Prognostic impact of hypothalamic perforation in adult patients with craniopharyngioma: a cohort study.

CONTEXT: Outcome of craniopharyngioma is related to its locoregional extension, which impacts resectability and the risk of surgical complications. To maximize resection and minimize complications, optic tract localization, temporal lobe extension and hypothalamic involvement are essential for surgical management. OBJECTIVE: To assess the outcome of craniopharyngiomas depending on their relation to the hypothalamus location. METHODS: We conducted a retrospective analysis of 79 patients with a craniopharyngioma who underwent surgery from 2007 to 2022. Craniopharyngiomas were classified in three groups, depending on the type of hypothalamus involvement assessed by preoperative MRI: infra-hypothalamic (type A, n=33); perforating the hypothalamus (type B, n=40); supra-hypothalamic (type C, n=6). Surgical strategy was guided by the type of hypothalamic involvement, favoring endonasal approaches for type A and type B, and transcranial approaches for type C. RESULTS: Long-term disease control was achieved in 33/33 (100%), 37/40 (92%) and 5/6 (83%) patients in type A, B and C respectively. In type B, vision was improved in 32/36 (89%) patients, while hypothalamic function was improved, stable or worsened in 6/40 (15%), 32/40 (80%) and 2/40 (5%) patients respectively. Papillary craniopharyngiomas were found in 5/33 (15%), 9/40 (22%) and 3/6 (50%) patients in types A, B and C respectively. In four patients, BRAF/MEK inhibitors were used, with significant tumor shrinkage in all cases. CONCLUSION: Craniopharyngiomas located below the hypothalamus or perforating it can be safely treated by transsphenoidal surgery. For supra-hypothalamic craniopharyngiomas, postoperative results are less favorable, and documenting a BRAF-mutation may improve outcome, if targeted therapy was efficient enough to replace surgical debulking.

Late-onset vascular complications of radiotherapy for primary brain tumors: a case-control and cross-sectional analysis.

PURPOSE: Radiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT). METHODS: We retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study. RESULTS: A total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%). CONCLUSIONS: Stroke prevalence is increased in long-surviving PBT patients treated with cranial RT. IMPLICATIONS FOR CANCER SURVIVORS: CV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.

Improving personalised care and support planning for people living with treatable-but-not-curable cancer.

People living with treatable-but-not-curable (TbnC) cancer encounter cancer-related needs. While the NHS long-term plan commits to offering a Holistic Needs Assessment (HNA) and care plan to all people diagnosed with cancer, the content, delivery and timing of this intervention differs across practice. Understanding how people make sense of their cancer experience can support personalised care. A conceptual framework based on personal narratives of living with and beyond cancer (across different cancer types and all stages of the disease trajectory), identified three interlinked themes: Adversity, Restoration and Compatibility, resulting in the ARC framework.Our aim was to use the ARC framework to underpin the HNA to improve the experience of personalised care and support planning for people living with TbnC cancer. We used clinical work experience to operationalise the ARC framework and develop the intervention, called the ARC HNA, and service-level structure, called the ARC clinic. We sought expert input on the proposed content and structure from patients and clinicians through involvement and engagement activities. Delivered alongside standard care, the ARC HNA was piloted with patients on the TbnC cancer (myeloma and metastatic breast, prostate or lung) pathway, who were 6-24 months into their treatment. Iterations were made to the content, delivery and timing of the intervention based on user feedback.Fifty-one patients received the intervention. An average of 12 new concerns were identified per patient, and 96% of patients achieved at least one of their goals. Patients valued the space for reflection and follow-up, and clinicians valued the collaborative approach to meeting patients' supportive care needs. Compared with routine initial HNA and care plan completion rates of 13%, ARC clinic achieved 90% with all care plans shared with general practitioners. The ARC clinic adopts a novel and proactive approach to delivering HNAs and care plans in a meaningful and personalised way.

Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol.

INTRODUCTION AND AIMS: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions. METHODS AND ANALYSIS: The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson's disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals.

Prehabilitation in the lung cancer pathway: a scoping review.

BACKGROUND: Lung cancer is the third most common type of cancer in the UK. Treatment outcomes are poor and UK deaths from lung cancer are higher than any other cancer. Prehabilitation has shown to be an important means of preparing patients both physically and psychologically for cancer treatment. However, little is understood about the context and mechanisms of prehabilitation that can impact physiological and psychological wellbeing. Our aim was to review and summarise primary research on prehabilitation in the lung cancer pathway using a realist approach. METHODS: A scoping review of empirical primary research was conducted. Five online medical databases from 2016 - February 2023 were searched. All articles reporting on prehabilitation in lung cancer were included in the review. For this review, prehabilitation was defined as either a uni-modal or multi-modal intervention including exercise, nutrition and/or psychosocial support within a home, community or hospital based setting. A realist framework of context, mechanism and outcome was used to assist with the interpretation of findings. RESULTS: In total, 31 studies were included in the review, of which, three were published study protocols. Over 95% of studies featured an exercise component as part of a prehabilitation programme. Twenty-six of the studies had a surgical focus. Only two studies reported using theory to underpin the design of this complex intervention. There was large heterogeneity across all studies as well as a lack of clinical trials to provide definitive evidence on the programme design, setting, type of intervention, patient criteria, delivery, duration and outcome measures used. CONCLUSION: A standardised prehabilitation programme for lung cancer patients does not yet exist. Future lung cancer prehabilitation programmes should take into account patient led values, needs, goals, support structures and beliefs, as these factors can affect the delivery and engagement of interventions. Future research should consider using a conceptual framework to conceptualise the living with and beyond cancer experience to help shape and inform personalised prehabilitation services.

Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline.

PURPOSE: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). MATERIALS AND METHODS: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. RESULTS: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. CONCLUSION: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

Radiotherapy for newly diagnosed primary central nervous system lymphoma: role and perspective.

Whole brain radiotherapy (WBRT) has long been a key treatment of newly diagnosed primary central nervous system lymphoma (PCNSL). In the 1990s, the addition of high dose Methotrexate-based induction chemotherapy (HD MTX-based CT) has enabled a drastic improvement in PCNSL patients outcome. However, combined treatment has led to radiation-induced delayed neurotoxicity, especially in older patients. Alternative treatment strategies have been assessed to improve the efficacy and neurotoxicity ratio. Nowadays, in the elderly patients WBRT is widely omitted or deferred, and in younger patients WBRT is challenged by high dose chemotherapy with autologous stem cell transplant (HCT-ASCT) for consolidation treatment after HD MTX-based CT. In this setting, this review is addressed to clinicians with the aim to summarize the role of WBRT in the treatment of newly diagnosed PCNSL and its perspectives.

Brain radiotherapy in patients treated for a newly diagnosed primary central nervous system lymphoma: professional practice evaluation in 19 French centers.

INTRODUCTION: The objective of this study was a multicentric evaluation of professional practices, analyzing the irradiation technique itself and its impact on survival and recurrence sites, in primary central nervous system lymphomas (PCNSLs). METHODS: We retrospectively analyzed the technical and clinical records of 79 PCNSL patients included in the database of the national expert network for oculocerebral lymphoma ('LOC') who were treated with brain radiotherapy as first-line treatment for newly diagnosed primary central nervous system lymphoma between 2011 and 2018. RESULTS: The number of patients treated with brain radiotherapy gradually decreased over time. The heterogeneity of radiotherapy prescriptions was significant, and 55% of them did not comply with published recommendations in terms of irradiation dose and/or volume. The proportion of complete responders to induction chemotherapy treated with reduced-dose radiotherapy increased over time. Partial brain radiotherapy was associated with significantly lower overall survival in univariate analysis. In partial responders to induction chemotherapy, increasing the total dose to the brain >30 Gy and adding a boost to the WBRT induced a trend toward improved progression-free and overall survival. Five recurrences (13%) occurred exclusively in the eyes, all in patients whose eyes had been excluded from the irradiation target volume and including 2 patients without ocular involvement at diagnosis. CONCLUSION: The visibility of recommendations for prescribing brain radiotherapy for the treatment of newly diagnosed primary central nervous system lymphoma needs to be improved to harmonize practices and improve their quality. We propose an update of the recommendations.

Long-Term Outcomes in Head and Neck Paragangliomas Managed with Intensity-Modulated Radiotherapy.

OBJECTIVES: Head & Neck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in Head & Neck paragangliomas. METHODS: This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed. RESULTS: Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity. CONCLUSION: IMRT seems an ideal treatment, whether exclusive or post-operative for Head & Neck paragangliomas. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:607-614, 2023.

Symptoms of Depression and Anxiety in Adults with High-Grade Glioma: A Literature Review and Findings in a Group of Patients before Chemoradiotherapy and One Year Later.

High-grade glioma (HGG) is associated with several external and internal stressors that may induce mood alterations at all stages of the disease. Symptoms of depression and anxiety in persons with glioma have multifactorial etiology and require active follow-up. We reviewed the literature data on the prevalence, mechanisms likely involved in the etiology of mood alterations in persons with HGG and psychosocial interventions found beneficial in treating these symptoms. We also investigated the prevalence and clinical variables that could increase the risk of depression and anxiety symptoms in a group of patients with HGG at two disease time-points: after surgery, before and 1 year after chemoradiotherapy. Literature findings revealed complex mechanisms underlying these symptoms and highlighted the importance of providing early access to palliative care. Our results show a high rate of anxiety and depression symptoms in the first stage of the disease and increased concomitance of these symptoms at the 1-year follow-up. Depression and anxiety symptoms at 1 year after the end of chemoradiotherapy were associated with the presence of symptoms at the first stage of the disease and tumor progression. Antiepileptic drugs and corticosteroid intake did not increase the risk of depressive and anxious symptoms among patients. Active management of mood alterations is an essential part of the care and contributes to patients' well-being and quality of life.

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors.

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18-69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Dosimetric study between a single isocenter dynamic conformal arc therapy technique and Gamma Knife radiosurgery for multiple brain metastases treatment: impact of target volume geometrical characteristics.

PURPOSE: To compare linac-based mono-isocentric radiosurgery with Brainlab Elements Multiple Brain Mets (MBM) SRS and the Gamma Knife using a specific statistical method and to analyze the dosimetric impact of the target volume geometric characteristics. A dose fall-off analysis allowed to evaluate the Gradient Index relevancy for the dose spillage characterization. MATERIAL AND METHODS: Treatments were planned on twenty patients with three to nine brain metastases with MBM 2.0 and GammaPlan 11.0. Ninety-five metastases ranging from 0.02 to 9.61 cc were included. Paddick Index (PI), Gradient Index (GI), dose fall-off, volume of healthy brain receiving more than 12 Gy (V12Gy) and DVH were used for the plan comparison according to target volume, major axis diameter and Sphericity Index (SI). The multivariate regression approach allowed to analyze the impact of each geometric characteristic keeping all the others unchanged. A parallel study was led to evaluate the impact of the isodose line (IDL) prescription on the MBM plan quality. RESULTS: For mono-isocentric linac-based radiosurgery, the IDL around 70-75% was the best compromise found. For both techniques, the GI and the dose fall-off decreased with the target volume. In comparison, PI was slightly improved with MBM for targets < 1 cc or SI > 0.78. GI was improved with GP for targets < 2.5 cc. The V12Gy was higher with MBM for lesions > 0.4 cc or SI < 0.84 and exceeded 10 cc for targets > 5 cc against 6.5 cc with GP. The presence of OAR close to the PTV had no impact on the dose fall off values. The dose fall-off was higher for volumes < 3.8 cc with GP which had the sharpest dose fall-off in the infero-superior direction up to 30%/mm. The mean beam-on time was 94 min with GP against 13 min with MBM. CONCLUSIONS: The dose fall-off and the V12Gy were more relevant indicators than the GI for the low dose spillage assessment. Both evaluated techniques have comparable plan qualities with a slightly improved selectivity with MBM for smaller lesions but with a healthy tissues sparing slightly favorable to GP at the expense of a considerably longer irradiation time. However, a higher healthy tissue exposure must be considered for large volumes in MBM plans.

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma.

INTRODUCTION: Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) have been used to assess cognition in these patients. Here we assessed the sensitivity of the MoCA in screening for cognitive impairment in a cohort of 156 patients with newly-diagnosed high-grade glioma, after surgery and before radiochemotherapy. METHODS: We assessed cognitive performance with the MoCA and a neuropsychological battery. Cognitive scores were analyzed in terms of a previously validated framework designed to control false positives and data for 1003 control participants from the GRECOGVASC study. After comparison of performance on the tests, we used stepwise logistic regression to produce a cognitive summary score from the neuropsychological battery. Then we analyzed sensitivity and specificity of the MoCA with receiver operator characteristic (ROC) curve analysis. RESULTS: Both raw and adjusted MoCA scores showed only moderate sensitivity. The area under the ROC curve was 0.759 (95% CI 0.703-0.815) for the raw score and 0.788 (95% CI 0.734-0.842) for the adjusted score. Optimal discrimination was obtained with a raw score ≤ 25 (sensitivity: 0.526; specificity: 0.832; positive predictive value: 0.2; negative predictive value: 0.96) and an adjusted score - 0.603 (sensitivity: 0.716; specificity: 0.768; positive predictive value: 0.24; negative predictive value: 0.96). CONCLUSION: The moderate sensitivity of MoCA indicates that it is not a suitable screening tool for detecting cognitive impairment in patients with newly-diagnosed high-grade glioma.

Stereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients.

BACKGROUND: The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. PATIENTS AND METHODS: From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%). RESULTS: The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age ≥65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis ≤4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis. CONCLUSION: SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.

Treatment of grade II-III intracranial meningioma with helical tomotherapy.

Meningiomas account for 30-35% of intracranial tumors. Grade I meningiomas are most common and carry the best prognosis. Grade II and III meningiomas are more aggressive and the outcomes after surgical resection alone remain unsatisfactory. The main objective of this retrospective, single-center study was to assess our results of treatment of grade II-III intracranial meningioma with helical tomotherapy (HT). We retrospectively reviewed patients with histologically proven (WHO 2007) grade II-III meningioma irradiated with HT. Patients were treated one session a day, 5 days a week, to a total dose of 59.4 Gy and 68.4 Gy delivered in 33 and 38 fractions of 1.8 Gy each to the LR PTV and HR PTV, with or without simultaneous integrated boost. From May 2011 to January 2015, 19 patients (15 with grade II and 4 with grade III meningiomas) were treated. Median follow-up for patients with Grade II or Grade III meningiomas, was 29.2 months (range, 10.7-52.4) and 21.3 months (range, 2.4-51.3), respectively. Disease free survival at 1, 2 and 3 years was 89.2%, 83.6% and 56.3% respectively. Overall survival at 1, 2 and 3 years was 94.7%, 94.7% and 78.9%, respectively. No patient had neurological toxicity greater than grade 2 in the acute period. During follow-up, only one patient had neurological toxicity greater than or equal to grade 3. The management of grade II to III meningiomas using HT with doses exceeding 60 Gy is associated with good local control and acceptable survival results.

Cognitive impairment and morphological changes after radiation therapy in brain tumors: A review.

Life expectancy of patients treated for brain tumors has lengthened due to the therapeutic improvements. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. Technical evolutions aim at enhancing the therapeutic ratio. Sparing of the healthy tissues has been improved using various approaches; however, few dose constraints have been established regarding brain structures associated with cognitive functions. The aims of this literature review are to report the main brain areas involved in cognitive adverse effects induced by radiotherapy as described in literature, to better understand brain radiosensitivity and to describe potential future improvements.

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study.

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among "very elderly" patients affected by GBM. Patients 80 and older should be considered for management based on RT.

Dosimetric Effects of the Interfraction Variations during Whole Breast Radiotherapy: A Prospective Study.

INTRODUCTION: The aim of this work was to assess the dosimetric impact of the interfraction variations during breast radiotherapy. MATERIALS AND METHODS: Daily portal imaging measurements were prospectively performed in 10 patients treated with adjuvant whole breast irradiation (50 Gy/25 fractions). Margins between the clinical target volume and the planning target volume (PTV) were 5 mm in the three dimensions. Parameters of interest were the central lung distance (CLD) and the inferior central margin (ICM). Daily movements were applied to the baseline treatment planning (TP1) to design a further TP (TP2). The PTV coverage and organ at risk exposure were measured on both TP1 and TP2, before being compared. RESULTS: A total of 241 portal images were analyzed. The random and systematic errors were 2.6 and 3.7 mm for the CLD, 4.3 and 6.9 mm for the ICM, respectively. No significant consequence on the PTV treatments was observed (mean variations: +0.1%, p = 0.56 and -1.8%, p = 0.08 for the breast and the tumor bed, respectively). The ipsilateral lung and heart exposure was not significantly modified. CONCLUSION: In our series, the daily interfraction variations had no significant effect on the PTV coverage or healthy tissue exposure during breast radiotherapy.

Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab therapy: a bi-institutional case series.

We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.