tbuckley/cabot-search huggingface dataset:
Impact of tumor metabolic response by PET/CT on the survival after salvage re-irradiation of head and neck cancers.
Authors: Tawee Tanvetyanon, Nikhil G Rao, Tapan Padhya, Judith C McCaffrey, Jimmy J. Caudell, Julie Ann Kish, Ronald C. De Conti, Andy Trotti, Edward A Eikman
Journal: Journal of Clinical Oncology (2014)

6047 Background: Re-irradiation (Re-RT) is a treatment option for recurrent, previously irradiated head and neck cancers. Nevertheless, most patients will still develop progressive disease after Re-RT. We sought to evaluate the predictive value of metabolic response by 18F-FDG-PET/CT (PET/CT) on the survival after Re-RT. Methods: Patients with locally recurrent squamous cell carcinoma of head and neck treated by Re-RT at our institution during 2005-2012 who had pre- and post-treatment PET/CT were identified. Their scans were re-analyzed by a nuclear medicine physician who was unaware of patient outcome. PET/CT analysis comprised qualitative analysis and measurement of maximum standardized uptake value (SUVmax) as a semi-quantitative index of relative tissue uptake. Complete metabolic response (CR) was defined as resolution of hypermetabolism without new lesion. Results: Fifty-five patients were analyzed: 41 patients (76%) had definitive Re-RT and 13 patients (24%) had adjuvant Re-RT. Median radiation dose delivered was 60 Gy (40-70 Gy). Concurrent chemotherapy was cisplatin in 28, carboplatin in 13, cetuximab in 10, and none in 3 patients. Median pre- and post-treatment SUVmax were 8.5 (range 3.3-18.9) and 4.3 (range 0-15.7), respectively. At a median of 13 weeks after Re-RT, the median metabolic response was 63% (range -80-100%), with 16 patients (30%) achieving CR. Median overall survival was 38.7 months among patients with CR vs. 12.2 months among those without CR (p<0.0001); Median PFS was 29.3 vs. 5.6 months (p<0.0001); and 5-year survival rates were 37% vs. 3%, respectively. Multivariate analysis adjusting for age, duration since previous radiation, comorbidity, organ dysfunction and sum of tumor sizes showed that achieving CR was a strong, independent predictor of survival, Hazard Ratio 5.52 (95% CI: 2.3-13.5). We found no significant difference in the survival of patients with partial metabolic response (≥50% reduction of SUVmax) and those without response. For the prediction of 5-year survival, the negative predictive value of achieving CR by PET/CT was 97%. Conclusions: Failure to achieve a complete metabolic response after Re-RT is highly predictive of disease progression or death.
Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis
Authors: Angela C. Cheung, Willem J. Lammers, Carla F. Murillo Perez, Henk R. van Buuren, Aliya Gulamhusein, Palak J. Trivedi, Konstantinos N. Lazaridis, Cyriel Y. Ponsioen, Annarosa Floreani, Gideon M. Hirschfield, Christophe Corpechot, Marlyn J. Mayo, Pietro Invernizzi, Pier Maria Battezzati, Albert Parés, Frederik Nevens, Douglas Thorburn, Andrew L. Mason, Marco Carbone, Kris V. Kowdley, Tony Bruns, George N. Dalekos, Nikolaos K. Gatselis, Xavier Verhelst, Keith D. Lindor, Ana Lleo, Raoul Poupon, Harry L.A. Janssen, Bettina E. Hansen
Journal: Clinical Gastroenterology and Hepatology (2019)
Health literacy: a new piece of the puzzle in psoriasis care? A cross‐sectional study
Authors: M.H. Larsen, Y.A.S. Strumse, C.R. Borge, R. Osborne, M.H. Andersen, A.K. Wahl
Journal: British Journal of Dermatology (2018)

Health literacy (HL) - the ability to seek, understand and utilize health information - is important for good health. Suboptimal HL has been associated with poorer health outcomes in other chronic conditions, although this has not previously been studied in patients with psoriasis.To investigate the HL strengths and weaknesses of a cohort of patients with moderate-to-severe psoriasis. Another aim was to examine possible associations between patients' quality of life, their demographic, clinical and self-management characteristics, and dimensions of HL.A cross-sectional study was conducted. Data were collected from a cohort of patients with psoriasis who had received climate helio therapy from 2011 to 2016 (n = 825). HL was assessed by the Health Literacy Questionnaire (HLQ). The association between HL domains, demographic, clinical and self-management variables were analysed using bivariate correlation and a four-step linear multiple regression model.The scores on all HLQ dimensions indicated lower health literacy than other populations. The linear regression models showed a significant association between HL, quality of life and self-management variables, with higher HL predicting higher quality of life, self-efficacy and psoriasis knowledge. Sex, educational attainment, age and disease severity had less influence on health literacy.Improving HL may be a useful strategy for reducing disparities in self-management skills for patients with psoriasis. Interventions that aim to reduce disease severity and increase psoriasis knowledge, self-efficacy and quality of life may positively increase HL.
Looking beyond the first cycle in phase I cancer clinical trials.
Authors: Shing Mirn Lee, Ying Kuen Cheung, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2014)

6587 Background: Phase I cancer trials use toxicity data from the first cycle to define dose limiting toxicity and guide dose escalation. Since doses are assigned only after outcomes for previous patients are observed, a short assessment period allows for more realistic time-frames to complete studies when using conventional methods to determine the maximum tolerated dose. However, in phase II and III clinical trials, toxicities are generally summarized for the entire treatment period into a maximal toxicity grade. Methods: Toxicity data from two phase II lung cancer trials conducted by the Southwest Oncology Group were obtained. Toxicities were graded for each cycle of treatment up to six cycles. The percentage and severity of toxicities in cycle 1 are compared to the maximal toxicity across all cycles. Moreover, summarizing toxicities by patient, the percentage of patients with dose limiting toxicities using data cycle 1 versus all cycles are compared. Results: For the first study, 779 toxicities were reported for 57 patients and summarized into 610 maximal toxicities. Out of the 610 maximal toxicities, 28% were not reported in cycle 1. Among the 442 maximal toxicities that were present in cycle 1, 9% worsened in a later cycle. Using data from cycle 1 yielded 7 dose limiting toxicities (12%); across all cycles, the dose limiting toxicity rate was 47% (27/57). The second study had a higher number of toxicities and of greater severity. There were 3510 toxicities coming from 115 patients. These yielded 1655 maximal toxicities. 46% were not reported in cycle 1. Among the 901 toxicities that were present in cycle 1, 18% worsened in a later cycle. Using data from cycle 1 yielded 60 dose limiting toxicities (52%); across all cycles, the dose limiting toxicity rate was 90% (103/115). Conclusions: Given the substantial amount of under reporting observed, further research is warranted to compare toxicity data from cycle 1 alone versus all cycles in a prospective manner. If discrepancy exists, the time-to-event continual reassessment method, a model-based design for estimating the maximum tolerated dose, can be used since it allows for inclusion of late-onset toxicities during dose escalation and uninterrupted patient recruitment due to toxicity assessment.
Final analysis of European patients from the Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) study: Baseline characteristics and staging systems.
Authors: Bruno Daniele, Vlad Ratziu, Per I Stal, Fatima Serejo, Gyorgy Bodoky, Adina E Croitoru, Christos Papandreou, Juan Turnes, Marc Mardoche Fellous, Philippe Mathurin, Jean-Pierre Bronowicki
Journal: Journal of Clinical Oncology (2014)

4088 Background: The global, prospective, non-interventional GIDEON study recruiting >3,000 patients with unresectable hepatocellular carcinoma treated with sorafenib is complete. We report the final analysis of the prognostic value of baseline characteristics and staging systems in European patients. Methods: Baseline characteristics were recorded at study entry; safety/outcomes were collected at follow-up. Results: Median overall survival (OS) and time to progression (TTP) for baseline characteristics and staging systems in the intent-to-treat population (n=1115) are shown (Table). The safety profile of sorafenib in European patients was consistent with that reported for the interim analyses and in phase III studies. Conclusions: Data from European patients indicates that baseline characteristics and staging systems, including Child-Pugh status, BCLC stage, and CLIP and MELD scores, appear to be useful prognostic factors for OS and TTP, while TNM and ECOG PS appear to be predictive of OS only. Clinical trial information: NCT00812175.Overall survival and time to progression by baseline characteristics/staging system. n Median OS (months) Median TTP (months) Baseline characteristicsa ECOG PS 0 504 19.3 7.6 1 438 9.7 6.2 2 114 3.9 3.1 3 17 2.3 4.6 Bilirubin, µmol/Lb <34 926 13.5 6.7 34-50 90 4.6 3.4 >50 66 3.3 4.5 Albumin, g/Lb >35 637 16.4 6.8 28-35 318 6.9 5.5 <28 57 3.3 4.5 AFP, ng/mL <400 681 15.0 7.2 ≥400 332 6.1 4.3 Staging systema Child-Pughb A 726 15.0 6.7 B 219 4.9 2.4 C 12 1.5 1.2 BCLCb A 94 NR 11.6 B 270 14.9 7.6 C 591 9.4 5.2 D 45 4.0 3.4 MELD <10 481 15.1 6.7 10-<20 300 8.4 5.4 20-<30 16 NR 8.1 30-<40 5 8.5 7.6 CLIPb 0 94 22.9 10.1 1 280 20.2 8.1 2 254 9.2 5.4 3 147 6.2 4.8 4-6 91 3.0 3.1 TNMb I 196 19.0 7.8 II 176 15.2 6.9 IIIa 286 10.4 6.9 IIIb 24 9.3 8.5 IIIc 83 8.4 5.7 IV 163 7.7 4.1 aAt study entry; bUnknown/Not evaluable patients not shown. AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; CLIP, Cancer of the Liver Italian Program; ECOG PS, Eastern Cooperative Oncology Group performance status; MELD, model for end-stage liver disease; NR, not reached; TNM, tumor node metastasis.
Savings impact of a second-to-market oncology pathway.
Authors: Michael A. Kolodziej, Ira Klein, Tim Olson, David Garofalo, Amy Supraner, Maria Sipala, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2014)

e17538 Background: Clinical pathways can change practice patterns that result in benefits for all stakeholders; however, their impact on other regional payers is unknown. Will a first-to-market pathway serve as a rising tide that benefits all regional payers or result in higher resource utilization for other payers? Aetna and Cardinal Health implemented an oncology pathway in which the dominant regional commercial payer had previously implemented a similar pathway program. We assessed cost of care associated with this second-to-market oncology pathway. Methods: Using claims data for the baseline and first operational years of the pathway (7/1/2010- 6/30/2012), we compared chemotherapy, supportive care, emergency room (ER) and hospital admission costs for patients (pts) with breast, lung, and colorectal cancer treated by providers voluntarily participating in the pathway program with pts treated by nonparticipating providers. Savings were determined by comparing year-over-year cancer-related drug and hospital costs/pt for the study and control groups. Costs were calculated according to the Aetna Market Fee Schedule. Results: Pt cohorts were adjusted for variations in tumor type and age using the distribution for the operational year study group (n=51) as a baseline. In the operational year, cost/pt for chemotherapy and supportive care drugs decreased by 18.3% among participating providers and increased by 3.8% among nonparticipating providers. The average number of ER admissions decreased by 0.8% among participating providers and increased by 8.5% among nonparticipating providers. Inpatient days/pt decreased in both groups; however, inpatient days/pt were significantly higher for the control arm in the baseline year. The difference in the drug-cost trend between participating and nonparticipating providers was 22% resulting in a savings of $7,037/pt/year. The aggregated savings for drug costs and ER admissions was $7,402/pt/year. Conclusions: These results suggest that collaborative pathway programs can be successful in improving evidence-based care and lowering costs, even when implemented by payers with low market penetration and in markets in which providers are actively participating in another payer-sponsored pathway program.
Comparison of hypofractionated radiation with temozolomide to the current standard of care in the treatment of glioblastoma: Results from a single institution.
Authors: Melissa Azoulay, Jose Mansure, George Shenouda, Maria Patyka, Siham Sabri, Bassam Abdulkarim
Journal: Journal of Clinical Oncology (2014)

2089 Background: The multimodality treatment of patients with glioblastoma (GBM) includes adjuvant radiation with concomitant chemotherapy. At this time the optimal radiation fractionation is yet to be determined. In this retrospective study, we compared different fractionation regimens and identified independent prognostic variables associated with outcome. Methods: 457 underwent surgery for GBM between January 2005 and December 2012. Data related to clinical information, extent of surgery and adjuvant treatment was collected using electronic records and patient charts. Patients excluded were those who did not receive or complete adjuvant radiation and patients with infra-tentorial lesions. Univariate and multivariate analysis was performed using Cox model in order to identify variables associated with the primary endpoint, overall survival (OS). Results: 276 patients with a median follow-up of 13.4 months were included in this analysis. There were 147 patients in the conventional fractionation (CF) group of 60 Gy/30 fractions, 86 patients in the hypofractionation group of 60 G/20 fractions (HF60), and 43 patients in the 40 Gy/15 fractions group (HF40). Ninety-five percent of patients in both the CF and HF60 group received concomitant temozolomide, while 49% in HF40 group of patients received it. The median survival (MS) was 15.7 months for the CF group with a 2 year OS of 30.6%. MS was 13.8 months and 7 months in the HF60 and HF40 groups with a 2-year OS of 26.2% and 5.3%, respectively. Cox analysis showed no significant difference in terms of OS between the CF and HF60 group (HR1.22, P=0.20) but worse outcome in the HF40 group (HR 2.09, P=0.004). Multivariate analysis showed age, performance status, extent of surgery, repeat surgery, concomitant chemotherapy and methylation status to be significant factors associated with survival. Conclusions: HF60 shows OS comparable to CF while allowing for a shorter treatment time and potential radiobiological benefit without added toxicity. Our data also confirms that HF40 should be reserved for the palliative setting. There is a need for a prospective trial comparing the HF60 regimen to the current standard of care.
Correlation of tumor-derived circulating cell free DNA (cfDNA) measured by digital PCR (DigPCR) with tumor burden measured radiographically in patients (pts) with BRAF<sup>V600E </sup>mutated melanoma (mel) treated with RAF inhibitor (RAFi) and/or ipilimumab (Ipi).
Authors: Parisa Momtaz, Alice A. Gaskell, Taha Merghoub, Agnes Viale, Paul B. Chapman
Journal: Journal of Clinical Oncology (2014)

9085 Background: We hypothesized that tumor-derived cfDNA in plasma may reflect accurately total tumor burden. DigPCR is a quantitative technique that carries out individual PCR reactions simultaneously in thousands of droplets. By utilizing fluorescently-labeled probes specific for a unique tumor-specific mutation (e.g. BRAFV600E) it is possible to quantify mutated and wild-type (WT) DNA in plasma with high sensitivity (1 copy of BRAFV600E/ml plasma). Methods: Plasma from 11 pts with BRAFV600E mutated mel treated with vemurafenib, or dabrafenib, and/or Ipi were collected at various time points. cfDNA extraction from pt plasma was performed and the ratio of the concentration of mutant BRAFV600E to WT cfDNA was determined using DigPCR. The ratio of BRAFV600E /BRAFWT cfDNA was correlated with tumor burden measured radiographically as the sum of target lesion diameters. Results: 1 pt had a complete response, 8 had partial responses, and 2 had stable disease. 6 pts progressed after responding. All 4 pts assessed at the time when they were free of disease radiographically had undetectable cfDNA. False negative readings were seen in some samples from 2 pts (radiographic evidence of tumor but no detectable tumor-derived cfDNA despite adequate amount of cfDNA). In 1 pt, cfDNA levels increased despite a decrease in the sum of target lesions but this pt had progression in non-target bone metastases indicating that in some situations, cfDNA may more accurately reflect tumor burden than traditional radiographic measurements. In a pt undergoing resection of bulky metastatic melanoma, we measured the half-life of cfDNA to be approximately 3.5 hours. Conclusions: Tumor-derived cfDNA appears to correlate well with tumor burden measured by radiographic imaging. We are currently analyzing our retrospective plasma collection as well as prospectively collecting plasma on BRAFV600Emutated mel patients treated with RAFi and/or Ipi to assess more formally the value of cfDNA in reflecting tumor volume. Support: Rohan Melanoma Res. Fund.
Biomimetic polycaprolactone-chitosan nanofibrous substrate influenced cell cycle and ECM secretion affect cellular uptake of nanoclusters
Authors: Dhwani Jhala, Hilal Rather, Dhaval Kedaria, Juhi Shah, Sanjay Singh, Rajesh Vasita
Journal: Bioactive Materials (2018)

Biomimetic cell culture substrates are developed as an alternative to the conventional substrates. They provide necessary biochemical and biophysical cues to the cells from their surrounding environment for their optimal growth, behaviour and physiology. Changes in physiology of cells growing on biomimetic substrate can essentially affect results of in vitro biological experiments such as drug cytotoxicity, nanoparticle internalization or signalling pathways. As majority of ECM proteins are fibrous in nature, nanofibrous scaffolds have more biomimicking properties. Therefore, in this study, we developed ECM mimicking polycaprolactone-chitosan nanofiber substrate and evaluated its effect on cell morphology, proliferation, cell cycle and ECM production. Further, cellular uptake of BSA-AuNCs has been assessed on conventional and biomimetic substrate in order to demonstrate the effect of these events on cellular properties. It was observed that the cells that were grown for 15 days on the nanofibers, had majority of cells in the proliferative phase of cell cycle compared to TCPS. Moreover, these cells showed extensive collagen and fibronectin production. Due to these conditions C3H10T1/2 cells displayed higher cell internalization of BSA-AuNCs. Overall, this study indicates that the nano-topographical and biochemical environment could alter the cell proliferative behaviour and ECM production, which affects the cell internalization of BSA-AuNCs. Also, PCL-chitosan nanofibrous substrate could be a better alternative to TCPS for cell culture studies.
Gemcitabine plus nab-paclitaxel as second line and beyond for metastatic pancreatic cancer (MPC): A single institution retrospective analysis.
Authors: Alberto Zaniboni, Paola Bertocchi, Chiara Abeni, Chiara Ogliosi, Anna Rizzi, Luigina Rota, Brunella Di Biasi, Tiziana Prochilo, Francesca Aroldi, Fausto Meriggi
Journal: Journal of Clinical Oncology (2014)

e15202 Background: Gemcitabine (G) plus nab-paclitaxel (nab-P) is an effective first line treatment for MPC (Von Hoff DD, et al. NEJM 2013; 369: 1691-703), nevertheless there are fewer data about its efficacy and tolerability in pretreated patients (pts). Methods: We performed a retrospective data collection of MPC pts treated at our Oncology Department with second line and beyond G + nab-P from 09/2011 to 01/2014. We analyzed responses, survivals and toxicities. Results: 23 pts were treated with G + nab-P (nab-P 125mg/mq + G 1,000mg/mq days 1,8,15 q28), for at least 1 cycle, with GCSF support (days 10 to 13). Median age was 60 years (range 48-77), male/female 18/5, median PS (ECOG) 1 (range 0-2). 5 pts had 3 or more metastatic sites; 14 had liver, 9 nodes, 6 lung, 6 peritoneal and 3 bone metastasis. 18 pts were pre-treated with G, 15 with G + Oxaliplatin and 7 with folfirinox. The median number of cycles was 3 (range 1-10). All patients had initial 20% dose reductions of G or nab-P and 65% of pts required further dose reductions. 4 (17.4%) pts had a partial response (PR), 6 (26.1%) pts had a stable disease (SD) and 12 (52.2%) pts had a progressive disease (PD), for a clinical benefit (PR+SD) of 43.5%; 1 (4.3%) patient is too early for response assessment. 8 (34.8%) pts had a biochemical response with a >50% decrease in CA19.9 level. 2 out 7 pts refractory to folfirinox achieved a PR, while 1 achieved a SD. Median time to treatment failure (TTF) was 3 months (range 0.5-8.8), median overall survival (OS) was 5 months (range 1.6-13.5) and 6-months OS was 47.8%. Most common grade ≥3 (CTCAE v4.03) adverse events were thrombocytopenia (4 pts), neutropenia (2 pts), anemia (2 pts) and neuropathy (3 pts). Alopecia (all grades) was reported in 85% of pts. Conclusions: G + nab-P with GCSF support seems an active treatment even for folfirinox pretreated pts with MPC. Side effects were manageable and the 6-mos OS appears encouraging. N (%) RR Clinical benefit (PR+SD) TTF OS 6-mos OS ↓≥50% CA19.9 2 line 16 (69.6%) 12.5% 37.5% 2.3 (0.8-8.8) 4.6 (2.3-13.5) 43.8% 5pt (31.2%) ≥3 line 7 (30.4%) 28.6% 57.1% 5.3 (0.5-8) 5.9 (1.6-11.5) 57.1% 3pt (42.9%)