RESUMO
BACKGROUND: Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment. METHODS: We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT. RESULTS: A total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0-2, 3, and 4-5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001). CONCLUSIONS: Male sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Cuidados Paliativos , Radiocirurgia , Humanos , Masculino , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/mortalidade , Radiocirurgia/métodos , Idoso , Cuidados Paliativos/métodos , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Irradiação Craniana/métodos , Adulto , Avaliação de Estado de KarnofskyRESUMO
BACKGROUND AND PURPOSE: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). METHODS: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. RESULTS: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. CONCLUSION: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Neoplasias Pulmonares , Imageamento por Ressonância Magnética , Terapia de Salvação , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Irradiação Craniana/métodos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Estudos Retrospectivos , Estadiamento de Neoplasias , Adulto , Quimiorradioterapia/métodosRESUMO
Background: The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. Method: In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. Result: A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. Conclusion: WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.
Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Irradiação Craniana , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irradiação Craniana/métodos , Adulto , Idoso , Radioterapia de Intensidade Modulada/métodos , Hipofracionamento da Dose de Radiação , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases. PATIENTS AND METHODS: The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed. RESULTS: Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis. CONCLUSION: The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor.
Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Prognóstico , Irradiação Craniana/métodos , Terapia Combinada , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. METHODS: Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. RESULTS: Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.
Assuntos
Neoplasias Encefálicas , Disfunção Cognitiva , Irradiação Craniana , Hipocampo , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Idoso , Estudos Prospectivos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Disfunção Cognitiva/etiologia , Irradiação Craniana/métodos , Irradiação Craniana/efeitos adversos , Hipocampo/patologia , Hipocampo/efeitos da radiação , Hipocampo/diagnóstico por imagem , Aprendizagem Verbal , Adulto , China , Imageamento por Ressonância MagnéticaRESUMO
RATIONALE: Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. PATIENT CONCERNS: Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. DIAGNOSIS: Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. INTERVENTION AND OUTCOMES: Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. LESSONS: Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Hipocampo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Hipocampo/efeitos da radiação , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND AND AIM: Audit of brain metastasis (BM) patients treated with radiation therapy (RT) in a tertiary cancer center from South India was carried out to assess the incidence of BM by site with a specific focus on their primary origin, with an aim to evaluate the relationship between the primary site and the site of metastases, pattern of care, and RT over the years. MATERIALS AND METHODS: All consecutive BM patients who received RT with whole-brain radiation therapy (WBRT), hippocampal avoidance WBRT (HA-WBRT), and radiosurgery SRS between 2007 and 2022 after radiologic confirmation of a known case of malignancy or histology-proven BM were audited. RESULTS: From January 2007 to December 2022, hospital information system (HIS)-identified 778 patients with BM treated with RT were audited. Incidence of BM was 0.64% in 2008 and over the years, it had increased to 0.89% in 2020, 0.93% in 2021, and 1.24% in 2022. Usage of SRS was almost nil in 2007, whereas in 2022, it was 40%. Also, 593 (76%) patients were treated with WBRT, 157 (20%) with SRS, and only 23 (3%) received HA-WBRT. Lung and breast cancers (40%) were the most common primary, and among rare primary tumors were those of larynx (two), tonsil (one), tongue (three), pancreas (one), and blood disorders (two). Lung primary presented with frontal lesion in 51%, parietal lesion in 43%, cerebellar lesion in 38%, and temporal lesion in 33% of cases. CONCLUSIONS: Audit of BM in the Indian population suggests a shift in treatment paradigm from WBRT to SRS as a primary modality in oligo-brain metastasis with a good performance status. This audit provides us information regarding geographic variation in presentation and primary site.
Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/radioterapia , Índia , Feminino , Masculino , Radiocirurgia/métodos , Pessoa de Meia-Idade , Adulto , Irradiação Craniana , Idoso , Incidência , Auditoria MédicaRESUMO
Radiation-induced cognitive impairment has recently fueled scientific interest with an increasing prevalence of cancer patients requiring whole brain irradiation (WBI) in their treatment algorithm. Saxagliptin (SAXA), a dipeptidyl peptidase-IV (DPP-IV) inhibitor, has exhibited competent neuroprotective effects against varied neurodegenerative disorders. Hence, this study aimed at examining the efficacy of SAXA in alleviating WBI-induced cognitive deficits. Male Sprague Dawley rats were distributed into control group, WBI group exposed to 20 Gy Ï-radiation, SAXA group treated for three weeks with SAXA (10 mg/kg. orally, once daily), and WBI/SAXA group exposed to 20 Gy Ï-radiation then treated with SAXA (10 mg/kg. orally, once daily). SAXA effectively reversed memory deterioration and motor dysfunction induced by 20 Gy WBI during behavioural tests and preserved normal histological architecture of the hippocampal tissues of irradiated rats. Mechanistically, SAXA inhibited WBI-induced hippocampal oxidative stress via decreasing lipid peroxidation while restoring catalase antioxidant activity. Moreover, SAXA abrogated radiation-induced hippocampal neuronal apoptosis through downregulating proapoptotic Bcl-2 Associated X-protein (Bax) and upregulating antiapoptotic B-cell lymphoma 2 (Bcl-2) expressions and eventually diminishing expression of cleaved caspase 3. Furthermore, SAXA boosted hippocampal neurogenesis by upregulating brain-derived neurotrophic factor (BDNF) expression. These valuable neuroprotective capabilities of SAXA were linked to activating protein kinase B (Akt), and cAMP-response element-binding protein (CREB) along with elevating the expression of sirtuin 1 (SIRT-1). SAXA successfully mitigated cognitive dysfunction triggered by WBI, attenuated oxidative injury, and neuronal apoptosis, and enhanced neurogenesis through switching on Akt/CREB/BDNF/SIRT-1 signaling axes. Such fruitful neurorestorative effects of SAXA provide an innovative therapeutic strategy for improving the cognitive capacity of cancer patients exposed to radiotherapy.
Assuntos
Adamantano , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Dipeptídeos , Fármacos Neuroprotetores , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1 , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Sirtuína 1/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dipeptídeos/farmacologia , Ratos , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Adamantano/análogos & derivados , Adamantano/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/efeitos da radiação , Hipocampo/metabolismo , Hipocampo/patologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Irradiação Craniana/efeitos adversos , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/efeitos da radiaçãoRESUMO
BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.
Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Receptores ErbB/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Irradiação Craniana/métodos , Mutação , Término Precoce de Ensaios Clínicos , Adulto , Intervalo Livre de Progressão , Idoso de 80 Anos ou maisRESUMO
PURPOSE: To identify dosimetric predictive factors of sensorineural hearing loss (SNHL) in children after cranial radiation therapy (RT) in a single institution using dosimetric data from the French National Registry PediaRT. METHODS AND MATERIALS: Complete audiological follow-up data were available for 44 children treated with cranial RT between 2014 and 2021 at our institution. The median age at the time of RT initiation was 9 years (range: 2-17 years). No children presented with hearing loss prior to treatment. SNHL was defined as a Chang ototoxicity grade ≥ 1a or higher. RESULTS: Median audiometric follow-up duration was 51 months. Seven children (16 %) developed SNHL with a median time to occurrence of 33 months (range, 18-46 months). The estimated SNHL cumulative rate at 2 years post-RT was 4,5% ± 3,1% and at 5 years was 21 % ± 7.2 %. Multiple Cox regression models showed that the association of the age at radiotherapy and the dosimetric values to the inner ear canal and cochlea were the most significant predictive factors of SNHL occurrence. No child who received less than 35 Gy on average to both cochleae (n = 26) suffered from SNHL, whereas the 5-year SNHL cumulative incidence for the children who received greater than or equal to 35 Gy on average to either cochlea (n = 18) was 51.8 % ± 15.1 %. CONCLUSION: Doses received by the inner ear canal and cochlea, associated with the age at RT initiation, are the main predictive factors for radiation-induced SNHL. A median dose to either cochlea over 35 Gy significantly increases the risk of SNHL and justify close audiometric monitoring to detect and equip hearing loss at an early stage.
Assuntos
Irradiação Craniana , Perda Auditiva Neurossensorial , Sistema de Registros , Humanos , Criança , Pré-Escolar , Masculino , Adolescente , Feminino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/epidemiologia , França , Irradiação Craniana/efeitos adversos , Dosagem Radioterapêutica , Neoplasias Encefálicas/radioterapia , SeguimentosRESUMO
BACKGROUND AND PURPOSE: In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. MATERIALS AND METHODS: MEDLINE, Embase, and Scopus were searched with the terms "Hippocampus", "Brain Neoplasms", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. RESULTS: Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 - 27 %) and 9.2 % (3 - 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 - 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). CONCLUSION: The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Hipocampo , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Hipocampo/efeitos da radiação , Hipocampo/patologia , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Incidência , Tratamentos com Preservação do Órgão/métodosRESUMO
OBJECTIVE: Moyamoya arteriopathy can develop in patients with brain tumors, particularly when associated with neurofibromatosis type 1 (NF1) or cranial irradiation. The present study aimed to analyze the clinical outcomes of moyamoya after brain tumor treatment and elucidate the effect of revascularization on brain tumors. METHODS: The authors retrospectively reviewed clinical and radiographic findings in 27 patients with brain tumors who developed moyamoya requiring revascularization surgery between January 1985 and June 2017 at a single institution. The long-term clinical and neuroimaging-based outcomes were analyzed. RESULTS: Among 27 patients, 22 patients underwent radiotherapy, and 12 patients had NF1. The mean ages at diagnosis of brain tumors and moyamoya were 4.4 years and 10.3 years, respectively. The mean interval between radiotherapy and moyamoya diagnosis was 4.0 years. The mean follow-up period after revascularization surgery was 8.5 years. Among 46 affected hemispheres in 27 patients, the patients who underwent radiotherapy (30 hemispheres in 22 patients) had a higher incidence of Suzuki stage 5 or 6 (20% [6/30] vs 0% [0/8]) and infarction (63.6% [14/22] vs 0% [0/5]) compared with patients without radiotherapy (8 hemispheres in 5 patients). After revascularization, stroke occurred in 4 patients, and 6 hemispheres showed Matsushima grade C, all of which occurred in patients with a history of radiotherapy. The residual brain tumors progressed in 4 of 21 patients (19%) after revascularization, comparable to the progression rates of brain tumors without revascularization in previous literature. CONCLUSIONS: Patients with brain tumors can develop moyamoya that exhibits characteristic clinical and radiographic features of idiopathic MMD. Moyamoya associated with cranial irradiation has a higher incidence of stroke with less capacity for revascularization, requiring thorough evaluations and timely treatment. Revascularization does not appear to have any effect on the progression of existing brain tumors.
Assuntos
Neoplasias Encefálicas , Revascularização Cerebral , Doença de Moyamoya , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/complicações , Doença de Moyamoya/cirurgia , Masculino , Feminino , Criança , Estudos Retrospectivos , Pré-Escolar , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Revascularização Cerebral/métodos , Adolescente , Lactente , Resultado do Tratamento , Seguimentos , Irradiação Craniana/efeitos adversos , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Angiografia CerebralRESUMO
BACKGROUND/AIM: Blood tests, such as those included in the validated LabBM score (laboratory parameters in patients with brain metastases) predict survival after treatment of brain metastases. The model incorporates five test results [serum lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin, platelets and hemoglobin]. However, many other abnormalities, albeit less well-studied, may be present in patients with metastatic cancer. Therefore, this study aimed to examine a broader range of blood tests. PATIENTS AND METHODS: This retrospective analysis included 132 patients managed with primary whole-brain radiotherapy. Additional tests, such as liver enzymes, lymphopenia, hyponatremia, and others, were also conducted. Extracranial disease extent was also analyzed. RESULTS: According to forward conditional Cox regression analyses, blood tests (albumin, hemoglobin, lymphopenia, hyponatremia) in conjunction with the number of organs affected by extracranial metastases (at least two, such as liver and bones) provided the best prognostic model. Based on these parameters, at least four prognostic strata can be assigned (median survival between 4.6 and <1 months, p=0.0001). CONCLUSION: This initial pilot study in a limited number of patients suggests that numerous blood test results may contribute to further refinement of existing prognostic models, and provides justification for additional large-scale studies.
Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Adulto , Irradiação Craniana/métodos , Testes Hematológicos , Idoso de 80 Anos ou mais , Projetos PilotoRESUMO
Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20â¯Gy X-ray cranial irradiation (5â¯Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.
Assuntos
Irradiação Craniana , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-kit , Espermatogênese , Animais , Masculino , Espermatogênese/efeitos da radiação , Camundongos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estresse Oxidativo/efeitos da radiação , Irradiação Craniana/efeitos adversos , Testículo/efeitos da radiação , Testículo/patologia , Transdução de Sinais/efeitos da radiação , Fator de Células-Tronco/metabolismo , InflamaçãoRESUMO
This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.
Assuntos
Neoplasias Encefálicas , Hipocampo , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Hipocampo/efeitos da radiação , Hipocampo/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Masculino , Órgãos em Risco/efeitos da radiação , Feminino , Pessoa de Meia-Idade , Adulto , Dosagem Radioterapêutica , Estudos Retrospectivos , Idoso , Tratamentos com Preservação do Órgão/métodos , Irradiação Craniana/métodosRESUMO
Cranial irradiation used to control brain malignancies invariably leads to progressive and debilitating declines in cognition. Clinical efforts implementing hippocampal avoidance and NMDAR antagonism, have sought to minimize dose to radiosensitive neurogenic regions while normalizing excitatory/inhibitory (E/I) tone. Results of these trials have yielded only marginal benefits to cognition, prompting current studies to evaluate the potential of systemic extracellular vesicle (EV) therapy to restore neurocognitive functionality in the irradiated brain. Here we tested the hypothesis that EVs derived from inhibitory but not excitatory neuronal cultures would prove beneficial to cognition and associated pathology. Rats subjected to a clinically relevant, fractionated cranial irradiation paradigm were given multiple injections of either GABAergic- or glutamatergic-derived EV and subjected to behavioral testing. Rats treated with GABAergic but not glutamatergic EVs showed significant improvements on hippocampal- and cortical-dependent behavioral tasks. While each treatment enhanced levels of the neurotrophic factors BDNF and GDNF, only GABAergic EVs preserved granule cell neuron dendritic spine density. Additional studies conducted with GABAergic EVs, confirmed significant benefits on amygdala-dependent behavior and modest changes in synaptic plasticity as measured by long-term potentiation. These data point to a potentially more efficacious approach for resolving radiation-induced neurological deficits, possibly through a mechanism able to restore homeostatic E/I balance.
Assuntos
Irradiação Craniana , Vesículas Extracelulares , Neurônios GABAérgicos , Animais , Vesículas Extracelulares/metabolismo , Ratos , Irradiação Craniana/efeitos adversos , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos da radiação , Masculino , Hipocampo/efeitos da radiação , Hipocampo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neurônios/efeitos da radiação , Neurônios/metabolismo , Ácido Glutâmico/metabolismo , Plasticidade Neuronal/efeitos da radiação , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Comportamento Animal/efeitos da radiaçãoRESUMO
BACKGROUND: Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study aimed to develop and evaluate normal-tissue complication probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year, and 2-year Neurocognitive Decline (ND) postradiotherapy. METHODS: A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included. Controlled oral word association test, Hopkins verbal learning test-revised, and trail making test were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modeling. Clinical, dose-volume and combined models were constructed and internally tested in terms of discrimination (area under the curve, AUC), calibration (mean absolute error, MAE), and net benefit. RESULTS: Fifty percent, 44.5%, and 42.7% of the patients developed ND at 6-month, 1-year, and 2-year time points, respectively. The following predictors were included in the combined model for 6-month ND: age at radiotherapyâ >â 56 years (ORâ =â 5.71), overweight (ORâ =â 0.49), obesity (ORâ =â 0.35), chemotherapy (ORâ =â 2.23), brain V20 Gyâ ≥â 20% (ORâ =â 3.53), brainstem volumeâ ≥â 26 cc (ORâ =â 0.39), and hypothalamus volumeâ ≥â 0.5 cc (ORâ =â 0.4). Decision curve analysis showed that the combined models had the highest net benefits at 6-month (AUCâ =â 0.79, MAEâ =â 0.021), 1-year (AUCâ =â 0.72, MAEâ =â 0.027), and 2-year (AUCâ =â 0.69, MAEâ =â 0.038) time points. CONCLUSIONS: The proposed NTCP models use easy-to-obtain predictors to identify patients at high risk of ND after brain RT. These models can potentially provide a base for RT-related decisions and post-therapy neurocognitive rehabilitation interventions.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Humanos , Masculino , Feminino , Neoplasias Encefálicas/radioterapia , Pessoa de Meia-Idade , Irradiação Craniana/efeitos adversos , Adulto , Idoso , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Seguimentos , Prognóstico , Transtornos Neurocognitivos/etiologia , Disfunção Cognitiva/etiologia , Fatores de RiscoRESUMO
OBJECTIVES: For inpatients with metastatic intracranial disease burden exceeding established guidelines for stereotactic radiosurgery (SRS), the standard of care involves whole brain radiation therapy (WBRT), typically administered as a 2-week course of treatment with biologically effective dose (BED) of 60 Gy. However, shorter course WBRT provides theoretical advantages in quality of life and decreasing systemic therapy delay. This retrospective study evaluates our early experience with BED-comparable short-course WBRT (23 Gy in 5 fractions; BED=58.3 Gy) for metastatic intracranial disease. METHODS: Over a recent 2-month timeframe, 3 inpatients with intracranial disease burden exceeding SRS guidelines were administered BED-comparable short-course WBRT. Due to the high intracranial disease burden, 23 Gy was chosen over 20 Gy for 5-fraction WBRT due to the desire to optimally mimic the durability of the classic 30 Gy in 10 fraction treatment regimen. RESULTS: The mean age at treatment was 65.7 years, the mean Karnofsky Performance Status (KPS) was 60, and the mean number of intracranial metastases was 20.3. The mean duration between inpatient Radiation Oncology consultation and the start of WBRT (following CT radiation therapy simulation) was 6.7 days. All patients completed WBRT no later than 2 weeks from the initial inpatient consultation. CONCLUSIONS: For inpatients with intracranial metastatic disease burden exceeding established SRS guidelines, BED-comparable short-course WBRT administered to 23 Gy in 5 fractions (4.6 Gy/fraction) is safe and efficacious. Given previous literature indicating that nearly half of the patients prescribed traditional 2-week WBRT die without completing treatment, BED-comparable WBRT represents an attractive and promising WBRT alternative in this patient population.
Assuntos
Neoplasias Encefálicas , Irradiação Craniana , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Idoso , Irradiação Craniana/métodos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Eficiência Biológica Relativa , Fracionamento da Dose de Radiação , Dosagem Radioterapêutica , Radiocirurgia/métodosRESUMO
PURPOSE: We aimed to demonstrate the clinical feasibility and safety of simulation-free hippocampal avoidance whole brain radiation therapy (HA-WBRT) in a pilot study (National Clinical Trial 05096286). METHODS AND MATERIALS: Ten HA-WBRT candidates were enrolled for treatment on a commercially available computed tomography (CT)-guided linear accelerator with online adaptive capabilities. Planning structures were contoured on patient-specific diagnostic magnetic resonance imaging (MRI), which were registered to a CT of similar head shape, obtained from an atlas-based database (AB-CT). These patient-specific diagnostic MRI and AB-CT data sets were used for preplan calculation, using NRG-CC001 constraints. At first fraction, AB-CTs were used as primary data sets and deformed to patient-specific cone beam CTs (CBCT) to give patient-matched density information. Brain, ventricle, and brain stem contours were matched through rigid translation and rotation to the corresponding anatomy on CBCT. Lens, optic nerve, and brain contours were manually edited based on CBCT visualization. Preplans were then reoptimized through online adaptation to create final, simulation-free plans, which were used if they met all objectives. Workflow tasks were timed. In addition, patients underwent CT-simulation to create immobilization devices and for prospective dosimetric comparison of simulation-free and simulation-based plans. RESULTS: Median time from MRI importation to completion of "preplan" was 1 weekday (range, 1-4). Median on-table workflow duration was 41 minutes (range, 34-70). NRG-CC001 constraints were achieved by 90% of the simulation-free plans. One patient's simulation-free plan failed a planning target volume coverage objective (89% instead of 90% coverage); this was deemed acceptable for first-fraction delivery, with an offline replan used for subsequent fractions. Both simulation-free and simulation CT-based plans otherwise met constraints, without clinically meaningful differences. CONCLUSIONS: Simulation-free HA-WBRT using online adaptive radiation therapy is feasible, safe, and results in dosimetrically comparable treatment plans to simulation CT-based workflows while providing convenience and time savings for patients.
Assuntos
Neoplasias Encefálicas , Tomografia Computadorizada de Feixe Cônico , Irradiação Craniana , Estudos de Viabilidade , Hipocampo , Imageamento por Ressonância Magnética , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Humanos , Projetos Piloto , Planejamento da Radioterapia Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Irradiação Craniana/métodos , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Radioterapia Guiada por Imagem/métodos , Tratamentos com Preservação do Órgão/métodos , MasculinoRESUMO
BACKGROUND AND PURPOSE: Multiple studies demonstrated hypothalamic-pituitary dysfunction in survivors of pediatric brain tumors. However, few studies investigated the trajectories of pituitary height in these patients and their associations with pituitary function. We aimed to evaluate longitudinal changes of pituitary height in children and adolescents with brain tumors, and their association with endocrine deficiencies. MATERIALS AND METHODS: We conducted a retrospective analysis of 193 pediatric patients (54.9% male) diagnosed with brain tumors from 2002 to 2018, with a minimum of two years of radiological follow-up. Pituitary height was measured using MRI scans at diagnosis and at 2, 5, and 10 years post-diagnosis, with clinical data sourced from patient charts. RESULTS: Average age at diagnosis was 7.6 ± 4.5 years, with a follow-up of 6.1 ± 3.4 years. 52.8% underwent radiotherapy and 37.8% experienced pituitary hormone deficiency. Radiation treatment was a significant predictor of decreased pituitary height at all observed time points (p = 0.016, p < 0.001, p = 0.008, respectively). Additionally, chemotherapy (p = 0.004) or radiotherapy (p = 0.022) history and pituitary height at 10 years (p = 0.047) were predictors of endocrine deficiencies. ANOVA revealed an expected increase in pituitary height over time in pediatric patients, but this growth was significantly impacted by radiation treatment and gender (p for interaction = 0.005 and 0.025, respectively). CONCLUSION: Cranial irradiation in pediatric patients is associated with impairment of the physiologic increase in pituitary size; in turn, decreased pituitary height is associated with endocrine dysfunction. We suggest that pituitary gland should be evaluated on surveillance imaging of pediatric brain tumor survivors, and if small for age, clinical endocrine evaluation should be pursued.