Research Progress on Risk Factors of Brain Metastasis in Non-small Cell Lung Cancer / 中国肺癌杂志

Brain metastasis of non-small cell lung cancer (NSCLC) is a common treatment failure mode, and the median survival time of NSCLC patients with brain metastasis is only 1 mon-2 mon. Prophylactic cranial irradiation (PCI) can delay the occurrence of brain metastasis, but the survival benefits of NSCLC patients are still controversial. It is particularly important to identify the patients who are most likely to benefit from PCI. This article reviews the high risk factors of brain metastasis in NSCLC.
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Small cell bladder cancer: should we consider prophylactic cranial irradiation?

ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

The value of prophylactic cranial irradiation in limited-stage small cell lung cancer: should it always be recommended?

PURPOSE: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. MATERIALS AND METHODS: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. RESULTS: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I–II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I–II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. CONCLUSION: There should be less concern about omitting PCI in patients with comorbidities if they have stage I–II or a CR, with brain metastasis control being comparable to those patients who receive PCI.

Outcome and Prognostic Factors in Pediatric Precursor T-Cell Acute Lymphoblastic Leukemia: A Single-Center Experience / 임상소아혈액종양

BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

Prognostic factors and treatment of pediatric acute lymphoblastic leukemia / 소아과

The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse. Specific high risk subgroups, such as Philadelphia chromosome-positive (Ph+) ALL and infant ALL continue to have significantly lower survival than other ALL patients. The introduction of tyrosine kinase inhibitors into therapy has led to enhanced outcome for Ph+ ALL patients. Infant ALL patients, particularly those with MLL rearrangements, continue to have poor outcome, despite treatment intensification including allogeneic hematopoietic cell transplantation. Relapsed ALL is a leading cause of mortality in pediatric cancer. Recent advances in immunotherapy targeting the CD19 of the ALL blast have shown remarkable efficacy in some of these relapsed and refractory patients. With improved survival, much of the current focus is on decreasing the long-term toxicities of treatment.

Research progress of prophylactic cranial irradiation for locally advanced non-small cell lung cancer / 中华肿瘤杂志

As multi-modality treatments are now able to ensure better local control and a lower rate of extra-cranial metastasis, brain metastasis has become a major concern in locally advanced non-small cell lung cancer (LA-NSCLC). Prophylactic cranial irradiation (PCI) is now a standard treatment for patients with small cell lung cancer (SCLC), it decreases the incidence of brain metastases and increases the survival rate. Despite the relatively high incidence of brain metastases in LA-NSCLC, the role of PCI in patients treated with radical intent has not been established yet. The objective of this systematic review was to establish whether PCI prevents the development of brain metastasis and increases survival in LA-NSCLC patients, the characteristics of the benefit patients, the tolerance and toxicity, the effective dose and timing of PCI. The main concern in this review is to establish the definitive role of PCI in the treatment of locally advanced NSCLC.

Multiple Endocrine Neoplasia Type 1 Presenting with an Invasive Giant Prolactinoma / 대한내과학회지

Pituitary tumors occur in 15-50% of patients with multiple endocrine neoplasia of type 1 (MEN1). To the best of our knowledge, no MEN1 case in which the initial lesion was an invasive giant prolactinoma has been reported from Korea. We describe a patient in whom a skull-base tumor involved the sellar and parasellar spaces. A 49 year-old female presented with headache and diplopia. The tumor was ultimately identified as a giant prolactinoma; the serum prolactin concentration increased from 155.6 ng/mL to 3,234.3 ng/mL after cranial irradiation. She was evaluated in terms of incidental hypercalcemia and was found to have parathyroid hyperplasia. Genetic analysis revealed a missense mutation in the MEN1 gene (c.643G>A, p.Val215Met). Two years of treatment with a dopamine agonist reduced, but did not normalize, the serum prolactin concentration. We highlight the aggressive behavior of the giant skull-base tumor, and the diagnostic delay caused by a high-dose hook effect of the MEN1-related prolactinoma.

The Younger Patients Have More Better Prognosis in Limited Disease Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Factors associated with the prognosis of patients with small cell lung cancer (SCLC) is relatively unknown, than of those with non-small cell lung cancer. This study was undertaken to identify the prognostic factors of SCLC. METHODS: The medical records of 333 patients diagnosed with SCLC at tertiary hospital from January 1, 2008, to December 31, 2012 were retrospectively reviewed. Patients were categorized by age (≤65 years vs. >65 years) and by extent of disease (limited disease [LD] vs extensive disease [ED]). Overall survival and progression free survival rates were determined. Factors associated with prognosis were calculated using Cox's proportional hazard regression model. RESULTS: Most baseline characteristics were similar in the LD and ED groups. Eastern Cooperative Oncology Group (ECOG) performance status (PS), first chemotherapy regimen, and prophylactic cranial irradiation (PCI) differed significantly in patients with LD and ED. Mean ECOG PS was significantly lower (p65 years) patients, but prognosis in the ED group was unrelated to age. CONCLUSION: This study showed that overall survival (OS) was significantly improved in younger than in older patients with LD-SCLC. Univariate and multivariate analyses showed that age, PCI and the sum of cycles were significant predictors of OS in patients with LD-SCLC. However, prognosis in the ED group was unrelated to age.

Radiation-induced Leukoencephalopathy Presenting as Lower Body Parkinsonism

No abstract available.

Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy

The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.

Moyamoya Syndrome: A Window of Moyamoya Disease

Moyamoya-like vasculopathy develops in association with various systemic diseases and conditions, which is termed moyamoya syndrome. Relatively common diseases and conditions are related to moyamoya syndrome, including neurofibromatosis type 1, Down syndrome, thyroid disease, and cranial irradiation. Moyamoya syndrome shares phenotypical characteristics with idiopathic moyamoya disease. However, they differ in other details, including clinical presentations, natural history, and treatment considerations. The study of moyamoya syndrome can provide clinicians and researchers with valuable knowledge and insight. Although it is infrequently encountered in clinical practice, moyamoya-like vasculopathy can severely complicate outcomes for patients with various underlying diseases when the clinician fails to expect or diagnose moyamoya syndrome development. Furthermore, moyamoya syndrome could be used as a doorway to more enigmatic moyamoya disease in research. More comprehensive survey and investigation are required to uncover the secrets of all the moyamoya-like phenomena.

Local Control of Brain Metastasis: Treatment Outcome of Focal Brain Treatments in Relation to Subtypes / 한국유방암학회지

PURPOSE: To investigate treatment options for local control of metastasis in the brain, we compared focal brain treatment (FBT) with or without whole brain radiotherapy (WBRT) vs. WBRT alone, for breast cancer patients with tumor relapse in the brain. We also evaluated treatment outcomes according to the subtypes. METHODS: We conducted a retrospective review of breast cancer patients with brain metastasis after primary surgery. All patients received at least one local treatment for brain metastasis. Surgery or stereotactic radiosurgery was categorized as FBT. Patients were divided into two groups: the FBT group received FBT+/-WBRT, whereas the non-FBT group received WBRT alone. Subtypes were defined as follows: hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). We examined the overall survival after brain metastasis (OSBM), brain metastasis-specific survival (BMSS), and brain metastasis-specific progression-free survival (BMPFS). RESULTS: A total of 116 patients were identified. After a median follow-up of 50.9 months, the median OSBM was 11.5 months (95% confidence interval, 9.0-14.1 months). The FBT group showed significantly superior OSBM and BMSS. However, FBT was not an independent prognostic factor for OSBM and BMSS on multivariate analyses. In contrast, multivariate analyses showed that patients who underwent surgery had improved BMPFS, indicating local control of metastasis in the brain. FBT resulted in better BMPFS in patients with HR-negative/HER2-positive cancer or the TN subtype. CONCLUSION: We found that patients who underwent surgery experienced improved local control of brain metastasis, regardless of its extent. Furthermore, FBT showed positive results and could be considered for better local control of brain metastasis in patients with aggressive subtypes such as HER2-positive and TN.

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)

Implantes extraorais em pacientes irradiados / Extraoral implants in irradiated pacients

O objetivo deste trabalho foi avaliar o resultado da osseointegração de implantes extraorais lemento de suporte e retenção de próteses nas reabilitações de deformidades faciais. MÉTODO: Estudo retrospectivo de prontuários de 59 indivíduos operados de câncer, submetidos a 164 implantes para retenção de prótese facial. RESULTADOS: Dos 59 indivíduos, 14 foram previamente irradiados e receberam 42 implantes. Quarenta e cinco indivíduos não foram irradiados e receberam 122 implantes. Do total de 164 implantes, oito não osseointegraram, dos quais dois foram instalados em osso previamente irradiados. O resultado representou o sucesso de 116 (95,1%) implantes osseointegrados nos indivíduos não irradiados. E sucesso de 40 (95,3%) implantes osseointegrados em ossos irradiados. CONCLUSÃO: Concluiu-se que o uso de implantes extraorais é uma técnica segura e eficaz como suporte e retenção para próteses faciais em indivíduos com deformidades nessa região. A radioterapia não impede a osseointegração.

The aim of this study is to analyze the success of extraoral osseointegrated implants used to support designed to rehabilitate craniofacial deformities. METHOD: This study was based on the retrospective assessment of charts from 59 patients submitted to cancer surgery and who received 164 extraoral implants to contain facial prosthesis. RESULTS: Among 164 implants, 42 were fixed in previously irradiated regions. Eight of the implants did not have osseointegration; and from these, two were fixed in irradiated bone. The result show 116 (95.1%) successfully osseointegrated implants in non-irradiated sites. The success rate among 42 implants fixed in previously irradiated bones was 40 (95.3%) osseointegrated implants. CONCLUSION: The use of extraoral craniofacial implants represents a safe and effective approach to treat facial deformities as a support for the rehabilitation prosthesis. Radiotherapy treatment does not prevent osseointegration.

Trinta anos de irradiação craniana profilática em pacientes com câncer de pulmão de pequenas células: uma meta-análise de ensaios clínicos randomizados / Thirty years of prophylactic cranial irradiation in patients with small cell lung cancer: a meta-analysis of randomized clinical trials

OBJETIVO: Determinar o papel da irradiação craniana profilática (ICP) em pacientes com câncer de pulmão de pequenas células (CPPC). MÉTODOS: Foi realizada uma pesquisa para selecionar estudos em várias bases de dados, com os seguintes critérios de inclusão: ensaios clínicos randomizados, publicados em periódicos ou em anais de congressos nos últimos 30 anos, avaliando o papel da ICP sobre a mortalidade em pacientes com CPPC que receberam ICP ou não. RESULTADOS: Foram considerados elegíveis 16 estudos clínicos randomizados, os quais envolveram 1.983 pacientes. Entre esses, 1.021 foram submetidos a ICP e 962 não foram submetidos a ICP. Houve uma redução absoluta na mortalidade de 4,4% nos pacientes submetidos a ICP quando comparados com o grupo controle (OR = 0,73; IC95%: 0,57-0,97; p = 0,01), principalmente naqueles com resposta completa à quimioterapia de indução (OR = 0,68; IC95%: 0,50-0,93; p = 0.02) e que foram submetidos a ICP ao término desse tratamento (OR = 0,68; IC95%: 0,49-0,94; p = 0.03). A diminuição da mortalidade não se correlacionou com o estádio da doença: doença limitada (OR = 0,73; IC95%: 0,55-0,97; p = 0,03) e doença extensa (OR = 0,48; IC95%: 0,26-0,87; p = 0,02). CONCLUSÕES: Nossos achados sugerem que a ICP reduz a mortalidade em pacientes com CPPC, principalmente naqueles com resposta a quimioterapia de indução e que sejam submetidos a ICP ao término desse tratamento, independentemente do estadiamento da doença.

OBJECTIVE: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). METHODS: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. RESULTS: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). CONCLUSIONS: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease.

A Case of Oligodendroglioma after Treatment of Acute Lymphoblastic Leukemia in Childhood / 임상소아혈액종양

Secondary brain tumors after cranial irradiation have been reported in survivors of childhood acute lymphoblastic leukemia (ALL). We report a case of secondary oligodendroglioma, occurring in a 19-year-old male, 12 years after the diagnosis of ALL. He was treated with vincristine, asparaginase, doxorubicin, methotrexate, prednisone, 6-mercaptopurine and cytarabine followed by prophylactic cranial irradiation at the age of 7 years. After treatment of ALL was completed at the age of 10 years, he showed symptoms of seizure, headache and decreased visual acuity at the age of 19 years. Magnetic resonance imaging (MRI) of the brain showed a mass lesion which was revealed as low-grade oligodendroglioma by stereotactic biopsy. He was treated with cranial radiotherapy, followed by 4 cycles of chemotherapy composed of PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) for oligodendroglioma, and sodium valproate for seizure control. The patient showed stable disease and no recurrence of seizure 8 months after treatment.

Angiosarcoma of the scalp diagnosed by the presence of neck inflammation: a case report / 国际口腔科学杂志·英文版

Angiosarcoma is an uncommon malignancy, which spread out from the endothelial cells of vessels. Scalp angiosarcoma with cervical lymph node metastasis is particularly rare. This article describes a rare case of angiosarcoma of the scalp, presenting as neck inflammation. Imaging procedures such as computed tomography (CT), magnetic resonance image (MRI) and ultrasonography (US) were not sufficient to diagnose this case. A needle biopsy provided an effective and accurate diagnosis of cervical lymph node metastasis. Additional observation and physical examination was required to diagnose the origin of the primary cancerous lesion. Once the angiosarcoma diagnosis was confirmed histologically, sequential weekly and monthly docetaxel (DTX) treatment was effective in preventing reoccurrence. Nonetheless, the optimization of angiosarcoma treatment remains a future goal. Although patients generally describe pain and swelling at the primary lesion site, this patient complained only of painful neck inflammation, without any indication of pain or swelling of the scalp. A revised diagnostic protocol should note that cervical lymph node metastasis of unknown primary origin may result from angiosarcoma of the scalp.