非小细胞肺癌脑转移不同治疗的疗效分析

目的比较不同治疗方法在非小细胞肺癌脑转移中的作用。方法回顾性分析56例非小细胞肺癌脑转移患者,7例接受开颅手术治疗,13例接受开颅手术 术后放疗,22例接受全脑放疗(WBRT),9例接受立体定向放射治疗(SRT),5例接受全脑放疗 立体定向放疗,全部病例定期随访直至死亡。结果总的1年生存率为39.2%,中位生存期是220天。单纯开颅手术组1年生存率为71.4%,中位生存期517天;开颅手术 术后放疗组1年生存率76.9%,中位生存期533天;全脑放疗组1年生存率4.5%,中位生存期78天;立体定向放疗组1年生存率44.4%,中位生存期187天;全脑放疗 立体定向放疗组1年生存期62.0%,中位生存期509天;年龄大于60岁组1年生存率为26.7%,年龄小于60岁组1年生存率53.8%。结论对于一般情况较好,能耐受手术的单发脑转移患者,开颅手术 术后放疗是一种较好的治疗手段。无开颅手术条件的脑转移患者,选择SRT或SRT联合WBRT较单纯WBRT治疗可能更有效。     

Prolonged survival after multifocal brain radiation necrosis associated with whole brain radiation for brain metastases: case report

Radiation necrosis of the brain is a well documented adverse effect of radiation therapy. The authors report an unusual case of relapsing multifocal radiation necrosis following whole brain radiation therapy (WBRT) for brain metastases from a systemic germ cell tumor. Anticoagulation with warfarin may have had therapeutic benefit. The patient is alive without a neurological deficit 10 years after the diagnosis of radiation necrosis.     

立体定向放射治疗肺癌脑转移疗效分析

目的探讨不同放射治疗方法对肺癌脑转移的疗效.方法176例由病理学证实的肺癌脑转移患者分为4组:单纯全脑放疗(WBRT)组、全脑放疗加立体定向放射外科(WBRT SRS)组、单纯立体定向放射治疗(SRT)组、全脑放疗加立体定向放射治疗(WBRT SRT)组.SRS治疗单次靶区平均周边剂量8～20Gy,总剂量20～32Gy;SRT治疗单次靶区平均周边剂量2～5Gy,总剂量25～60Gy;WBRT1.8～2Gy/次,总剂量30～40Gy.结果四组的局部控制率分别为47.0%、87.7%、86.5%和78.0%;中位生存期分别为5.0,11.0,11.5和10.0个月;局部无进展生存期分别为3.33,8.33,9.33和7.67个月;颅脑无新病灶生存期分别为4.11,8.57,9.03和6.12个月.在死因分析中,WBRT组死于脑转移的比率为57.6%,较其他三组高.而WBRT SRS组的晚期放射反应的发生率为12.2%,较其他组高.结论肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗,治疗失败后再行挽救性全脑照射或立体定向放疗.对于多发脑转移,全脑放疗加立体定向放射治疗(WBRT SRT)在提高生存率以及减少并发症方面优于其他治疗方法.     

Herpes Simplex Encephalitis as a Complication of Whole-Brain Radiotherapy: A Case Report and Review of the Literature

A 55-year-old male recently diagnosed with stage IV lung adenocarcinoma presented with altered mental status approximately 1 week after the completion of 14 fractions of whole-brain radiotherapy (WBRT) for brain metastases. On admission, he was somnolent but oriented and without focal neurological deficits. Brain imaging revealed marked regression of his brain metastases. Laboratory values were only significant for hyponatremia with urine hyperosmolality consistent with syndrome of inappropriate antidiuretic hormone secretion. The patient developed seizures 3 days after admission, at which time cerebrospinal fluid was significant for positive herpes simplex virus (HSV)-1 PCR but with a negative cell count, and acyclovir was started for HSV encephalitis (HSE). After 3 weeks of acyclovir 10 mg/dl i.v. 3 times per day, he had significant neurological recovery and was discharged. Although HSE is a relatively rare condition, it is the most common cause of sporadic encephalitis in Western countries. Since the pathogenesis is believed to be due to the reactivation of latent HSV, it is possible that patients who are immunosuppressed are at higher risk for HSE. In addition, patients who are immunosuppressed or immunocompromised often present atypically, which may delay time to diagnosis and treatment, thus significantly worsening prognosis. This case report intends to raise awareness of this severe condition in the context of patients who have received WBRT and immunosuppressive therapy. In addition, important considerations of diagnosis and treatment of HSE in this patient population are discussed.Key words: Herpes simplex encephalitis, Cranial irradiation, Brain metastasis, Lung adenocarcinoma, Immunosuppression     

小细胞肺癌脑转移全脑放疗失败后挽救性分次立体定向放疗疗效分析

目的 评价小细胞肺癌(SCLC)全脑放疗(WBRT)后颅内失败分次立体定向放疗(FSRT)挽救的价值。方法 回顾分析WBRT失败后使用FSRT挽救的35例SCLC脑转移患者的生存情况,多因素分析确定和生存相关的预后因素。结果 随访率为100%,中位随访时间11个月。全组总中位生存期为10.3个月,多因素分析显示颅外疾病控制状态和患者的生存相关(χ²=4.02,P=0.045)。自诊断脑转移开始中位生存期为22.0个月,未发现严重晚期不良反应。6、12个月局部控制率分别为91%、76%。6例局部未控患者中3例行二程FSRT挽救,挽救治疗后生存时间分别为3、9、13个月。6例患者FSRT后出现治疗野外新病灶,出现新病灶中位时间为4个月。32例患者死亡,其中14例死于颅内进展,14例死于颅外疾病进展,1例死于脑脊髓膜广泛转移,3例死于其他原因(2例肺部感染,1例死因不明)。结论 FSRT挽救治疗对WBRT后复发SCLC脑转移安全有效。     

Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis

Considering whole-brain radiotherapy (WBRT) for asymptomatic brain metastases can reduce performance status and delay systemic treatment, primary chemotherapy can be a feasible alternative treatment. Good and rapid response to epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) treatment makes this an attractive option for never-smokers with adenocarcinoma of the lung. Between January 2005 and August 2007, 23 Korean never-smoking patients with adenocarcinoma of the lung who had synchronous asymptomatic brain metastasis were consecutively treated with EGFR TKI therapy, either gefitinib 250 mg or erlotinib 150 mg once daily, as first-line treatment after giving informed consent, until disease progression, unacceptable toxicity or patient's refusal. They have not received either any prior chemotherapy or any radiotherapy including stereotactic radiosurgery. Objective tumor responses were assessed 1 month after treatment and then every 2 months or when clinically indicated. Out of the 23 patients treated, 16 achieved a PR and 3 experienced stable disease (SD) while 4 experienced progressive disease (PD), resulting in a response rate of 69.6% and a disease control rate of 82.6%. Intracranial tumor responses were observed in 17 patients (73.9%). After a median follow-up of 21.8 months, the median progression-free and overall survival (OS) time was 7.1 and 18.8 months, respectively. Eleven patients received WBRT with a median time-to-local-treatment for intracranial tumors of 19.3 months. In conclusion, EGFR TKI treatment showed promising antitumor activity against both intracranial and extracranial tumors in chemotherapy-naïve never-smokers with adenocarcinoma of the lung. Therefore, these agents should be considered as the treatment of choice in this clinical setting.     

原发性中枢神经系统淋巴瘤的影像学特点及治疗

原发性中枢神经系统淋巴瘤是一种比较罕见的结外原发非霍奇金淋巴瘤（NHL）,其细胞来源多为弥漫大B淋巴细胞,淋巴细胞影像学表现为单发或多发的深部脑实质、脑室周围或脑膜等处的病变。其治疗尚无标准方案,目前多采用放化疗结合的综合治疗。化疗采用以大剂量MTX为主的方案,全脑放疗已被公认为治疗PCNSL的有效手段。但最佳的化疗方案组合、MTX最佳剂量及放疗剂量仍无定论。我们收治一例原发性中枢神经系统淋巴瘤,于外院行肿瘤切除术,术后予阿糖胞苷加大剂量MTX化疗6程后残留,现经多学科讨论后认为应予辅助放疗加替莫唑胺维持化疗。现患者已完成放疗,替莫唑胺维持化疗中。本文就此病例的影像特点及治疗进行讨论。     

Complete Remission of Brain Metastases in Non-Small Cell Lung Cancer Patients Harboring an EGFR Mutation Treated with Tyrosine Kinase Inhibitor without Radiotherapy: A Report of 3 Cases

Brain parenchymal metastasis from a solid tumor is a serious clinical condition associated with a poor outcome because systemic chemotherapy is usually ineffective for treating brain metastases (BM) due to the blood-brain barrier. Therefore, radiotherapy such as whole brain radiotherapy (WBRT) and stereotactic radiosurgery have taken on a central role in the management of BM. However, WBRT can delay subsequent systemic treatment or cause neurologic complications such as a decline in cognitive function. Therefore, suspending WBRT is worth considering if there is an effective alternative. Although there have been no large prospective studies, many reports are available about the favorable effect of tyrosine kinase inhibitors (TKIs) for treating BM in patients with non-small cell lung cancer (NSCLC). Here, we report 3 NSCLC cases that showed a complete response in BM after TKI treatment without WBRT. Based on these remarkable response rates of BM to a TKI, the potential toxicity of WBRT can be avoided, particularly in patients with small metastatic nodules and an epidermal growth factor receptor activating mutation.Key words: Non-small cell lung cancer, Tyrosine kinase inhibitor, Brain metastases, Whole brain radiotherapy     

Outcome of Patients with Brain Metastases after Combined Modality Therapy in Small Cell Lung Cancer (SCLC): a Retrospective Study

Abstract

The authors evaluated the role of whole brain radiotherapy (WBRT) on the outcome of brain metastasis and survival in 41 patients with small cell lung cancer (SCLC) treated in their department. In addition to chemotherapy, radiotherapy was given to the primary site in all responder patients. Six patients presented brain metastasis initially and 10 patients after the fourth course of chemotherapy. Brain metastases were symptomatic in 12 of 16 patients with a median time of 5 months (1-14) until symptoms developed. All patients but 2 with brain metastasis received WBRT (30 Gy in 10 fractions) in addition to chemotherapy. The median survival time of patients with brain metastasis was 8.3 months (3.5 to 16) compared to 12 months (4 to 34+) for patients without brain metastasis. In addition, the median survival time for patients with brain metastasis who responded to systemic chemotherapy was better than that of non-responders. The authors found no improvement in survival in patients who received concomitant WBRT after chemotherapy compared to patients who received WBRT after completion of chemotherapy. In conclusion, the role of consolidating cranial irradiation in addition to chemotherapy in SCLC patients is unclear and warrants prospective randomized studies.     

Mixed germ cell tumors with abundant sarcomatous component in the temporal lobe after radiochemotherapy of neurohypophyseal germinoma: a case report

We report a case of intracranial germ cell tumor that showed pathological changes from neurohypophyseal germinoma to mixed germ cell tumors consisting exclusively of undifferentiated sarcomatous component after radiochemotherapy. Three surgical specimens and autopsied brain from the patient were histologically examined. An initial specimen from the neurohypophyseal tumor was diagnosed as germinoma with a two-cell pattern. Five years later, after repeated radiochemotherapy, the second specimen resected from the right temporal lobe showed mixed germ cell tumors consisting of the three components of germinoma, choriocarcinoma, and immature teratoma. Six months later after intensive radiotherapy, the right temporal tumor recurred and was surgically removed. The histological diagnosis was mixed germ cell tumors with abundant immature teratoma component. The patient died of uncontrollable tumor growth with repeated intratumoral hemorrhages. The autopsied brain showed sarcoma with angionecrosis. This pathological alteration indicated an increase in the sarcomatous component after undergoing various treatments. We discuss the histological changes of intracranial germ cell tumor modified by treatment.     

Brain metastasis of choriocarcinoma in males. Apropos of a case. Review of the literature]

A 22 year-old male patient had a choriocarcinoma of the mediastinum metastatic to the brain, liver, lung and skin. He was treated with five cycles of chemotherapy containing cisplatinum, vinblastine, VP16 and bleomycin and he achieved a partial remission. Then he developed a progressive disease exclusively located to the brain and he died of an intracranial hemorrhage. The autopsy showed the mediastinum and the lung being free of residual trophoblastic tumor. Pure choriocarcinoma is rare in males, but brain metastases are frequently present in this case. Therapeutic guidelines are uncertain, so they must refer to the experience obtained in gestational choriocarcinoma. Two groups of patients are individualized both in male germ cell tumors and in placental choriocarcinoma: one group of patients with brain metastases at diagnosis, with a better prognosis, and one group of patients with brain metastases occurring in the course of the disease, with a poor outcome. The risk of intratumoral hemorrhage is common to all varieties of choriocarcinoma brain metastases and is not lowered by greater effectiveness of the chemotherapy. Brain metastases found at the moment of the choriocarcinoma diagnosis require chemotherapy and radiotherapy and in some selected cases, a surgical removal.     

Successful management of brain metastasis from malignant germ cell tumours with standard induction chemotherapy

Because of possible long-term toxicity, cranial radiotherapy (RT) was withheld as part of standard treatment for brain metastasis (BM) from non-seminomatous germ cell tumours (NSGCT). This study evaluates this change in management in our institute. Twenty-two consecutive patients with BM from NSGCT were analysed. Ten patients presented with BM at initial diagnosis (group 1), two patients developed BM at extra-cranial complete remission (CR) (group 2), and ten patients during treatment of the primary tumour without achieving CR (group 3). All patients received cisplatin-based induction chemotherapy. In group 1, three patients with a single metastasis and three patients with multiple BM underwent craniotomy. Five patients received chemotherapy and whole brain RT (WBRT), and five patients received chemotherapy without WBRT. In group 2, both patients underwent craniotomy for a relapse with multiple BM. One patient received additional high-dose (HD) chemotherapy with WBRT, and the other HD chemotherapy without WBRT. In group 3, one patient underwent craniotomy, seven patients received WBRT, and four patients additional HD chemotherapy. In group 1, five of ten patients (50%) achieved CR (follow-up 49–245 months), in four of those five without WBRT. In group 2, both patients achieved CR (follow-up 146 and 211 months). In group 3, one of ten patients (10%) achieved CR after HD chemotherapy and WBRT (follow-up 107 months). It is concluded that cure in patients with BM from NSGCT can be achieved with standard induction chemotherapy without WBRT.     

Braf mutation in interdigitating dendritic cell sarcoma: a case report and review of the literature

Interdigitating dendritic cell sarcoma is an extremely rare tumor. The diagnosis is difficult and is based on clinical, pathological and immunohistochemical evaluation. Differential diagnosis includes melanoma, mesenchymal and hematological malignancies. The mainstay of treatment is surgery for limited disease and different chemotherapy combinations have been tested for advanced disease. No evidence from prospective trials is currently available. We report the case of a 59 year-old male patient who experienced axillary lymphadenopathy with initial diagnosis of large-cell lung cancer on tumor biopsy. He underwent surgical resection with radical intent. Pathological diagnosis of interdigitating dendritic cell sarcoma was obtained on surgical samples. Nine months after radical surgery, he experienced systemic recurrence of disease and underwent chemotherapy with epirubicin and ifosfamide for 4 courses. During chemotherapy, he developed brain disease progression and underwent whole-brain radiotherapy. Systemic progression was then observed and molecular characterization was performed. B-RAF evaluation resulted positive for V600E mutation and the patient was treated with Vemurafenib according to molecular findings. He thus obtained initial clinical benefit but eventually died of brain hemorrhage. In conclusion, we report a case of B-RAF mutation detected in an interdigitating dendritic cell sarcoma patient treated with targeted therapy. B-RAF pathway could have a role in pathogenesis and evolution of this rare disease and could open new perspectives of treatment.     

非小细胞肺癌脑转移全脑及病灶局部大分割放射治疗

高达40%的非小细胞肺癌患者在疾病进程中出现脑转移,且非小细胞肺癌脑转移常为多发转移。脑转移患者的预后较差,中位生存期不到1年。脑转移的放射治疗已经从全脑放疗逐渐发展到多种放射治疗策略广泛应用的时代。目前已证实单纯全脑放疗、手术+全脑放疗、立体定向放射治疗+全脑放射治疗、同步调强全脑放射治疗等对比未治疗患者能提高总生存期。近年来,全脑放疗对认知功能的损害受到广泛关注,针对预期生存时间较长的患者,采取何种放疗模式尚存在争议。本文将分别论述非小细胞肺癌脑转移不同的全脑放射治疗策略及治疗副作用。     

Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients

BACKGROUND: Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS: Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS: The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs > or =60 years, P = .020), KPS > or =70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs < or =12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS: Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.     

Pulsed Reduced Dose-rate Radiotherapy as Re-irradiation for Brain Metastasis in a Patient with Lung Squamous-celled Carcinoma

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.     

Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases

BACKGROUND: The efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the treatment of 1-4 brain metastases, using a non invasive fixation of the skull, was investigated. METHODS: Between 04/2001 and 01/2006 30 patients with 44 brain metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44 lesions received HSRT boost with a median dose fraction of 6 Gy, the fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy was delivered to the tumor isocenter. RESULTS: The median survival period was 9.15 months, the actuarial 1-year overall survival and freedom from new brain metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky Performance Status (KPS) was statistically significant (P = 0.05); the actuarial 1-year local control for the 41/44 lesions was 86.1%. No patient had acute or late complications. CONCLUSIONS: HSRT as a concomitant boost during WBRT is a safe and well tolerated treatment for selected patients with brain metastases.     

Acute respiratory distress syndrome in poor prognostic germ cell tumor with multiple lung metastases: A case report

We report a case which is unique as this patient was diagnosed pathologically as adenocarcinoma of the endometrium but clinically progressed as germ cell tumor. This was evident by progressive and rapid raised tumor markers (BHCG & LDH) with the development of multiple bilateral lung metastases. She was treated by administrating low doses of systemic combination chemotherapy as per the literature. Unfortunately, she developed acute respiratory distress syndrome as the complication of treatment and died due to it. Keywords: Poor prognostic germ cell tumor, bilateral lung metastases, acute respiratory distress syndrome.     

Brain metastases and testicular tumors: long-term survival.

In this updated and expanded retrospective analysis, the treatment records of 24 patients with brain metastases from nonseminomatous germ cell testicular tumors (NSGCT's) treated at the Indiana University Department of Radiation Oncology from 1975 through 1988 were reviewed. All patients received standard cisplatin-based induction chemotherapy. These patients were divided into three groups. Group 1 (n = 10) consisted of patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) consisted of those patients who, after achieving a complete response (CR) with cisplatin, vinblastine, and bleomycin (PVB) +/- doxorubicin, developed a relapse confined to the brain. Group 3 (n = 10) consisted of those patients who were initially treated with PVB +/- doxorubicin or bleomycin, etoposide, and cisplatin (BEP) and eventually developed progressive disease and brain metastases. Group 1 was treated with whole brain irradiation (WBRT) and PVB +/- doxorubicin or BEP. Group 2 was treated with WBRT, cisplatin-based chemotherapy +/- surgical excision. Group 3 was usually treated with WBRT palliatively. Six patients, three in Group 1 and three in Group 2, are alive and disease-free with follow-up of 5+ years from beginning WBRT. Two additional patients in Group 1 survived 5+ years from beginning WBRT before dying with disease. No patient in Group 3 survived. Patients with brain metastases who have potentially controllable systemic disease should be treated curatively with WBRT (5000 cGy/25 fractions) +/- surgical excision and concomitant chemotherapy.     

Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study

PURPOSE: To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma. METHODS AND MATERIALS: We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes. RESULTS: The median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834). CONCLUSION: Despite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population.