Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424.

PURPOSE: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). METHODS AND MATERIALS: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. RESULTS: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. CONCLUSIONS: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

The association of health-related quality of life and cognitive function in patients receiving memantine for the prevention of cognitive dysfunction during whole-brain radiotherapy.

BACKGROUND: This study evaluated the association between health-related quality of life (HRQOL) and cognition in patients receiving memantine for prevention of cognitive dysfunction during whole-brain radiotherapy (WBRT). METHODS: Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine, 20 mg per day, within 3 days of initiating radiotherapy, for 24 weeks. The Functional Assessment of Cancer Therapy-Brain module (FACT-Br) and Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C) were completed in coordination with serial standardized tests of cognitive function. RESULTS: Of the 508 eligible patients, 442 (87%) consented to participate in the HRQOL portion and contributed to baseline analyses. Evaluable patients at 24 weeks (n = 246) included surviving patients completing FACT-Br, MOS-C, and objective cognitive assessments (n = 146, 59%) and patients alive at time of missed assessment (n = 100, 41%). Baseline cognitive function correlated significantly with FACT-Br and MOS-C self-reports. All domains of objective cognitive function showed declines over time. Neither FACT-Br nor MOS-C differed between the treatment arms. Emotional and functional well-being subscales of the FACT improved over time while the remainder of the FACT-Br domains remained stable. MOS-C scores declined over time. CONCLUSION: Baseline cognitive function correlated significantly with FACT-Br and MOS-C scores. No by-arm differences in HRQOL were observed despite differences in objective cognitive function. Patient attrition and poor testing compliance remain significant problems in studies of cognitive function of brain metastases patients and further effort is needed to improve compliance with testing and sensitivity of patient-reported measures.

Patient counseling materials: The effect of patient health literacy on the comprehension of printed prescription drug information.

BACKGROUND: Counseling patients with written materials relies equally on patients' health literacy to understand their disease and its treatment, and the written materials' effectiveness communicating clearly in accessible and actionable ways. Only about 12% of the US population is adequately health literate. OBJECTIVES: To explore the impact of reducing the health literacy demands of written patient health information. METHODS: 805 patients were screened for health literacy, and recruited for balanced cohorts of adequate and low literacy, and high and normal blood pressure. Half of each patient cohort received either standard or "health literacy-friendly" drug summaries (i.e. Patient Package Inserts, or PPIs or "leaflets") along with a standardized health literacy assessment scale. RESULTS: The literacy-friendly drug summary improved comprehension of drug-related information overall from 50% to 71% correct responses. Adequate literacy patients improved from 58% correct to 90%, while lower literacy patients improved from 42% to 52% correct in response to the health literacy-friendly PPIs. CONCLUSIONS: Health literacy demands require special attention in developing and using written drug summary materials. Additionally, pharmacists should be provided additional information and counseling support materials to facilitate communications with low health literacy level patients.

Reflections on 50 Years of Neuroscience Nursing: Neuro-Oncology, Moving Forward by Looking Back.

During the past 50 years, there have been more than 100 articles published in the Journal of Neuroscience Nursing covering the topic of neuro-oncology. This article will explore the historical implications and milestones from these articles. The analysis highlights the scope and depth of the many articles as they relate to the advancements in neuro-oncology.

A test of the revised auricular surface aging method on a modern European population.

The accurate age estimation of adults is an important step in the construction of the biological profile of skeletonized remains. The auricular surface of the ilium as it was developed in 1985 by Lovejoy et al., is one of the methods employed for age estimation. This study presents the results of a blind test of the revised auricular surface aging method developed by Buckberry and Chamberlain. A sample of 120 individuals from the Athens Collection was used to test this revised aging technique. Almost all features and composite score were positively correlated with known age-at-death. The calculation of bias demonstrated no obvious trend for either overestimation or underestimation of age when all individuals were pooled together. Inaccuracy showed that absolute errors of estimated ages against known ages are substantial. The data generated from this study suggest that the revised method can be reliable for age estimation on a modern European population.

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). METHODS: Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. RESULTS: Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. CONCLUSIONS: Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

A simple technique for imaging the human skeleton using a flatbed scanner.

A simple technique for imaging the human skeleton with a flatbed scanner is presented using the auricular surface of the ilium as an example. A flatbed scanner with resolution capabilities of 600 dpi or greater allows for images of human bones. The auricular surface of the ilium was selected to demonstrate this technique as it is a fairly three-dimensional area that can be difficult to record photographically. Fifty left ilia of various ages at death from the Athens Collection were selected from which three observers (SCF, CE, and IM) scored the morphology of the auricular surface using a well-established aging method. Observations were taken of the dry bone, of digital photographs of the bone, and of scanned images of the bone, and in that sequence. Results indicate that scores of scanned images are equivalent or better than digital images of the same ilia. This technique allows for sharing data electronically with ease.

Sex determination using metacarpal biometric data from the Athens Collection.

Forensic anthropologists and bioarchaeologists usually determine sex by analyzing quantitative and qualitative characters of the human skeleton. In general, the pelvis and skull are the skeletal parts used most often, but in many cases these parts are missing or fragmentary. In such circumstances, it is necessary to use techniques based on other skeletal elements. The primary aim of this work is to determine whether metacarpals can be used for the determination of sex specifically in a Greek population. A secondary step is to describe and develop linear discriminant function equations for sex determination based on a contemporary Greek population using metacarpal biometric data. The skeletal sample of the modern Greeks is housed at the National and Kapodistrian University of Athens (NKUA) is comprised of 993 metacarpals (left and right), corresponding to 151 adult individuals (84 males and 67 females). The correct sex classification reached an accuracy of 83.7-88.1% for left and 83.8-89.7%, for right metacarpals. Our results suggest that metacarpals can be used for sexing in bioarchaeological, and forensic studies, in addition to other sex determination techniques.

Health related quality of life and cognitive status in patients with glioblastoma multiforme receiving escalating doses of conformal three dimensional radiation on RTOG 98-03.

The Radiation Therapy Oncology Group (RTOG) embarked on a phase I/II study of patients suffering from glioblastoma multiforme (protocol 98-03) to assess the impact of dose escalation with 3-D conformal techniques. The primary endpoints were feasibility and survival. This report describes the outcome of secondary endpoints (quality of life and neurocognitive function). Patients with supratentorial GBM were treated with a combination of carmustine (BCNU) and conformal irradiation (dose levels: 66, 72, 78, 84 Gy, respectively). Quality of Life was assessed with the Spitzer Quality of Life Index. Neurocognitive function was determined by the Mini Mental Status Examination. The latter tests were administered at the start of irradiation, at the end of irradiation and then at 4 month intervals. Relatively high compliance was achieved with both of the tools (SQLI; MMSE). Overall rates of survival between baseline SQLI scores <7 and 7-10 were statistically significantly different [HR = 1.72, 95% CI (1.22, 2.4), P = 0.0015]. The significant impact of high SQLI score on survival was preserved in multivariate analysis. The component of this index which made the greatest contribution was the patient's independence. There was continual deterioration of neurocognitive function within the populations studied. No correlation was seen between dose escalation and the secondary endpoints studied. Radiation dose escalation and assessment of its impact on life quality and neurocognition can be carried out in a large international trial. Baseline SQLI is a statistically significant determinant of survival. Those who maintain independence have superior survival to those who are reliant on others.

Quality of life in adults with brain tumors: current knowledge and future directions.

Quality of life is an important area of clinical neurooncology that is increasingly relevant as survivorship increases and as patients experience potential morbidities associated with new therapies. This review of quality-of-life studies in the brain tumor population aims to summarize what is currently known about quality of life in patients with both low-grade and high-grade tumors and suggest how we may use this knowledge to direct future research. To date, reports on quality of life have been primarily qualitative and focused on specific symptoms such as fatigue, sleep disorders, and cognitive dysfunction, as well as some symptom clusters. However, the increasing interest in exploring quality of life as a primary end point for cancer therapy has established a need for prospective, controlled studies to assess baseline and serial quality-of-life parameters in brain tumor patients in order to plan and evaluate appropriate and timely interventions for their symptoms.

Prospective evaluation of quality of life and neurocognitive effects in patients with multiple brain metastases receiving whole-brain radiotherapy with or without thalidomide on Radiation Therapy Oncology Group (RTOG) trial 0118.

PURPOSE: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) +/- thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. METHODS AND MATERIALS: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. RESULTS: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. CONCLUSIONS: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population.

Symptom clusters and quality of life in survivors of ovarian cancer.

Ovarian cancer has nonspecific symptoms, and no screening tool is available for early diagnosis; therefore, only 19% of ovarian cancers are found at an early stage. Given the late diagnosis, women with ovarian cancer often have a prolonged course of treatment and significant morbidity that lasts into survivorship. However, distressing symptoms and their effects on quality of life have been relatively understudied, particularly in survivors of the disease. The purpose of this study was to describe a symptom cluster and its relationship to quality of life in women with ovarian cancer who were recruited from an online cancer support group. Descriptive statistics and hierarchical regression techniques were used to analyze the data obtained from a larger study testing the psychometric properties of a quality-of-life instrument. Most participants had stage III ovarian cancer, and nearly all (97%) had undergone treatment before the study. A symptom cluster composed of depression and fatigue was identified using work by Kim and colleagues [Symptom clusters: concept analysis and clinical implications for cancer nursing. Cancer Nurs. 2005;28(4):270-282]. The symptom cluster explained 41% (P = .000) of the variance in quality of life. These results suggest that fatigue and depression are significant problems for survivors of ovarian cancer.

Symptom clusters in patients with high-grade glioma.

PURPOSE: To describe the co-occurring symptoms (depression, fatigue, pain, sleep disturbance, and cognitive impairment), quality of life (QoL), and functional status in patients with high-grade glioma. DESIGN: Correlational, descriptive study of 73 participants with high-grade glioma in the U.S. METHODS: Nine brief measures were obtained with a mailed survey. Participants were recruited from the online message board of The Healing Exchange BRAIN TRUST, a nonprofit organization dedicated to improving quality of life for people with brain tumors. FINDINGS: Two symptom cluster models were examined. Four co-occurring symptoms were significantly correlated with each other and explained 29% of the variance in QoL: depression, fatigue, sleep disturbance, and cognitive impairment. Depression, fatigue, sleep disturbance, cognitive impairment, and pain were significantly correlated with each other and explained 62% of the variance in functional status. CONCLUSIONS: The interrelationships of the symptoms examined in this study and their relationships with QoL and functional status meet the criteria for defining a symptom cluster. The differences in the models of QoL and functional status indicates that symptom clusters may have unique characteristics in patients with gliomas.

End-of-Life care concepts in Journal of Neuroscience Nursing.

This descriptive study evaluated concepts relating to end-of-life care addressed in Journal of Neuroscience Nursing during a 10-year period. An analysis of 377 articles published from 1993 to 2002 found 40 articles addressing some area of end-of-life content. Of 2,558 pages reviewed, 201 pages (7.8%) contained end-of-life content. The primary areas of end-of-life care discussed in the articles were needs assessment for families, coping strategies and support systems, and recognition of family and caregiver needs. The most common diseases and disorders addressed were epilepsy, stroke, traumatic brain injury, multiple sclerosis, and Parkinson's disease. To increase overall content in the field of palliative and end-of-life care, authors can include end-of-life content in articles submitted for publication.

Symptom clusters and quality of life in survivors of lung cancer.

PURPOSE/OBJECTIVES: To explore the prevalence and intensity of depression, fatigue, and pain in survivors of lung cancer; to examine the relationship of symptoms in a cluster; and to examine the relationship of the symptom cluster to quality of life (QOL). DESIGN: Secondary data analysis. SETTING: Online lung cancer support group. SAMPLE: 51 patients diagnosed with lung cancer. METHODS: Mailed survey with self-report of depression, fatigue, and pain measured by subscales of the Short-Form 36 Health Status Survey and QOL measured by the Fox Simple QOL Scale. Pearson's correlation and multiple regression analyses were used to examine the possible symptom cluster. MAIN RESEARCH VARIABLES: Depression, fatigue, pain, and QOL. FINDINGS: Depression, fatigue, and pain were found in a majority of survivors, with pain being the least common symptom. Fatigue was the most intense of the three symptoms. Two significantly correlated symptoms were depression and fatigue. The cluster explained 29% (p less than 0.01) of the variance in QOL in the lung cancer survivors. CONCLUSIONS: The data provided preliminary support for the presence of a symptom cluster in patients with lung cancer consisting of depression and fatigue. The cluster had a negative relationship with QOL. Survivors of lung cancer have depression and fatigue that affect QOL. IMPLICATIONS FOR NURSING: Healthcare providers must assess the potential for symptoms to cluster, adversely affecting key patient outcomes such as QOL. Through increased knowledge of symptom clusters, clinicians will be able to more effectively target the most distressing set of symptoms for intervention.

Complementary therapy use and quality of life in persons with high-grade gliomas.

Studies have indicated that 30%-80% of cancer patients use complementary and alternative practices and products (CAPPs), but little is known about CAPPs use by persons with brain tumors. This secondary analysis of Glioma Outcomes Project data compared CAPPs users with nonusers, compared those who stopped using CAPPs with those who continued use, described frequency and patterns of CAPPs use, and compared the relationship of CAPPs use to self-reported quality of life (QOL) over time, in 186 persons with high-grade gliomas. CAPPs users at all three measurement points rated QOL higher, although not significantly higher, than nonusers. Study findings support further exploration of CAPPs use and its effects on key outcomes in persons with high-grade gliomas.

Cognitive impairment in patients with brain tumors: assessment and intervention in the clinic setting.

Cognitive impairment is the most common neurologic problem associated with brain tumors and is present in many people with brain tumors from the time of diagnosis. Treatment of primary brain tumors with surgery, radiation, chemotherapy, and adjunctive medications such as corticosteroids results in further adverse effects on cognitive function. To plan the best care for patients with brain tumors, healthcare providers must initiate systematic and accurate assessment of cognitive functioning at the first clinic visit and extend assessment throughout the course of illness. This article outlines the range of cognitive dysfunction that may be seen in patients with primary brain tumors and offers information for clinicians seeking to develop their skills and implement a systematic approach to cognitive screening. The use of cognitive screening to guide timely intervention, such as referral to a neuropsychologist and the provision of anticipatory guidance to people with brain tumors and their families, is discussed.

The questionable contribution of the Neolithic and the Bronze Age to European craniofacial form.

Many human craniofacial dimensions are largely of neutral adaptive significance, and an analysis of their variation can serve as an indication of the extent to which any given population is genetically related to or differs from any other. When 24 craniofacial measurements of a series of human populations are used to generate neighbor-joining dendrograms, it is no surprise that all modern European groups, ranging all of the way from Scandinavia to eastern Europe and throughout the Mediterranean to the Middle East, show that they are closely related to each other. The surprise is that the Neolithic peoples of Europe and their Bronze Age successors are not closely related to the modern inhabitants, although the prehistoric/modern ties are somewhat more apparent in southern Europe. It is a further surprise that the Epipalaeolithic Natufian of Israel from whom the Neolithic realm was assumed to arise has a clear link to Sub-Saharan Africa. Basques and Canary Islanders are clearly associated with modern Europeans. When canonical variates are plotted, neither sample ties in with Cro-Magnon as was once suggested. The data treated here support the idea that the Neolithic moved out of the Near East into the circum-Mediterranean areas and Europe by a process of demic diffusion but that subsequently the in situ residents of those areas, derived from the Late Pleistocene inhabitants, absorbed both the agricultural life way and the people who had brought it.