Doctor of Philosophy

dissertationAttention on an ill spouse usually shifts a caregiver's attention to self-care to a lower priority of concern, particularly when the ill spouse has a primary brain tumor (PBT). This study's aim was to explore the psychosocial processes that shape the personal health behaviors of caregivers whose spouse/partner has a PBT. Constructivist Grounded Theory design provided the analytical tools for participants and researcher to co-construct a theory of self-care within the PBT spousal caregiving context. Thirty-seven participants were either caregivers (n=19), care receivers (n=15), or healthcare providers (n=3) who contributed data through medical records, questionnaires, interviews, and/or focus group discussion. Most caregivers were Caucasian (83%) females (61%), ranging in age from 34-85 years (mean=52.1). Care receivers were aged 52.7 years (mean), diagnosed with PBT 3 months to 13 years (mean =5.0 years) before study entry, and most (78%) experienced at least one episode of disease recurrence with 5 dying of their disease during the study. A trajectory of self-care emerged reflecting a process of three phases through which a PBT caregiver transitions: 1) initially, sensing that time stops, 2) taking steps towards self-care, and eventually 3) a new normal is created where health maintenance, screening, and prevention are addressed. A theoretical model was constructed to explain the influences of self-care within the context of caregiving for a spouse or partner with a PBT. A number of factors influence caregiver self-care performance; however, the basic psychosocial process that explains their motivation for self-care was reciprocating intimacy as communicated through domains of connectedness, touch, and shared values and goals. Caregivers seek to find and fill voids where intimacy is not reciprocated as an attempt to restore ‘wholeness' in their lives.Providers can make a significant difference in caregivers' lives - by listening to and understanding the context of how the PBT affects both members of the spousal/partnered dyad. Tailored messages to caregivers in each stage of the PBT disease trajectory may lessen the burden on a caregiver's health. Research is needed that measures relationship factors such as intimacy in the spousal/partnered relationship and aims interventions at caregivers with greatest risk for negative health consequences

Intraoperative Confocal Microscopy in the Visualization of 5-Aminolevulinic Acid Fluorescence in Low-Grade Gliomas: Clinical Article

Object. Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5- ALA)-induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000ξ magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection. Methods. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence. Results. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses. Conclusions. Intraoperative confocal microscopy can visualize cellular 5-ALA-induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors\u27 institution

Stereotactic radiosurgery of petroclival meningiomas: a multicenter study

Petroclival meningiomas are difficult to treat due to their intimate location with critical structures, and complete microsurgical resection is often associated with significant morbidity. In this study, we evaluate the outcomes of petroclival meningiomas treated with Gamma Knife radiosurgery (GKRS) as an adjunct to microsurgery or a primary treatment modality. A multicenter study of 254 patients with a benign petroclival meningioma was conducted through the North American Gamma Knife Consortium. One hundred and forty patients were treated with upfront radiosurgery, and 114 following surgery. Multivariate analysis was used to determine predictors of favorable defined as no tumor progression following radiosurgery and the absence of any new or worsening neurological function. At mean follow up of 71 months (range 6–252), tumor volumes increased in 9 % of tumors, remained stable in 52 %, and decreased in 39 %. Kaplan–Meier actuarial progression free survival rates at 3, 5, 8, 10, and 12 years were 97, 93, 87, 84, and 80 % respectively. At last clinical follow-up, 93.6 % of patients demonstrated no change or improvement in their neurological condition whereas 6.4 % of patients experienced progression of symptoms. Favorable outcome was achieved in 87 % of patients and multivariate predictors of favorable outcome included smaller tumor volume (OR = 0.92; 95 % CI 0.87–0.97, p = 0.003), female gender (OR 0.37; 95 % CI 0.15–0.89, p = 0.027), no prior radiotherapy (OR 0.03; 95 % CI 0.01–0.36, p = 0.006), and decreasing maximal dose (OR 0.92; 95 % CI 0.96–0.98, p = 0.010). GKRS of petroclival meningiomas achieves neurological preservation in most patients and with a high rate of tumor control

Gamma knife radiosurgery for cerebellopontine angle meningiomas: a multicenter study

Resection of cerebellopontine angle (CPA) meningiomas may result in significant neurological morbidity. Radiosurgery offers a minimally invasive alternative to surgery. To evaluate, in a multicenter cohort study, the outcomes of patients harboring CPA meningiomas who underwent Gamma Knife radiosurgery (GKRS). From 7 institutions participating in the North American Gamma Knife Consortium, 177 patients with benign CPA meningiomas treated with GKRS and at least 6 months radiologic follow-up were included for analysis. The mean age was 59 years and 84% were female. Dizziness or imbalance (48%) and cranial nerve (CN) VIII dysfunction (45%) were the most common presenting symptoms. The median tumor volume and prescription dose were 3.6 cc and 13 Gy, respectively. The mean radiologic and clinical follow-up durations were 47 and 46 months, respectively. Multivariate regression analyses were performed to identify the predictors of tumor progression and neurological deterioration. The actuarial rates of progression-free survival at 5 and 10 years were 93% and 77%, respectively. Male sex (P = .014), prior fractionated radiation therapy (P = .010), and ataxia at presentation (P = .002) were independent predictors of tumor progression. Symptomatic adverse radiation effects and permanent neurological deterioration were observed in 1.1% and 9% of patients, respectively. Facial spasms at presentation (P = .007) and lower maximal dose (P = .011) were independently associated with neurological deterioration. GKRS is an effective therapy for CPA meningiomas. Depending on the patient and tumor characteristics, radiosurgery can be an adjuvant treatment to initial surgical resection or a standalone procedure that obviates the need for resection in most patients

Gamma Knife radiosurgery for posterior fossa meningiomas: a multicenter study

Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa. At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12-89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm(3), and a median margin dose of 13.6 Gy (range 8-40 Gy) was delivered to the tumor. At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30-4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69-15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01-1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01-1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05-3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively. Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression

Gamma Knife Radiosurgery for Sellar and Parasellar Meningiomas: A Multicenter Study: Clinical Article

Object. Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality. Methods. A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. Results. The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8-90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6-216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose \u3c 13 Gy significantly increased the likelihood of tumor progression after GKRS. At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021). Conclusions. Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients. ©AANS, 2014