DNA repair, such has BRCA1- and BRCA2-mutated breast cancers, are targets for PARP inhibitors (PARPi) through the exploitation of synthetic lethality. A number of PARPi are currently undergoing clinical evaluation in breast cancer, with olaparib and talazoparib having demonstrated superior efficacy compared with standard chemotherapy in advanced germline BRCA-mutated cancer. This review describes the biological rationale for PARPi and presents the accumulating data on PARPi use in breast cancer.