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Value of radiation therapy in the management of patients with cerebral metastases from malignant melanoma: R.T.O.G. brain metastases phases I & II
... It has been suggested that up to 14% of cerebral malignant melanoma metastases respond to radiotherapy 7 and symptomatic improvement has been documented. 18 Malignant melanoma cells have a very complex radiobiology with growth rate, hypoxic fraction and a number of repair mechanisms all interacting to influence the radiosensitivity of a particular cell line. 19 A striking heterogeneity of response to radiation is present among individual melanoma cell lines and melanoma multicellular spheroids. ...
... In patients presenting with multiple cerebral metastases, radiation therapy may be considered as a palliative measure to help relieve symptoms. 18 No significant response of cerebral metastases from malignant melanoma to chemotherapy or other experimental modalities has been reported. ...
Six hundred and fifty-two patients with histologically proven primary malignant melanoma have been followed by the London Regional Cancer Centre from 1960 to 1985. Neurological signs and symptoms secondary to metastases to the brain developed in fifty-five patients (8.4%). The median age was 49 years; 71% were male and 29% female. Multiple lesions were found in 61% and a single metastasis in 39%. The most common site for the primary lesion was the trunk in males (44%) and the lower limb in females (37%). Six month survival for patients with a single metastasis was 58% if surgical excision was possible and 25% of these patients survived greater than two years. In patients with multiple metastases that received radiotherapy, survival times of greater than six months were found in 12% of the patients. Patients with a single metastasis appear to benefit by being managed by surgical removal of the lesion.
... The median time for primary melanoma to metastasize to the brain was similar to that described by Retsas (1988) and Merimsky et al (1992). The overall median survival time for our series was 4 months, which is similar to that reported in previous studies (Gottlieb et al, 1972; Amer et al, 1978; Carella et al, 1980; Zimm et al, 1981; Retsas, 1988). Patients presenting with one cerebral metastasis survived for a longer period of time than patients with two or more metastases. ...
... Malignant melanoma is relatively radioresistant. Radiotherapy used to treat central nervous system metastases has given conflicting results; some showing an increase in survival (Mastrangelo et al, 1985) and others showing no improvement in survival (Carella et al, 1980; Byrne et al, 1983; Fernandez et al, 1984; Madajewicz et al, 1984). Our results show that the majority of patients were treated with radiotherapy and dexamethasone but showed no improvement in survival compared with patients who received dexamethasone alone. ...
Cerebral metastases of cutaneous melanoma carry a very poor prognosis. We report our experience of 31 patients who presented with cerebral metastasis of cutaneous melanoma in a 5-year period between mid-1991 and mid-1996. Cerebral metastases were diagnosed on computerized tomography (CT) scan after patients became symptomatic. The overall median survival in our series was 4 months. Seventeen patients (55%) received treatment with radiotherapy and dexamethasone with resolution of their symptoms, although median survival remained at 4 months. Six patients (19%) had surgery followed by whole brain radiotherapy, with median survival of 5 months. The remaining eight patients received dexamethasone alone. Data from patients surviving less than 2 months and over 6 months suggest that the poor prognostic factors are the presence of more than one cerebral metastasis and additional extracranial metastases.
... In our study 8% (16 out of 201) of the patients unexpectedly were found to have CNS engagement at postmortem examination. In accordance with other studies, all other patients in this study exhibited marked symptoms of the CNS metastases with focal neurologic loss, headache and mental deficits as the most common ones (1,28,30). The majority of the patients presented with grave symptoms of incapacity at the emergency unit. ...
The objectives of this population-based study were to assess putative prognostic factors for central nervous system (CNS) metastases among patients with cutaneous malignant melanoma, to assess the cumulative risk of CNS metastases in different subsets of patients with recurrent disease, and to describe patient outcome. At a median follow-up of 11 years, 201/2516 patients with melanoma had developed CNS metastases, corresponding to a cumulative risk at 5 years of 7%. In 41 of these 201 patients the CNS metastases were recorded as the first site of recurrence. In a Cox's multivariate model, primary tumor thickness and ulceration in stage I patients were independent risk factors. The cumulative rates of incidence of CNS metastases 5 years after local or regional recurrence as first event were 5 and 42%, respectively. These results may help to form an individually based risk assessment, which might be of value for melanoma patients in certain occupations.
... 7,8,12 Melanoma is relatively resistant to radiotherapy, and therefore external beam radiotherapy provides minimal benefit in patients with melanoma neoplastic meningitis. 13,14 Systemic chemotherapy, such as dacarbazine, carmustine, or vincristine, is only marginally active against extraneural melanoma and of virtually no benefit to patients with melanoma neoplastic meningitis. 7,15,16 Intrathecal chemotherapy with methotrexate, cytosine arabinoside, or thio-TEPA similarly produces only a trivial benefit. ...
Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressive hearing loss, severe headaches, nausea, vomiting, and a rapid decline in neurologic status. She was referred to Duke University Medical Center after conventional chemotherapy for malignant melanoma failed. She was enrolled in a Phase I trial of 131I-labeled monoclonal antibody Mel-14 F(ab′)2 fragment administered intrathecally. Within a year after her treatment, she recovered, having a normal neurologic exam except for residual bilateral hearing loss. The authors discuss dosimetry, preclinical, and clinical studies conducted with Mel-14 F(ab′)2 and introduce a potentially promising therapy option in the treatment of neoplastic meningitis in patients with malignant melanoma. Currently, the patient remains neurologically normal except for a mild bilateral hearing loss more than 4 years after treatment and has no radiographic evidence of neoplastic meningitis. Cancer 2001;91:1809–13. © 2001 American Cancer Society.
... Leptomeningeal melanomatosis is an incapacitating complication of melanoma. With previously reported poor response to conventional intrathecal chemotherapy and radiotherapy [19][20][21][22][23] and variable responses and neurotoxicity associated with intrathecal immunotherapy, [24][25][26][27][28][29] reliable prognostic factors are needed to guide therapeutic decision making. ...
The purpose of this study was to describe a cohort of patients with leptomeningeal melanomatosis (LM) and to determine prognostic factors for outcomes in these patients. The primary hypothesis was that more extensive burden of CNS metastasis at the time of diagnosis of LM (as evidenced by imaging of the CNS parenchyma and meninges and cerebrospinal fluid [CSF] cytology status [positive versus negative]) correlates with poorer outcomes. The records of all patients with LM treated at M. D. Anderson Cancer Center between 1944 and 2002 were reviewed. Information on clinical course and outcomes was gathered. Univariate and multivariate analyses were performed on 110 patients using Cox proportional hazards regression analysis to examine the effects of possible predictive factors on survival. The overall median survival from LM diagnosis was 10 weeks, with a 95% confidence interval (CI) of 8-14 weeks. Eighty-six (78.2%) patients had cutaneous primary lesions, and 23 (20.9%) had melanoma of unknown primary site. The primary hypothesis was not proven. Neither the presence of parenchymal CNS metastases, nor greater imaging evidence of LM, nor positive CSF cytology at diagnosis correlated with survival outcomes. Univariate analyses revealed possible predictors of longer survival, including the presence of supratentorial or spinal LM on imaging at diagnosis versus its absence and any treatment of LM, whereas elevated serum lactate dehydrogenase at the time of LM diagnosis predicted shorter survival. Multivariate analysis revealed that a history of a primary melanoma lesion originating on the trunk predicted shorter survival after LM diagnosis (hazard ratio [HR] = 2.0, 95% CI = 1.0-3.8, p = 0.035), and treatment with intrathecal chemotherapy predicted longer survival (HR = 0.5, 95% CI = 0.4-0.8, p = 0.0036). The positive result with respect to treatment is unreliable due to the inability to remove treatment selection bias from the analysis. This retrospective analysis confirmed the dismal prognosis associated with LM. The amount of CNS tumor burden at the time of diagnosis of LM did not inversely correlate with survival outcomes, contrary to our hypothesis.
... 7,8,12 Melanoma is relatively resistant to radiotherapy, and therefore external beam radiotherapy provides minimal benefit in patients with melanoma neoplastic meningitis. 13,14 Systemic chemotherapy, such as dacarbazine, carmustine, or vincristine, is only marginally active against extraneural melanoma and of virtually no benefit to patients with melanoma neoplastic meningitis. 7,15,16 Intrathecal chemotherapy with methotrexate, cytosine arabinoside, or thio-TEPA similarly produces only a trivial benefit. ...
Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressive hearing loss, severe headaches, nausea, vomiting, and a rapid decline in neurologic status. She was referred to Duke University Medical Center after conventional chemotherapy for malignant melanoma failed. She was enrolled in a Phase I trial of (131)I-labeled monoclonal antibody Mel-14 F(ab')(2) fragment administered intrathecally. Within a year after her treatment, she recovered, having a normal neurologic exam except for residual bilateral hearing loss. The authors discuss dosimetry, preclinical, and clinical studies conducted with Mel-14 F(ab')(2) and introduce a potentially promising therapy option in the treatment of neoplastic meningitis in patients with malignant melanoma. Currently, the patient remains neurologically normal except for a mild bilateral hearing loss more than 4 years after treatment and has no radiographic evidence of neoplastic meningitis.
The development and structure of the normal nasopharynx have an important bearing on the histogenesis and histomorphology of cancers that may arise in this area. Approximately 60% of the nasopharyngeal surface in adults is lined by stratified squamous epithelium which shows little or no keratinization [1]. Patches of ciliated epithelium and transitional or intermediate-type epithelium occur throughout the nasopharyngeal surface.
Cancer of the nasopharynx is a disease which is managed by radiation therapy as the major method of treatment. The disease location and its propensity for spread to the lymph nodes of the neck limits the surgical approach to the treatment of this disease. As the cancer has a tendency to be localized in the head and neck region in its clinical course and is reasonably sensitive to radiation, the role of adjuvent chemotherapy for this disease has yet to be established. In addition, the tumor burden and histology, an epithelial malignancy, limits the use of chemotherapy. As the disease becomes more advanced, the tumor invades the base of the brain with destruction of the sphenoid bone. Distant metastases may develop in the liver, lungs and bones. In the treatment of this tumor, local control can be achieved both in the primary lesion and in the lymph nodes with proper treatment. The dose limiting tissues include the brain, spinal cord, and mandible and in some clinical situations, the orbital contents may also become a dose limiting tissue.
This chapter discusses cancers of the upper aero digestive tract, which are collectively classified as head and neck cancers and include lesions of the nose and paranasal sinuses, pharyngeal spaces, and larynx. Evidence suggestive of a human papillomavirus etiology in lung and esophagus cancer is reviewed. Oral cavity lesions are discussed elsewhere in this text (see chapter by S. Syrjänen, this volume) and thus are omitted here.
To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.
Purpose. – The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases.Patients and methods. – Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m–2 on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d–1, days 1–5, 3 consecutive weeks).Results. – Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test).Conclusion. – Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.
The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. the 30-day mortality was zero. the 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). the seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2–4 months), and those treated with chemotherapy alone (median, 2–4 months). the excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases.
In order to determine the natural history and results of treatment of intracerebral metastases in solid-tumor patients, the records of 191 patients with an antemortem diagnosis of intracerebral metastasis made during the period from August 1974 to November 1978 were reviewed. Malignancies included lung (122 patients), breast (26), unknown primary (16), melanoma (8), colorectal (6), hypernephroma (4), and others (12). Favorable prognostic factors included solitary brain metastasis (P < 0.001), ambulatory performance status (P < 0.001), symptoms of headache (P < 0.001), or visual disturbances (P < 0.02), and estrogen receptor positivity in breast cancer patients (P = 0.055). Poor prognostic factors included advanced age (P < 0.04) and evidence of impaired consciousness, i.e., disorientation, lethargy, stupor, or coma (P < 0.007). Median survival time after diagnosis of intracerebral metastasis was 3.7 months for the entire series. In those patients with a single intracerebral metastasis and minimal tumor burden, the type of treatment used had a significant impact on survival. Those cases treated with surgery and radiation had a median survival time of 9.7 months versus 3.7 months for those treated with radiation alone (P < 0.02). When using a proportional hazard regression analysis to adjust for the three most important prognostic factors, treatment (surgery and radiation versus radiation alone) still appeared to be important. Intracerebral metastases were the immediate or contributing cause of death in 50% of the patients in this series. Patients at greater risk of dying of intracerebral metastases included those in whom the brain was the first site of distant metastasis, those with an intracerebral metastasis from an unknown primary site, and those whose presentation of malignancy was with symptoms of a brain metastasis. Although the therapeutic goal in intracerebral metastases is generally palliative, it appears that there are categories of cases that may benefit from more aggressive treatment.
BACKGROUND
Brain metastases complicate the course of malignant melanoma in at least 20% of adult cases. These events are commonly preceded by metastases to other sites. Due to the rarity of malignant melanoma in children, little is known about the incidence, clinical features, and outcome of children with melanoma who develop brain metastases.METHODS
The authors reviewed the records of 44 children with malignant melanoma treated at St. Jude Children's Research Hospital over a 33-year period. Eight (18%) developed brain metastases during the course of their disease. The authors reviewed the clinical and radiologic features of six of these cases, for whom complete clinical information and imaging studies were available.RESULTSThe median age at diagnosis of malignant melanoma was 15 years (range, 11-21 years). Brain metastases developed a median of 20 months (range, 0-50 months) after diagnosis and were preceded by metastases to other organs in 5 patients. In most cases, lesions were supratentorial and multiple. Most showed radiologic signs of intralesional hemorrhage. All patients received whole brain radiotherapy, and one had surgical resection. Three patients received chemotherapy. Five patients died a median of 5 months (range, 2-10 months) after diagnosis of brain involvement. One patient, who had a single brain metastasis at diagnosis, is alive more than 34 months later.CONCLUSIONS
Brain metastases develop in a significant proportion of children with malignant melanoma and are associated with a poor outcome. The incidence, features, and outcome in children do not appear to differ from those in adults. Cancer 1997; 79:2440-5. © 1997 American Cancer Society.
We report results of a conservative treatment for brain metastases from malignant melanoma with a combination of irradiation and chemotherapy (fotemustine and/or DTIC). To date, 12 patients have been treated. There was a complete remission of the brain metastases in four patients. In two patients a partial remission was observed. The mean survival of the responder was 8.2 months (95% confidence interval 3.8–12.6 months). The most common side effects were thrombocytopenia, leukopenia, and alopecia. Altogether, the treatment was well tolerated. As the outcome of patients with brain metastases from malignant melanoma is generally poor, this combined chemo- and radiation therapy may provide improved care for such patients.
The aim of this study was to determine the relationship between nuclear factor κB and the prognosis of patients with nasopharyngeal carcinoma. We used immunohistochemical studies to examine nuclear factor κB expression in 42 patients with nasopharyngeal carcinoma. The results showed that tumors positive for nuclear factor κB were associated with an increased relapse potential, poor disease-free survival, and reduced overall survival in nasopharyngeal carcinoma. Our study indicates that nuclear factor κB could be an independent molecular marker for predicting poor prognosis among patients with nasopharyngeal carcinoma. Understanding the biology of nuclear factor κB-mediated pathways may lead to the development of novel therapeutic strategies for nasopharyngeal carcinoma.
Brain metastasis is common in patients with malignant melanoma and represents a significant cause of morbidity and mortality. Nearly 37% of patients with malignant melanoma eventually develop brain metastasis, and autopsy reports show that 75% of those who died of this disease developed brain metastasis.
We review the level I and level II evidence that guides indications for treatment with surgery, stereotactic radiosurgery, chemotherapy, and immunotherapy for patients with melanoma brain metastasis.
Level I evidence supports the role of whole brain radiotherapy, microsurgery, and radiosurgery alone or in combination for the treatment of patients with melanoma brain metastasis. Chemotherapy has been ineffective. Ongoing studies continue to assess the effects of immunotherapy and agents in development.
Brain metastasis is a common and formidable challenge in patients with malignant melanoma. Although there have been no randomized controlled trials exclusively in patients with melanoma brain metastasis, care can be guided by the application of level I evidence for the treatment of brain metastasis in general and phase II studies focusing specifically on melanoma brain metastasis. Promising new agents and approaches are needed and will hopefully be identified in the near future.
The records of all patients receiving palliative radiotherapy for malignant melanoma metastatic to brain, to bone, or with spinal cord compression were reviewed. The median survival of 77 patients with brain metastases from the initiation of radiotherapy was 14 weeks. A statistically improved survival was observed only in the 10 patients who underwent subtotal to total resection of a solitary brain metastasis prior to radiotherapy (median = 36 weeks). No improved survival was observed in the 12 patients with a solitary brain metastasis treated by radiotherapy alone (median = 16 weeks). Multivariate analysis revealed that fraction size, total dose, patient age, sex, and duration of the interval between initial diagnosis and appearance of brain metastases did not significantly influence survival, but the use of chemotherapy was associated with a decreased survival. Twenty six patients with symptomatic and radiographic evidence of 39 bone metastases showed a palliative response rate of 85%. 18 of 20 bony lesions treated with high-dose-per-fraction (greater than or equal to 400 cGy) and 15 of 19 bony lesions treated with conventional fractionation (less than or equal to 300 cGy) were palliated. Total dose, patient age, sex, interval between initial diagnosis of malignant melanoma and the appearance of bone metastases, prior or concurrent chemotherapy, or lesion location did not significantly influence palliation. Seventeen patients were identified with symptomatic and myelographic evidence of spinal cord compression. Complete palliation was observed in 47% (8/17) and partial palliation was observed in 24% (4/17). The overall palliation response rate for neurologic symptoms due to spinal cord compression of 71% appeared to be independent of fraction size and total dose.
One hundred ninety-four patients with intracranial metastatic melanoma were treated at the M. D. Anderson Hospital between January 1972 and September 1977, using seven different accelerated irradiation regimens. The total tumor dose varied from 3000 to 4800 rad, and the overall treatment time from 1 to 2 weeks. In these patients, whose disease had progressed to brain metastases, freedom from such metastases had decreased logarithmically with time from initial presentation. This suggests a random distribution of progression rates with a mean time of 2.5 years between diagnosis and development of intracranial metastases. Overall, there was no significant improvement in the results from accelerated fractionation in the treatment of intracranial metastases. The result of treatment did not depend on the site of the primary, the number of intracranial metastases, the total dose, or the dose per fraction. There were, however, two subgroups not mutually exclusive, that benefited significantly from the accelerated fractionation: patients having had a complete resection of brain metastases, and those having no detectable extracranial metastases at the time of their treatment for intracranial metastases.
Thirty-nine patients who completed whole-brain irradiation treatment for brain metastases from malignant melanoma were analyzed. Median survival was 2 months, mean survival 4 months. Only 3 patients survived for 1 year, the longest survival being 19 months after irradiation. Twenty-one (53.8%) showed marked clinical improvement and 6 (40%) of the 15 evaluable patients had some objective regression of the brain metastases. A treatment of 7 fractions of 4.8 Gy in 9 to 14 days and concomitant chemotherapy with dacarbazine and lomustine in 16 patients was well tolerated. This seems to be a beneficial treatment for patients with a comparatively small intracranial tumour burden.
Eighty-one patients with brain metastasis from melanoma were identified at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1980. Of 78 evaluable patients, 51 (65%) had multiple brain metastases. Of 64 patients with non-contrast CT scans, 29% had hemorrhagic metastases. Leptomeningeal metastases were found in 15 patients. Patients were grouped into three categories: Group 1, multiple brain metastases treated with radiation therapy (RT) (n = 49); Group 2, single brain metastasis treated with RT (n = 17); Group 3, single brain metastasis treated with surgery with or without RT (n = 9). Median survivals for Groups 1, 2 and 3 were 11, 9 and 41 weeks, respectively. Eighty-six percent, 65% and 33% of patients in Groups 1, 2 and 3, respectively, were steroid-dependent until death. Seizures occurred in 38 patients (48%). In 17 (21%), seizures were the first manifestation of metastasis. Of 51 patients not receiving prophylactic anticonvulsants, 37% had seizures. Of 12 patients treated prophylactically, 17% developed seizures. Surgical extirpation should be considered in highly selected patients with brain metastasis from melanoma. Prophylactic anticonvulsants are recommended if there is no contraindication.
A 36-year-old woman underwent removal of a stage II malignant melanoma from the left ankle in 1985. A single brain metastasis to the right frontal lobe was removed in July 1986. Postoperatively, she received 5-fluorouracil, cisplatin, and etoposide (VP-16) in conjunction with radiation therapy. She achieved remission until March 1988, when left hemiparesis occurred suddenly. Computed tomography and magnetic resonance scans revealed multiple brain metastases. She was treated with a combination of 5-fluorouracil, 1,000 mg/m2 in a 24-hour continuous IV infusion for 5 days; interferon-alpha, 10 million units in subcutaneous injection daily for 10 days; and oral cimetidine, 1,200 mg daily for 7 days. This regimen, repeated every 4 to 6 weeks for four cycles, was well tolerated, with complete remission of neurological deficits and resolution of the lesions seen on the brain scans until she died 11 months later of intracranial hemorrhage secondary to severe thrombocytopenia.
The current study evaluates the efficacy of interstitial 125-iodine radiosurgery (brachytherapy) in 93 patients with circumscribed, spherical, mostly solitary metastases. In all patients the histological diagnosis was established by stereotactic biopsy. The treatment results of three therapeutic regimens have been examined retrospectively: Group A (38 patients) had interstitial radiosurgery with a reference tumour dose of 60 Gy in combination with percutaneous radiotherapy (40 Gy). Group B (34 patients) was treated by interstitial radiosurgery alone (reference dose 60 Gy). Group C (21 patients with recurrent metastases after previous radiotherapy/surgery) was treated by interstitial radiosurgery alone (reference dose 60 Gy). Median survival after interstitial radiosurgery was 17 months in group A, 15 months in group B, 6 months in group C. Favourable prognostic factors were a Karnofsky performance rating > or = 70, solitary metastasis, absence of disseminated disease, and a time interval > 1 year between diagnosis of the primary tumour and diagnosis of the cerebral metastases. Interstitial radiosurgery plus percutaneous radiotherapy did not prove to be superior to interstitial radiosurgery alone. No patient died of a locally irradiated metastasis. We conclude that interstitial radiosurgery achieves control of the growth of solitary spherical cerebral metastases in any location without radiation toxicity.
Although reports have been published describing clinical results in a large series of patients with metastatic brain tumors treated by stereotactic radiosurgery (SRS), clinical neuropathological correlation has rarely been available. The present paper describes three autopsy cases and one surgical case treated with linear accelerator based radiosurgery. The cases comprised a lung cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological sections of each tumor were analyzed by light microscopy based on the Ohosi and Shimosato's histopathological classification of the effects of radiation therapy. In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and osteosarcoma), a large area of the tumors consisted of coagulation necrosis and non-viable tumor cells, while coagulation necrosis and non-viable tumor cells comprised a very small part of the malignant melanoma. Histopathological type of the metastatic brain tumor may be one of the factors influencing outcome after SRS.
A careful history and physical examination remain the most important aspects of headache assessment. enabling the neurologist to decide if any further studies are necessary. Only a minority of patients who have headaches have brain tumors; however, recognition of the headaches characteristically associated with tumors is most important. Some locations are more likely to produce headache (eg, a posterior fossa tumor causes headache more often than a supratentorial tumor). Rapidly growing tumors are more likely to be associated with headache. Uncommon headache presentations can occur with tumors, includin paroxysmal cough, cluster headache, and TACs. The classic brain tumor headache is not as common as a tension-type presentation or migraine. Patients who have prior primary headaches may have more headache symptoms if they have a tumor and of course they still have their primary headache disorder. Mass lesions progress and inevitably develop other symptoms and signs besides headache, and these new symptoms and signs must be sought and found. Metastatic leptomeningeal involvement can present with headache and spinal pain in the neck and back. Imaging of headache patients for tumors, if they have primary headache disorders, such as migraine and typical cluster, generally is not cost effective but is necessary if there are any atypical features. Treatment of headache in patients who have metastatic brain tumors should be aggressive in terms of pain and symptoms control. Treatment of primary CNS tumors is dictated by the kind of neoplasm and site, but control of headache should not be ignored.
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