RESUMEN

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02-1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03-1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08-1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.

Asunto(s)

RESUMEN

Introduction Radiation necrosis in the brain is a frequent complication of brain radiation therapy (RT) and is characterized by various neurological symptoms including cognitive dysfunction, headaches, weakness, apraxia, aphasia, and numbness. These symptoms may be progressive and treatment-resistant. Currently, risk factors for radiation necrosis are not well characterized. The goal of this study is to identify risk factors for cerebral radiation necrosis in order to improve clinicians' ability to appropriately weigh the risks and benefits of brain RT. Methods A retrospective chart review was performed on patients who were diagnosed with brain tumors and received RT (3D conformal therapy, volumetric modulated arc therapy, stereotactic radiosurgery, or stereotactic radiotherapy) at the University of Arkansas for Medical Sciences from July 1, 2017, to July 1, 2019. Data regarding demographics, characteristics of cancer, chemotherapy status and class, comorbidities, and additional medications of patients were collected via EPIC. Total RT dose, fraction size, volume of brain receiving 12 Gy (V12), and retreatment of locally recurrent tumors were recorded from Eclipse. The diagnosis of radiation necrosis was based on MRI reports that were examined for a time period of 24 months following the completion of radiation treatment and confirmed, when possible, by biopsy. Cases that did not have an MRI available at least two months after the completion of RT were excluded. Statistical association analyses were used to identify candidate risk factors to radiation necrosis. These candidate risk factors were further used to assess their associations to demographics and other characteristics of cancer and treatments. Finally, adjusted and unadjusted logistic regression models were used to predict radiation necrosis using a single risk factor or multiple risk factors. ROC curves were used to evaluate the performance of prediction or discrimination of the logistic regression models. Results A total of 139 patients were studied. The mean ± standard deviation (SD) for age was 60.4 ± 13.6 years, female:male ratio was 71:68, and White:African American:other race ratio was 112:24:3. A total of 43 (30.9%) patients were diagnosed with radiation necrosis. Radiation adjuvant to surgery, concurrent systemic therapy status, total dose, and V12 were found to be significantly associated with radiation necrosis and considered candidate risk factors of radiation necrosis in the study. Predictive models showed adjusted odds ratios ([aORs] 95% confidence intervals or CIs) of 3.70 (1.01-13.56) and 8.19 (1.78-37.78) with radiation adjuvant to surgery and concurrent systemic therapy, respectively. For every one unit (log-transformed) increase of total dose and V12, the aORs (95% CI's) were 27.35 (3.74-200.16) and 1.63 (1.15-2.32), respectively. Conclusion Our study suggested a positive correlation of concurrent systemic therapy status and post-surgical adjuvant RT with the incidence of radiation necrosis. It further demonstrated that greater total RT dose and V12 were related to the risk of developing radiation necrosis following brain RT. Given the findings of this study, the aforementioned factors should be considered when weighing the risk of radiation necrosis with the benefits of treatment.

RESUMEN

Background: The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality. Methods: In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a "watch-and-wait" policy). Findings: Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41). Interpretation: Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic. Funding: National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

RESUMEN

BACKGROUND AND PURPOSE: The study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain necrosis (RN). MATERIALS AND METHODS: We included head and neck cancer survivors with RN from a radiation complications registry study. A total of 495 eligible patients were 7:3 randomly allocated to a training cohort and an internal validation cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select significant predictors of post-RN survival in the training cohort, and a multivariable Cox model was used to develop the nomogram. The performance of the nomogram was assessed using the internal validation cohort and externally validated using additional 88 RN patients. RESULTS: We identified five predictors of post-RN survival using the training data: age, tumor progression before RN, lower cranial nerves injury, bilateral necrosis, and history of stroke. The nomogram showed favorable performance in the internal validation cohort (C-index 0.761, 95% CI 0.676 to 0.847) and in the external validation cohort (C-index 0.795, 95% CI 0.717 to 0.874). The decision curve analysis indicated that the nomogram was clinically useful when the probabilities of death ranging from 1% to 48% at 1 year, from 3% to 50% at 3 years, and exceeding 2% at 5 years after being diagnosed with RN. CONCLUSION: In this LASSO-Cox model-based nomogram study, we developed and validated an easily applied model to predict overall survival in head and neck cancer survivors following an RN diagnosis.

Asunto(s)

RESUMEN

Radiation-induced brain necrosis (RIBN) is a serious late and irreversible complication after radiation therapy for primary or secondary brain tumors as well as head and neck tumors, and there is no effective treatment. In recent years, bevacizumab has been increasingly applied in the treatment of RIBN, which has been proven to yield certain efficacy and improve patient survival. However, the optimal treatment timing and regimen have been controversial and lack of basic consensus. In this article, research progress on these issues was briefly reviewed.

RESUMEN

BACKGROUND: Blood-brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI). METHODS: Forty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse. RESULTS: The extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially K trans (Kruskal-Wallis test, P < 0.001). In the RN group, bevacizumab-induced K trans and v e decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline K trans, K ep, and v p positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab K trans level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546-0.943, sensitivity = 0.800, specificity = 0.631). CONCLUSIONS: Bevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.

RESUMEN

OBJECTIVE: Our aim was to compare the clinical outcomes of patients treated with bevacizumab combined with corticosteroids and those with bevacizumab monotherapy from a radiation-induced brain necrosis (RN) registry cohort (NCT03908502). METHODS: We utilized clinical data from a prospective RN registry cohort (NCT03908502) from July 2017 to June 2020. Patients were considered eligible if they had symptomatic RN after radiotherapy for nasopharyngeal carcinoma (NPC) and received bevacizumab (5 mg/kg, two to four cycles) with a minimum follow-up time of 3 months. The primary outcome was a 2-month response rate determined by MRI and clinical symptoms. Secondary outcomes included quality of life [evaluated by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire] and cognitive function (evaluated by the Montreal Cognitive Assessment scale) at 2 months, RN recurrence during follow-up, and adverse events. RESULTS: A total of 123 patients (34 in the combined therapy group and 89 in the monotherapy group) were enrolled in our study with a median follow-up time of 0.97 year [interquartile range (IQR) = 0.35-2.60 years]. The clinical efficacy of RN did not differ significantly between patients in these two groups [odds ratio (OR) = 1.642, 95%CI = 0.584-4.614, p = 0.347]. Furthermore, bevacizumab combined with corticosteroids did not reduce recurrence compared with bevacizumab monotherapy [hazard ratio (HR) = 1.329, 95%CI = 0.849-2.079, p = 0.213]. The most common adverse events of bevacizumab were hypertension (17.89%), followed by nosebleed (8.13%) and fatigue (8.13%). There was no difference in grade 2 or more severe adverse events between the two groups (p = 0.811). INTERPRETATION: Our results showed that the treatment strategy of combining bevacizumab with corticosteroids did not lead to better clinical outcomes for RN patients with a background of radiotherapy for nasopharyngeal carcinoma.

RESUMEN

BACKGROUND: Radiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids. MATERIALS AND METHODS: We searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis. RESULTS: Overall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%-80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%-74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p < 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p < 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences. CONCLUSIONS: Patients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

RESUMEN

Radiotherapy is one of the most effective treatments for head and neck tumors. However, delayed radiation-induced brain necrosis (RN) remains a serious issue due to the lack of satisfying prevention and effective treatment. The pathological role of radiation in the delayed onset of brain necrosis is still largely unknown, and the traditional animal model of whole brain irradiation, although being widely used, does not produce reliable and localized brain necrosis mimicking clinical features of RN. In this study, we demonstrated a successful RN mouse model using optimized gamma knife irradiation in male C57BL/6 mice. On the premise that brain necrosis started to appear at 6 weeks postirradiation in our RN model, as confirmed by both MRI and histopathological examinations, we systematically examined different time points before the onset of RN for the histopathological changes and biochemical indicators. Our initial results demonstrated that in the ipsilateral hemisphere of the irradiated brains, a significant decrease in neuronal numbers that occurred at 4 weeks and a sustained increase in TNF-α, iNOS, and other inflammatory cytokines beginning at 1-week postirradiation. Changes of cell morphology and cell numbers of both microglia and astrocytes occurred as early as 1-week postirradiation, and intervention by bevacizumab administration resulted in reduced microglia activation and reduction of radiation-induced lesion volume, indicating that chronic glial activation may result in subsequent elevation of inflammatory factors, which led to the delayed onset of neuronal loss and brain necrosis. Since C57BL/6 is the most widely used strain of genetic engineered mouse model, our data provide an invaluable platform for the mechanistic study of RN pathogenesis, identification of potential imaging and biological biomarkers, and the development of therapeutic treatment for the disease.

Asunto(s)

RESUMEN

PURPOSE: To assess the neurocognitive function and neurological toxicity of frameless linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in patients with 10 or more brain metastases (BM). PATIENTS AND METHODS: Forty consecutive adult patients who received SRS for ten or more 10 BM < 3 cm in maximum size were evaluated. All plans were generated using a single-isocenter multiple-target (SIMT) SRS technique with doses of 22 Gy for lesions < 2 cm and 16-18 Gy for those ≥ 2 cm in size. Survival analyses were estimated by Kaplan-Meier method from the date of SRS. Neurocognitive function using the Hopkins verbal learning test-revised (HVLT-R) and activity of daily living scale (ADLS) were collected prospectively at baseline and at 3,6 and 12-month follow-up. Toxicity was assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (Version 5.0). RESULTS: With a median follow-up of 10.8 months, 1-year survival and local control rates were 65% and 86%, respectively. Grade 2 or 3 toxicity occurred in eleven patients, being associated with radiological changes suggestive of radiation necrosis in seven patients. Three months after SRS, the mean relative decline was 14.2% for HVLT-R delayed recall, 12.3% for HVLT-R recognition, and 9.8% for HVLT-R total recall. A significant deterioration of HVLT-R scores ranged from 5.5 to 18.7% of patients at different time points. ADLS scores declined over time, but changes were not significant. CONCLUSIONS: SRS is an effective and safe approach for patients with 10 or more BM able to maintain the pretreatment neurocognitive function in the majority of patients.

Asunto(s)

RESUMEN

INTRODUCTION: The apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio is recognized as a clinical indicator of cardiovascular disease and ischemic cerebral disease. Cerebrovascular dysfunction is also involved in head and neck radiotherapy. The aim of this study was to investigate the correlation between ApoB/ApoA1 ratio and the severity of radiation-induced brain necrosis (RN) in patients who underwent radiotherapy after nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 191 NPC patients diagnosed with RN were evaluated. Clinical characteristics, serum lipid, apolipoproteins, and brain magnetic resonance imaging findings were collected. Serum lipid and apolipoproteins were quantified using standard diagnostic assays, and the quality of life (QOL) was assessed by the World Health Organization quality of life abbreviated instrument (WHOQOL-BREF). RESULTS: ApoB/ApoA1 ratio was positively correlated with lesion volume (r = .18, p = .03) and negatively correlated with WHOQOL-BREF scores (r = -.28, p < .01). The ApoB/ApoA1 ratio and intensity-modulated radiation therapy (IMRT) were independent risk factor of RN volume. Moreover, ApoB/ApoA1 ratio was significantly negatively correlated with physical health (r = -.29, p < .01), psychological (r = -.27, p < .01), social relationships (r = -.17, p = .02), and environment (r = -.27, p < .01) domains of WHOQOL-BREF. CONCLUSIONS: Serum ApoB/ApoA1 ratio is positively correlated with RN volume, which indicated serum ApoB/ApoA1 ratio as an independent risk factor for lesion volume in patients with RN after radiotherapy for NPC, suggesting a bright intervention target in RN treatment.

Asunto(s)

RESUMEN

BACKGROUND: Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain necrosis (RN). Intravenous steroids have been considered as an effective treatment for RN. However, evidence concerning the efficacy of different doses of intravenous steroid therapy remains insufficient to establish the optimal regimen for NPC patients with RN. METHODS: We retrospectively reviewed charts of 169 patients who were diagnosed with RN after radiotherapy for NPC, treated with low-dose or high-dose intravenous methylprednisolone (IVMP) and followed up for 12 months. We collected the clinical data, including the Late Effects of Normal Tissue (LENT)/Subjective, Objective, Management, Analytic (SOMA) scales score and Montreal Cognitive Assessment (MoCA) score. Magnetic resonance imaging (MRI) was performed pre- and post-treatment to define the radiographic response. RESULTS: There were no significant differences in the treatment response based on MRI, or changes in clinical symptoms and cognitive function between low and high-dose groups. Thirty of 93 low-dose patients (32.3%) and 21 of 76 high-dose patients (27.6%) presented effective response in MRI, with no significant differences between groups (P = 0.515). Neither group showed a significant difference in the effective rate based on the MoCA total score and LENT/SOMA score. The most commonly reported grade 3 adverse events in the high-dose group (n = 76) were infections and infestations (3 [3.9%] vs. none for low-dose group). CONCLUSIONS: We found low-dose IVMP was not inferior to high-dose IVMP for NPC patients with RN. In addition, treatment-related infections and infestations were likewise more common with high-dose steroid than low-dose steroid.

Asunto(s)

RESUMEN

BACKGROUND: To investigate the prognostic value of hyponatremia, defined as serum sodium level < 135 mEq/L, in radiation-induced brain necrosis (RN) patients. METHODS: We performed a retrospective analysis of the RN patients (The patients included in our study had a history of primary cancers including nasopharyngeal carcinoma/glioma/oral cancer and received radiotherapy previously and then were diagnosed with RN) treated in Sun yat-sen Memorial Hospital from January 2013 to August 2015. Patients without cranial magnetic resonance imaging (MRI) scan and serum sodium data were excluded. Progression was identified when the increase of edema area ≥ 25% on the MRI taken in six months comparing with those taken at the baseline. Factors that might associate with prognosis of RN were collected. Multivariable logistic regression analyses were used to identify potential predictors. RESULTS: We total included 135 patients, 32 (23.7%) of them with hyponatremia and 36 (26.7%) with RN progression. Percentage of progression was roughly three fold in hyponatremia patients compared with nonhyponatremia patients (53.1% versus 18.4%), translating into a 5-fold increased odds ratio (P <  0.001). Multivariable analyses identified hyponatremia as a potential predictor of progression (OR, 4.82; 95% CI [1.94-11.94]; P = 0.001). CONCLUSIONS: Hyponatremia was identified as a potential predictor for the progression of patients with RN. Hyponatremia management in patients with RN should be paid much more concern in clinical practice.

Asunto(s)

RESUMEN

Objective To explore the effects and safety of bevacizumab monotherapy on radiationinduced brain necrosis in patients with head and neck cancer.Methods Twenty-three patients with radiation-induced brain necrosis received intravenous injection of bevacizumab 5 mg/kg every 2 weeks for 4 cycles.Before and 2 weeks after the treatment LENT/SOMA scoring system,Montreal Cognitive Assessment (MoCA),and MRI were used to evaluate the scores of subjective and objective items,cognitive scores,and the extent of edema.Adverse effects were observed.Results Two patients suffered from grade 2 rhinorrhagia after the first dose and had to give up the therapy.Twenty-one patients received the full dose of bevacizumab and showed improvement in clinical signs and symptoms.The MoCA score after treatment was significantly higher than that before treatment (t =3.166,P ＜ 0.05).MRI T2-weighted image showed that the volume of brain edema was decreased by (53.9 ± 22.13)％ on average (Z =-5.645,P ＜0.05).One patient showed mild exacerbation of the extent of focus on MRI after the second cycle therapy but still showed significant improvement at the end of four cycles.Of the 21 cases that successfully finished the whole treatment,one suffered from grade 2 rash and one had mild intracranial hemorrhage,however,no grade 3 to 5 adverse reactions were observed.Conclusions Bevacizumab monotherapy may have a rapid and safe therapeutic effect on radiation necrosis.