Brain metastasis from non-seminomatous germ cell tumor of the testis

Brain metastasis occurs rarely in patients with testicular cancer in the modern era where cisplatin-based chemotherapy regimens are used. The occurrence of brain metastasis can be synchronous or metachronous (with or without concurrent systemic disease). Long-term survival can be achieved in some patients. The vast majority of testicular cancer cases with brain metastasis reported in the literature involve nonseminomatous germ cell tumor and this subtype will be the focus of this review. This article reviews the literature of the diagnosis and management of brain metastasis from nonseminomatous germ cell tumor of the testis.     

Brain metastasis from non-seminomatous germ cell tumor of the testis

Brain metastasis occurs rarely in patients with testicular cancer in the modern era where cisplatin-based chemotherapy regimens are used. The occurrence of brain metastasis can be synchronous or metachronous (with or without concurrent systemic disease). Long-term survival can be achieved in some patients. The vast majority of testicular cancer cases with brain metastasis reported in the literature involve nonseminomatous germ cell tumor and this subtype will be the focus of this review. This article reviews the literature of the diagnosis and management of brain metastasis from nonseminomatous germ cell tumor of the testis.     

Four cases of meningeal hemangiopericytoma treated with surgery and radiotherapy.

We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation.     

Lung carcinoma with metastasis to testicular seminoma.

Tumor-to-tumor metastases are uncommon. The most frequent donor tumors are the lung, whereas renal cell carcinoma is by far the most common recipient. In this report the authors describe a lung tumor that metastasized to a testicular seminoma. This is the first reported case of tumor-to-tumor metastases in which seminoma of the testis is the recipient. The authors performed mucin and immunohistochemical studies on this case and on ten cases of nonseminomatous germ cell tumors containing embryonal carcinoma and endodermal sinus tumor for comparison. Mucin positivity as well as immunoreactivity for epithelial membrane and carcinoembryonic antigens were confined to metastatic adenocarcinoma in this case, whereas Ki-1 and alpha-fetoprotein immunostaining were restricted to the ten control cases of germ cell tumors. Although the majority of second malignant components found in a seminoma are other nonseminomatous germ cell components, the rare possibility exists that a second malignant component is a metastasis from elsewhere in the body.     

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.     

X射线立体定向放射治疗多发脑转移瘤的价值

目的　探讨X射线立体定向放射治疗多发脑转移瘤的疗效。方法　在 4种预后因素(年龄、治疗前卡氏评分、有无其他部位转移及转移灶数目 )相同或相似的条件下 ,配对选择两组病例。X射线立体定向放射治疗加常规放射治疗组 (研究组 )和常规放射治疗组 (对照组 )各 53例。在研究组中 ,X射线立体定向放射治疗采用单次照射 40例 ,分次照射 1 3例 ;单次靶区平均周边剂量为 2 0Gy,分次照射剂量为 4～ 1 2Gy/次 ,2次 /周 ,总剂量为 1 5～ 30Gy。X射线立体定向放射治疗结束后即开始全脑放射治疗。对照组采用全脑照射 30～ 40Gy,3～ 4周。结果　研究组和对照组中位生存期分别为1 1 .6、6 .7个月 (P <0 .0 5) ;1年生存率分别为 44 .3 %、1 7.1 % (P <0 .0 1 ) ;1年局部控制率分别为50 .9%、1 3 .2 % (P <0 .0 5) ;治疗后 1个月卡氏评分增加者分别占 69.8%、30 .2 % (P <0 .0 1 ) ;治疗后 3个月影像学上的有效率分别为 82 .0 %、55 .0 % (P <0 .0 1 )。在死因分析中 ,研究组死于脑转移的占2 3 .3 % ,比对照组的 51 .0 %低 (P <0 .0 5)。两组病例放射并发症的发生率相似。结论　对于多发脑转移瘤 ,X射线立体定向放射治疗加常规放射疗在提高局部控制率、延长生存期和提高生存质量方面均优于单纯放射治疗。     

Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity

BACKGROUND: Melanoma is the primary malignancy that is most likely to metastasize to the brain. Because such an event carries an almost uniformly poor prognosis, the current study reviewed outcomes and identified associated prognostic indicators for 51 consecutive patients receiving gamma knife (GK) radiosurgery in the initial treatment of 188 intracranial melanoma metastases. METHODS: Data were collected retrospectively from a single-center GK radiosurgery database and from primary patient medical records and radiographs. RESULTS: At presentation, 71% of patients had multiple intracranial metastases, and extracranial metastases were present in 66% of patients. Thirty-two patients (63%) were initially treated with GK radiosurgery alone, whereas the remainder received GK radiosurgery in combination with surgery and/or whole-brain radiotherapy (WBRT). Overall median survival from time of GK radiosurgery was 26 weeks. Subgroup analysis revealed a median survival of 77 weeks for patients presenting with a single lesion, compared with 20 weeks for patients presenting with multiple lesions (P = 0.003). Patients in recursive partitioning analysis (RPA) Class I survived a median of 57 weeks, compared with a median survival of 20 weeks for patients in RPA Class II or III (P = 0.002). Although long-term imaging follow-up revealed that a majority of patients experienced distant brain metastases, multivariate analysis showed that distant metastases occurred significantly sooner in patients with extracranial metastases (P = 0.0004). Addition of initial WBRT had no significant effect on the time to development of new brain metastases (P = 0.13). Local control (crude) was observed in 81% of lesions initially treated with GK. Patients experienced improved or stable symptoms for a median of 37 weeks post-GK radiosurgery. CONCLUSIONS: Survival analyses supported the use of GK radiosurgery in the initial treatment of patients with melanoma brain metastases, with best results occurring in patients presenting with a single lesion.     

Treatment of brain metastases from germ cell tumors

Brain metastases occur in approximately 10% of patients with advanced metastatic germ cell tumors. Patients with nonseminomatous histology, lung metastases, and high β-human chorionic gonadotropin levels are at higher risk for synchronous brain metastases at first diagnosis and for relapsing with brain metastases after successful cisplatin-based chemotherapy. Patients with brain metastases should undergo multimodal treatment strategies, including cisplatin-based combination chemotherapy plus radiotherapy or surgery. However, the optimal combination and sequence of these strategies remain unclear and may differ between subgroups. But in all cases, chemotherapy must be part of treatment, even in patients with isolated cerebral relapse without systemic disease.     

Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) by stereotactic linac-based radiosurgery: prognostic factors

A restrospective study of patients with brain metastases from non-small cell lung cancer (NSCLC) is performed to identify patients who benefit from radiosurgery and to determine prognostic factors for survival. Eighty-six consecutive patients with a total of 110 brain metastases from NSCLC were treated with linac-based radiosurgery. Six patients with eight brain metastases who received radiosurgery as a focal boost to whole brain radiotherapy where excluded. Median age at treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used to identify potential prognostic factors for local control of brain metastases and survival of the patients. Median follow-up was 6 months (range 1 1/2-77 months) with 17/80 patients still alive. Median actuarial survival was significantly longer (P<0.004) in patients with metachronous onset of brain metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was significantly increased after radiosurgery in the absence of extracranial tumor progression (P<0.03). Eleven patients (14%) developed new brain metastases after radiosurgery after a latency of median 5 months. Actuarial local control rate was 96% after 3 months. Local control was significantly increased with a prescribed dose > or=18 Gy/80%-isodose (P<0.01). We conclude that especially patients with poor prognostic factors and a limited number of brain metastases may be palliatively treated with radiosurgery alone. This approach allows to effectively control CNS manifestation of the disease and can be integrated into chemotherapeutic protocols.     

Results of retroperitoneal lymph node dissection and postoperative adjuvant chemotherapy with dactinomycin in the treatment of retroperitoneal metastases of nonseminomatous testicular germ cell tumors

This article discusses 103 patients with a nonseminomatous testicular germ cell tumor. Treatment of 87 patients in clinical Stages I, II-A, and II-B consisted of bilateral retroperitoneal lymph node dissection. In Stage I (54 patients), no further treatment was given. The three-year survival was 96%, while recurrence-free survival was 98%. Of 33 patients in Stages II-A and II-B, 26 received adjuvant chemotherapy with dactinomycin, and ten of these were given radiotherapy (peritoneum/mediastinum) as well. The three-year survival was 88% and recurrence-free survival was 85%. Seven patients in Stages II-A and II-B received no adjuvant chemotherapy; four of them died. Treatment of 14 patients in Stage II-C primarily consisted of dactinomycin therapy, subsequently combined with surgery and radiotherapy. The three-year survival was 28.5%. These findings raise the question whether adjuvant single-agent chemotherapy with dactinomycin for patients with a nonseminomatous testicular germ cell tumor should not be re-evaluated.     

Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity.

PURPOSE: To prospectively evaluate efficacy and side effects of hypofractionated stereotactic radiotherapy (hfSRT) for irresectable brain metastases not amenable to radiosurgery (SRS). METHODS AND MATERIALS: From 1/2003 to 2/2005, 51 patients with 72 brain metastases were included in a prospective phase II-trial and accepted for treatment at the dedicated stereotactic radiosurgery system Novalis (BrainLAB, Heimstetten, Germany). In case of planned or prior whole brain radiotherapy (WBRT), hfSRT was to be performed with 5 x 6 Gy, otherwise with 5 x 7 Gy. This dose was prescribed to the 90% isodose line which should cover 100% of the planning target volume (PTV). RESULTS: Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 66.7%, 18.1%, 12.5% and 2.8%, respectively, after a median follow-up of 7 months. Median survival was 11 months. Disease-specific survival and survival related to brain metastases were strongly associated with the size of gross tumor volume (GTV), the planning target volume (PTV), Karnofsky Performance Score (KPS) and number of metastases. Side effects, i.e., increase in T2w-signal area, duration of steroid intake and size of new or progressive necrotic centre of metastasis, were dependent on the volume of normal brain irradiated with more than 4 Gy per fraction (V(4Gy)). Significantly more patients with a V(4Gy)> or =23 cc developed radiological signs of side effects from hfSRT. CONCLUSION: Hypofractionated stereotactic radiotherapy with 5 x 6-7 Gy is an effective and safe treatment for brain metastases not amenable to single high-dose radiosurgery. The normal brain volume receiving >4 Gy per fraction may not exceed 20 cc.     

Intracaval and intracardiac metastatic nonseminomatous germ cell tumor: a rare cause of hemolytic anemia and thrombocytopenia

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.     

A clinico-statistical study of testicular tumors--a reevaluation of 90 cases at the Nagasaki University Hospital and affiliated hospitals

We have treated 90 cases of testicular tumors at our institutes from April, 1962 to March, 1986. Of 75 which were germ cell type tumors, 35 were a seminoma, for which the 5-year survival rate was 100% for patients in stage I, and 50% for those in stage III, respectively. Forty cases were non-seminomas, and all cases determined as being in stage I survived for 5 years, whereas 47.6% cases of those in stage III survived for 4.5 years. Thirty-six percent of those with a stage I germ cell tumor were treated with a orchiectomy alone, while other cases also combined radiotherapy and/or chemotherapy. Almost all cases of an advanced tumor received combined retroperitoneal lymph node resection, radiotherapy and/or chemotherapy. Patients with an advanced nonseminomatous tumor showed better a survival rate if they were given CDDP chemotherapy.     

Intracaval and Intracardiac Metastatic Nonseminomatous Germ Cell Tumor: A Rare Cause of Hemolytic Anemia and Thrombocytopenia

Intracaval and intracardiac nonseminomatous germ cell tumor metastases although rare have been previously reported in the literature. Most cases arise as a result of direct hematogenous spread via invasion of the internal spermatic vein, or from lymphatic venous shunting. We report a unique case of disseminated testicular germ cell tumor that presented with extensive intracaval and intracardiac metastatic teratoma and with valvular involvement. These findings were heralded by the presence of a new cardiac murmur, anemia, and severe thrombocytopenia. Resection of the intracardiac mass, prompted by rapid tumor progression despite treatment with systemic chemotherapy, demonstrated mature teratoma and resulted in prompt normalization of the patients hematologic profile.     

Factors associated with tumor response and survival in radiosurgery for brain metastasis

Background We reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival. Methods Our study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy. Results Median survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (P<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (P=0.0031). Conclusion We concluded that radiosurgery is effective in controlling small brain metastasis. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease. Part of this work was presented at the 7th Asian and Oceanian Congress of Radiology, Kuala Lumpur, Malaysia, May 28-June 1, 1995.     

Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22-73% of the cases after whole brain radiotherapy, but the percentage of reirradiated patients is 3-10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status > 70, age < 65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an "in-field" recurrence of spinal metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An alpha/beta ratio of 1.9-3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.     

Stereotactic radiosurgery for metastatic brain tumors

We report on a prospective phase TI study utilizing stereotactic radiosurgery for patients with intracranial parenchymal metastases. Fifty patients ranging in age from 38 to 77 years with 1 to 3 intraparenchymal brain metastases were treated with stereotactic radiosurgery either immediately following whole brain radiotherapy or at the time of intracranial disease progression following failure of whole brain radiotherapy. Twenty patients treated with adjuvant therapy received a median radiosurgical dose of 20 Gy. Thirty patients treated with salvage therapy received a median radiosurgical dose of 20 Gy. No immediate neurotoxicity was seen following radiosurgery however, 4 patients (8%) developed symptomatic radiation necrosis. Median survival was 6.5 and 6.0 months for patients treated with adjuvant and salvage radiosurgery respectively. In patients with oligometastatic brain metastases manifesting intracranial disease progression after whole brain radiotherapy, salvage radiotherapy appears to offer improved palliation when compared to retreatment with whole brain radiotherapy. The results of patients treated with up-front adjuvant radiosurgery when compared to historical controls treated with whole brain radiotherapy only are less clear as to benefit and require a phase III study before definitive recommendations can be made.     

Successful management of metastatic and primary germ cell tumors in the brain

Nine men and one woman with brain metastases from nonseminomatous germ cell tumors have been treated between 1977 and 1984. All the men had lung metastases. Nine patients had elevated serum values of human chorionic gonadotrophin (HCG), the level was greater than 40,000 IU/l in seven. They were treated with sequential combination chemotherapy either POMB/ACE or EP/OMB in which the methotrexate was given at a dose of 1 g/m2 and intrathecal methotrexate was given during courses not containing intravenous methotrexate. Eight of ten patients are alive, off treatment with no evidence of active disease, of whom five have been in remission and off treatment for more than 18 months. Two patients with primary intracranial nonseminomatous germ cell tumors were treated in a similar fashion. One patient died from enlargement of differentiated teratoma; the other is alive 9+ months off treatment with no evidence of disease. These results, which are better than any previously reported, indicate that chemotherapy is the preferred treatment of primary or metastatic nonseminomatous germ cell tumors of the brain and that only rarely will these patients benefit from surgery or radiotherapy.     

28例脑转移瘤放射治疗疗效分析

目的:探讨脑转移瘤放疗疗效及预后因素。方法:从2000年5月～2002年5月对28例脑转移瘤进行放射治疗。采用6MV-X线,两侧平行相对野作全脑照射,(1.8～2)Gy/次,(36～40)Gy后缩野针对转移灶加量(14～20)Gy。结果:影像学有效率64.3%。中位生存期5.6个月,6个月生存率46.4%,1年生存率21.4%。结论:影响预后的因素主要有:KPS评分、脑转移数目、颅外有无转移和原发灶是否控制。