Intra-cavitary dosimetry for IMRT head and neck treatment using thermoluminescent dosimeters in a naso-oesophageal tube.

Complex intensity-modulated radiation therapy (IMRT) treatment plans require rigorous quality assurance tests. The aim of this study was to independently verify the delivered dose inside the patient in the region of the treatment site. A flexible naso-gastric tube containing thermoluminescent dosimeters (TLDs) was inserted into the oesophagus via the sinus cavity before the patient's first treatment. Lead markers were also inserted into the tube in order that the TLD positions could be accurately determined from the lateral and anterior-posterior electronic portal images taken prior to treatment. The measured dose was corrected for both daily linac output variations and the estimated dose received from the portal images. The predicted dose for each TLD was determined from the treatment planning system and compared to the measured TLD doses. The results comprise 431 TLD measurements on 43 patients. The mean measured-to-predicted dose ratio was 0.988 +/- 0.011 (95% confidence interval) for measured doses above 0.2 Gy. There was a variation in this ratio when the measurements were separated into low dose (0.2-1.0 Gy), medium dose (1.0-1.8 Gy) and high dose (>1.8 Gy) measurements. The TLD-loaded, naso-oesophageal tube for in vivo dose verification is straightforward to implement, and well tolerated by patients. It provides independent reassurance of the delivered dose for head and neck IMRT.

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial.

BACKGROUND: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only. PATIENTS AND METHODS: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry. RESULTS: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study. CONCLUSION: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.

Brain metastases from hepatocellular carcinoma. A case report.

Brain metastasis from hepatocarcinoma are a decidedly rare occurrence in countries where this pathology is most frequent. The authors describe a case of metastases from hepatocellular carcinoma in a patient suffering from post-HBV hepatic cirrhosis with hemorrhagic onset. The "stroke-like" presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient's general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature is too small to draw any definite conclusion. Promising molecular biology studies are under way to evaluate the role of oncosuppresor gene expression in hepatocarcinogenesis and in the way the disease spreads.

Use of spiral computerized tomography angiography in patients with cerebral aneurysm. Our experience.

BACKGROUND: The purpose is to highlight the usefulness of CT angiography (CTA) in the diagnosis and surgical treatment of cerebral aneurysms. METHODS: Thirty-one patients with subarachnoid haemorrhages were subjected to CT angiography and in those cases where this test did not reveal the aneurysm or did not supply sufficient information relating to it, subsequently a digital subtraction angiography was also performed. Each aneurysm-positive CTA was re-processed using the 3-D techniques, with the neuro-radiologist and the neuro-surgeon working in close co-operation. RESULTS: In 27 cases the CTA diagnosed an aneurysm, and in the 4 cases where no vascular malformations were revealed, also the traditional angiography did not show any pathology. In 17 out of 18 cases operated on in order to clip the aneurysm, the CTA supplied all the information needed for the surgery and it was possibile to reconstruct images similar to those of the surgical field. This led to improvement in the programming of the surgical intervention; in 1 case only was it also necessary to perform the DSA before the operation. CONCLUSIONS: CT angiography, because it is non-invasive, easy to perform, diagnostically reliable, and because the 3-D re-constructions offer the chance to create images of the possible operating field, is the first-choice test to be adopted in the treatment of subarachnoid haemorrhages, even though in some cases the use of the traditional angiography is still necessary and should be carried out whenever the CTA does not reveal vascular malformations.

The early growth response gene EGR-1 behaves as a suppressor gene that is down-regulated independent of ARF/Mdm2 but not p53 alterations in fresh human gliomas.

PURPOSE: EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas. EXPERIMENTAL DESIGN: Thirty-one human gliomas with different grades of malignancy were investigated for Egr-1 mRNA and the protein expression, frequency, and spectrum of p53 gene mutations, mdm2 gene amplification, and p16/INK4a/ARF allele loss. RESULTS: The amplification of Mdm2 and the deletion of the p16/INK4a gene was found in 3 and 5 cases, respectively, whereas mutations of p53, including two novel mutations, were observed in 10 other cases. The three types of changes occurred strictly mutually exclusively, emphasizing that these genes operate in a common pathway critical to glioma progression. EGR-1 mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%) and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall, EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31 cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4 of 31 cases with residual EGR-1 expression as well as the highest EGR-1 variance segregated with p53 mutations. Immunohistochemical analyses confirmed the suppression of EGR-1 protein. CONCLUSIONS: These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.

Single brain metastasis from thyroid cancer: report of twelve cases and review of the literature.

Brain metastases from thyroid carcinoma is unusual, with a frequency of 1%. We report twelve patients, with single brain metastases and with a karnofsky performance scale score >60 at admission. No metastasis was seen during the uptake of iodine-131, even in the cases from differentiated thyroid carcinoma, suggesting absence of differentiation between primary and metastasic disease. The histopathology of thyroid carcinomas was anaplastic in five cases, differentiated in six, and medullary in one. Only in four patients, brain was the unique site of metastatic spread; in others, bones and lungs were also involved. All metastases were surgically removed, and all patients were treated with radiotherapy (45 Gy) in the postoperative course. The survival average was 19.8 months, and the quality of life was satisfactory in all patients. One patient remained alive till 5 years. Anaplastic histopathology and size of the primitive, and also bone involvement of thyroid disease were significant risk factors in our cases (p < 0.05). According to the literature, surgery is the best therapeutical choice. Alternative strategies in the management of brain metastasis, such as iodine-131 therapy, are discussed, paying particular attention to the relevant side effects.

Human herpesvirus 6 infection in neoplastic and normal brain tissue.

The presence and variant distribution of human herpesvirus 6 (HHV-6) was investigated by a nested polymerase chain reaction (PCR) in 118 biopsies from patients affected by nervous tissue tumor (115 primary tumors and 3 metastasis) and in 31 autopsy samples from the brain of healthy individuals. HHV-6 DNA sequences were detected in normal and neoplastic nervous tissue at a frequency of 32% and 37%, respectively. In both tissues, variant A was three times more frequent than the variant B. Peripheral blood lymphocytes (PBLs) derived from seven tumor affected patients contained the same variant as their respective brain sample, as judged by PCR. The expression of HHV-6 encoded immediate early protein p41 was detected by immunohistochemistry in neoplastic but not in normal brain. This may reflect viral reactivation from latency in immunocompromised patients. The seroepidemiological data indicated a frequency distribution of anti-HHV-6 antibodies in patients with brain tumors similar to that found in healthy donors.

Cavernous angiomas of the nervous system in Italy: clinical and genetic study.

We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.

Cerebral metastasis from ovarian carcinoma. Some observations about treatment.

Systemic metastases from ovarian carcinoma are frequent, but they rarely affect the central nervous system. The treatment of this type of metastases in not clear. Two cases of solitary cerebral metastasis from ovarian carcinoma are reported. Two patients, submitted to therapeutic protocol established for ovarian carcinoma, presented after 17 and 25 months respectively the appearance of symptoms from brain solitary metastasis without other metastases. They underwent surgery, radiotherapy and chemotherapy for solitary cerebral metastasis. Treatment of the brain lesion resulted in KPS improvement (KPS = 90) and survival was 16 and 30 months, respectively. From the 2 cases presented and the review of the literature, it appears that a better outcome may be obtained by a combined treatment of metastases, including surgery, radiotherapy and chemotherapy.

Intracerebral schwannoma. Case report.

A case of intraparenchymal schwannoma is presented. A 61-year-old woman, with stigmata of von Recklinghausen's neurofibromatosis (NF-2), presented with a history of weakness of the right lower limb for 2 months. She was investigated by MR which showed a circular mass with a maximum diameter of 5 cm in the right parieto-occipital lobe. The tumor was removed in toto via a left parieto-occipital craniotomy. The patient was discharged two weeks after the operation and remains well now 2 years later. The clinical and neuroradiological findings of reported intraparenchymal schwannomas, including the case reported here, are discussed.

[Epidermoid cyst of the cranial vault. Neuroradiological and therapeutic considerations]. / Cisti epidermoide della volta cranica. Considerazioni neuroradiologiche e terapeutiche.

AIM: Intradiploic epidermoid cyst is a slow-growing tumor affecting only rarely the cranial bones. PATIENT: The authors describe a case of intradiploic epidermoid cyst of the cranial vault in which there was a predominantly intracranial extension. Roentgenographic and CT findings do not permit a differential diagnosis. Complete removal of the cyst and its capsule was accomplished, with complete recovery. CONCLUSION: Total removal oft the tumor and its capsule is associated with a very good long-term prognosis without recurrences.

Sarcoma metastatic to the brain: a series of 15 cases.

METHODS: We report on 15 patients surgically treated for intraparenchymal brain metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS). RESULT: Median survival after craniotomy was 9.3 months. Patients with a preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3 months for those with a Karnofsky performance score < 70 (p=0.03). Patients with evidence of only lung metastases at the time of surgery (nine cases) survived 8.6 months, which was similar to the 10.4-month survival for patients with disease limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas are alive at 15 and 20 months after surgery. CONCLUSION: We conclude that surgery is effective in treating selected patients with sarcoma metastatic to the brain and that patients with metastasis from ASPS may have a relatively good prognosis if they are surgically treated. The complete removal of all brain metastases and a Karnofsky performance score > 70 are associated with a favorable prognosis; the presence of concurrent lung metastases is not a contraindication to surgery.

Long-term survival in patients with supratentorial glioblastoma.

The authors report 11 patients with cerebral glioblastoma who lived at least 5 years after their initial diagnosis. There were 6 female and 5 male; the mean age was 39 years (range 24-55 years). All patients were treated surgically and postoperatively received whole-brain radiotherapy and chemotherapy. Five patients (45%) presented local recurrences after an average interval of 3.9 years from treatment. At average follow-up of 9 years (range 5-14 years), 7 patients (64%) were alive after an average interval of 8.1 years; 4 patients (36%) died from local relapse. Survival was influenced by patient age and, to a lesser degree, by treatment. A review of the literature, together with our own series, suggest that death from recurrence disease is unusual in glioblastoma patients who survive more than 5 years.

[Neurinomas and ependymomas of the cauda equina. A review of the clinical characteristics]. / Neurinomi ed ependimomi della cauda equina. Revisione delle caratteristiche cliniche.

A retrospective review of 603 cases of intradural benign tumors of the cauda equina are presented (283 schwannomas and 320 ependymomas). For each tumor, the clinical course and long-term postoperative results were analyzed: it emerged that differential diagnosis between neurinomas and non tumoral lesions is not possible if based on clinical findings alone and that neuroradiological diagnosis is more accurate when MRI is employed. Long-term prognosis of neurinomas was always favourable, while in the ependymomas, early diagnosis gives excellent results because prognosis is apparently directly correlated to the length of preoperative clinical history.

High-dose radiation-induced meningiomas.

BACKGROUND: Numerous neoplasms within the CNS have been reported as radiogenic in origin; radiation-induced meningiomas are at least five times more numerous than gliomas or sarcomas in the world literature. METHODS: The authors review 10 cases of cerebral meningiomas following high-dose radiotherapy in patients operated for neoplasm of the nervous system. The pathologic and clinical aspects of this unusual complication are analyzed in all cases in the world literature. RESULTS: There is a female predominance (F-M ratio: 3:2) and the patients are young (mean age: 33.1 years; median: 29 years). The average latency period is 14.4 years (range: 9-21 years). The first disease is acute lymphocytic leukemia (ALL) in 40% of cases. Radiation induced meningiomas are atypical in four cases. Recurrence was observed in one case without malignant transformation. CONCLUSION: High-dose radiation-induced meningiomas have the following characteristics: (1) children appear particularly sensitive to the development of this tumor; (2) there is a female predominance, otherwise than is observed in low-dose meningioma; (3) these tumors present a peak frequency in the third decade of life; and (4) frequently, these tumors are atypical and recur. Finally, it is essential that every new case be reported to throw light on this particular pathologic correlation with its many grey areas.

Multicentric and multifocal primary cerebral tumours. Methods of diagnosis and treatment.

Forty patients with multifocal and multicentric cerebral tumours were retrospectively studied. The patients were divided into two groups: ten patients with multicentric tumours (group A), and 30 patients with multifocal tumours. As far as their preoperative clinical history and the incidence of the various symptoms and signs are concerned, there were no significant differences between the two groups. CT permitted a correct diagnosis in 90% of the cases. All of the patients underwent the removal of the tumour(s) and received radiotherapy; 30 patients also received chemotherapy. In group A, nine patients died and one was lost to follow-up one year after treatment; the average survival was ten months from the appearance of the multicentric tumour. In group B, 29 patients died and one is still alive two years after treatment; the average survival was six months. We consider the problems of diagnosis and the long-term follow-up of patients.

Central neurocytoma: clinical features of 8 cases.

The authors report 8 cases of central neurocytoma with a minimum follow-up of 3 years. Five patients were males and 3 females with average age of 21 years. All patients underwent surgical removal of tumor, and radiotherapy was delivered to 2 of the 3 patients in whom removal had been partial. At an average follow-up of 5 years, all patients are alive and none of them has presented signs of recurrence or progression of the disease. Some typical clinical and histological features of this tumor are pointed out.

Gliomas of the conus medullaris.

AIMS AND BACKGROUND: Gliomas of the conus medullaris often show characteristic clinical, radiological, and intraoperative features which differ from gliomas involving other parts of the spinal cord. METHODS: Eight patients with histologically verified gliomas of the conus medullaris were diagnosed and studied. RESULTS: There were five men and three women ranging in age from 21 to 59 years. Predominant initial symptoms were back pain (4 cases) and leg weakness (4 cases). The most common findings on admission were flaccid paraparesis with impaired sensation and bladder dysfunction. Postoperative magnetic resonance (MR) images with more than 95% removal of a tumour were defined as "subtotal removal" (noted in 4 of 8 cases), and less than 95% as "partial removal" (4 of 8 cases). All patients had postoperative radiotherapy. During the follow-up period ranging from 3 to 10 years, there was no tumour recurrence or regrowth on MR images. CONCLUSIONS: The postoperative radiotherapy in gliomas of the conus medullaris where total resection is not possible seems provide a beneficial effect on preventing tumour regrowth.

Solitary cerebral metastasis from melanoma: value of the 'en bloc' resection.

The authors report 19 cases of solitary cerebral metastases from malignant melanoma. In 15 patients, the primary lesion was known at the time the metastasis was diagnosed; deltoid-scapular in 4 cases, thoracic in 5, inguinal in 4 and neck in 2. The primary location was unknown in 4 patients. Presenting symptoms were: epileptic seizures in 9 cases, headache in 8, strength deficit of the limbs in 2. In 3 patients (16%) neurological symptoms were the first clinical sign of the systemic tumor; in 16 cases (84%) there was a long interval between treatment of the primary and appearance of the cerebral metastasis (average 3.8 years; median 3.4 years). All patients were submitted to surgery and radiotherapy (whole-brain in 14 and radiosurgery in 5). In 10 cases the lesion was removed 'en bloc' (no internal touch technique). Average survival was 9 months (median 8 months) and was influenced by 'en bloc' resection and whole-brain irradiation. None of the patients operated by the 'no touch technique' presented a recurrence.

Intracranial meningioma at the site of a previous cranial fracture: case report and review of the literature.

The authors present a case of post-traumatic intracranial meningioma, selected according to the criteria specified in the relevant literature. Assessment of the clinical characteristics of our patient and those reported in the literature seems to confirm that, in some cases, head trauma may be a factor contributing to the development of meningioma.