Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation.

INTRODUCTION: The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT. METHODS: PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals. RESULTS: Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL. CONCLUSIONS: Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.

R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma.

High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m(2)), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154.

Cognitive effects of donepezil therapy in patients with brain tumors: a pilot study.

Cognitive dysfunction is prevalent among brain tumor patients treated with radiotherapy (RT) and chemotherapy. However, there are no approved pharmacological interventions for cognitive dysfunction in cancer patients. The goal of this pilot study was to examine the efficacy of donepezil, an acetylcholinesterase inhibitor used to treat Alzheimer's disease, in improving cognitive functions in brain tumor patients previously treated with RT + chemotherapy or chemotherapy alone. Fifteen patients with a brain tumor received a single daily dose of donepezil for 24 weeks (5 mg for 4 weeks, then 10 mg for 20 weeks). Patients completed cognitive evaluations prior to initiating therapy (baseline), and about 12 weeks (mid-study) and 24 weeks (end-of-study) subsequent to initiation of donepezil therapy. The results of linear mixed models analysis, controlling for each patient's baseline cognitive test score, showed a significant post-baseline improvement in attention (WAIS-III digit span forward; p = 0.037), graphomotor speed (WAIS-III digit symbol; p = 0.035) and visual memory (BVMT-R-delay; p = 0.025). There was also an improvement in self-reported quality of life (FACT-Br, social well-being subscale; p = 0.01). The findings of this pilot study suggest that treatment with donepezil may improve some aspects of cognitive functions and quality of life in brain tumor patients. Similar findings were reported in two prior trials of donepezil in brain tumor survivors.

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

Background Many patients with hematological malignancies treated with stem cell transplantation (SCT) experience cognitive dysfunction. However, few studies have investigated treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high dose chemotherapy (HDC) and autologous SCT (HDC/ASCT). In this study, we examined gray matter (GM) volume, resting state functional connectivity (RSFC), neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Methods Eighteen MM patients underwent magnetic resonance imaging, neurocognitive tests, and serum PCy measurement prior to HDC/ASCT, and fifteen patients completed follow ups an average of five months post-HDC/ASCT. Results There were significant decreases in RSFC from pre- to post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022), and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029); these comparisons were no longer significant after multiple comparisons correction. There were no significant changes in GM volumes or NF, except for improvement in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). Conclusions This pilot study showed decreased RSFC involving the left frontal, right posterior parietal and right anterior cingulate cortices in MM patients post-HDC/ASCT, relatively stable NF, and increases in PCy. These findings are congruent with studies in patients with hematological malignancies and other cancers and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy adverse effects.

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were significant decreases in RSFC post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022) and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029). There were no significant changes in GM or NF, except for improvements in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). In conclusion, RSFC decreased in frontal, parietal, and cingulate cortices post-HDC/ASCT, NF was relatively stable, and several PCy increased. These findings are congruent with other studies in cancer patients and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy's adverse effects.

Longitudinal Evaluation of Brain Plasticity in Low-Grade Gliomas: fMRI and Graph-Theory Provide Insights on Language Reorganization.

Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and standardized language assessment. We hypothesized that functional networks obtained from tb-fMRI would show connectivity changes over time, with increased right-hemispheric participation. We recruited five right-handed patients (4M, mean age 47.6Y) with left-hemispheric LGG. Tb-fMRI and language assessment were conducted pre-operatively (pre-op), and post-operatively: post-op1 (4-8 months), post-op2 (10-14 months) and post-op3 (16-23 months). We computed the individual functional networks applying optimal percolation thresholding. Language dominance and hemispheric connectivity were quantified by laterality indices (LI) on fMRI maps and connectivity matrices. A fixed linear mixed model was used to assess the intra-patient correlation trend of LI values over time and their correlation with language performance. Individual networks showed increased inter-hemispheric and right-sided connectivity involving language areas homologues. Two patterns of language reorganization emerged: Three/five patients demonstrated a left-to-codominant shift from pre-op to post-op3 (type 1). Two/five patients started as atypical dominant at pre-op, and remained unchanged at post-op3 (type 2). LI obtained from tb-fMRI showed a significant left-to-right trend in all patients across timepoints. There were no significant changes in language performance over time. Type 1 language reorganization may be related to the treatment, while type 2 may be tumor-induced, since it was already present at pre-op. Increased inter-hemispheric and right-side connectivity may represent the initial step to develop functional plasticity.

Cognitive function and quality of life in ovarian cancer.

OBJECTIVES: As advances in treatment have prolonged survival for many patients with ovarian cancer, there has been growing interest in assessing the adverse effects of disease and treatment. The aim of this study was to review the literature on cognitive function and quality of life (QOL) in this population. METHODS: A review of published studies including formal assessment of neurocognitive functions and self-reported domains of quality of life, with an emphasis on cognitive function, was performed. RESULTS: The small number of studies including formal evaluations of neurocognitive function suggests that many ovarian cancer patients experience cognitive difficulties associated with their disease and treatment. Several studies described declines in self-reported cognitive function that may impact QOL, but the results were not consistent across studies. CONCLUSIONS: Adequately powered longitudinal studies including formal neurocognitive and QOL assessments are needed to advance our understanding of the incidence of cognitive dysfunction and its impact on functional ability and QOL in ovarian cancer patients. These research efforts may ultimately contribute to treatment decision-making through the identification of vulnerable patients, and to the development of appropriate intervention strategies to improve cognitive function and QOL.

Altered regional homogeneity in patients with ovarian cancer treated with chemotherapy: a resting state fMRI study.

Many patients treated with chemotherapy for non-central nervous system (CNS) cancers experience cognitive dysfunction. However, few studies have investigated treatment-related neurotoxicity in women with ovarian cancer. The goal of this study was to assess regional brain function in patients with ovarian cancer after first-line chemotherapy. Seventeen patients with ovarian cancer and seventeen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1-4 months after completion of first line taxane/platinum chemotherapy. All participants underwent resting state functional MRI (rsfMRI) and regional homogeneity (ReHo) indices were calculated. The results showed that patients had significantly decreased average ReHo values in the left middle frontal gyrus, medial prefrontal cortex, and right superior parietal lobule, compared to healthy controls. This is the first rsfMRI study showing ReHo alterations in frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. The findings are overall congruent with prior studies in non-CNS cancer populations and provide supporting evidence for the prevailing notion that frontal areas are particularly vulnerable to the adverse effects of chemotherapy.

Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis.

PURPOSE: Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. PATIENTS AND METHODS: We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM. We enrolled patients with other solid tumors to an exploratory pCSI group. For the randomized groups, patients were assigned (2:1), stratified by histology and systemic disease status, to pCSI or IFRT. The primary end point was CNS PFS. Secondary end points included overall survival (OS) and treatment-related adverse events (TAEs). RESULTS: Between April 16, 2020, and October 11, 2021, 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS PFS was observed with pCSI (median 7.5 months; 95% CI, 6.6 months to not reached) compared with IFRT (2.3 months; 95% CI, 1.2 to 5.8 months; P < .001). We also observed OS benefit with pCSI (9.9 months; 95% CI, 7.5 months to not reached) versus IFRT (6.0 months; 95% CI, 3.9 months to not reached; P = .029). There was no difference in the rate of grade 3 and 4 TAEs (P = .19). In the exploratory pCSI group, 35 patients enrolled, the median CNS PFS was 5.8 months (95% CI, 4.4 to 9.1 months) and OS was 6.6 months (95% CI, 5.4 to 11 months). CONCLUSION: Compared with photon IFRT, we found pCSI improved CNS PFS and OS for patients with non-small-cell lung cancer and breast cancer with LM with no increase in serious TAEs.

Cognitive functions in long-term survivors of ovarian cancer.

BACKGROUND: Women diagnosed with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about the incidence of cognitive adverse effects of chemotherapy in survivors of this disease. This cross-sectional study assessed neuropsychological functions in long-term survivors of ovarian cancer who were either in complete remission or with evidence of recurrent disease. METHODS: Forty-eight women diagnosed with ovarian cancer 5 to 10 years prior to study enrollment underwent a brief neuropsychological evaluation; 22 patients were disease free and without history of recurrence (Group 1), and 26 patients had recurrent disease and were receiving treatment with chemotherapy or hormonal therapy (Group 2). RESULTS: There were no statistically significant differences between the two patient groups on tests of attention, memory, and executive functions. Group mean cognitive test scores were within the average range on all tests; however 28% of patients met criteria for cognitive impairment, a significantly higher frequency (p=0.03) than reported in healthy populations. CONCLUSIONS: In this study, neuropsychological test performance did not differ significantly between ovarian cancer survivors who were in remission and patients with recurrent disease and receiving treatment. Cognitive impairment was evident in a subset of patients, although group means test scores were within the average range. Additional research using prospective longitudinal designs is needed to clarify the contribution of disease, chemotherapy, hormonal therapy, and other risk factors to cognitive outcome in this clinical population.

Neurocognitive function in brain tumors.

Cognitive dysfunction associated with both the disease and the adverse effects of radiotherapy (RT) and chemotherapy is a significant problem among brain tumor patients. Currently, it is considered the most frequent complication among long-term survivors. A review of the literature indicates that whole-brain RT alone or in combination with chemotherapy results in cognitive dysfunction more pronounced than from either partial RT or chemotherapy alone. The cognitive domains sensitive to treatment adverse effects include attention, executive functions, memory, and graphomotor speed. An increasing number of studies and clinical trials have incorporated cognitive outcome measures and have provided relevant information about therapy-related neurotoxicity and the incidence of cognitive dysfunction. Recent studies have begun to elucidate the pathophysiologic mechanisms that may underlie RT and chemotherapy injury to the brain. Although there are no established preventive or therapeutic interventions for treatment-induced cognitive dysfunction, this is an area of growing interest, and several approaches are currently under investigation.

Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy.

High-dose chemotherapy and whole brain radiotherapy (WBRT) can prolong survival in primary CNS lymphoma (PCNSL) patients, but is often associated with clinically significant cognitive decline. In this study we assessed neuropsychological functioning prospectively in newly diagnosed PCNSL patients treated with induction chemotherapy followed by reduced-dose WBRT. Twelve patients underwent neuropsychological evaluations at diagnosis, after induction chemotherapy, and 6 and 12 months after WBRT. Nine patients completed additional cognitive evaluations 18 and 24 months post-treatment. At diagnosis, patients had impairments in Executive Functions, Verbal Memory, and Motor Speed. There was a significant improvement in Executive Functions (P < 0.01) and Verbal Memory (P < 0.05) following induction chemotherapy, and scores remained relatively stable up to 12 months post-treatment. Among the nine patients who completed a 2-year follow-up, there was a significant improvement in the Executive domain (P < 0.05) and a trend toward a decline in the Verbal Memory domain. Executive and Verbal Memory functions improved following induction chemotherapy, likely due to decreased tumor burden and discontinuation of corticosteroid and anticonvulsant medications. There was no significant cognitive decline up to 24 months post-chemotherapy and reduced-dose WBRT in this group of PCNSL patients, however, difficulties in Verbal Memory and Motor speed persisted over the follow-up period.

Genetic variants and cognitive functions in patients with brain tumors.

BACKGROUND: Patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer's disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population. METHODS: One hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood-brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs. RESULTS: Multivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities. CONCLUSION: This novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

Cognitive effects of hormonal therapy in older adults.

There is ample preclinical evidence that gonadal steroids (estrogens and androgens) play an important role in central nervous system development and function. The abrupt decline of estrogen levels in women after menopause, and the slower, subtler decline in total and bioavailable testosterone serum levels that occurs in aging men ("andropause," "male menopause," partial androgen deficiency in ageing males [PADAM]), have been implicated in the pathogenesis of cognitive dysfunction prevalent in elderly adults. However, the current clinical evidence supporting hormonal replacement as a neuroprotective therapy is at best inconclusive. Anti-estrogen and anti-androgen hormonal therapies are used in the treatment of breast and prostate carcinomas, respectively. Although generally considered less toxic than conventional cytotoxic chemotherapy, these hormonal manipulations have side effects that are not trivial. This review will summarize the available evidence regarding the impact of these hormonal therapies on cognitive function in older adults. Additional clinical research in this field is needed to confirm the existence and severity of such a possible cognitive impact, which may then need to be considered prior to initiating hormonal therapies in the elderly, as many patients may be in the prodromal phase or early stages of a neurodegenerative disorder, such as Alzheimer's disease, and this information may influence treatment decision-making and subsequent management.

Educação em saúde para a prevenção de câncer do colo de útero decorrente do HPV / Health education for the prevention of uterus cancer resulting from HPV: a literature review / Educación sanitária para la prevención del cáncer de cuello uterino por HPV: uma revisión de la literatura

Objetivo: analisar o que a literatura descreve a respeito da forma de transmissão, prevenção e rastreamento do HPV; os métodos de prevenção de câncer de Cólon relacionado ao HPV; bem como as ações educativas a respeito do HPV voltadas a adolescentes. Método: Trata-se de uma revisão integrativa da literatura. As pesquisas dos artigos foram feitas nas bases de dados SCIELO, BDENF, LILACS, MEDLINE, utilizando os descritores: Educação em saúde, Papilomavirus, Saúde do adolescente. Os critérios de inclusão estabelecidos na estratégia, foram de artigos originais, em português, disponível na íntegra e publicados entre 2016 a 2021. Resultados: Foram incluídos nesta revisão de literatura 12 artigos científicos. Com isso, emergiram-se três temas: Estratégia de prevenção relacionadas a transmissão de HPV; Detecção precoce do câncer do colo de útero; relação entre HPV e o câncer de colo de útero; esquema vacinal na prevenção primária contra o HPV. Conclusão: verifica-se que o câncer de colo de útero é um problema sério de saúde pública no Brasil, sendo também uma das principais causa de morte no mundo. É de fundamental importância o acompanhamento para detecção precoce, o que pode prevenir esta neoplasia

Objective: analyze what the literature describes about the transmission, prevention and tracking of HPV; HPV-related colon cancer prevention methods; as well as educational actions about HPV aimed at adolescents. Método: this is a integrative review of the literature. At article searches were made in the database SCIELO, BDENF, LILACS, PUBMED, MEDLINE, REBEN using the keywords: health education, Papilomavirus, teen health. The Inclusion discretion established in the strategy were original articles in portuguese, available in full and published between 2016 to 2021. Results: Thirteen scientific articles were included in this literature review. With that, three topics emerged: prevention strategy related to HPV transmission; Early detection of cervical cancer; Relationship between HPV and Cervical Cancer; Vaccination scheme for primary prevention against HPV. Conclusion: cervical cancer is a public health problem in Brazil, being one of the leading causes of death in the world. It is of fundamental importance the effective screening for early detection, which can prevent neoplasia.

Objetivo: analizar lo que describe la literatura sobre la transmisión, prevención y seguimiento del VPH; Métodos de prevención del cáncer de colon relacionados con el VPH; así como acciones educativas sobre VPH dirigidas a adolescentes. Método: Ésta es una revisión integradora de la literatura. Los artículos fueron buscados en las bases de datos SCIELO, BDENF, LILACS, MEDLINE, utilizando los descriptores: Educación en salud, Papilomavirus, Salud adolescente. Los criterios de inclusión establecidos en la estrategia fueron artículos originales, en portugués, disponibles íntegramente y publicados entre 2016 y 2021. Resultados: Se incluyeron 12 artículos científicos en esta revisión de la literatura. Así, surgieron tres temas: estrategia de prevención relacionada con la transmisión del VPH; Detección temprana del cáncer de cuello uterino; relación entre el VPH y el cáncer de cuello uterino; calendario de vacunación en prevención primaria contra el VPH. Conclusión: parece que el cáncer de cuello uterino es un grave problema de salud pública en Brasil, y también es una de las principales causas de muerte en el mundo. El seguimiento para la detección temprana es de fundamental importancia, lo que puede prevenir esta neoplasia.

Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma.

BACKGROUND: Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication. METHODS: Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test-Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy-Brain [FACT-Br]). RESULTS: Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment. CONCLUSIONS: Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.

Cognitive functions in brain tumor patients.

As effective treatment interventions have increased survival rates, there has been greater awareness that many brain tumor patients experience cognitive dysfunction despite adequate disease control. Cognitive difficulties often have an impact on quality of life and interfere with the patient's ability to function at premorbid levels; however, the incidence of cognitive dysfunction in brain tumor patients is unknown, because it has not been investigated systematically. Future prospective clinical trials in neuro-oncology should include cognitive outcome measures to increase understanding of the contribution of the tumor and the delayed effects of treatment to cognitive dysfunction.

A phase I study of D-methadone in patients with chronic pain.

D-Methadone is the d optical isomer of racemic mixture (DL-methadone) used clinically to treat pain and addiction in the United States. D-Methadone is practically devoid of opioid activity but maintains N-methyl-D-aspartate (NMDA) receptor antagonism. Evidence from extensive preclinical studies suggests that NMDA receptor antagonists attenuate neuronal plasticity, reverse opioid analgesic tolerance, and alleviate chronic pain states. The authors conducted a phase I open label study of D-methadone administered for the first time to patients with chronic pain to determine the safety and tolerability of D-methadone. In addition to their long-term regimen of opioids, the patients received 40 mg of D-methadone twice daily for 12 days. Analgesia and toxicity were recorded by the patients in a daily diary and assessed in clinic on days 1, 8, and 12. Eight patients of the 10 enrolled completed the study. Pain scores on Edmonton Symptom Assessment System (ESAS) did not change between days 1 and 12, but five of eight patients (62.5 percent) characterized D-methadone as moderately or very effective in relieving pain on the Global Assessment for pain. Five of the eight patients (62.5 percent) who completed the study requested to start treatment with commercially available methadone (DL-racemic methadone) after completing the study. D-Methadone at the dose of 40 mg PO Q 12 hours was well tolerated. Perspective: This is the first clinical study of D-methadone in patients suffering from chronic pain. Additional phase I and phase II studies are needed to confirm its safety and analgesic effects. If D-methadone is well tolerated, it is likely to become a useful adjuvant to the treatment of a wide spectrum of pain syndromes.

COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.

BACKGROUND: Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors. METHODS: One hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed. RESULTS: Multivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores. CONCLUSION: This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.