Long-term survival after brain metastasis from lung cancer

A case is reported of prolonged survival after lobectomy for large cell undifferentiated carcinoma of the lung and resection of metastatic carcinoma of the brain. The patient had survived 11 years 5 months after lung resection and 10 years 4 months after excision of brain metastasis. A review of the reports of another 12 patients who survived 5 years or longer after craniotomy, shows that the surgical excision of a single metastatic lesion of the brain with or without postoperative irradiation offers the best hope for prolonged survival.     

Long-term survival after successful surgical treatment of a solitary brain metastasis

Background We investigated the factors associated with survival duration in 9 patients with brain metastases who survived for more than 6 years, and focused on the factors associated with long survival. Methods Of 9 primary lesions, 5 were lung cancer, 1 was colon cancer, 1 was uterine cancer, 1 was choriocarcinoma, and 1 was renal cancer. All patients underwent total removal of a solitary brain metastasis. Of the 9 patients, 6 received chemotherapy and adjuvant radiation therapy, 1 patient received only radiation therapy, and 2 patients had no adjuvant therapy. Results The factors we isolated in the 9 long-term survivors were that they were relatively young, their systemic diseases were well controlled, there was a relatively long interval between diagnosis of the primary tumor and the brain metastasis, the metastatic lesion was located in the nondominant hemisphere, and the patients were generally in good condition or had only a mild neurologic deficit. Conclusion In some patients with controlled or absent extracranial tumor activity in whom a single brain metastatic tumor is identified after a prolonged period, surgery and local radiotherapy may provide hope for a long survival period.     

颅内转移瘤的治疗现状及进展

近年来,随着影像诊断学技术的发展,脑转移瘤的确诊病例数日益增多,但迄今为止仍无十分有效的单一治疗手段.单发脑转移瘤外科术后复发率高,多发脑转移瘤若原发病灶得不到有效控制,外科切除并不能延长生存.全脑放射治疗是多发脑转移瘤的基本放疗手段,立体定向放射治疗只适用于某些脑转移瘤患者.单纯化疗有效率并不理想.因此,应根据综合治疗这一原则,将手术、放疗、化疗等多种治疗手段有机的结合起来.     

颅内转移瘤的治疗现状及进展

近年来,随着影像诊断学技术的发展,脑转移瘤的确诊病例数日益增多,但迄今为止仍无十分有效的单一治疗手段。单发脑转移瘤外科术后复发率高,多发脑转移瘤若原发病灶得不到有效控制,外科切除并不能延长生存。全脑放射治疗是多发脑转移瘤的基本放疗手段,立体定向放射治疗只适用于某些脑转移瘤患者。单纯化疗有效率并不理想。因此,应根据综合治疗这一原则,将手术、放疗、化疗等多种治疗手段有机的结合起来。     

Cerebral metastasis in patients with uterine cervical cancer

We report on eight patients who developed brain metastases following uterine cervical cancer. The mean interval between diagnosis of the primary cancer and diagnosis of the brain metastasis was 28.4 months (range: 6.1-61.8 months). Nausea and vomiting due to increased intracranial pressure were the most frequent symptoms. Surgical excision of the brain lesions, followed by postoperative radiotherapy, was performed in three patients. The other five patients received only cranial radiotherapy. When the metastatic brain lesions were detected, other distant metastatic lesions were confirmed at the same time in five patients. The median survival time after diagnosis of the brain metastases was only 3.0 months.      

Involvement of the central nervous system by ovarian carcinoma

Ovarian carcinoma rarely metastasizes to the central nervous system (CNS). Of 110 patients with epithelial ovarian carcinoma treated at the Northern Israel Oncology Center between the years 1979 and 1985, only five (4.5%) had CNS involvement. The median age of the patients with 54.5 years. All of them had treatment with cisplatin and Adriamycin (doxorubicin). The median duration from diagnosis to the development of brain involvement was 17 months. The median survival time was 28 months from diagnosis of carcinoma and 2 months from diagnosis of CNS disease. The increased incidence of this kind of metastasis in patients achieving local control of their advanced disease suggests that a change in the pattern of metastatic spread or the prolonged survival permits occult CNS metastases to become apparent. A routine computerized axial tomography (CAT) scan of the brain should therefore be performed on patients with ovarian carcinoma with prolonged survival.     

Malignant insulinoma: spectrum of unusual clinical features

BACKGROUND: Malignant insulinoma occurs in a few patients with insulinoma. Due to the small sample of patients, there are little data regarding their clinical manifestation as well as the preferred treatment modalities. The aims of the current study were to summarize the National Institutes of Health experience during the last two decades and to conduct a critical review of the current literature. METHODS: The authors identified 10 patients with metastatic insulinoma. RESULTS: The patients presented with four patterns of clinical behavior. First, four patients presented with lymph node metastasis and, after surgical excision, maintained a prolonged tumor-free survival. Second, four patients presented with metastatic disease to the liver, which appeared years after the initial diagnosis and presumed curative surgery. Third, one patient presented with a large alpha-fetoprotein-secreting liver mass. Finally, 9 of the 10 patients had a prolonged survival. Various treatment modalities were used to control hypoglycemia. Short-term benefits were most often achieved with embolization and diazoxide. Less successful modalities included radiofrequency ablation, radical debulking surgery, verapamil therapy, octreotide therapy, and chemotherapy. CONCLUSIONS: The current study, as well as others, suggested that metastatic insulinoma may have a variable natural history. After the initial surgical resection, the biology of the tumor, rather than any treatment modality, was most likely the major determinant of long-term survival.     

Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse.     

Two cases of lung cancer patients with postoperative brain metastases obtaining long-term survival after gamma knife radiosurgery

We report two cases of lung cancer patients with postoperative solitary brain metastases obtaining long-term survival after gamma knife stereotactic radiosurgery. Both were seventies men and had good performance status without active extracranial disease. In one case, an asymptomatic metastatic brain tumor 1.8 cm in maximum diameter appeared one year and two months after the operation and was irradiated with gamma knife resulting in complete local control for seven years. He is alive with solitary lung metastasis in good performance status. In the other case, gamma knife was employed for a metastatic brain tumor 2.7 cm in maximum diameter that appeared nine months after the operation accompanying incomplete left hemiplegia. Six months later, the tumor was enlarged and gamma knife was repeated, but the tumor growth could not be suppressed. Following deterioration of hemiplegia and appearance of convulsion, he died of neurological disorder three years and two months after the onset of brain metastasis. Gamma knife stereotactic radiosurgery for metastatic brain tumors is less invasive and a repeatable technique, and is expected to provide a good local control and a survival benefit for appropriately selected patients.     

Increasing incidence of brain metastasis in patients with advanced hepatocellular carcinoma in the era of antiangiogenic targeted therapy

Aim.

Brain metastasis was regarded, until recently, as a rare and late-stage event in patients with hepatocellular carcinoma (HCC). With the prolongation of survival in patients with advanced HCC by molecular targeted agents, this may have changed. We aimed to examine whether or not the incidence of brain metastasis in these patients has increased.

Methods.

Between June 2005 and May 2009, 158 advanced HCC patients in total with either metastatic or locally advanced disease untreatable by locoregional therapies were enrolled in clinical trials of first-line antiangiogenic therapies. The clinicopathologic features and survival times of those who developed brain metastasis were analyzed.

Results.

Eleven (7%) of 158 advanced HCC patients, with a median follow-up of 26.6 months, were diagnosed with brain metastasis as a result of compatible symptoms, confirmed by brain imaging. All 11 patients had extrahepatic metastasis upon enrollment, and 10 of them had lung metastasis. The median time to brain metastasis was 9.6 months (range, 0.6–19.6 months). The median overall survival (OS) time after diagnosis of brain metastasis was 4.6 months (range, 0.7–12.6 months). Four patients received brain tumor excision, and their survival duration after brain metastasis tended to be longer than that of those who did not (median OS time, 6.1 months versus 3.1 months).

Conclusions.

In the era of antiangiogenic targeted therapy, the importance of brain metastasis for advanced HCC patients may have increased.     

Variates of survival in metastatic uveal melanoma.

PURPOSE: The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. PATIENTS AND METHODS: All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. RESULTS: The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. CONCLUSION: A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.     

Brain metastases from carcinomas of the digestive organs--a comparative study with those from pulmonary carcinomas

During the past 11 years, we have experienced 7 cases of a metastatic brain tumor with the primary lesion in the digestive organs. Their clinical courses were retrospectively compared with those of 19 cases with a brain metastases from pulmonary carcinomas. Leptomeningeal carcinomatosis was found in 2 patients of the former group but none in the latter. Six out of 7 brain metastases in the former group were found to have averaged 13 months before their appearance after the diagnosis of the primary lesion. In contrast, 14 out of 19 patients in the latter group had an onset with symptoms of a brain metastasis. The average survival after intracranial surgery on the metastatic tumor was 174 days for the former group and 268 days for the latter. The prognosis of a brain metastasis from a carcinoma of the digestive organ appears to be extremely probable.     

Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature

AIMS AND BACKGROUND: Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. PATIENTS AND METHODS: Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). RESULTS: Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). CONCLUSIONS: Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.     

Extrahepatic spread from hepatocellular carcinoma: who are candidates for aggressive anti-cancer treatment?

BACKGROUND: There is no standard treatment for patients with extrahepatic spread from hepatocellular carcinoma. The aim of this retrospective study was to identify candidates for aggressive intervention or new drug trial among such patients. METHODS: Retrospective exploration was performed to extract a patient cohort step by step using univariate and multivariate analyses. RESULTS: There were 201 subjects from the past 12 years. The 1-, 3- and 5-year survival rates were 31.0, 9.2 and 4.5%, respectively. The upper limit of the 95% confidence interval of median survival time did not reach 3 months in patients with a performance status of 2 or worse, or with Child-Pugh grades B or C. After excluding those, univariate and multivariate analyses were performed in the remaining 124 subjects. Three independent prognostic factors--brain metastasis, number of metastatic tumors and primary tumor status--were identified. The final cohort was set at 121 after excluding three with brain metastasis. Among these 121, there were 11 with a solitary metastatic tumor and T1/2 primary tumor. In this subgroup, 10 underwent complete removal of the metastatic tumor, and the median survival time exceeded 5 years. CONCLUSION: Candidates for anti-cancer treatment should meet the following requirements: a performance status of 0 or 1, a Child-Pugh grade A and no brain metastasis. Among these, challenging locoregional intervention was acceptable only for patients with solitary metastatic tumor and T1/2 primary tumor.     

Radiotherapeutic management of brain metastases: a systematic review and meta-analysis

BACKGROUND: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness. METHODS: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity. RESULTS: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive. CONCLUSION: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.     

Protracted survival after resection of metastatic uveal melanoma

BACKGROUND: The objective of this study was to evaluate the usefulness of resection of metastatic uveal melanoma and to analyze the characteristics of patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve patients underwent surgical removal of metastasis between 1976 and 1998. Data regarding primary uveal melanoma, systemic metastasis, surgical procedures, and outcomes were reviewed retrospectively. RESULTS: There were seven patients with liver metastases, two with lung metastases, one with brain metastasis, and two patients with metastases in the liver and other organs. Median time to systemic metastasis was 8 years. Seven of 12 patients were asymptomatic when they were found to have metastasis. Ten patients underwent complete resection of metastasis. No significant surgical complications were experienced. Median recurrence free and overall survival periods after complete resection were 19 months (range, 6-78 months) and greater than 27 months (range, 11-86 months), respectively. Recurrence free and overall 5-year survival rates of those patients were 15.6% and 53.3%, respectively. Three of these patients had no further systemic recurrence. All patients whose time to systemic metastasis was within 5 years developed further systemic recurrence within 2 years after surgery. In contrast, in 8 patients whose time to systemic metastases was greater than 5 years, 4 patients either were recurrence free or developed second metastasis more than 4 years after surgery. CONCLUSIONS: Complete surgical removal of metastatic uveal melanoma provided unexpectedly long survival without significant morbidity for the selected patients. These results are encouraging and justify a trial in which patients eligible for resection are randomized between standard treatment and surgery.     

Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment

Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3–6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.     

Supraclavicular lymph node metastasis from carcinoma of the uterine cervix after radiotherapy--analysis of 219 patients

From Mar. 1958 to Dec. 1985, 13547 patients with cervical cancer in stages I-III were treated by radiotherapy in our hospital. Supraclavicular lymph node metastasis developed in 219 (1.62%), 83.1% on the left, 7.7% on the right and 9.13% bilateral. 61.2% of the metastasis occurred within 2 years and 86.75% within 5 years after radiotherapy. The majority of these patients (88.3%, 191/215), except 4 who are still being followed, had died within 1.5 years of metastasis with a mean survival of 9.3 months. If radiotherapy in adequate dose is given to the supraclavicular metastatic area, the mean survival can be prolonged for 3.7 months. The prognosis is very poor for these patients no matter what the clinical stage is or when the metastasis develops. The more advanced clinical stage, the higher metastasis rate (P less than 0.001). In this series, 47/219 (21.5%) were found to have concurrent metastasis to the other organs.     

Two cases of ovarian metastasis of colon cancer

CASE 1: A 45-year-old female underwent sigmoidectomy, simple total hysterectomy and bilateral adnexotomy for sigmoid colon cancer and a right ovarian metastasis in December 2007. As adjuvant chemotherapy, S-1 was conducted for six months. She remains disease-free for 38 months after the surgery. CASE 2: A 61-year-old female underwent simple total hysterectomy and bilateral adnexotomy for bilateral ovarian tumors following the surgery for colon cancer, metastatic liver cancer and gastric cancer in January 2010. As adjuvant chemotherapy, capecitabine was administered seven times. Five months after the last surgery, para-aortic lymph node recurrence was diagnosed. FOLFIRI/panitumumab therapy was maintained. For both of the two cases in immune-staining, CK20 staining was positive, and CK7 staining was negative. Ovarian tumors were diagnosed as metastasis from colon cancer. Ovarian metastasis of colon cancer is a relatively rare event, but a long-term survival case has been reported by multimodality therapy including surgery.     

Surgical treatment of solitary pulmonary metastasis.

Seventeen patients undergoing pulmonary excision for metastatic tumors of the lung from 1965 to 1975 are reviewed with an overall four-year survival of 72%. From this group, four patients are alive five years and more after operation. In two patients however, multiple metastases in the contralateral lung and bones have appeared. One of them underwent a second removal of metastatic tumor in the other lung. On the basis of this limited experience and the one reported in the literature, we believe that excision of pulmonary metastasis in selected cases improve the prognosis of those patients, prolong life, and in some cases may even result in cure of the basic disease.