tbuckley/cabot-search huggingface dataset:
MNGI-27. THE LONG-TERM DISEASE BURDEN OF MENINGIOMA PATIENTS: RESULTS ON HEALTH-RELATED QUALITY OF LIFE, COGNITIVE FUNCTION, ANXIETY AND DEPRESSION
Authors: Amir Zamanipoor Najafabadi, Pim van der Meer, Florien Boele, Rob Nabuurs, Johan Koekkoek, Frank Lagerwaard, Jaap Reijneveld, Wilco Peul, Martin Taphoorn, Martin Klein, Wouter van Furth, Linda Dirven, Saskia Peerdeman
Journal: Neuro-Oncology (2018)

Previous studies reported that meningioma patients have impaired health-related quality of life (HRQoL) and cognitive function up to 5 years after intervention. We aimed to assess the long-term disease burden of meningioma patients. In this multicenter cross-sectional study, intracranial meningioma patients at a median of 9.9 years after anti-tumor therapy were included. HRQoL was measured with the SF-36 and EORTC QLQ-BN20, anxiety and depression with the Hospital Anxiety and Depression Scale (11/21 points is indicative for probable anxiety or depression), and objective cognitive functioning on six domains (z-score< -1.5 is defined as a clinically relevant deficit). Generalized linear models were used to compare meningioma patients with healthy controls, corrected for age, sex, educational level and comorbidities, and one-sample t-tests to compare meningioma patients with data of newly diagnosed glioblastoma. Patient recruitment and data collection is still in progress. 164 meningioma patients were included (mean age:63.9 years, WHO grade I:91.7%, surgery:89.2%, radiotherapy:14.6%). Compared with 110 controls, meningioma patients had worse HRQoL scores on 4/10 SF-36 scales/component scores: role limitations due to physical problems and emotional problems, social functioning, and the mental component score (range mean difference: 4.4–13.8, all p<0.05). Meningioma patients scored similar to glioblastoma on 5/11 EORTC QLQ-BN20 items/scale (visual deficits, headache, seizure, drowsiness, and hair loss; range difference: 1.6–3.7, all p>0.05), and better on all other items/scales. More patients suffered from probable anxiety (14.3%) and depression (7.5%) than controls (anxiety: 3.7%, p=0.015; depression: 7.5%, p=0.011). Clinically relevant cognitive deficits were found in executive function (10.9%), verbal memory (19.4%), working memory (13.4%), attention (10.3%), information processing (25.0%) and psychomotor speed (14.4%). Almost 10 years after the last anti-tumor treatment, meningioma disease burden is still significant. A considerable number of patients have impaired HRQoL, suffer from cognitive deficits and report high levels of anxiety and depression.
Changes in sperm banking rates within the first seven months of a formal male oncofertility program.
Authors: Diana Maria Lopategui, Emad Ibrahim, Raphael Yechieli, Nancy Brackett, Ranjith Ramasamy
Journal: Journal of Clinical Oncology (2017)

e21587 Background: Oncofertility counseling is an essential part of the care for cancer patients with risk of infertility. In June 2016, our institution formally initiated a standardized program for fertility preservation, including nursing and physician education. After the first 7 months of functioning, we here examine the sperm banking rates amongst male cancer patients, and its variation respect previous years. Methods: We retrospectively reviewed the charts of men newly diagnosed with cancer at our institution. We assessed the rates of sperm banking amongst this patient population before the implementation of a standardized fertility preservation program, and again after: from January 2011 to May 2016 and from June 2016 to December 2016, respectively. Results: Sperm banking rate amongst male cancer patients before the initiation of the program was 3.3% (30 out of 902 patients). Along the 7 months after initiation of the program, rate of fertility preservation increased 6.2 folds, up to 20.6% (21 out of 102). Patients undergoing sperm banking through the fertility preservation program were aged 14 to 62 years old; mean ± standard deviation = 25.9± 6.9 years. Two of the patients were minors under care of Pediatric Oncology department. 76.7% of the samples (17 patients) were obtained by masturbation. In the other 4 patients, viable sperm could not be preserved from ejaculation, but it was successfully obtained by testicular or epidydimal sperm extraction. Conclusions: The initiation of a formal fertility preservation program at our institution quickly increased the rate of sperm banking; in more than 6 folds within its first 7 months of functioning. Oncofertility is an essential component of the care of oncologic patients in reproductive age or younger, and our results manifest the benefit of a standardized program at academic institutions. Counseling in fertility preservation should be offered to all patients at risk prior to initiation of oncologic treatment.
Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin (PLD): Use of left ventricular ejection fraction (EF).
Authors: Keith M. Skubitz, Anne Hudson Blaes, Suma Konety, Gary S. Francis
Journal: Journal of Clinical Oncology (2016)

e14026 Background: The use of doxorubicin (D) is limited by cardiotoxicity. Cumulative dose is an important risk factor for D-induced heart failure (D-HF). Retrospective studies found a ~7.5% incidence of clinical HF at a cumulative dose of 550 mg/m2, and prospective trials have found even higher rates. The administration of D by continuous intravenous infusion (CIVI) has less cardiotoxicity than when given by bolus administration. Pegylated-liposomal doxorubicin (PLD) has a longer half-life in blood, and a toxicity profile more similar to that of CIVI-D, and may have lower cardiotoxicity. Limiting D use based on ejection fraction (EF) is commonly performed. Despite the wide use of EF to monitor D-HF, evidence for its utility to predict D-HF is limited, and monitoring adds cost. There is even less information regarding large cumulative doses of PLD and its effect on D-HF and EF. We examined the incidence of D-HF in patients who received a large cumulative dose of D as PLD, and its relation to EF and HF. Methods: A retrospective chart review of patients who received a large cumulative dose of PLD, sometimes following previous free D, was performed. Results: No definite D-HF was observed in 42 patients who received a cumulative D dose (free + PLD) of > 450 mg/m2, 37 of whom received > 500 mg/m2, 12 > 1000 mg/m2, and 5 > 1400 mg/m2. The EF varied greatly over time in some patients in the absence of symptoms or signs of HF. Conclusions: The findings provide further evidence for the low risk of D-HF with PLD. Although this study is subject to the usual limits of a retrospective study, the doses received and long-term follow-up are noteworthy. While the determination of EF is commonly used to monitor D cardiotoxicity, it has many limitations. Frequent, regular monitoring of EF during treatment may not be helpful, at least in the case of PLD and CIVI-D in adults. Indeed, given the lack of prognostic clarity regarding modest EF changes, regular measurement of EF may sometimes inappropriately limit patient access to this useful drug. These findings may not apply to children or other liposomal formulations, such as non-pegylated formulations.
Prevalence of critical malnutrition (CMN) in patients enrolling on phase I/II (P1/2) clinical trials.
Authors: Rishi Jain, Elizabeth Handorf, Vipin Khare, Yana Chertock, Michael J. Hall
Journal: Journal of Clinical Oncology (2017)

e21700 Background: Cancer therapies undergo evaluation in P1/2 trials, frequently in patients (pts) with disrupted caloric intake, weight loss, and other adverse effects of cancer on physical and psychological functioning. CMN and sarcopenia may increase treatment related toxicity (TRT) due to acquired pharmacokinetic variability and altered drug metabolism. Little is known about the prevalence of CMN among pts enrolling on P1/2 trials, its association with abnormal physical and psychological functioning, and its role in mediating TRT. Methods: Pts initiating a P1/2 trial were recruited. Study acceptance rate was &gt; 95%. Pts had a comprehensive nutritional assessment using the validated PG-SGA, a short, 3-5 minute tool that evaluates multiple nutritional domains [symptom burden, functional status, metabolic stress and physical exam (muscle/fat status)]. CMN is defined as a PG-SGA score of ≥ 9. Distress, anxiety, depression and physical activity were also measured. BMI and albumin were extracted from the chart. Statistical significance was determined by Fisher’s exact test. Results: 54 pts (85% P1) were enrolled. CMN was identified in 39%. Pts with gastrointestinal (GI) cancers were more likely to have CMN than non-GI cancers (75% vs 24%, p = 0.001); otherwise, CMN rates were not different by age ( &lt; 60 vs 60+), gender, race, or trial phase (1 vs 2). CMN was also associated with number of lines of therapy, but was surprisingly less common among patients with &gt; 2 therapies compared to those with 0-2 (29% vs 57%, p = 0.051). Strong associations of CMN to distress (p = 0.028), depression (p = 0.020) and sedentary lifestyle (p = 0.012) were also seen. Clinical “red flags” of MN such as low BMI ( &lt; 25) and low albumin ( &lt; 3.5) had poor sensitivity (66.7% and 33.3%) and specificity (57.6% and 78.8%) for CMN. Correlation of CMN to TRT is underway. Conclusions: CMN is prevalent among P1/2 trial pts, notably in those with GI cancers and with fewer lines of therapy, and is associated with physical inactivity, distress and depression. BMI and albumin are poorly predictive of CMN. Undiagnosed CMN may, through multiple pathways, increase the vulnerability of pts on P1/2 studies to TRT. Comprehensive nutritional assessment of P1/2 pts should be considered.
Periodontal complications with age
Authors: Goesta Rutger Persson
Journal: Periodontology 2000 (2018)

Abstract The present literature review on periodontal complications in aging focuses on the diagnosis, etiology and development of periodontal complications as a complete entity. In addition, the review also focuses on some of the common systemic diseases that either may further add to periodontal complications or, as result of anti‐inflammatory treatment, limit the expression of periodontal disease. There is no evidence to suggest that clinical methods to provide periodontal therapies have been developed especially for older individuals. There is evidence that aging can be associated with periodontally healthy conditions through life and with a high level of tooth retention and function. Periodontal complications that are difficult to manage are usually associated with concurrent medical diseases and complications, or with socio‐economic factors that limit the ability to provide dental care for the aging population. Currently, some systemic medical conditions are managed with anti‐inflammatory medications with positive effects, while slowing the progression and expression of chronic periodontitis. The lack of data from clinical studies on how to manage periodontal complications in aging is obvious.
Abstract 188: Manipulation of Excitation-contraction Coupling in Cardiomyocytes Using Conductive Polyaniline Scaffolds
Authors: Eleanor J Humphrey, Michaella Kapnisi, Damia Mawad, Nicholas S Peters, Molly M Stevens, Cesare M Terracciano
Journal: Circulation Research (2017)

The application of tissue engineered patches made of conductive polymer scaffolds combined with cardiomyocytes (CMs) could provide a dual method of improving the damaged myocardium after an infarction: firstly by introducing functional CMs to the area; secondly the conductive polymer could modulate electrical transmission across the scar tissue. Polyaniline (PANI) scaffolds are one such example, however, the consequences of growing CMs on conductive PANI scaffolds with regards to CM electrophysiology are unknown. In this study we assess the hypothesis that conductive PANI scaffolds affect CM calcium transients and action potential morphology in culture. Neonatal rat ventricular myocytes (NRVMs) and neonatal rat fibroblasts were co-cultured on conductive and non-conductive (sodium hydroxide treated) PANI scaffolds and remained viable after four days of culture, covering the surface of the construct. Compared to those cultured on non-conductive PANI scaffolds, NRVM cultured on conductive PANI scaffolds show faster calcium transients, measured using Fluo-4AM and field stimulated at 1 Hz, with a decrease in the time to peak (t p non-conductive=105±6 ms, t p conductive= 85±5 ms, p&lt;0.05, n=6) and time to 50% (t 50 non-conductive=212±12 ms, t 50 conductive= 116±7 ms, p&lt;0.001, n=6) and 90% decay (t 90 non-conductive=404±24 ms, t 90 conductive= 266±15 ms, p&lt;0.001, n=6). Action potential morphology, assessed using FluoVolt membrane potential dye and stimulated at 1 Hz, remain unchanged for conductive and non-conductive PANI scaffolds. The PANI scaffolds are compatible with NRVMs and the cells have good viability after four days in culture. The conductive PANI scaffolds have a significant effect on myocyte calcium cycling but this is not caused by a change in action potential morphology. Further work is required to understand the mechanism behind the change in calcium handling in the CMs on the conductive PANI scaffolds.
Imatinib versus interferon as adjuvant therapy in a phase II study in patients with highrisk C-Kit mutated melanoma.
Authors: Li Li Mao, Lu Si, Yan Kong, Xuan Wang, BIN LIAN, Zhihong Chi, Chuanliang Cui, Xinan Sheng, Jun Guo
Journal: Journal of Clinical Oncology (2016)

e21073 Background: Imatinib, a selective inhibitor targeting Abl as well as C-Kit and the platelet-derived growth factor receptor, has changed the treatment paradigm for metastatic melanoma with c-KIT alterations in recent years.High-dose interferon (HDI) is FDA approved adjuvant therapy for patients(pts) with highrisk melanoma.This study (NCT01782508) aims to confirm whether imatinib is equally effective as interferon alfa-2b in adjuvant therapy for patients with C-Kit mutated melanomas. Methods: This study enrolled C-Kit mutated (exon 9,11 or 13), high risk (Stage IIB to Stage IIIC) melanoma pts, who had radical surgery but no prior systemic therapy. Hence randomized them (ratio of 1:2) to receive either imatinib(400mg daily for a year) or HDI(interferon a-2b 15X106 U/m2 d1–5/w×4w plus 9X106 U tiw×48w) in the absence of disease progression or unacceptable toxicity. Recurrence-free survival (RFS) was the primary endpoint, and secondary endpoints were overall survival (OS) and tolerability. Results: Forty-eight out of 528pts were enrolled : 16 in imatinib arm and 32 in HDI arm. The most common mutations were found in L576P (13/48).On the end of October 2015, The median RFS of patients who received HDI was 29.8 months (23.3–36.3 months), which wassignificantly superior than those with imatinib(10.0 months, 95% CI 0-20.0 months) (P = 0.029), respectively. Similar trend was observed in pts harboring L576P mutation (median RFS:4.8months in imatinib arm vs.34.2 months in interferonarm(P = 0.005). The median OS was not reached in both groups. The estimated median OS was similar in the both arms: 34.5months (range: 4.6-37.3 months) versus 38.4months (range:12.3-40 months)(P = 0.5).The toxicities were consistent with the previous reported studies. Conclusions: Up to now, this is the first clinical trial comparing imatinib and interferon in the post-surgery highrisk c-Kit mutated melanoma patients.Imatinib may not prolong recurrence -free survival when compared with HDI. On the basis of our data, we do not recommend imatinib in the adjuvant treatment of curatively resected high risk melanoma. Clinical trial information: NCT01782508.
ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone
Authors: Frederique M. F. Cornelis, Silvia Monteagudo, Laura-An K. A. Guns, Wouter den Hollander, Rob G. H. H. Nelissen, Lies Storms, Tine Peeters, Ilse Jonkers, Ingrid Meulenbelt, Rik J. Lories
Journal: Science Translational Medicine (2018)

ANP32A is a transcriptional regulator of ATM and provides protection against oxidative stress to prevent joint, brain, and bone disease.
Correlation of overall survival (OS) in patients (pts) with inoperable hepatocellular carcinoma (iHCC) receiving tivozanib (TIVO) with baseline performance status.
Authors: Sunyoung S. Lee, Smitha S. Krishnamurthi, Austin Miller, Bassam N. Estfan, Chong Wang, Andrea Frazer, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2018)

e16122 Background: Therapeutic approaches and prognosis in cancer depend on the baseline performance status and comorbidities. The first line therapy for iHCC has been sorafenib since 2007, the only FDA-approved medication as first line. Agents with better tolerability are needed since most pts with iHCC have underlying comorbidities. TIVO is an inhibitor of VEGF tyrosine kinase and angiogenesis critical in HCC. Methods: A phase 1b/2 study with iHCC pts with a measurable disease, ECOG ≤ 2, Child-Pugh class A, and no prior systemic therapy was performed. Phase 1b portion followed a modified 3 + 3 design; phase 2 portion was a two-stage, single arm, un-blinded study. Adverse events were categorized based on CTCAE, and tumor imaging was assessed per RECIST. Results: Twenty one (21) eligible pts were enrolled from 3 centers with IRB approval. Eight (8) pts were enrolled in phase 1b with a starting dose of 1 mg once daily for 21days with one week off. The accrual of remaining patients to the phase 2 portion occurred at the same dose. In a total of 19 pts, median follow up was 16.9 months (mo). Twelve (12) pts (63.2%) had ECOG 0 at baseline; those with ECOG 1 were 7 (36.8%). The primary endpoint of median progression-free-survival (PFS) and PFS at week 24 were 5.5 mo and 47%. PFS responders at 24 weeks were 7/12 (58.3%) in pts with ECOG 0, and 2/5 (41.7%) with ECOG 1. This was not statistically significantly different (p = 0.3498). The secondary endpoint of OS at 6 and 12 mo was 58% and 25%. Median OS was 7.5 mo. OS was statistically significantly different with 9.1 (5.1 – 27.8) mo and 5.4 (4.3 – 8.6) mo in pts with ECOG 0 and 1 (p = 0.034), respectively. Survival rate (SR) at 26 weeks was 0.75 and 0.34 in pts with ECOG 0 and 1; SR was 0.43 and 0.00 at 52 weeks, respectively. Of note, 4/19 pts survived for more than 24 mo, and these pts were those with ECOG 0. Conclusions: OS in pts with iHCC receiving TIVO correlates with baseline performance status. Sequencing and biomarker studies in pts with a durable response to TIVO are warranted. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Aveo Oncology. Clinical trial information: NCT01835223.
P01.102 Cost effectiveness of treating glioblastoma patients age 65 years or older with Tumor Treating Fields plus Temozolomide versus Temozolomide alone
Authors: G F Guzauskas, B C M Wang, E L Pollom, V W Stieber, A Kinzel, C Proescholdt, L Garrison
Journal: Neuro-Oncology (2018)

The subgroup of patients age 65 and older showed the the greatest survival benefit from TTFields plus TMZ treatment in the EF-14 trial (hazard ratio 0.51 [CI 0.33–0.77]). This is the first report on the cost-effectiveness of adding TTFields to the maintainance phase of the first line treatment protocol for elderly GBM patients from a U.S. health system perspective. The endpoint of this analysis was the projected incremental cost-effectiveness ratio (ICER) of adding TTFields to the standard-of-care for newly diagnosed GBM in the maintenance phase of treatment for patients over 65 years of age. Patient outcomes were simulated using a 3-state area under the curve model including alive with stable disease, progressed disease, and death. Survival was modelled over a lifetime horizon by integrating the 5-year survival results for elderly patients reported in the EF-14 trial with long-term GBM epidemiology data and U.S. background mortality rates. Data on patient utilities used to calculate quality-adjusted life years (QALYs) were based on a previous analysis of GBM-specific health-state preferences. Frequency of adverse events associated with TTFields and TMZ were derived from the EF-14 trial for the patients over 65 years. Costs for adverse events and supportive care cost estimates were used according to published literature. Future survival benefits and costs were discounted to present value at a rate of 3%. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability. Patients treated with TTFields and maintenance TMZ achieved mean lifetime survival of 3.66 years before discounting and 3.04 years after discounting future survival. Patients treated with TMZ alone achieved a mean lifetime survival of 1.32 years without discounting and 1.29 years after discounting future survival. The resulting incremental life years gained were 1.75 years after discounting future survival benefits, andthe incremental quality-adjusted life years (QALYs) were 1.35. The incremental total cost was $192,000. The ICER was $109,500 per LYG and $142,400per QALY gained. The probability of TTFields being cost-effective was 85% at a willingness-to-pay threshold of $200,000 per QALY. Treating newly diagnosed GBM patients over 65 years of age with TTFields and TMZ has the potential to increase mean lifetime survival and quality-adjusted survival substantially compared to treatment with TMZ alone. TTFields therapy, even when evaluated at its full list price, demonstrated a high probability of cost-effectiveness at willingness-to-pay thresholds reported in economic literature for the United States. These results indicate that patients over age 65 may not only benefit from TTFields treatment more than other subgroups, but also that their treatment may be more cost-effective.
Non–small cell lung cancer in veterans: Disparities in prevalence and survival among different histologic subtypes.
Authors: Hussein Assi, Efstratios Koutroumpakis, Sun Jung Kang, Syed Arzoo Mehdi, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2016)

e20590 Background: Since the 1980s, adenocarcinoma (AC) of the lung has become more common than squamous cell carcinoma (SCC). Given the differences in smoking patterns, it is unclear if the same holds true among veterans. In this study, we compare the distribution of lung AC and SCC in the veterans' population to that in the general population. We also looked at the survival of patients with different histologies in the VA population. Methods: We performed a retrospective analysis of the Veteran's Affairs Comprehensive Cancer Registry of NSCLC (non-small cell lung cancer) patients diagnosed between 1995 and 2009. Data was analyzed on SPSS program. Survival estimates were derived using the Kaplan Meier Method and Cox proportional hazard model. A value of P <0.05 was considered statistically significant. Data was compared to data from the Surveillance, Epidemiology, and End Results (SEER). The study was approved by the local institutional IRB. Results: This analysis included 64,689 patients with NSCLC. The histological subtypes of NSCLC in the VA population and comparison with SEER data is summarized in the table below. The proportion of AC was significantly higher in the SEER database, while SCC was more common in the VA population. Veteran patients with AC presented more frequently with metastatic disease compared to SCC (47.0% vs 32.2%, p<0.001). On multivariate analysis, median survival was higher in SCC than in AC (9.6 vs 8.2 months, p<0.001). AC was associated with worse overall survival (hazard ratio 1.06; 95% confidence interval 1.03-1.09). Conclusions: There is a significant difference in histologic subtypes of NSCLC between veterans and the general population. AC tended to present at a more advanced stage than SCC, and was associated with inferior survival. Veteran specific research is necessary in order to improve lung cancer outcomes for that specific cohort. Histology VA population (%) n = 64689 SEER data (%) n = 101018 One-tailed P-value Adenocarcinoma 35.1 47.0 <0.001 Squamous cell carcinoma 43.1 31.9 <0.001 Large cell carcinoma 5.5 2.6 <0.001 NOS 16.3 18.5 <0.001