Pattern of care of brain tumor patients in the last months of life: analysis of a cohort of 3045 patients in the last 10 years.

BACKGROUND: End-of-life in patients with brain cancer presents special challenges, and palliative care approach is underutilized. Patients with brain cancer, in the last months of life, receive frequent hospital readmissions, highlighting bad end-of-life care quality. Early integration of palliative care improves quality of care in advanced stage of disease and patient's quality of death. PURPOSE: We retrospectively analyzed a consecutive series of patients with brain cancer discharged after diagnosis to evaluate pattern of treatment and rate of hospital readmission in the last months of life. DESIGN: Data were collected from the Lazio Region Healthcare database. SETTING: Adult patients discharged with diagnosis ICD-9 191.* between January 1, 2010, and December 31, 2019 were included. RESULTS: A total of 6672 patients were identified, and 3045 deaths were included. In the last 30 days 33% were readmitted to the hospital and 24.2% to the emergency room. 11.7% were treated with chemotherapy and 6% with radiotherapy. Most indicators of end-of-life care showed wide variability by hospital of discharge. CONCLUSIONS: Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and reduce healthcare costs. Variability observed by hospital of discharge indicates the lack of a standard approach to end-of-life care.

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit "Regina Elena" National Cancer Institute.

BACKGROUND: The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and short duration response rate. Although clinical trials represent the "gold standard" for providing evidence on efficacy of specific treatment strategies, real-world data can be considered more representative of the "real" GBM population. OBJECTIVE: To describe the management of GBM recurrence in a large real-world sample. METHODS: We analysed retrospectively the data stored in the database of the Neuro-oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. We considered only data of patients with histological diagnosis of GBM and disease recurrence during their follow-up. We excluded patients who did not receive treatment after the diagnosis. RESULTS: We analysed 422 patients (64% males, 36% females) with a mean age of 59.6 (range 16-87) years. At GBM recurrence, 135 (32.0%) patients underwent palliative care, and 287 (68.0%) underwent other treatments. Patients on palliative care were older, had a worse performance status, and a shorter time between GBM diagnosis and its recurrence. Patients who received chemotherapy in combination with other treatments (surgery and/or radiation therapy) at GBM recurrence had a longer survival than those in palliative care (p < 0.001). Surgery or radiation therapy alone did not have any effect on survival as compared with palliative care (p < 0.001). CONCLUSION: This study confirms the importance of a multidisciplinary approach even at GBM recurrence, suggesting that combination treatments play a key role in management of disease.

COV-BT Ire study: safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with brain tumors.

BACKGROUND: The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older. OBJECTIVE: The aim of this observational study was to evaluate safety and efficacy of vaccine in patients affected by primary brain tumor (PBT). METHODS: We proposed COVID-19 vaccine to all patients affected by PBT followed by Neuroncology Unit of National Cancer Institute Regina Elena. RESULTS: 102 patients received the first dose, 100 the second, and 73 patients received the booster dose. After first dose, we observed one patient with fever and severe fatigue, while after the second one, we recorded adverse events in ten patients. No correlation was observed between adverse events and comorbidities. CONCLUSIONS: The COVID-19 vaccine is safe and well tolerated in PBT patients.

Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial.

Introduction: Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter. Methods: This was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity. Results: Forty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%). Discussion: The addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter. Clinical trial registration: https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

Prognostication in brain tumors.

Despite the use of aggressive multimodality therapies, the prognosis of brain tumor patients remains poor. Tumors of glial origin typically have the worst prognosis, with a predicted median survival of 12-15months for glioblastoma multiforme (WHO grade IV) and 2-5years for anaplastic glioma (WHO grade III). Palliative care problems and needs in patients with primary and secondary brain tumors are significantly different, both due to different trajectory of disease and to variable prognosis which in metastatic brain tumors is related to the natural history of primary tumors. This chapter describes the complex interactions influencing communication and the treatment decision process in primary brain tumor patients. The whole trajectory of disease and particularly the end-of-life (EOL) phase of brain tumor (BT) patients are quite different in respect to the expected trajectory observed in the general cancer population. The need to improve the communication of prognosis in BT patients has been clearly reported in neuro-oncological literature, but several issues may hinder a good communication in these patients. Adequate prognostic awareness (PA) is important for several reasons: to respect patient autonomy, to obtain her/his preferences about treatments and goal of care, and to share EOL treatment decisions. The high incidence of cognitive deficits in BT patients is one of the most challenging issues influencing the quality of communication and the participation of patients in the process of treatment decisions. Impaired neurocognitive functions may impact capacities of understanding, appreciation, reasoning, and expression of choice, reducing Medical Decisions Capacity (MDC). The lack of capacity to express preferences about EOL treatment decisions represents an important ethical issue, with a great impact on both the patient's family and healthcare professionals involved in the decision processes. Also, patients' coping styles may have an important influence in critical aspects of care such as communication of diagnosis and prognosis, discussion with patients and their caregivers about goal of treatments, early introduction of PC, and advanced planning of patients' preferences concerning EOL treatment and issues. Several barriers hinder good communication in BT patients. This chapter analyzes emerging literature data and possible strategies to improve communication about prognosis and goals of care and to promote patients' involvement in the treatment decision process particularly in the palliative care setting.

Coping Style in Glioma Patients and Their Caregiver: Evaluation During Disease Trajectory.

Background: Patients with glioma have a poor prognosis and, in a short period of time, have to deal with severe forms of disability, which compromise their psychological distress and quality of life. The caregivers of these patients consequently carry a heavy burden in terms of emotional and patient care. The study aims to evaluate the coping strategies of patients and their caregivers during the course of the disease in order to frame the adaptation process in a rapidly progressing pathology. Methods: A prospective study on 24 dyads of patients affected by malignant glioma and their caregivers was conducted between May 2016 and July 2018. Questionnaires designed to identify the coping style (MINI-MaC Scale) and psychological distress (HADS scores) and assess QOL (EQ-5D) were administered at two time points: at first lines of treatment and at disease recurrence. Results: Patients and their caregiver structure adaptive coping strategies during the disease: a coping style oriented toward a fighting spirit prevails at baseline (Mini-Mac Mean 3.23); fatalism prevails at recurrence (Mini-Mac Mean 3.03). Psychological distress affects the coping style expressed: high levels of anxiety symptoms were found to be significantly associated with a coping style oriented toward anxious preoccupation, helpless-hopeless, and fatalism; low depressive symptoms were inversely correlated with fighting spirit coping style. Patients' and caregivers' perceptions of quality of life were correlated between them and with performance status assessed by clinicians. In a dyadic perspective, the adaptation of a member of the couple varies as a function of the other partner's coping style. Conclusions: Our data are in line with previous literature on cancer patients, demonstrating that coping style is not a persistent dimension of personality, but can change depending on the situation. Despite the disease rapid course, patients and their caregivers can structure adaptive and functional defenses to manage the disease.

Entacapone in elderly Parkinsonian patients experiencing levodopa-related wearing-off: a pilot study.

Levodopa (LD) provides the most effective symptomatic treatment for Parkinson's disease (PD). Long-term treatment with LD, however, is often associated with the development of response fluctuations. Previous evidence suggests that the short half-life of LD is a major contributor to the development of response fluctuations and the wearing-off phenomenon in particular. Entacapone, a peripheral catechol-O-methyltransferase inhibitor has been shown to reduce OFF time and increase ON time in several therapeutic trials on PD patients treated with LD experiencing motor fluctuations. However, data are missing on the tolerability and efficacy of entacapone in elderly PD patients. This is of particular relevance, as most PD patients develop LD-related motor fluctuations after several years of disease duration. Here we report that addition of entacapone in a group of 45 elderly PD patients with LD-related motor fluctuations is well tolerated and efficacious in reducing the time, frequency and severity of the OFF periods. These data suggest that the drug can be used safely and efficaciously in elderly PD patients.

Chronic Pain in the Elderly with Cognitive Decline: A Narrative Review.

The presence of pain in elderly persons with cognitive decline is often neglected, under-reported, underestimated, misdiagnosed and not adequately treated, with consequences that have a strong impact on health, independence in activities of daily living and quality of life. There is no empirical evidence that people with dementia experience less pain; therefore, in patients with severe cognitive impairment the progression of cognitive decline dramatically affects the ability to verbalize the presence of pain. Self-assessment scales are considered the "gold standard" for pain assessment, but the presence of cognitive impairment is likely to reduce the reliability of these measures. Treatment of pain in elderly with cognitive decline or dementia is based on non-pharmacological and pharmacological strategies. Pharmacological treatment should consider physiological changes, high comorbidity and drug interactions that occur frequently in the elderly. This narrative review aims to describe current knowledge, methods of detection and treatment approaches for chronic pain in elderly persons with cognitive deficits.

Hemiparkinsonism due to frontal meningioma.

We describe a case with right hemiparkinsonism due to a frontal meningioma with surrounding edema compressing the basal ganglia. The initial diagnosis of idiopathic Parkinson's disease (PD) was made in another institution on the basis of the positive family history, the clinical symptoms and the asymmetric reduction of striatal tracer binding in a single photon emission computed tomography study for the dopamine transporter. The symptoms of parkinsonism resolved completely shortly after surgery for removal of the tumor. This case points to the significance of structural neuroimaging in the evaluation of parkinsonism even in cases that fulfill all the necessary clinical criteria for idiopathic PD.

Effects of the intravenous administration of [Lys7]dermorphin on local cerebral glucose utilization in the rat.

The use of analgesic opioids in the clinical setting is hampered by the reinforcing and addictive properties of these drugs. Moreover, chronic administration of conventional opioids is accompanied by progressive reduction of the analgesic effects, that often forces clinicians to increase dosages, exposing a subject to serious side-effects. Thus, interest is growing in the development and characterization of synthetic opioid agonists with lower reinforcing properties than conventional opioids. [Lys7]dermorphin is a mu1 receptor agonist with 20-30 times stronger analgesic properties than morphine. Previous data indicate that the drug causes fewer side-effects than conventional opioids, and is less likely to produce physical dependence than morphine. In this study we investigated the effects of the intravenous administration of a range of doses of [Lys7]dermorphin (0.002, 0.01 and 0.05 mg/kg) on local cerebral glucose utilization in the rat, by means of the quantitative [14C]2-deoxyglucose method. The results of the study showed dose-related reductions of cerebral metabolic rates for glucose in limbic, sensory-motor and autonomic regions following the intravenous administration of [Lys7]dermorphin. Such pattern of changes is similar to those measured earlier following the administration of analgesic doses of drugs stimulating mu-opioid receptors. Within the nucleus accumbens, and the shell portion in particular, we did not measure any increase of glucose utilization, rather a significant decrease following the administration of the higher dose of [Lys7]dermorphin. These findings contribute to the definition of the functional consequences of the administration of [Lys7]dermorphin, and indirectly suggest the lack of effect of the drug on mesolimbic dopamine neurotransmission.

Home care for brain tumor patients.

BACKGROUND: Brain tumor patients are quite different from other populations of cancer patients due to the complexity of supportive care needs, the trajectory of disease, the very short life expectancy, and resulting need for a specific palliative approach. METHODS: A pilot program of comprehensive palliative care for brain tumor patients was started in the Regina Elena National Cancer Institute of Rome in October 2000, supported by the Lazio Regional Health System. The aim of this model of assistance was to meet patient's needs for care in all stages of disease, support the families, and reduce the rehospitalization rate. The efficacy of the model of care was evaluated analyzing the place of death, caregiver satisfaction, rehospitalization rate, and the impact on costs to the health system. RESULTS: From October 2000 to December 2012, 848 patients affected by brain tumor were enrolled in a comprehensive program of neuro-oncological home care. Out of 529 patients who died, 323 (61%) were assisted at home until death, 117 (22.2%) died in hospital, and 89 (16.8%) died in hospice. A cost-effectiveness analysis demonstrated a significant reduction in hospital readmission rates in the last 2 months of life compared with the control group (16.7% vs 38%; P < .001). CONCLUSIONS: Our findings concerning death at home, rehospitalization rate, quality of life, and satisfaction of patients and their relatives with the care received suggest that a neuro-oncologic palliative home-care program has a positive impact on the quality of care for brain tumor patients, particularly at the end of life.

The impact of extended release dopamine agonists on prescribing patterns for therapy of early Parkinson's disease: an observational study.

BACKGROUND: Dopamine agonists (DA) are the first-choice drug for treatment of the early stage of Parkinson's disease (PD) in subjects younger than 70 years. Recently, a number of third generation DA have been marketed, including transdermal patch of rotigotine and extended release oral formulation of ropinirole and pramipexole.We investigated the impact of third generation DA on management of the early stage of PD in an outpatient service for Movement Disorders in Italy. METHODS: Two 12-month observation periods were selected (January - December, 2007, and January - December, 2011) as representative for prescription of immediate and extended release formulations of DA respectively. Within each period, PD patients were divided into subgroups according to age (<65 years; 65-75 years; >75 years) or functional requirement (high; moderate; low). For each period, the number of subjects receiving monotherapy with DA, monotherapy with levodopa (LD), or combined DA/LD therapy and the relative doses were calculated. The severity of parkinsonian motor symptoms was calculated by means of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The frequency and severity of side-effects leading to discontinuation or reduction of DA drugs at each time point were also calculated. RESULTS: We found a significant reduction of daily LD dose (both as mono- and combined therapy) between the second and the first observation period. There was also a significant increase of monotherapy with DA and corresponding reduction of monotherapy with LD in patients aged 65-75 years, as well as in PD patients with moderate functional requirements. A significant reduction of frequency of side-effects was measured with extended release DA as compared to immediate release formulations. There were no significant differences of the UPDRS-III scores between the 2 observation periods in any subgroup. CONCLUSIONS: Our results suggest that extended release DA might optimize therapeutic management of the early stages of PD even in patients older than 70 years of age.

Sad and happy facial emotion recognition impairment in progressive supranuclear palsy in comparison with Parkinson's disease.

The severity of motor and non-motor symptoms of progressive supranuclear palsy (PSP) has a profound impact on social interactions of affected individuals and may, consequently, contribute to alter emotion recognition. Here we investigated facial emotion recognition impairment in PSP with respect to Parkinson's disease (PD), with the primary aim of outlining the differences between the two disorders. Moreover, we applied an intensity-dependent paradigm to examine the different threshold of encoding emotional faces in PSP and PD. The Penn emotion recognition test (PERT) was used to assess facial emotion recognition ability in PSP and PD patients. The 2 groups were matched for age, disease duration, global cognition, depression, anxiety, and daily L-Dopa intake. PSP patients displayed significantly lower recognition of sad and happy emotional faces with respect to PD ones. This applied to global recognition, as well as to low-intensity and high-intensity facial emotion recognition. These results indicate specific impairment of recognition of sad and happy facial emotions in PSP with respect to PD patients. The differences may depend upon diverse involvement of cortical-subcortical loops integrating emotional states and cognition between the two conditions, and might represent a neuropsychological correlate of the apathetic syndrome frequently encountered in PSP.

Quality of care and rehospitalization rate in the last stage of disease in brain tumor patients assisted at home: a cost effectiveness study.

UNLABELLED: Despite aggressive multimodality treatment the prognosis of patients with primary brain tumors (BT) remains poor. At present, there are no data about the role of palliative home-care services and their impact on quality of care. We report the results of a pilot project of palliative home care for BT patients started in 2000 in the National Cancer Institute Regina Elena of Rome. We report also the result of a cost/effectiveness analysis utilizing administrative data on re-hospitalization rate in the last two months of life. METHODS: Since October 2000 until December 2009, 572 patients have been followed by our home care staff. Among 394 patients who died, 276 (70%) were followed at home until death. A cost/effectiveness analysis was carried out evaluating the rehospitalization rate in the last 2 months of life in a subgroup of patients (group 1 assisted at home, 72 patients; group 2 not assisted at home, 71). The number of hospital readmission in the last 2 months of life, and length and cost of hospitalization were retrospectively analyzed from hospital discharge records. RESULTS: Hospitalization rate of group 1 (16.7%) was lower than group 2 (38%) (95% CI: 0.18-0.65, p = 0.001). Costs of hospitalization also differed substantially: 517 Euros (95% CI: 512-522) in group 1 vs 24, 076 Euros (95%: 24,040-24,112 Euros) in group 2. CONCLUSION: Home-care may represent an alternative to in-hospital care for the management of brain tumor patients and may improve the end-of-life quality of care.

Prodromal non-motor symptoms of Parkinson's disease.

The motor symptoms of Parkinson's disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents.