Alvina Acquaye

Bio: Alvina Acquaye is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Medicine & Mood. The author has an hindex of 9, co-authored 18 publications receiving 238 citations. Previous affiliations of Alvina Acquaye include National Institutes of Health & University of Texas Health Science Center at San Antonio.

The symptom burden of primary brain tumors: evidence for a core set of tumor and treatment-related symptoms

Abstract: BACKGROUND: A set of common cancer and treatment-related symptoms has been proposed to enhance both quality of care and clinical research in patients with a variety of solid tumors. These symptoms include anorexia, anxiety, constipation, depression, diarrhea, dyspnea, fatigue, insomnia, nausea, pain, neuropathy, and vomiting. Using data from several prospective studies, this study evaluated the impact of tumor grade, disease stage and treatment in patients with primary brain tumors on the reporting of symptoms. METHODS: Aggregate symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 617 patients enrolled in 8 clinical studies was used. Descriptive statistics were used to report the prevalence and severity of symptoms as they relate to tumor grade, treatment stage (newly diagnosed, on active treatment, on surveillance, at recurrence), and KPS. RESULTS: The sample was primarily white(83%) males(59%), with high grade gliomas(75%) with KPS ≥ 90(71%). Over 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting at least 3 moderate-severe symptoms. Fatigue, drowsiness, difficulty remembering, difficulty with sleep, and distress were the most severe symptoms reported by all tumor grades. Patients with either grade 4 tumors or tumor recurrence reported weakness and difficulty speaking as severe. Newly diagnosed patients or on active treatment also reported irritability and problems concentrating as most severe. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients. Low KPS was associated with more severe symptoms and functional impact. CONCLUSIONS: These results support a core set of symptoms that are common across brain tumor patients that may impact clinical care, and assessment of treatment benefit. Although some symptoms overlap with those reported in patients with other solid tumors, the additional symptoms and functional limitations underscore the clinical complexity of patients with brain tumors.

Uncertainty, mood states, and symptom distress in patients with primary brain tumors: analysis of a conceptual model using structural equation modeling.

Abstract: BACKGROUND Patients with primary brain tumors (PBTs) face uncertainty related to prognosis, symptoms, treatment response, and toxicity. The authors of this report examined the direct/indirect relations among patients' uncertainty, mood states, and symptoms. METHODS In total, 186 patients with PBTs were accrued at various points in the illness trajectory. Data-collection tools included an investigator-completed clinician checklist, a patient-completed demographic data sheet, the Mishel Uncertainty in Illness Scale-Brain Tumor Form (MUIS-BT), the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT), and the Profile of Mood States-Short Form (POMS-SF). Structural equation modeling was used to explore correlations among variables. RESULTS Participants were primarily white (80%) men (53%) with a variety of brain tumors. They ranged in age from 19 to 80 years (mean ± standard deviation, 44.2 ± 12.6 years). Lower functional status and earlier point in the illness trajectory were associated with greater uncertainty (P < .01 for both). Uncertainty (P < .05), except in the model of “confusion,” and the 5 negative mood states measured by the POMS-SF were directly associated with symptom severity perceived by patients (P < .01 for all). The impact of uncertainty on perceived symptom severity also was mediated significantly by mood states. CONCLUSIONS The results from the study clearly demonstrated distinct pathways for the relations between uncertainty-mood states-symptom severity for patients with PBTs. Uncertainty in patients with PBTs is higher for those who have a poor performance status and directly impacts negative mood states, which mediate patient-perceived symptom severity. This conceptual model suggests that interventions designed to reduce uncertainty or that target mood states may help lessen patients' perception of symptom severity, which, in turn, may result in better treatment outcomes and quality of life. Cancer 2013;119:2796–2806. © 2013 American Cancer Society.

The impact of symptom interference using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) on prediction of recurrence in primary brain tumor patients.

Abstract: BACKGROUND: Tumor grade, age, extent of resection, and performance status are established prognostic factors for survival in primary brain tumor (PBT) patients. Development of disease-related symptoms is predictive of tumor recurrence in other cancers but has not been reported in the PBT population. METHODS: A cross-sectional sample of 294 PBT patients participated. Progression was based on the radiologist report of the magnetic resonance imaging (MRI). The relation of clinical variables (age, extent of resection, tumor grade, and Karnofsky performance status [KPS]) and MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) mean symptom and interference subscales with progression was examined using logistic regression. RESULTS: The study enrolled more men (60%, n = 175); median age was 46 years. The majority had less than a gross total resection (n = 186, 64%), and a good KPS (KPS ≥ 90) (N = 208). The majority had a grade 3 or 4 tumor (n = 199) and 24% of patients had recurrence. Tumor grade and activity-related interference were significantly related to progression. Patients with tumor grade 4 were 2.4 times more likely to have recurrence (95% CI, 1.2-5.; P < .015). Patients with significant (ratings of ≥5) activity-related interference were 3.8 times more likely to have recurrence (95% CI, 2.14-6.80; P < .001). Mean activity-related score was 4.8 for those with progression on MRI and 2.2 for those with stable disease. CONCLUSIONS: Significant activity-related interference and tumor grade were associated with recurrence but not KPS, age, or extent of resection. These results provide preliminary support for the use of symptom interference in assessment of disease status. Because the authors used a cross-sectional sample, future studies evaluating change over time are needed. Cancer 2011. © 2011 American Cancer Society.

Congruence of primary brain tumor patient and caregiver symptom report.

Abstract: BACKGROUND: Evaluating the severity of symptoms in patients with primary brain tumors (PBTs) is important in clinical care and research but may be difficult due to patient neurocognitive (NC) impairment. This study was conducted to evaluate the congruence of symptom reporting in patient and caregiver dyads, examining potential impact of NC impairment and Karnofsky performance status (KPS). METHODS: PBT patients undergoing NC testing and their caregivers were included in this study. These dyads (paired patient and caregiver group) completed the MD Anderson Symptom Inventory-Brain Tumor Module prior to testing, and impairment was categorized based on NC test scores. Concordance and equivalency was then assessed using Bland-Altman analysis and 2 one-sided techniques. RESULTS: A total of 115 dyads participated. Median patient and caregiver age was 49 and 51 years, respectively, and 63% of patients were male (73% female caregivers). Most patients had a good KPS (≥90, 66%) but were classified as NC impaired (58%). Caregiver's report of patient symptoms are congruent to the self-report of the patient. Equivalency between patient and caregiver report were found using prespecified confidence intervals. KPS group (good, ≥90; poor, ≤80) comparisons of equivalency indicated no significant differences in symptoms and interference reporting between dyads (good = 0.49, P > .05; and poor = 0.3, P > .05) overall, but there was a tendency for higher report by caregivers if the patients had a poor KPS. CONCLUSIONS: Caregivers of PBT patients have similar assessments of symptom severity (highly congruent) with patient self-report regardless of NC function or KPS. These findings suggest that caregivers may serve as proxy report of symptoms for primary brain tumor patients. Cancer 2012. © 2012 American Cancer Society.

The relationship between corticosteroids and symptoms in patients with primary brain tumors: utility of the Dexamethasone Symptom Questionnaire–Chronic

Abstract: Corticosteroids are routinely used for the control of peritumoral edema in patients with brain tumors.1 They are generally used as adjuncts to tumor-directed therapies, including surgery, radiation, and chemo. The mechanisms of action of corticosteroids leading to the control of vasogenic edema and, conversely, their lack of efficacy with intracellular or toxic edema are not fully understood.1,2 Dexamethasone is the most commonly prescribed corticosteroid for this patient population, primarily because of its low mineralocorticoid activity.3 However, there has been limited study of the efficacy of other types of synthetic corticosteroids in this population. Corticosteroid dosing is often determined based on clinical evaluation and imaging findings. A common dose prescribed at the time of diagnosis of a brain tumor is in the range of 8 to 16 mg/day in divided doses, which is thought to be derived from the dose–response curves generated in the first case series of preoperative dexamethasone use in patients with primary brain tumors3,4 Corticosteroids are also commonly used at the time of tumor recurrence or to manage treatment-related reactions such as radionecrosis, but there has been little investigation about the optimal dose and duration of corticosteroids in these settings.1,5,6 Despite the well-established morbidity associated with corticosteroid use, the reporting of actual dose and duration and associated side effects is often not routine and they are not usually assessed in patients with brain tumors.1 As a result, we have limited data regarding the severity and frequency of signs and symptoms associated with the use of corticosteroids in patients with both primary and metastatic brain tumors. One retrospective study of neuro-oncology patients found that 51% (30/59) had at least one steroid toxicity and 19% (11/59) required hospital admission due to steroid-related complications.7 Another study, of 88 patients with brain metastases, reported more toxicity in those who received more than 16 mg of dexamethasone per day at the time of commencement of radiotherapy, with 91% reporting at least one dexamethasone-related side effect at some point in the treatment course.8 The use of prolonged corticosteroids has been shown to impact functional status in select patients.9 Vecht and colleagues reported that mean improvement in KPS during radiation in patients with metastatic brain tumors was less in those who experienced a corticosteroid-related side effect such as ankle edema, proximal myopathy, or Cushingoid facies. The Dexamethasone Symptom Questionnaire (DSQ) is a self-report intended as a descriptive measure to determine the incidence and severity of side effects over the last week and to examine changes in side effects associated with dexamethasone when used longitudinally. Items were generated by literature review and expert opinion and were then reviewed for content validity by the use of focus groups of cancer patients receiving dexamethasone.10 Responses are formatted using a 4-point Likert scale (1 = not at all, 2 = a little bit, 3 = quite a bit, 4 = very much). The burden of completing the DSQ is low, taking 2–3 minutes to complete. The DSQ has demonstrated face and content validity and has been used to evaluate corticosteroid-related symptoms in breast cancer patients receiving dexamethasone as an anti-emetic10,11 and to evaluate the impact in brain metastases patients undergoing radiation therapy.12 The “Chronic” revision of the questionnaire (DSQ-C) contains the original 13 items with additional sign/symptom items (for roundness of face, anger/irritability, difficulty standing from a seated position or walking, problems with fragile skin, stretch marks or easy bruising, and headaches) added by the original developers after focus-group input to better measure long-term complications associated with dexamethasone use. Given the prolonged course of corticosteroid use to control cerebral edema in brain tumor patients and the few studies on the associated signs and symptoms, we undertook this study to redress the paucity of data and evaluate the utility of the DSQ-C in brain tumor patients.

What is Cancer

Abstract: This chapter discusses different aspects of cancer. Many of the attitudes toward cancer today are similar to the popular prejudices that were held about infections before the germ theory was worked out and before the causes of different infections were understood. One of the popular misconceptions about cancer is that it is a single disease. In fact, cancer is a group of many different disorders affecting the different parts of the body, and cancer of one part is quite different from cancer of another part. It is a common belief that cancer is always incurable, but in truth, 70%–90% of patients can be completely cured of certain types of cancers. It is also believed that cancer can be transmitted by coming in contact with a cancer patient and that it is caused by dirty living, by knocks or blows, or by tinned foods. Doctors have recognized that lung cancer is associated with cigarette smoking even though they have not completely worked out the combination of chemicals that causes this effect.

Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma

Abstract: Temozolomide plus radiotherapy is standard treatment for newly diagnosed glioblastoma (GBM) patients.1 Recent attempts to improve front-line treatment with bevacizumab2,3 or cilengitide4 have failed to improve survival when combined with standard treatment. Following front-line treatment, nearly all GBMs recur, and there are no effective treatments with durable benefit for recurrent GBM.5 Recurrent GBM has an extremely poor prognosis, with a median overall survival (OS) of ∼9 months and a 12-month OS of 14%.5 Treatment failure is associated with the development of resistance to temozolomide and is primarily mediated by overexpression of specific proteins (O[6]-methylguanine methyltransferase [MGMT] and O[6]-alkylguanine-DNA-alkyl-transferase [AGAT]).6 Nevertheless, temozolomide is well tolerated and may have activity despite prior exposure if novel dose schedules are used.7,8 For example, protracted, low-dose (metronomic) temozolomide may deplete MGMT and AGAT9 and restore temozolomide sensitivity in the recurrent setting. Activation of the ErbB family of receptors, including the epidermal growth factor receptor (EGFR), can initiate downstream signaling pathways involved in cell growth and proliferation.10 ErbB pathway regulation plays an important role in glioma progression, and certain germline EGFR polymorphisms may contribute to the glioma pathogenesis.11 EGFR is amplified and overexpressed in ∼50%–60% of GBMs, and multiple EGFR gene mutations occur in GBM tumors.12,13 The EGFRvIII mutation is expressed in 30% of GBMs, including 41%–60% of those with EGFR amplification.12 HER2 (ErbB2) is a possible low-penetrance gene candidate associated with GBM development.11 The high frequency of EGFR pathway alterations in GBM has triggered interest in therapeutically targeting the ErbB family, including EGFR. EGFR inhibition in vitro has activity against GBM; however, reversible EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have had limited impact on survival of recurrent GBM patients, either as monotherapy or in combination with other agents.14–26 Afatinib is a potent, orally bioavailable ErbB family blocker that irreversibly binds to the ATP binding pocket of the ErbB family of receptors, inhibiting the activity of EGFR (including the EGFRvIII variant), HER, and ErbB4 and blocks transphosphorylation of ErbB3.27,28 Afatinib is active against ErbB family-driven tumors, including lung cancer.29–31 In vitro, afatinib inhibits cells harboring mutations that are frequently found in GBM, including EGFRvIII and EGFR R108K.28,32 Furthermore, unlike erlotinib and gefitinib, cytochrome P450 metabolism of afatinib is negligible.33 Phase I of this study aimed to establish the maximum tolerated dose (MTD) and pharmacokinetics (PKs) of afatinib plus temozolomide among recurrent malignant glioma patients. Phase II assessed the efficacy and safety of afatinib (±temozolomide) versus temozolomide monotherapy in patients with recurrent GBM.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

Abstract: BACKGROUND: The Macdonald criteria and RANO criteria define radiologic parameters to classify therapeutic outcome among malignant glioma patients. While both scales specify that clinical status must be incorporated for overall assessment, neither provides specific parameters to do so. Furthermore, both scales prioritize clinical status over radiology in that response requires at least stable clinical status, while clinical deterioration is sufficient to declare progression. We hypothesized that a standardized metric to measure neurologic function will permit better overall response assessment in neuro-oncology. METHODS: An international group of neuro-oncologists convened bi- weekly for the past year to draft the Neurologic Assessment in Neuro-Oncology (NANO) criteria as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. RESULTS: The NANO scale is a quick, clinician-friendly, and quantifiable evaluation of eight relevant neurologic domains based on direct observation/testing conducted during routine office visits. The score defines criteria for domain-specific and overall scores of response, progression, stable disease and not assessed. A given domain will be scored non-evaluable if it cannot be accurately assessed due to pre-existing conditions, co-morbid events, and/or concurrent medications. CONCLUSION: The NANO criteria aims to provide a more detailed and objective measure of neurologic function than currently exists. These criteria are designed to enable a consistent evaluation of neurologic function which will facilitate comparisons across clinical trials and therapeutic interventions. Implementation and validation of these criteria are planned, and future modifications are anticipated for further optimization.

Biology and management of ependymomas

Abstract: Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life.

The symptom burden of primary brain tumors: evidence for a core set of tumor and treatment-related symptoms

Abstract: BACKGROUND: A set of common cancer and treatment-related symptoms has been proposed to enhance both quality of care and clinical research in patients with a variety of solid tumors. These symptoms include anorexia, anxiety, constipation, depression, diarrhea, dyspnea, fatigue, insomnia, nausea, pain, neuropathy, and vomiting. Using data from several prospective studies, this study evaluated the impact of tumor grade, disease stage and treatment in patients with primary brain tumors on the reporting of symptoms. METHODS: Aggregate symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 617 patients enrolled in 8 clinical studies was used. Descriptive statistics were used to report the prevalence and severity of symptoms as they relate to tumor grade, treatment stage (newly diagnosed, on active treatment, on surveillance, at recurrence), and KPS. RESULTS: The sample was primarily white(83%) males(59%), with high grade gliomas(75%) with KPS ≥ 90(71%). Over 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting at least 3 moderate-severe symptoms. Fatigue, drowsiness, difficulty remembering, difficulty with sleep, and distress were the most severe symptoms reported by all tumor grades. Patients with either grade 4 tumors or tumor recurrence reported weakness and difficulty speaking as severe. Newly diagnosed patients or on active treatment also reported irritability and problems concentrating as most severe. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients. Low KPS was associated with more severe symptoms and functional impact. CONCLUSIONS: These results support a core set of symptoms that are common across brain tumor patients that may impact clinical care, and assessment of treatment benefit. Although some symptoms overlap with those reported in patients with other solid tumors, the additional symptoms and functional limitations underscore the clinical complexity of patients with brain tumors.