Clinicopathological and molecular landscape of 5-year IDH-wild-type glioblastoma survivors: A multicentric retrospective study.

Five-year glioblastoma (GBM) survivors (LTS) are the minority of the isocitrate dehydrogenase (IDH)-wild-type GBM patients, and their molecular fingerprint is still largely unexplored. This multicenter retrospective study analyzed a large LTS-GBM cohort from nine Italian institutions and molecularly characterized a subgroup of patients by mutation, DNA methylation (DNAm) and copy number variation (CNV) profiling, comparing it to standard survival GBM. Mutation scan allowed the identification of pathogenic variants in most cases, showing a similar mutational spectrum in both groups, and highlighted TP53 as the most commonly mutated gene in the LTS group. We confirmed DNAm as a valuable tool for GBM classification with a diagnostic refinement by using brain tumor classifier v12.5. LTS were more heterogeneous with more cases classified as diffuse pediatric high-grade glioma subtypes and having peculiar CNVs. We observed a global higher methylation in CpG islands and in gene promoters of LTS with methylation levels of distinct gene promoters correlating with prognosis.

Psychosocial factors associated with workability after surgery in cancer survivors: An explorative study.

This study aimed to evaluate the work ability and its associated factors in patients with glioma (II, III) and breast cancer after 6 (T0) and 12 (T1) months from surgery. A total of 99 patients were evaluated with self-reported questionnaires at T0 and T1. Correlation and Mann-Whitney tests were used to investigate the association between work ability and sociodemographic, clinical, and psychosocial factors. The Wilcoxon test was used to investigate the longitudinal change in work ability. Our sample showed a decrease in work ability level between T0 and T1. Work ability was associated with emotional distress, disability, resilience, and social support in glioma III patients at T0, and with fatigue, disability, and clinical treatments in patients with breast cancer at T0 and T1. Work ability levels decreased in patients with glioma and breast cancer and were associated with different psychosocial factors after surgery. Their investigation is suggested to facilitate the return to work.

Pathways of follow-up care in an Italian center: retrospective study on patients with gliomas II and III.

INTRODUCTION: Glioma is the most common primary brain cancer in adults. Long-term and progression-free survivals are dependent on the type and grade of glioma, as well as on the extent of resection and postoperative treatments. In Italy, it is unclear how long follow-up care should last and whether the primary care sector is either willing or able to take this on. The aim is to determine pathways of follow-up care and evaluate the professional attitude of doctors to prescribe to patient visits and exams after surgery. METHODS: A retrospective study was performed on patients with glioma II and III who underwent surgery at tertiary care Neurological Institute Besta of Milan (FINCB) from 2012 to 2020. Data were collected through electronic medical records and inserted in an ad hoc developed database. RESULTS: Three pathways have been identified: a common preliminary pathway (from the pre-operative visit to surgery) for all patients undergoing surgery for gliomas II and III and two follow-up pathways (with or without second surgery). CONCLUSIONS: FINCB has developed care pathways that are sometimes personalized according to the doctor's expertise and attitude to prescribe new examinations. Given the lack of guidelines on this issue, we can cautiously conclude that it is necessary to identify whether, in addition to standard care, personalized supportive care intervention and pathway plan can significantly improve patients' outcome.

Isocaloric Ketogenic Diet in Adults with High-Grade Gliomas: A Prospective Metabolic Study.

The use of the ketogenic diet (KD) as an adjuvant therapy in high-grade gliomas (HGG) is supported by preclinical studies, but clinical data on its effects on metabolism are currently lacking. In this study, we describe the effects of a KD on glucose profile, ketonemia, energy metabolism, and nutritional status, in adults affected by HGG. This was a single-arm prospective study. An isocaloric 3:1 KD was administered for 1 mo. Glucose profile was assessed by using fasting glycemia, insulin, and glycated hemoglobin. To evaluate ketonemia changes, a hand-held ketone meter was used from home. Energy metabolism was assessed by indirect calorimetry. Nutritional status was evaluated through changes in body composition and in lipid and hepatic profile. No changes in fasting glycemia were observed; however, insulinemia dropped to half of baseline levels. The KD shifted the metabolism, rising ketonemia and decreasing glucose oxidation rate to a quarter of the initial values. Moreover, the KD was generally safe. One-month intervention with the KD was able to act upon key metabolic substrates potentially involved in HGG metabolism. The lack of a significant reduction in fasting glycemia should be investigated in future studies.

Employment and Work Ability of Persons With Brain Tumors: A Systematic Review.

Brain tumors (BT) are between the eight most common cancers among persons aged 40 years, with an average survival time of 10 years for patients affected by non-malignant brain tumor. Some patients continue to work, reporting difficulties in work-related activities, or even job loss. The purpose of the present study was to review the existing information about the ability people with BT to return to work and to identify factors associated with job loss. We performed a systematic review on SCOPUS and EMBASE for peer-reviewed papers that reported studies assessing work ability in patients with BT that were published in the period from January 2010 to January 2020. Out of 800 identified records, 7 articles were selected for analysis, in which 1,507 participants with BT were enrolled overall. Three main themes emerged: the impact of neuropsychological functioning on work productivity, the change of employment status for long-term survivors and issues related to return to work processes. Based on the results of selected studies, it can be concluded that the impact of BT on workforce participation is determined by depressive symptoms and cognitive deficits, as well as by high short-term mortality but also on environmental barriers. Vocational Rehabilitation programs should be implemented to help patients wishing to return to or maintain their current work, as much as possible.

A novel lecithin-based delivery form of Boswellic acids as complementary treatment of radiochemotherapy-induced cerebral edema in patients with glioblastoma multiforme: a longitudinal pilot experience.

BACKGROUND: Glioblastoma multiforme (GBM) is an extremely challenging neurological disease for which the development of more effective therapeutic options and of adjuvant/complementary treatment is needed. We investigated the effects of an innovative phytosome-based delivery form of boswellic acids extract (Monoselect AKBA™) on radiochemotherapy-induced cerebral edema in patients with primary GBM. METHODS: Patients with de novo GBM treated with surgery, radiotherapy and chemotherapy with temozolomide were enrolled in this longitudinal study and received boswellia-based product 4500 mg/die for a maximum of 34 weeks. Cerebral edema was assessed at 4, 12, 22 and 34 weeks post-surgery, together with steroids consumption and patients' psychological status. RESULTS: A total of 20 patients were included in the study. The percentage of patients with reduced edema was constant during the study, while the percentage of those with reduced or stable edema tended to increase over time. Of note, two patients achieved a considerable reduction in brain edema, which led to a more favorable and beneficial surgical resection. In addition, a good percentage of patients assumed a stable/reduced steroids dose or were dexamethasone free during the study. Lastly, patients' QoL and psychological state were maintained throughout the study. CONCLUSIONS: Complementary treatment with Monoselect AKBA™ might exert a beneficial effect in reducing radiochemotherapy-induced cerebral edema, thanks to the anti-inflammatory properties of the boswellia serrata extract. The reduction in brain edema might diminish dexamethasone assumption, thus minimizing steroids-induced side effects, and in few cases may allow a complete surgical excision of the tumor mass.

Prognostic nutritional index as a prognostic marker in glioblastoma: Data from a cohort of 282 Italian patients.

Preoperative prognostic nutritional index (PNI) is linked to the clinical outcome of patients with malignant tumours, however few studies have investigated its utility in predicting outcome in glioblastoma multiforme (GBM). We performed a retrospective study on adult patients with GBM in order to evaluate the impact of PNI on overall survival (OS), after adjusting for known prognostic factor (age, extent of surgery, Karnofsky performance status, radiochemotherapy). This is an Italian, multicentre, retrospective, cohort study. The patient's cohort includes 282 individuals with a newly diagnosed GBM followed in 3 Lombardia Hospitals In all cases the diagnosis was supported by histological data. Patient's information including sex, age at onset, Karnofsky performance status (KPS), extension of surgical resection (EOR), adjuvant treatment, antiepileptic treatment, serum variables and survival data were collected. Univariate and multivariate analysis did not reveal an association between PNI and overall survival in our series of GBM patients. PNI is a controversial marker for prognosis in GBM patients and further prospective studies are necessary to elucidate its role.

Anthropometrics and Body Composition in Adults with High-Grade Gliomas: Effects of Disease-Related Variables.

Nutritional status in adults with high-grade gliomas (HGGs) has been poorly investigated. We studied anthropometrics and fat mass (FM), fat free mass (FFM), and body water in HGGs patients also in relation to disease-related variables. Fifty-one patients (17 III and 34 IV-grade) and fifty-one control group (CG) matched for sex, age, and BMI were enrolled. Neurological scales, anthropometry, bioimpedance, and blood sampling were performed and analyzed according to grade, lesion location, extent of resection, phase of treatment, current steroids and antiepileptic therapy, and age of patient. 41.2% were overweight and 15.7% obese. Compared to the CG, HGGs had similar anthropometrics and body composition. IV-grade, compared to the III, had higher BMI, waist circumference, FM and lower FFM. Only patients during concomitant radio and chemotherapy showed a negative BMI variation from baseline. In conclusion, overnutrition occurs in almost 6 out of 10 HGGs patients and is more relevant in IV-grade. Throughout all the treatment phases, there is a higher risk of weight loss occurred only during concomitant radio and chemotherapy. Body composition showed no specific features compared to controls. These results may assist intervention studies directed towards neurometabolic dietary treatment. Nutritional screening is warranted during the time course of disease.

Psychological features and quality of life in 50 adult patients with epilepsy and their caregivers from the Lecco epilepsy center, Italy.

Epilepsy is one of the most common neurological disorders. To the best of our knowledge, in Italy, the relationship between patients' and caregivers' psychological state has rarely been analyzed. Thus, we sought to evaluate both the psychological state of patients with epilepsy and that of their caregivers and the interrelationship between them. We also assessed the existing relation between psychological features and some clinical and demographic information, such as number of antiepileptic drugs (AEDs), epilepsy duration and education level of patients and their caregivers. We enrolled in the study 50 consecutive adult patients attending the epilepsy clinic of "A. Manzoni" Hospital and their caregivers. Both patients and their caregivers were administered Hospital Anxiety and Depression Scale (HADS) and 36-item Short-Form Health Survey (SF-36). Anxiety, depression and quality of life values of both patients and their caregivers did not differ significantly from the normative samples. No statistically significant correlation between epilepsy duration and patients' and caregivers' psychological features was found. Patients which took more than one AED reported lower values of "Vitality" (p <.05) and "Social Functioning" (p <.05) than their own caregivers. Caregivers with higher education level presented lower "Vitality" values than caregivers with lower education level (p <.05). Patients with pharmacoresistant seizures reported lower values of "Mental Health" than patients with non-pharmacoresistant seizures (p <.05). In this context, the role of coping mechanisms by patients and caregivers may explain apparently unexpected findings and suggests that strategies aimed at reinforcing them may be effective in selected cases. Therefore, while the severity of epilepsy may have an impact on the psychological state of adult patients with epilepsy and their caregivers, our results highlight the role of multidimensional determinants, including stigma. Further studies are needed to identify the factors related to epilepsy, patients, caregivers, treatments, and the environment that may be modifiable in order to improve self-perceived QoL.

Hidden reality: sexual sphere in brain tumor patients.

Most reports emphasize that tumors and their treatments affect sexual function. To date, no studies have focused on sexual functioning in patients with brain tumors. Our study's objective is to describe the sexual sphere of patients with brain tumors and examine the possible differences between patients who reported sexual dysfunctions and those who did not with respect to their psychological and functional status. We tested 46 patients with brain tumors. We used an ad hoc questionnaire to assess patients' subjective perception of their own sexual sphere. To assess patients' psychological status, we used the following questionnaires: Hospital Anxiety and Depression Scale; Psychological Distress Inventory; EORTC QLQ-C30; EORTC QLQ-BN20. Fifty-eight percent of patients reported sexual disturbance. Our data showed that a lack of or decrease in sexual desire is the most common sexual problem reported by our patients (56%). Patients with sexual problems reported higher levels of anxiety and depression and a worse self-reported quality of life (QoL) than did those who did not perceive adverse changes in their sexual sphere. In addition, we found that patients with a better performance status (KPS) reported more changes in sexual behaviors than did those who had performance difficulties. Of the patients, 15.2% received information regarding possible changes in the sexual sphere by physicians. Additionally, 10.8 of 15.2% of the patients reported having explicitly requested information from physicians. The study demonstrated a relation between QoL and sexual function. Therefore, it would be important to encourage clinicians to ask questions regarding patients' sexual issues, thus providing them with an opportunity to expose their difficulties and receive adequate support.

Caring for Brain Tumour Patients: Psychological reactions after bereavement.

AIM: The aim of this study was to describe the changes in quality of life and in levels of anxiety and depression experienced by caregivers of patients with brain tumour 18 months after their bereavement. METHODS: This longitudinal study employed data from two time points: time 1, during the hospital stay of the caregiver's loved one; and time 2, approximately 18 months after the death of the patient. A total of 51 caregivers agreed to participate in the study at both time points. We used the Hospital Anxiety and Depression Scale and the 36-Item Short Form Health Survey; we compared the data obtained at the two time points using the paired-samples t-test. RESULTS: Caring for someone with a brain tumour had a greater impact on the caregivers' mental health than on their physical well-being. At time 2, the caregivers' levels of anxiety and depression and psychological burden were decreased, indicating that they were in a better emotional state than they had been in time 1. However, the mean values in the depression, vitality, and mental health subscales were lower than those in the normative data, indicating that these caregivers had a worse psychological status than members of the normative group. CONCLUSION: Our study underscores the necessity of supporting caregivers and monitoring their suffering levels; such suffering can compromise their social and work lives, not only during the disease trajectory but also in bereavement. Providing psychological and emotional support for caregivers of patients with brain tumour during both periods could lessen the suffering and unhappiness of these caregivers.

Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.

Hereditary spastic paraplegias are a heterogeneous group of neurodegenerative disorders, clinically classified in pure and complex forms. Genetically, more than 70 different forms of spastic paraplegias have been characterized. A subgroup of complicate recessive forms has been distinguished for the presence of thin corpus callosum and white matter lesions at brain imaging. This group includes several genetic entities, but most of the cases are caused by mutations in the KIAA1840 (SPG11) and ZFYVE26 genes (SPG15). We studied a cohort of 61 consecutive patients with complicated spastic paraplegias, presenting at least one of the following features: mental retardation, thin corpus callosum and/or white matter lesions. DNA samples were screened for mutations in the SPG11/KIAA1840, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG48/AP5Z1 and SPG54/DDHD2 genes by direct sequencing. Sequence variants were found in 30 of 61 cases: 16 patients carried SPG11/KIAA1840 gene variants (26.2%), nine patients carried SPG15/ZFYVE26 variants (14.8%), three patients SPG35/FA2H (5%), and two patients carried SPG48/AP5Z1 gene variants (3%). Mean age at onset was similar in patients with SPG11 and with SPG15 (range 11-36), and the phenotype was mostly indistinguishable. Extrapyramidal signs were observed only in patients with SPG15, and epilepsy in three subjects with SPG11. Motor axonal neuropathy was found in 60% of cases with SPG11 and 70% of cases with SPG15. Subjects with SPG35 had intellectual impairment, spastic paraplegia, thin corpus callosum, white matter hyperintensities, and cerebellar atrophy. Two families had a late-onset presentation, and none had signs of brain iron accumulation. The patients with SPG48 were a 5-year-old child, homozygous for a missense SPG48/AP5Z1 variant, and a 51-year-old female, carrying two different nonsense variants. Both patients had intellectual deficits, thin corpus callosum and white matter lesions. None of the cases in our cohort carried mutations in the SPG21/ACP33 and SPG54/DDH2H genes. Our study confirms that the phenotype of patients with SPG11 and with SPG15 is homogeneous, whereas cases with SPG35 and with SPG48 cases present overlapping features, and a broader clinical spectrum. The large group of non-diagnosed subjects (51%) suggests further genetic heterogeneity. The observation of common clinical features in association with defects in different causative genes, suggest a general vulnerability of the corticospinal tract axons to a wide spectrum of cellular alterations.

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature.

We report the clinical case of a 43year old Italian woman and her family with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. PLOSL is a unique disease clinically characterized by a progressive presenile frontal-lobe dementia and multiple cystic bone lesions, typically leading to fractures of the limbs in the third decade of life. This rare recessively inherited disease is caused by mutations in one of two genes encoding different subunits of a receptor signalling complex, TYROBP and TREM2. In the present case fractures after microtrauma were not diagnosed, despite a radiological demonstration of the characteristic bone lesions in PLOSL. Further investigation led to the same diagnosis in her brother, with similar clinical presentation and the same mutation. Therefore a diagnosis of PLOSL should be considered in cases of presenile frontal-lobe dementia, even if the hallmark of pathological fractures is absent.

Living with a brain tumor : reaction profiles in patients and their caregivers.

PURPOSE: The psychological burden induced by brain tumor is profound both for the sick person and for their own family. This particular tumor not only impacts patients' quality of life, but also reduces seriously the caregivers' quality of life. We aim to describe brain tumor patients and their caregivers' quality of life during the illness and assess the existing relation between clinical and psychological features of patients and their caregivers. METHODS: The study involved 72 patients/caregivers couples. We used the following tools: Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy--Brain (FACT-Br) for patients and HADS, Caregiver Reaction Assessment Scale (CRA), 36-Item Short-Form Health Survey (SF-36) for caregivers. RESULTS: Quality of life was more compromised in caregivers than in their loved ones. The impairment of caregivers' quality of life appeared mainly in a significant reduction in their mental health. Most caregivers experienced more depressive and anxiety symptoms, as compared with patients. Clinical and psychological features of patients did not correlate with psychological patterns of their own caregivers. CONCLUSIONS: It is important to give caregivers appropriate help, care and support. Therefore, it is necessary to monitor and treat, if necessary, caregivers' anxious or depressive symptomatology that impacts their quality of life, making them more helpless, frustrated and less able to handle the situation of disease and caregiving situation. It would be desirable to give caregivers the possibility of a psychological support and equally important would be a continuous teamwork aimed to promote a better caregivers' adaptation to the patient's illness.

The burden of brain tumor: a single-institution study on psychological patterns in caregivers.

Quality of life and well-being in caregivers are usually partly neglected since all attention is focused on patients and the way they react to the illness. Carers also usually neglect their own needs, especially when the illness of the patient is as complex as a brain tumor. The aim of this study is to investigate how caregivers deal with a diagnosis of brain tumor in their relatives and how they manage their quality of life and psychosocial well-being. One hundred primary caregivers of patients with brain tumors were interviewed and were asked to fill in self-administered questionnaires detecting multidimensional levels of quality of life, anxiety, depression, and psychosocial reaction to the patient's illness. Data were related with some functional and psychosocial information collected about the patient's disease. Caregivers try to react to the illness of their relatives by mobilizing their physical reaction and growing their self-esteem, but they live with a clinically significant impairment of their quality of life, and experience a deep level of anxiety and depression. The caregivers' burden appears mainly in their ability to provide care and in financial strain. The length of disease and the functional status of patients significantly influence caregivers' psychosocial well-being. Despite the appearance they want to show their affected relatives, caregivers suffer from deep limitation in their quality of life. The relevance of caregivers' burden suggests the importance of psychological support to improve reaction to the illness.

Recurrent brain tumour: the impact of illness on patient's life.

PURPOSE: Despite advances in therapies that offer improved survival rates, clinical course of brain tumours leads to a progressive functional deterioration in patients with modifications in their psychological reaction to the disease. Patients with brain tumours are rarely assessed for quality of life and psychological variables, and even fewer studies have assessed patients who have experienced a recurrence of brain tumours. Therefore, the aim of the present study is to investigate the patients with recurrent brain tumours and their reaction to the illness. METHOD: We enrolled 81 patients with recurrent CNS tumours. Karnofsky Performance Status scale (KPS) was used to evaluate functional status of patients; the multidimensional aspect of quality of life was assessed through "Functional Assessment of Cancer Therapy-Brain" (FACT-Br), "Hospital Anxiety and Depression Scale" and "Psychological Distress Inventory". These were all used as tests of psychological well-being. RESULTS: Distress and almost all mean FACT-Br subscale scores seemed to be significantly lower in patients, in comparison with normative data. Surprisingly, the emotional well-being mean score was significantly higher in our recurrence sample than in patients with brain tumours at first diagnosis. Anxiety seemed not to be influenced by a relapse diagnosis; instead, depression was higher and differed significantly from normative data. Low correlation between KPS and FACT-Br total and some sub-scores was found. CONCLUSIONS: Apparent dissociation between patients' judgment on their quality of life (bad except for emotional) and their reported distress (low) is the most intriguing finding, suggesting highly preserved coping strategies in the emotional sphere, despite intact judgment and disease awareness.

Bevacizumab at recurrence in high-grade glioma.

Bevacizumab has been introduced in the management of high-grade gliomas after preliminary studies that showed an acceptable safety and a marked increase in clinico-radiological responses in comparison with second-line chemotherapy. The objective is to synthetically review the present use of bevacizumab--alone or in combination--in the context of recurrent high-grade glioma and highlight the future developments. The methodology of this study is to analyse and discuss relevant literature studies using bevacizumab in recurrent high-grade glioma. Bevacizumab may be used as single-agent therapy in recurrent high-grade glioma, with good clinico-radiological responses having little effect on survival. The open questions and developments include new MRI criteria for evaluation of response to anti-angiogenic agents, the identification of putative factors predicting response/failure of bevacizumab and the introduction of bevacizumab in first-line management of high-grade glioma.

Systemic sagopilone (ZK-EPO) treatment of patients with recurrent malignant gliomas.

It has been demonstrated that sagopilone (ZK-EPO) has antitumor activity in human orthotopic glioma models in vitro and in vivo. The objective of this study was to evaluate the safety and efficacy of ZK-EPO in patients with pretreated, recurrent malignant gliomas. Fifteen patients with recurrent malignant gliomas who had received prior surgery, radiotherapy, and >or=2 lines of alkylating chemotherapy were recruited. ZK-EPO (16 mg/m(2)) was administered iv for 3 h every 21 days. The primary end point was six months progression-free survival (PFS-6); secondary end points were safety, toxicity, response rate, and median time to progression (TTP). Magnetic resonance imaging (MRI) evaluations were performed every two cycles and toxicity was evaluated at each cycle using common terminology criteria for adverse events (CTCAE 3.0). A median of four cycles was administered. The median TTP was 13 weeks. PFS-6 was achieved in five patients (33%), three with glioblastoma multiforme and two with anaplastic astrocytoma. The most common treatment-related adverse event was neuropathy, which occurred in 6/15 patients. ZK-EPO had an acceptable safety profile and clinically relevant activity in patients with pretreated, recurrent malignant gliomas.

Cisplatinum and BCNU chemotherapy in primary glioblastoma patients.

BACKGROUND: The prognosis of patients with glioblastoma is very poor with a mean survival of 10-12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients. Methylated methylguanine methyltransferase (MGMT) promoter is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. METHODS: A retrospective analysis on 160 adult patients (> or =16 years) treated for histologically confirmed GBM between 2003 and 2005 at our Institution was performed. All patients were treated with conventional fractionated radiotherapy and a combined chemotherapy treatment with Cisplatin (CDDP) (100 mg/sqm on day 1) and carmustine (BCNU) (160 mg/sqm on day 2); the treatment was repeated every 6 weeks for five cycles. Toxicity, progression free survival and overall survival were assessed. RESULTS: The median number of chemotherapy cycles delivered to each patient was 5 (range 3-6), with no patients discontinuing treatment because of refusal or toxicity. Dose reduction was required in 16 patients (10%), and all patients completed radiotherapy, whereas 5 patients discontinued chemotherapy before completing all planned cycles for disease progression. The primary toxicities were: neutropenia (grade 3-4: 23%), thrombocytopenia (grade 3-4: 18.5%), and nausea and vomiting (13%). Median progression-free survival times and 1-year progression free survival were 7.6 months (95% CI 6.6-8.5) and 17.3%, respectively. OS was 15.6 months (95% CI 14.1-17.1). CONCLUSIONS: Our results for PFS and overall survival are comparable with those obtained with temozolomide, but the toxicity occurring in our series was more frequent and persistent. The toxicity, and mainly the modalities of administration associated with cisplatin and BCNU combination, argues against future use in the treatment of patients with GBM.

Treatment of recurrent glioblastoma: can local delivery of mitoxantrone improve survival?

In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir. The reservoir was used for locoregional chemotherapy with mitoxantrone. Two hundred seventy-six rGBL patients (pts) were divided into three subgroups: A 161 pts treated only with temozolomide, B 50 pts re-operated-on +temozolomide, and C 65 pts re-operated on + temozolomide + locoregional CHT. For group A, the 6 month PFS and 6 month survival (ST) were 39.3 and 43%, respectively, with a median survival time (mST) of 5 months (range 4-6) and 25% of pts alive at 9 months. For group B, the 6 month PFS and 6 month survivors were 64 and 74.1%, respectively, with a mST of 8 months (range 6-10) and 25% of pts alive at 12 months. For group C, the 6 month PFS and 6 month survivors were 70.7 and 87.7%, respectively, with a mST of 11 months (range 9-13) and 25% of pts alive at 18 months (A vs. B vs. C, log-rank P < 0.001) (B vs. C, P = 0.041) (A vs. B P = 0.009). Cox proportional hazard model was used to obtain Hazard Ratio (HR) for type of treatment corrected by age and time (in months) between diagnosis and first recurrence: second tumor debulking was statistically effective for survival, reducing by 36% the risk of death (HR = 0.64; 0.46-0.89), but the most significant favorable prognostic factor for survival was the local delivery of mitoxantrone which reduced the risk of death to 50% (HR = 0.50; 0.38-0.68).