The correlations between psychological distress, cognitive impairment and quality of life in patients with brain metastases after whole-brain radiotherapy.

BACKGROUND: Psychological distress and cognitive impairment are highly prevalent among patients with brain metastases after whole-brain radiotherapy (WBRT). Our purpose was to evaluate the correlations between psychological distress, cognitive impairment and quality of life in patients with brain metastases after WBRT. METHODS: Seventy-one patients with brain metastasis treated with WBRT were enrolled in this study and were investigated with several scales, including the Montreal Cognitive Assessment Scale (MoCA), the Functional Assessment of Cancer Therapy-Cognitive Function version 3 (FACT-Cog, version 3), the Functional Assessment of Cancer Therapy-Brain Module version 4 (FACT-Br, version 4) and the Psychological Distress Thermometer (DT), before and after WBRT. RESULTS: The MoCA, FACT-Cog and FACT-Br scores in patients with brain metastases were significantly decreased after WBRT compared with before WBRT (z = - 7.106, - 6.933 and - 6.250, respectively, P < 0.001), while the DT scores were significantly increased (z = 6.613, P < 0.001). There was an obvious negative correlation between the DT score and the FACT-Cog score (r = - 0.660, P < 0.001), a significant negative correlation between the DT score and the FACT-Br score (r = - 0.833, P < 0.001), and an obvious positive correlation between the FACT-Cog score and the FACT-Br score (r = 0.603, P < 0.001). These results suggest that WBRT can cause cognitive impairment in patients with brain metastases, increase their psychological distress and reduce their quality of life (QOL). CONCLUSION: After receiving WBRT, the cognitive function and QOL of patients with brain metastases were decreased, while psychological distress increased. The cognitive impairment and the decline of QOL after WBRT are associated with increased psychological distress, and that the decline of QOL is associated with cognitive impairment of patients.

Managing Central Nervous System Spread of Lung Cancer: The State of the Art.

Brain metastases (BrM) are common in both non-small-cell lung cancer and small-cell lung cancer. Substantial progress in BrM management has occurred in the past decade related to advances in both radiation and medical oncology. Recent and ongoing radiation trials have focused on increasing the candidacy for focal therapy of BrM with stereotactic radiosurgery; reducing the toxicity and improving patient selection for whole brain radiotherapy; and, in small-cell lung cancer, evaluating brain magnetic resonance imaging surveillance without prophylactic cranial irradiation, hippocampal avoidance in prophylactic cranial irradiation and whole brain radiotherapy, and the role of upfront stereotactic radiosurgery for BrM. In medical oncology, the development of multiple tyrosine kinase inhibitors with encouraging CNS activity and emerging data on the CNS activity of immune checkpoint inhibitors in some patients have opened the door to novel systemic and multidisciplinary treatment strategies for the management of BrM. Future research will focus on more robust characterizations of the CNS activity of targeted therapy and immunotherapies, as well as optimal integration and patient selection for multidisciplinary strategies involving CNS-active drugs, radiation therapy, and CNS surveillance.

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique.

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study.

Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyse retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes, are factors that significantly influence patient survival.

Antecedentes: La radioterapia holocraneal (WBRT) y la radiocirugía estereotáctica (SRS) son dos modalidades de tratamiento comúnmente empleados para el tratamiento de las metástasis cerebrales (BMs). Objetivo: El propósito de este estudio es analizar de forma retrospectiva el control local y la supervivencia de los pacientes con BMs de cáncer de mama (BC) tratados mediante radiocirugía empleando arcoterapia volumétrica modulada (VMAT-RS). Métodos: Se analizaron 18 pacientes con 41 BMs de BC tratados mediante VMAT-RS. Se clasificaron según el subtipo molecular de BC y el GPA (Graded Prognostic Assessment) modificado de cáncer de mama. Los pacientes presentaron de 1-4 BMs, las cuales fueron tratadas con 5 arcos VMAT no coplanares. Se analizó la distribución espacial de las BMs, la influencia del status del receptor en la localización de las lesiones y la supervivencia evaluada mediante el modelo de Kaplan-Meier. Resultados: La mediana del tiempo de supervivencia (MST) fue de 19.7 meses. Se hallaron diferencias estadísticamente significativas en el MST según el índice de Karnofsky (p= 0.02) y el status de HER2 (p= 0.004), siendo más prolongado en las pacientes HER2+. Por último, nuestros resultados mostraron que el cerebelo es el lugar predominante de las BMs de cáncer de mama, y también sugirieron que las BMs HER2+ presentaban una predilección por algunas estructuras de la circulación posterior, como el cerebelo, el tronco cerebral y los lóbulos occipitales (p= 0.048). Conclusiones: VMAT-RS es una técnica con una supervivencia global comparable a otras técnicas de radiocirugía. La situación basal en el momento del tratamiento, el GPA modificado de cáncer de mama así como los subtipos moleculares de cáncer de mama, son factores que influyen de forma significativa en la supervivencia de los pacientes.

Septum Pellucidum Cavernoma: A Case Report and Anatomical Consideration of an Extremely Rare Lesion.

Cavernous angiomas (cavernomas) are vascular malformations of the brain characterized by abnormal capillaries. Ventricular cavernomas are considered rare; however, an extremely unusual topography is the septum pellucidum, with only five reported cases in the English literature. These malformations may rupture and cause very large hematomas, leading to neurological impairment. Cavernomas can be familial or sporadic; additionally, these may appear following brain radiotherapy in extremely rare cases. Herein, we present an extremely rare and unique case of a septum pellucidum cavernoma that occurred in a young male who had previously undergone brain radiotherapy in childhood due to acute lymphoid leukemia. Following presentation, he was diagnosed with generalized seizures. The cavernoma was resected via an anterior interhemispheric transcallosal approach, following which the patient remained stable without neurological sequelae. To conclude, ventricular cavernomas are rare lesions, especially when located at the septum pellucidum, thus constitute a challenging neurosurgical approach.

Effect of photobiomodulation on the severity of oral mucositis and molecular changes in head and neck cancer patients undergoing radiotherapy: a study protocol for a cost-effectiveness randomized clinical trial.

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.

Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation.

BACKGROUND: Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) techniques have been developed to reduce radiation damage to the hippocampus. An inter-observer hippocampus delineation analysis was performed and the influence of the delineation variability on dose to the hippocampus was studied. MATERIALS AND METHODS: For five patients, seven observers delineated both hippocampi on brain MRI. The intra-class correlation (ICC) with absolute agreement and the generalized conformity index (CIgen) were computed. Median surfaces over all observers' delineations were created for each patient and regional outlining differences were analysed. HA-PCI dose plans were made from the median surfaces and we investigated whether dose constraints in the hippocampus could be met for all delineations. RESULTS: The ICC for the left and right hippocampus was 0.56 and 0.69, respectively, while the CIgen ranged from 0.55 to 0.70. The posterior and anterior-medial hippocampal regions had most variation with SDs ranging from approximately 1 to 2.5 mm. The mean dose (Dmean) constraint was met for all delineations, but for the dose received by 1% of the hippocampal volume (D1%) violations were observed. CONCLUSION: The relatively low ICC and CIgen indicate that delineation variability among observers for both left and right hippocampus was large. The posterior and anterior-medial border have the largest delineation inaccuracy. The hippocampus Dmean constraint was not violated.

Delayed tongue necrosis simultaneous with bilateral osteoradionecrosis of the jaw secondary to head and neck irradiation.

We present a rare case of massive tongue necrosis occurring simultaneously with bilateral osteoradionecrosis (ORN) of the jaw in a patient with a history of treatment, including surgery and postoperative radiotherapy, for a retromolar trigone carcinoma 8 years earlier. There is a distinct possibility that the extractions and administration of local anesthesia with a vasoconstrictor contributed to the onset of ORN; together, these events may have influenced the blood supply to the tongue. A glossectomy was performed after hyperbaric oxygen therapy. One month after the surgical procedure, the patient responded satisfactorily to the treatment, showing significant improvement in speech and oral food intake, as well as significant decrease in lingual pain. Although the simultaneous occurrence of these oral complications is rare, the practitioner must be aware of the factors that instigate ORN and compromise vasculature as well as the clinical signs of tongue necrosis. Additionally, the possibility of tongue necrosis secondary to irradiation of the head and neck should be taken into consideration when an irradiated patient undergoes tooth extractions under local anesthesia with agents containing epinephrine.

Ameliorative effect of black grape juice on systemic alterations and mandibular osteoradionecrosis induced by whole brain irradiation in rats.

PURPOSE: Whole brain irradiation (WBI) causes a variety of secondary side-effects including anorexia and bone necrosis. We evaluated the radiomodifying effect of black grape juice (BGJ) on WBI alterations in rats measuring food and water intake, body weight, hemogram, and morphological and histological mandibular parameters. MATERIALS AND METHODS: Forty male rats (200-250 g) were exposed to eight sessions of cranial X-ray irradiation. The total dose absorbed was 32 Gy delivered over 2 weeks. Four groups were defined: (i) NG: non-irradiated, glucose and fructose solution-supplemented (GFS); (ii) NJ: non-irradiated, BGJ-supplemented; (iii) RG: irradiated, GFS-supplemented; and (iv) RJ: irradiated, BGJ-supplemented. Rats received daily BGJ or GFS dosing by gavage starting 4 days before, continuing during, and ending 4 days after WBI. RESULTS: RJ rats ingested more food and water and showed less body weight loss than RG rats during the irradiation period. Forty days after WBI, irradiated animals started losing weight again compared with controls as a consequence of masticatory hypofunction by mandibular osteoradionecrosis (ORN). Osteoclastic activity and inflammation were apparent in RG rat mandibles. BGJ was able to attenuate the severity of ORN as well as to improve white and red blood cell counts. CONCLUSIONS: Fractionated whole brain irradiation induces mandibular changes that interfere with normal feeding. BGJ can be used to mitigate systemic side-effects of brain irradiation and ORN.

CNS Masson Tumors: Frequent Association With Therapeutic Radiation.

Masson tumor (MT, papillary endothelial hyperplasia) is an exaggerated form of thrombus reorganization rarely occurring in the central nervous system (CNS), where it presents as a mass or hemorrhage in parenchyma, meninges, or venous sinuses. MT is subclassified as type 1 arising within a histologically normal vessel, type 2 associated with a ruptured vascular malformation, and extravascular. Limited reports of CNS MT after radiosurgery, or especially external radiation therapy, have emerged. We searched our databases for cases reported from 2008 to present. Nine cases were identified, 6 of which were associated with receipt of therapeutic radiation for known lesions, with intervals of 1 to 25+ years to MT development (4 neoplasms=external beam radiation; 1 neoplasm=external beam radiation+radiosurgery, 1 arteriovenous malformation=radiosurgery). MTs were coassociated with radiation-induced vascular malformations (1 cavernoma-like, 1 massive) only in 2 of 6 irradiated patients, whereas the other 4 had MTs only. The 3 MTs in nonirradiated patients were extravascular, with 1 spontaneously developing in a hemangioblastoma. Seven of 9 MTs were intracerebral, 1 was within the spinal cord, and 1 was subdural. Papillary MT architecture was best appreciated by CD31 or CD34 immunohistochemistry, although ERG verified the endothelial monolayer population. Most CNS MTs at our institution have arisen in patients who have received therapeutic cranial radiation, many of whom received only external beam radiation. Although MTs could conceivably represent early, severe phases in radiation-induced cavernoma development, most were not found coassociated with the latter. This study further extends our knowledge of types of radiation-induced CNS vascular abnormalities.

Subcutaneous adipose tissue plays a beneficial effect on subclinical atherosclerosis in young survivors of acute lymphocytic leukemia.

PURPOSE: The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis. RESULTS: Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT (P=0.029), diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while negatively related to SAT (P=0.007). CONCLUSION: In young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.

Is high-dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high-dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA plan with multiple noncoplanar arcs, (2) a high-dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high-dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high-dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V12Gy) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for complex cases.

The incidence of second brain tumors related to cranial irradiation.

Secondary brain tumor (SBT) is a devastating complication of cranial irradiation (CI). We reviewed the literature to determine the incidence of SBT as related to specific radiation therapy (RT) treatment modalities. The relative risk of radiation-associated SBT after conventional and conformal RT is well established and ranges from 5.65 to 10.9; latent time to develop second tumor ranges from 5.8 to 22.4 years, depending on radiation dose and primary disease. Theories and dosimetric models suggest that intensity-modulated radiation therapy may result in an increased risk of SBT, but clinical evidence is limited. The incidence of stereotactic radiosurgery-related SBT is low. Initial data suggest that no increased risk from proton therapy and dosimetric models predict a lower incidence of SBT compared with photons. In conclusion, the incidence of SBT related to CI is low. Longer follow-up is needed to clarify the impact of intensity-modulated radiation therapy, proton therapy and other developing technologies.

Radiation injury to the normal brain measured by 3D-echo-planar spectroscopic imaging and diffusion tensor imaging: initial experience.

BACKGROUND AND PURPOSE: Whole brain radiation therapy (WBRT) may cause cognitive and neuropsychological impairment and hence objective assessment of adverse effects of radiation may be valuable to plan therapy. The purpose of our study was to determine the potential of echo planar spectroscopic imaging (EPSI) and diffusion tensor imaging (DTI) in detecting subacute radiation induced injury to the normal brain. MATERIALS AND METHODS: Four patients with brain metastases and three patients with lung cancer underwent cranial irradiation. These patients were subjected to 3D-EPSI and DTI at two time points (pre-radiation, and 1 month post-irradiation). Parametric maps of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), mean diffusivity (MD), and fractional anisotropy (FA) were generated and co-registered to post-contrast T1-weighted images. Normal appearing gray-matter and white-matter regions were compared between the two time points to assess sub-acute effects of radiation using independent sample t-tests. RESULTS: Significantly increased MD (P = .02), Cho/Cr (P = .02) and a trend towards a decrease in NAA/Cr (P = .06) was observed from the hippocampus. Significant decrease in FA (P = .02) from the centrum-semiovale and a significant increase in MD (P = .04) and Cho/Cr (P = .02) from genu of corpus-callosum was also observed. CONCLUSIONS: Our preliminary findings suggest that 3D-EPSI and DTI may provide quantitative measures of radiation induced injury to the normal brain.

Focal cranial hyperostosis from meningioma: a complication from previous radiation treatment for childhood T-cell acute lymphoblastic leukemia.

Nearly 75% of childhood cancer survivors will experience an adverse late effect from previous therapy. In patients previously treated with cranial irradiation, the late effect can manifest as secondary central nervous system tumors. Presented is a case of a 20 year man with a history of T-cell lymphoblastic leukemia diagnosed at age 22 months, treated with chemotherapy and cranial irradiation. He had developed increasing prominence of the top of his head over several months. Plain radiograph showed frontal calvarium thickening with focal "hair-on-end" periosteal reaction. Magnetic resonance imaging revealed an enhancing dural-based mass with transcalvarial extension, confirmed after resection to be meningioma (World Health Organization Grade I). This case illustrates an atypical presentation of a late effect of childhood cancer treatment and highlights the need to be informed about prior treatments received and potential attendant complications.

Neuropsychological assessment before and after radiotherapy in a child with an intracranial tumor: case report / Avaliação neuropsicológica antes e após radioterapia em uma criança com tumor intracraniano: relato de caso

INTRODUCTION: Brain tumors are the most common solid tumors and the second largest group of neoplasms diagnosed in childhood. Treatment includes surgery, radiotherapy, and chemotherapy. However, radiotherapy can cause complications, e.g., cognitive deficits. CASE DESCRIPTION: We describe the case of a child diagnosed with a brain tumor evaluated before and after radiotherapy to investigate cognitive decline after treatment. The results showed a decline in Intelligence Quotient (IQ) scores and reversal of the predominance of verbal and nonverbal skills. After radiotherapy, the subject showed slowness, academic deficits, and difficulties learning new information. COMMENTS: Even though the post-treatment evaluation showed scores compatible with the average, comparison between pre- and post-treatment evaluations demonstrated the impact of radiotherapy on the subject's cognitive profile. These results highlight the importance of evaluating patients who undergo radiotherapy before and after treatment and understanding neuropsychological scores associated with the subjects' complaints (AU)

INTRODUÇÃO: Tumores cerebrais são os tumores sólidos mais comuns e o segundo maior grupo de neoplasias diagnosticadas na infância. O tratamento inclui cirurgia, radioterapia e quimioterapia. No entanto, a radioterapia pode causar complicações, como, por exemplo, déficits cognitivos. DESCRIÇÃO DO CASO: Descrevemos o caso de uma criança diagnosticada com tumor cerebral e avaliada antes e após tratamento com radioterapia para investigar declínio cognitivo pós-tratamento. Os resultados demonstraram um declínio nos escores de Quociente de Inteligência (QI) e uma reversão da predominância em habilidades verbais e não verbais. Após a radioterapia, o sujeito demonstrou lentidão, déficits acadêmicos e dificuldade para aprender novas informações. COMENTÁRIO: Embora a avaliação pós-tratamento tenha mostrado escores compatíveis com a média, a comparação entre as avaliações pré e pós-tratamento evidenciaram o impacto da radioterapia sobre o perfil cognitivo do paciente. Esses resultados salientam a importância de avaliar pacientes tratados com radioterapia antes e após o tratamento e de entender os escores neuropsicológicos associados às queixas dos pacientes (AU)

Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases.

BACKGROUND AND PURPOSE: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. METHODS: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. RESULTS: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. CONCLUSION: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.