tbuckley/cabot-search huggingface dataset:
Preoperative geriatric assessment (GA) and surgical outcomes in older women with gynecological (gyn) cancer.
Authors: Daneng Li, Beatriz Korc-Grodzicki, Qin Zhou, Alexia Iasonos, Dennis Chi, Ginger J. Gardner, Stuart M. Lichtman, William P. Tew
Journal: Journal of Clinical Oncology (2012)

5108 Background: GA can predict surgical outcomes in older patients (pts); however, pre-surgical evaluation for older pts with gyn malignancies has not been well-described. This study will determine the association between GA variables with post-operative morbidity and mortality. Methods: Women 75yrs or older who had geriatric evaluation before any gyn surgery at Memorial Sloan Kettering Cancer Center (MSKCC) between 1/2010-6/2011 were identified. Pre-operative GA included: Mini-Cog Test (cognition), fall history, medication list, nutritional status (weight loss &gt;10lbs, albumin), functional status (activities of daily living (ADL), instrumental I-ADL), and Charlson comorbidity index. Outcomes included: delirium, length of hospital stay (LOS), 30-day surgical adverse events (AE, grade 1-5, via prospective-MSKCC surgical database), 30-day hospital readmission and 6-month mortality. Utilizing bivariate analyses, associations between GA measures and post-operative outcomes were evaluated. Results: 72 pts (median age 79yrs, range 75-92) with gyn cancer (54% uterine, 36% ovarian/peritoneal/tubal, 10% cervical/vaginal/vulvar) had gyn surgery. 34 pts (47%) had stage III/IV disease. 21pts (30%) had secondary cancer history. Pt’s baseline GA measures: ADL-dependent (13%), IADL-dependent (19%), weight loss (18%), fall history (18%), mini cog score (median 4, range 0-5), Charlson score (median 2, range 0-9). 24pts (33%) had surgical AE; no significant association with age or GA. Median LOS was 2 days (range 0-20); 11pts (15%) required 30-day readmission. Delirium (p=0.01), nutrition (weight loss p=0.04, albumin p=0.04), anemia (p=0.003) and high comorbidity index (p=0.013) were associated with longer LOS. Six-month mortality was 8%; older age (p=0.02), poor functional status (lower ADL and IADL, p&lt;0.001 and p=0.007), number of medications (p=0.05) and poor cognition (p&lt;0.001) were associated with shorter survival. Conclusions: Surgical morbidity is common in older pts. Although AE’s were not associated with GA variables, GA can detect high-risk features for longer LOS and shorter survival. Further prospective studies with pre-operative GA and interventions are warranted.
Multivariate screening of prognostic factors to identify a novel, simple, and objective marker to optimize patient selection and predict survival benefit in early-phase trials.
Authors: Chara Stavraka, David James Pinato, Sean Micheal O'Cathail, Farah J Williams, Michael Seckl, Sarah Patricia Blagden
Journal: Journal of Clinical Oncology (2012)

2608 Background: Several prognostic indices have been devised to optimize patient selection for phase I trials. However, there is no consensus as to the optimal score and none qualifies as a marker of response. We developed a simple score through a multivariate screening of individual variables and compared its performance with existing prognostic scores including the Royal Marsden, Nijmegen and Prince Margaret Hospital scores. Methods: We retrospectively analyzed characteristics and outcomes of 120 referrals to our phase I center (2007 - 2011). Independent predictors for overall survival (OS) were identified from univariate (Kaplan Meier) and multivariate (Cox regression) analyses and used to create the Hammersmith Hospital score (HS). This was compared with the other indices for predicting progression free survival (PFS), OS and 90 day mortality (90 DM). Multivariate logistic regression and ROC curves were used to estimate 90 DM and c-index was used to estimate the prognostic ability of the different indices. Changes in HS following treatment (ΔHS) were calculated at 6 weeks RECIST in a subset of patients receiving targeted therapies (n= 50). Results: Median age was 62 years (range: 28 – 80); median OS 4.3 months (range: 0.2 – 39); 34% male; 25% PS&gt;1. Multivariate screening identified albumin &lt;35 g/L, lactate dehydrogenase (LDH) &gt;450 U/L and sodium &lt;135mmol/L as the strongest independent predictors of OS (p&lt;0.05). These were entered into a 3-point score (HS) that classifies patients as being at high risk (score 2-3) vs. low risk (score 0-1) of worse OS (HR= 5.8, p&lt;0.001), PFS (HR= 2.7, p= 0.04) and 90 DM (OR= 5.9, p= 0.001). All scores predicted for OS on univariate analysis (p&lt;0.05). On multivariate analysis HS performed best to predict OS (HR= 3.9, p&lt;0.001 C-index score= 0.71), PFS (HR= 2.6 p= 0.04) and 90 DM with area under the ROC curve 0.71. ΔHS independently predicted for OS (p&lt;0.001), with worsening of the score reflecting poorer OS. Prospective validation is ongoing. Conclusions: HS is a simple score that outperforms other prognostic indices. This can be used to select individuals for future studies as well as an additional marker of response.
A phase II study combining ipilimumab and degarelix with or without radical prostatectomy (RP) in men with newly diagnosed metastatic noncastration prostate cancer (mNCPC) or biochemically recurrent (BR) NCPC.
Authors: Karen A. Autio, James Andrew Eastham, Daniel Costin Danila, Susan F. Slovin, Michael J. Morris, Wassim Abida, Vincent Paul Laudone, Karim A. Touijer, Anuradha Gopalan, Phillip Wong, Tracy Curley, Erica Simone Dayan, Lawrence P. Bellomo, Peter T. Scardino, Howard I. Scher
Journal: Journal of Clinical Oncology (2017)

203 Background: Androgen deprivation therapy (ADT) does not completely eliminate disease in mNCPC or BRPC. We explored a multimodality treatment (tx) approach combining ADT with ipilimumab (ipi) with the aim of achieving no evidence of disease or complete elimination of disease, given the potential for cure seen with immunotherapy. Methods: Cohort A (Coh A) enrolled men with ≤ 10 bone metastases treated with induction of degarelix (deg) and ipi prior to RP and subsequent ipi q3 weeks x 3 and 8 months (mos) total of deg. Cohort B (Coh B) opened later and enrolled men with BRNCPC after RP with a doubling time ≤ 12 mos, and received ipi q3 weeks x 4 and 8 mos of deg. The primary endpoint was an undetectable PSA (&lt;0.05) at 12 and 20 mos with non-castrate testosterone. Results: 16 pts (7 Coh A; 9 Coh B) were treated. No Coh A pts experienced immune related toxicities (irAE) that delayed surgery. 4/7 (57%) Coh A pts came off study for irAE, 1 (14%) for insurance reasons, and 2 (29%) completed all protocol requirements. In Coh B 6/9 (67%) pts have completed tx and entered follow-up. Conclusions: A combined modality approach with ipi 10mg/kg, ADT, and RP in mNCPC was associated with limiting toxicities, however 3mg/kg was better tolerated and more feasible in a BRNCPC cohort. One pt in Coh A (14%) had an undetectable PSA with testosterone recovery while evaluation of efficacy for Coh B is ongoing. The role for RP and other immunotherapeutic approaches in NCPC remain viable interests to the field. Clinical trial information: NCT02020070. [Table: see text]
Highly photostable nanogels for fluorescence-based theranostics
Authors: Dipendra Gyawali, Jimin P. Kim, Jian Yang
Journal: Bioactive Materials (2017)

A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability. The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free one-pot reaction, derived entirely from biocompatible monomers citric acid, maleic acid, L-cysteine, and poly(ethylene glycol). The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity, and demonstrate long-term structural stability in biological buffer for two weeks. To gauge potential in theranostic applications, the fluorescent nanogels were surface functionalized with biologically active RGD peptides and encapsulated with active anti-cancer drug Doxorubicin, resulting in a pH-responsive controlled drug release in acidic pH resembling tumor environments. The strong fluorescence of the nanogels enabled tracking of targeted drug delivery, showing that drug-loaded nanogels homed into the cytoplasmic regions of prostate cancer cells to significantly induce cell death. These photo-crosslinkable and biodegradable nanogels pose as a strong candidate for theranostic medicine, demonstrating versatile functionalization, high stability in biological buffers, and capacity for real-time fluorescence-based monitoring of targeted drug delivery.
Potential usefulness of OPG, a member of the tumor necrosis factor receptor superfamily, for the early diagnosis of bone metastasis in breast cancer patients
Authors: T. Ibrahim, E. Sacanna, L. Mercatali, E. Flamini, C. Tison, R. Ricci, M. Ricci, P. Serra, E. Scarpi, D. Amadori
Journal: Journal of Clinical Oncology (2009)

e22000 Background: Breast cancer is the most frequent tumor in women. About 80% of patients with metastatic disease present bone involvement, in which the OPG/RANKL/RANK system would seem to play an important role. Our aim was to evaluate the potential usefulness of OPG bone marker for the early diagnosis of bone metastases. Methods: The study was carried out on 120 individuals: 30 healthy donors, with a median age of 40 years (21–76) and 90 breast cancer patients, with a median age of 57 years (30–86). Among patients, 49 were disease-free (median age 52 years) and 41 were at first diagnosis of bone metastases (median age 63 years). OPG transcript was determined in peripheral blood samples using quantitative PCR analysis. A receiver operating characteristic (ROC) curve was used to calculate the diagnostic accuracy of the marker. Results: OPG values were not correlated with age in any of the subgroups. The OPG median value was not statistically different in healthy donors (median=1.9; range 0.6–4.7) and disease-free patients (median=1.7; range 0.4–8.9), whereas it was threefold higher than that observed in relapsed patients (median=0.6; range 0.1–5.2; p&lt;0.001), regardless of the number of metastatic sites. The area under the curve (AUC) in disease-free patients was 0.82 for OPG, with 71% sensitivity and 88% specificity, using a cut off ≤ 0.8. In a parallel analysis of 37 patients (14 disease-free and 23 with bone metastases) for whom CEA and CA15.3 information was available, specificity for each marker was 100%, whereas sensitivity was only 61% and 59%, respectively. When these markers were considered in combination with OPG, an increase in sensitivity, albeit not statistically significant, was observed for CEA (83%) and CA15.3 (82%). Conclusions: Our preliminary data show a potential role of the OPG bone turnover marker for the early diagnosis of bone metastases. Results now need to be confirmed in a larger case series. No significant financial relationships to disclose.
An engineered immunotherapy (NKTR-214) with altered selectivity toward the IL2 receptor: Efficacy and tolerability in a murine tumor model.
Authors: Deborah H. Charych, Murali Addepalli, Steve Lee, Thomas Chang, Xiaofeng Liu, Rhoneil Pena, Terry Sweeney, Ute Hoch, Stephen K. Doberstein, Seema S. Kantak
Journal: Journal of Clinical Oncology (2013)

3060 Background: Cytokine-based immunotherapy has been successful for the treatment of cancer, with potential for durable responses in multiple indications. One approach towards stimulating the immune system is to target the heterotrimeric interleukin2 receptor, IL2R. NKTR-214 uses polymer technology to alter receptor subunit selectivity to favor expansion of CD8+ memory effector T cells (CD8T) in the tumor over CD4+ regulatory T cells (Treg). In addition, polymer conjugation is designed to improve exposure and enhance tumor localization, significantly improving efficacy, modulating vascular leak syndrome (VLS) and allowing flexible dosing regimens. Methods: C57BL/6 mice bearing established subcutaneous B16F10 melanoma were treated with NKTR-214 at a variety of doses (0.25-4.0 mg/kg) and schedules (q5dx3 to q14dx2). Mice treated with clinically validated IL2 were administered 3mg/kg, bidx5 for 2 cycles. Efficacy was measured by monitoring tumor volumes. Tolerability was evaluated by survival. VLS was measured by injection of Evans Blue dye followed by colorimetry in lungs. Tumor immunotyping, by flow cytometry. Results: Tumors from mice receiving NKTR-214 had a CD8/Treg ratio of over 1,000 versus 14 for IL2. NKTR-214 administered at 2 mg/kg, q9dx3 was identified as the optimal regimen and showed tumor growth delay of 26 days compared to 9 days for optimally dosed IL2. 90% of NKTR-214 treated mice tolerated treatment compared to 67% for IL2. VLS was completely resolved prior to administration of the next dose of NKTR-214, unlike IL2. NKTR-214 was well tolerated in rats at two schedules, at MTD. Conclusions: NKTR-214 is a highly differentiated cytokine with a new mechanism of action that may provide options for cancer immunotherapy. Polymer conjugation of a clinically validated cytokine alters the IL2R selectivity to favor expansion of tumor killing immune cells (CD8T) over regulatory immune cells (Treg) in the tumor. The conjugate is also designed to improve exposure and enhance tumor localization, offering more options of dose and schedule. The optimal dose and schedule is cytokine-sparing, provides substantial tumor growth delay, and reduces toxicity.
Rituximab Treatment of Nivolumab-Induced Bullous Pemphigoid
Authors: Laura Sowerby, Anna K. Dewan, Scott Granter, Leena Gandhi, Nicole R. LeBoeuf
Journal: JAMA Dermatology (2017)

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BDNF expression and systemic dissemination via anoikis resistance in gastric cancer.
Authors: Yoshinaga Okugawa, Yasuhiro Inoue, Koji Tanaka, Mikio Kawamura, Susumu Saigusa, Junichiro Hiro, Yuji Toiyama, Masaki Ohi, Yasuhiko Mohri, Keiichi Uchida, Hidenori Yanagi, Masato Kusunoki
Journal: Journal of Clinical Oncology (2012)

e14541 Background: Anoikis (apoptosis resulting from loss of cell-matrix interaction) has been suggested to act as a physiological barrier to metastasis, and resistance to anoikis is necessary for cancer cell survival during systemic dissemination and metastasis. Brain-derived neurotrophic factor (BDNF) is one of the member of neurotropin family known to activate the high affinity tyrosine kinase (Trk)B receptor as a specific suppressor of anoikis. TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however no reports have shown the clinical and biological effects of BDNF/TrkB axis in gastric cancer. Methods: BDNF expression in gastric cancer tissue and clinicopathological data from 153 consective patients were analyzed by real-time PCR and immunohistochemistry. The extent of target gene expression was calculated from the standard curve, with quantitative normalization of the cDNA in each sample performed using GAPDH gene as an internal control. Recombinant human BDNF and Trk antagonist K252a were used for in vitro assays to evaluate the biological role of the BDNF/TrkB axis in gastric cancer cell lines. Results: The mean BDNF level in gastric cancer tissue was 284.5 (0-2834). One hundred eighteen (77.1%) of 153 patients showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with histological diffuse type (p=0.019), lymph node metastasis (p&lt;0.001), peritoneal dissemination (p=0.028) and poor prognosis (p=0.022). In addition, BDNF expression is an independent risk factor for lymph node metastasis and peritoneal dissemination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. In addition, these effects were generally inhibited by Trk antagonist K252a. Conclusions: BDNF appears to play an important role in gastric cancer progression, and blocking BDNF/TrkB axis might be clinically useful in developing therapies for patients with gastric cancer.
Evaluation of Vulnerable Elders Survey, G8 questionnaire and Predictors of Toxicity as screening tools for frailty and toxicities in geriatric patients with cancer.
Authors: Leopold Hentschel, Anke Rentsch, Beate Hornemann, Felicitas Lenz, Michael Baumann, Gerhard Ehninger, Jochen Schmitt, Markus Kajo Schuler
Journal: Journal of Clinical Oncology (2015)

e20538 Background: A comprehensive geriatric assessment (CGA) can help to improve cancer care in elderly patients. As completing a full CGA is both time and resource consuming, screening instruments such as the Vulnerable Elders Survey (VES-13), the G8 questionnaire (G8) or the Predictors of Toxicity (POT) are available for predicting frailty and toxicities. For the first time, we tested the predictive qualities of all three instruments compared to a full CGA during routine admission process at a Comprehensive Cancer Center (CCC). Methods: 84 patients with a first appearance at a CCC were included in this cross-sectional, cohort study. As part of the routine admission procedure, patients conducted a CGA, consisting of six dimensions (cognition, mood, instrumental activities of daily living, nutritional status, polypharmacy, falls) and the VES-13, G8, and POT. Analysis was performed for sensitivity, specificity, positive predictive value (ppv), and for the negative predictive value (npv). The area under the curve (AUC) of instruments’ ROC-curves was calculated. Results: 84 patients (52 men) with a median age of 73 years (range: 63 – 93) participated. 30 Patients (35.7%) were classified as “frail” by the CGA. There was no significant difference for ECOG status or age between frail and non-frail patients. Predictive values and AUC of the screening instruments are reported in the table below. Conclusions: The predictive values of three widely used screening instruments for frailty were assessed. 36% of all patients were classified as frail. Except for sensitivity of the G8, other values were in the range of published literature. The frailty in those studies was higher (range 67%-82%). With a high sensitivity (72.7%) and a npv (80.6%), the POT might be the overall most promising instrument for routine use in a CCC. VES13 G8 PoT 95% confidence interval 95% confidence interval 95% confidence interval Sensitivity 57,1% 44,5% - 69,8% 38,3% 25,9% - 50,7% 72,7% 61,2% - 84,3% Specificity 79,2% 68,8% - 89,5% 62,5% 50,1% - 74,9% 65,2% 52,9% - 77,6% ppv 61,2% 48,7% - 73,6% 37,0% 24,6% - 49,3% 54,6% 41,6% - 67,5% npv 76,3% 65,4% - 87,1% 63,8% 51,6% -76,1% 80,6% 70,4% - 90,9% AUC .732 .303 .781
PREVALENCE OF MUSCULOSKELETAL PAIN IN ELITE ROWERS
Authors: Katharina Trompeter, Daniela Fett, Petra Platen
Journal: British Journal of Sports Medicine (2017)

Background Rowing is a popular sport and considered to be among the most physically demanding endurance sports. Especially elite rowers are exposed to high strain of the musculoskeletal system due to their high training volume. Currently, there is no information on the prevalence of musculoskeletal pain in the German Elite. Objective This study aims to identify the prevalence of musculoskeletal symptoms in German elite rowers. Design The study was designed as a cross-sectional retrospective survey. Setting An online questionnaire based on the valid Nordic Questionnaire (Kuorinka, 1987) was sent to German elite division rowers. Participants N=84 German elite rowers (m=43, f=41; 20.7±3.4 yrs., 183.9±8.3 cm, 77.3±11.5 kg) took part in the survey. Main Outcome Measurements Lifetime prevalence (LTP) and point prevalence (PP) of musculoskeletal pain were determined. Results The most frequently occurring localization of pain was the lower back. LTP of low back pain (LBP) was 87%, followed by the neck (66%), knee (65%), shoulder (61%) thoracic spine (58%), wrist (53%), ankle (33%), hip (32%) and elbow (17%). The highest PP was found in the lower back (48%) followed by the neck (30%), wrist (25%), shoulder (23%), knee (22%), thoracic spine (20%), hip (15%), ankle (7%) and elbow (4%). There were no differences in prevalence regarding sex and age. Conclusions Our findings indicate that musculoskeletal pain and especially LBP is a relevant medical problem in elite rowing. This is in line with findings in the literature. Bahr (2004) described a LTP of LBP of 63% and a PP of 25% in elite rowers, and Fass (2012) found values of 68% and 19%, respectively. The results underline the necessity of LBP prevention and intervention programs in addition to the discipline specific training loads. Acknowledgement The study was supported by the Federal Institute for Sport Science, Germany (ZMVI1–080102A/11–18).
Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling
Authors: Esra Güç, Priscilla S. Briquez, Didier Foretay, Manuel A. Fankhauser, Jeffrey A. Hubbell, Witold W. Kilarski, Melody A. Swartz
Journal: Biomaterials (2017)

Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels.