Recent advances in the treatment of central nervous system germ cell tumors.
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Antineoplastic Agents↗
Biomedical subjects
H Shirato
Publications and source records attributed to H Shirato.
Three-dimensional movement of a liver tumor detected by high-speed magnetic resonance imaging.
OBJECTIVE: Three-dimensional (3D) movement of a spherical liver tumor during respiration was investigated with magnetic resonance imaging (MRI) using a high-speed sequence. METHODS: A marker was placed on the surface of the patient as a reference of distance. Repetition time (TR) was 7.7 ms, echo time (TE) was 4.2 ms, flip angle was 20 degrees, section thickness was 8 mm, and a 256 x 128 matrix was used. The acquisition time was 1.0 s followed by an interval of 0.5 s. The 20 tumor contours extracted during 30 s were superimposed on sagittal and coronal MR images. RESULTS: The maximum value of tumor edge location was 3.9 cm in the cranio-caudal direction, 2.3 cm in the ventro-dorsal direction, and 3.1 cm in the lateral direction. The mean length of tumor displacement observed was 2.1 cm in the cranio-caudal direction, 0.8 cm in the ventro-dorsal and 0.9 cm in the left-right direction, respectively. The locus of the center of the tumor contour in the sagittal cross section was inclined at 23 degrees and in the coronal cross section was inclined at 18 degrees to the cranio-caudal axis of body. CONCLUSION: In conclusion, 3D movement of a spherical liver tumor was detected using rapid MRI sequential examinations. Magnetic resonance imaging has a potential to improve the accuracy of the planning target volume of a liver tumor.
Humans↗
Small-field fractionated radiotherapy with or without stereotactic boost for vestibular schwannoma.
PURPOSE: To assess the efficacy and toxicity of small-field fractionated radiotherapy with or without stereotactic boost (SB) for vestibular schwannomas. METHODS AND MATERIALS: Thirty-nine patients with vestibular schwannoma were treated with irradiation between March 1991 and February 1996. Extra-meatal tumor diameters were under 30 mm. Thirty-three patients received small-field fractionated radiotherapy followed by SB. Basic dose schedule was 44 Gy in 22 fractions over 5 1/2 weeks plus 4 Gy in one session. Six patients received small-field fractionated radiotherapy only (40-44 Gy in 20-22 fractions over 5-5 1/2 weeks or 36 Gy in 20 fractions over 5 weeks).dash;p > RESULTS: Follow-up ranged from 6 to 69 months (median, 24 months). Tumors decreased in size in 13 cases (33%), were unchanged in 25 (64%), and increased in one (3%). The actuarial 2-year tumor control rate was 97%. Fifteen patients had useful hearing (Gardner-Robertson class 1-2) and 25 patients had testable hearing (class 1-4) before irradiation. The 2-year actuarial rates of useful hearing preservation (free of deterioration from class 1-2 to class 3-5) were 78%. The 2-year actuarial rates of any testable hearing preservation (free of deterioration from class 1-4 to class 5) were 96%. No permanent facial and trigeminal neuropathy developed after irradiation. The 2-year actuarial incidences of facial and trigeminal neuropathies were 8% and 16%, respectively. CONCLUSIONS: Small-field fractionated radiotherapy with or without SB provides excellent short-term local control and a relatively low incidence of complications for vestibular schwannoma, although further follow-up is necessary to evaluate the long-term results.
Actuarial Analysis↗
Role of radiotherapy for mucoepidermoid carcinoma of salivary gland.
This report analyzes 61 patients with mucoepidermoid carcinomas of the salivary gland treated by surgery alone or by surgery plus radiotherapy. Local control for all 61 patients at 5 and 10 years was achieved for 88.8 and 79.7% of the cases. Although the rate of positive surgical margin was higher in patients treated with surgery and radiotherapy (radiotherapy group) than in patients treated by surgery alone (surgery group), the local control rates of the two groups showed no statistically significant differences. There was no local recurrence in seven patients receiving post-operative radiotherapy above 55 Gy while there were three local relapses among 17 patients receiving 55 Gy or lower doses (P < 0.05). The 5- and 10-year actual survival rates were 73.4 and 63.3% respectively. Histopathologic subtype of mucoepidermoid carcinomas correlated with regional lymph node involvement and survival. There were no differences in the local control and survival rates of patients with major salivary gland tumors and patients with minor salivary gland tumors. Radiotherapy using 55 Gy or more combined with operation achieved local control and survival rates comparable with complete resection of tumors even if a positive surgical margin was more frequent in the radiotherapy groups.
Adolescent↗
Salvage therapy for recurrent germinomas in the central nervous system.
This report presents the results of salvage therapy for 15 recurrent germinomas. The first recurrence occurred at a median of 37 months (range 6-122 months) after primary therapy. By the median follow-up period of 57 months after the first recurrence, seven of the 15 patients had died of the recurrent disease. Eleven of 15 patients who had been treated with reirradiation once achieved a complete response. Of these 11 patients, six had a second recurrence and two developed disabling radiation necrosis. Six of the 15 patients received a platinum-based chemotherapy and they also achieved a complete response. However, the remissions after chemotherapy alone were not durable. Three of the six patients received an additional low-dose (20-24 Gy) of irradiation following the chemotherapy and remained tumour-free with a performance status of more than 70%. Overall, the recurrent germinomas were consistently responsive to salvage radiation therapy and chemotherapy. However, just reirradiation or platinum-based chemotherapy alone was not sufficient to prevent a further recurrence. A low-dose of radiation therapy following chemotherapy is therefore recommended.
Adolescent↗
Effect of temporary hepatic venous occlusion on hepatic arterial embolization. An experimental study.
RATIONALE AND OBJECTIVES: The authors evaluated the effect of hepatic venous occlusion on hepatic arterial embolization in rats. METHODS: A Lipiodol-Iopamidol mixture was injected into the proper hepatic artery in rats during clamping the right side of the hepatic venous confluence. The distribution of Lipiodol-Iopamidol mixture in the sinusoids was analyzed by histological examination with en bloc silver impregnation. The extent of the distribution of Lipiodol-Iopamidol mixture was compared in sinusoids with hepatic venous occlusion and in sinusoids without hepatic venous occlusion. RESULTS: Lipiodol-Iopamidol mixture was more widely distributed in the lobules with hepatic venous occlusion than in the lobules without occlusion. CONCLUSIONS: Hepatic venous occlusion may enhance the effect of hepatic arterial embolization using Lipiodol emulsions and could be useful in the treatment of hepatocellular carcinoma.
Animals↗
A phase II study of concomitant chemoradiotherapy for laryngeal carcinoma using carboplatin.
PURPOSE: We conducted a phase II study of concomitant chemoradiotherapy with carboplatin for laryngeal carcinoma. MATERIALS AND METHODS: Sixty-four patients with stage II-IV (stage II, 36; III, 19; IV 9) laryngeal carcinoma were treated with concomitant administration of carboplatin (CBDCA) during radiotherapy (CRT group) between 1991 and 1994. There were 36 supraglottic, 25 glottic, and 3 subglottic carcinomas. Patients with stage II and stage III-IV received intravenous CBDCA of 100 mg/m2 and 120 mg/m2 once a week, respectively. Tumor response was assessed at 40 Gy in 16 fractions to select the patients suitable for total laryngectomy or radical radiotherapy of 65 Gy in 26 fractions in 6.5 weeks. The treatment results were compared with the historical control consisting of 56 patients consecutively treated from 1988 to 1990 without chemotherapy (RT group). The two studies were comparable with regard to patient characteristics, including age distribution, gender, tumor location, size, and clinical stage. RESULTS: The actuarial 5-year survival rate was 80.3% for the CRT group and 81.3% for the RT group. A favorable response (complete response or partial response) at 40 Gy was observed in 87.5% of the patients of the CRT group and in 62.5% of the patients of the RT group (chi2 = 7.566, p < 0.01). The actuarial 5-year larynx preservation rate for the CRT group (75%) was significantly higher than that for the RT group (57%) in patients with T2 supraglottic carcinoma (p < 0.05). There was no difference in the larynx preservation rate between the two treatment arms for any T stage of glottic carcinomas. CONCLUSION: CRT using carboplatin improved the tumor response at 40 Gy and consequently achieved a higher larynx preservation rate for T2 supraglottic carcinoma. A clinical randomized trial is indicated to certify the findings of this phase II study.
Antineoplastic Agents↗
The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.
We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.
Animals↗
Occult neurohypophyseal germinomas in patients presenting with central diabetes insipidus.
Although neurohypophyseal germinoma is known be a common initial symptom in cases of diabetes insipidus (DI), its radiological detection may take months or years even by a high-resolution magnetic resonance (MR) imaging. The term "occult neurohypophyseal germinoma" denotes such cases, but its clinical picture remains obscure. Of seven patients with neurohypophyseal germinoma presenting with DI during the last 5 years, three patients showed no evidence of tumor at the onset of DI and were treated as "idiopathic" DI. Neurohypophyseal germinoma was eventually diagnosed in these three patients as the tumor became evident on sequential MR imaging studies and the patients were successfully treated with chemotherapy and radiation therapy. To delineate the clinical features of the occult neurohypophyseal germinoma, the authors analyzed endocrinological aspects and MR images in these patients and compared them with those in two patients with true idiopathic DI and four patients with overt neurohypophyseal germinoma and DI. Nine previously reported cases in the literature were reviewed. During the stage at which the germinoma gave no notable change on MR images, patients often displayed anterior pituitary dysfunction, particularly growth hormone (GH) deficiency, or an elevation of serum or cerebrospinal fluid human chorionic gonadotropin-beta. Preceding the appearance of an obvious tumor mass, a slight swelling of the pituitary stalk with loss of normal hyperintensity of the posterior pituitary lobe was a common finding on MR imaging. Central DI associated either with an enlarged stalk, decreased GH secretion, or an elevated serum human chorionic gonadotropin-beta should prompt the diagnosis of an occult germinoma.
Journal Article↗
Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations.
Recent studies suggest that a balance may exist between the cell cycle arrest and apoptosis-inducing functions of the p53 tumor suppressor gene. Adenoviral p21 transduction attenuates apoptosis, whereas deletion of the p21 gene promotes it, and p21-null xenografts respond better than isogenic p21-wild type tumors to irradiation. Hence, the role of p53 in dictating the clinical response to radiotherapy and chemotherapy may be more complex than previously thought. We have analyzed survival and radiation response (regrowth-free period) of 42 patients with glioblastomas whose p53 status was determined by a sensitive yeast functional assay. Multivariate analysis revealed that p53 mutation is associated with longer survival (P < 0.02). Among 36 radiation-treated patients, the regrowth-free period after treatment was significantly longer for tumors with p53 mutations (P < 0.0001), and p53 mutation was the sole independent factor predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth was independent of p53 status, suggesting that the difference in survival was related to the treatment rather than to the intrinsic aggressiveness of the tumor. Thus, in this Northern Japanese population, p53 mutation is a marker for better radiation response in glioblastomas, and this results in significantly longer survival.
Adolescent↗
High-dose-rate intracavitary irradiation using linear source arrangement for stage II and III squamous cell carcinoma of the uterine cervix.
PURPOSE: The purpose of this article is to evaluate fractionated high-dose-rate (HDR) intracavitary irradiation using linear source arrangement (LSA) for patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: The subjects consisted of 217 patients (71 patients with stage II and 146 with stage III disease) who received external beam therapy (EBT) followed by fractionated HDR intracavitary irradiation using LSA between January 1980 and June 1990. In EBT, 40 Gy in 20 fractions (40 Gy/20 Fr) or 39.6 Gy/22 Fr was delivered to the whole pelvis and an additional 10 Gy/5 Fr or 10.8 Gy/6 Fr was delivered to the parametrium. The intracavitary irradiation dose was 30 Gy/6 Fr or 35 Gy/7 Fr with a daily fraction size of 5 Gy and two fractions per week. During the intracavitary treatment, most patients were treated on an out-patient basis. RESULTS: Cause-specific 5-year survival rates were 77% for stage II and 50% for stage III. Pelvic failure rates were 13% for stage II and 36% for stage III. In multivariate analyses, improved cause-specific survival was significantly associated with stage II (P = 0.0003), higher pretreatment serum hemoglobin level (P = 0.0015), higher pretreatment serum total protein level (P = 0.0029), and shorter total treatment time (P = 0.0024). The rate of severe (grade 3 or 4) late complication was 2% for the rectum, 1% for the small intestine or sigmoid colon and 1% for the bladder. CONCLUSIONS: Fractionated HDR intracavitary irradiation using LSA is an effective treatment for patients with uterine cervical cancer without need for hospitalization.
Adult↗
A new mold material for customized patient positioning in radiotherapy.
MATERIALS: The new material consists of polystyrene beads coated in a polymerizing substance that when dampened, hardens within 10 min. RESULTS AND CONCLUSIONS: It has a density of less than a tenth of that of water and so is light-weight, a CT number of less than -800 and a minimal effect on the build-up of megavoltage photon beams.
Casts, Surgical↗
Pathologically-proven intracranial germinoma treated with radiation therapy.
BACKGROUND AND PURPOSE: A retrospective multi-institutional study was conducted to survey what percentage of intracranial germinomas were treated with pathological confirmation before radiotherapy and to investigate the influence of field selection on outcome. MATERIALS AND METHODS: Thirty-seven percent of patients (41 of 110 patients) were pathologically confirmed before radiotherapy during the past 16 years at eight institutions in Northern Japanese prefectures. Pathological confirmation was obtained in 26, 37 and 53% of cases during 1978-1983, 1984-1989 and 1990-1994, respectively. All 110 patients were examined using computed tomography (CT) scans. Among the 41 patients with pathologically confirmed germinoma, radiation fields were craniospinal in 23 patients, whole-brain in 10 patients and local without ventricle inclusion in eight patients. RESULTS: For the 41 patients with pathologically confirmed germinoma, the actuarial and cause-specific survival rates were 91/94% at 5 years and 87/90% at 10 years, respectively. The relapse-free survival rate at 10 years was 90. 76 and 22% for the craniospinal field, whole-brain field and local field without ventricle inclusion, respectively. CONCLUSION: Pathological confirmation was obtained in only 37% of CT-scan era cases, although the confirmations were more commonly carried out later in the study period. Limited local irradiation alone without ventricle inclusion cannot be recommended for localized tumors even with the help of CT scanning.
Adolescent↗
Retrospective multi-institutional study of radiotherapy for intracranial non-germinomatous germ cell tumors.
The treatment outcome of 24 patients with pathologically-proven non-germinomatous germ cell tumor was retrospectively investigated to determine the effectiveness of radiotherapy. The patients were divided into three groups as follows: group 1, five patients with mature teratoma with or without germinoma; group 2, six patients with immature teratoma with or without germinoma; group 3, 13 patients with other highly malignant tumors. The overall actuarial survival and relapse-free rates at 5 years were 82% and 59%, respectively, with a median follow-up period of 62 months. The actuarial relapse-free rate at 5 years was 100% for group 1, 63% for group 2 and 44% for group 3. There was no difference in the relapse-free rates between total resection and partial resection. Usage of chemotherapy was adversely related to survival probably due to selection bias. No local failure was observed with 10 Gy or more for group 1,40 Gy or more for group 2 and 54 Gy or more for group 3. In groups 1 and 2, there was no spinal relapses without craniospinal irradiation. In group 3, three of eight patients who did not receive craniospinal irradiation and none of five patients who received craniospinal irradiation experienced spinal relapse. In conclusion, highly malignant GCTs show a high incidence of spinal metastasis and craniospinal irradiation may reduce the risk of spinal metastasis. Radiation dose and volume are to be determined according to the histopathological aggressiveness.
Adolescent↗
Audiological assessment before and after fractionated stereotactic irradiation for vestibular schwannoma.
PURPOSE: To find the audiological outcome after LINAC-based fractionated stereotactic irradiation (STI). MATERIALS AND METHODS: Twenty-four patients with vestibular schwannoma treated by fractionated STI between 1991 and 1997 had measurable hearing before STI and were followed audiologically for more than 6 months. The pure tone average (PTA) was measured by averaging the air-conduction threshold for five main frequencies (250-4000 Hz) before and periodically after STI in the 24 patients. Several possible prognostic factors for hearing preservation (defined as a PTA change at the last follow-up of less than 10 dB) were investigated. The median follow-up time was 22 months, ranging from 5 to 69 months. The irradiation schedule was 36 Gy in 20 fractions in 5 weeks to 44 Gy in 22 fractions in 6 weeks followed by 4 Gy/1 fraction boost. RESULTS: The pure tone average before STI was distributed from 7 to 73 dB. Fifty percent of patients showed a change in PTA of less than 10 dB, 79.2% of patients showed a change in PTA of less than 20 dB and 20.8% of patients showed a change in PTA of more than 21 dB at the last follow-up. Only one patient (4%) became deaf. Cases with a sudden loss of hearing were more likely to experience hearing preservation than those with gradual loss of hearing (P<0.05). The mean age was younger in patients whose hearing was preserved (P<0.05). Poor pretreatment PTA appeared to linearly correspond to the changes in PTA (regression coefficient 0.78). The size of the tumor was not related to the change in PTA. No relationship was observed between the maximum or peripheral dose and the PTA change. The real benefit of stereotactic boost after small-field fractionated irradiation was not certain. CONCLUSION: Fractionated STI produced a hearing preservation rate compatible with meticulously collimated multi-spots single fraction irradiation. Further follow-up is required to confirm the long-term benefits of fractionation.
Audiometry↗
Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes.
Germ cell tumours (GCTs) of the central nervous system (CNS) encompass various histological subtypes, and their optimal management has been the subject of debate. To indicate a better management strategy for each subtype, we analysed the records of 111 patients (median age 14 years), who underwent treatment since 1970. With a median follow-up duration of 86 months, the probability of surviving 5 years was: 96% for pure germinoma patients, 100% for mature teratoma, 67% for immature teratoma and 69% immature teratoma mixed with germinoma. The probability of cause-specific progression of germinomas producing human chorionic gonadotropin (HCG) was higher than that of non-producing germinomas (P < 0.01). GCTs that included a highly malignant component, such as embryonal carcinoma or yolk sac tumour, exhibited a poor prognosis with 38% chance of 5-year survival. Late adverse effects of therapy included stroke, secondary malignancy and cognitive, endocrinological, auditory and visual dysfunctions. Of 85 survivors with a median follow-up period of 99 months, 58 patients needed hormone replacement therapy, 26 patients showed poor performance status and, to date, only 1 patient has fathered children. Because the outcomes varied widely for each subtype, the traditional categories, that is, germinoma and non-germinomatous GCT as an extrapolation from the gonadal GCTs, are not suitable for appropriately selecting therapeutic regimen for CNS GCTs.
Activities of Daily Living↗
Scintigraphic evaluation of long-term salivary function after bilateral whole parotid gland irradiation in radiotherapy for head and neck tumour.
In 25 patients with head and neck tumour, in whom bilateral whole parotid glands were totally included in the irradiation volume, parotid gland function was estimated and compared with that of 58 non-irradiated parotid glands in 29 patients, by symptomatic grading and radioisotope (RI) sialography. Sequential follow-up by RI sialography has suggested that if the total dose to the parotid gland is less than 52 Gy or if the time-dose fractionation (TDF) value is less than 80, then partial recovery of salivary function can be expected 1 or 2 years after irradiation, even if patients show severe xerostomia during the first 6 months. Long-term recovery rarely occurs in parotid glands which have been irradiated at doses exceeding 55 Gy or with TDF values of 88 or higher. The 50% complication probability (ED50) was less than 33 Gy for subacute xerostomia during the first 6 months and 52.5 Gy for chronic xerostomia after 12 months, respectively. Although a prospective study will be required for confirmation, differences between the dose-response curves of xerostomia at subacute and chronic phases suggest a basis in different biological mechanisms.
Acute Disease↗
Induction chemotherapy followed by reduced-volume radiation therapy for newly diagnosed central nervous system germinoma.
OBJECT: Although curative, radiation, which is conventionally administered for germinomas, causes significant neurological sequelae. This study aimed at reducing the volume and dose of radiation to a localized level of 24 Gy by pretreating the patient with chemotherapy. METHODS: Seventeen patients were divided into two risk groups based on serological findings and the extent of tumor. They were treated with chemotherapy prior to receiving localized radiation therapy. Six patients with solitary pure germinomas were treated with three or four cycles of cisplatin and etoposide (EP regimen) followed by 24-Gy local radiation therapy. Eleven patients with human chorionic gonadotropin (HCG)-secreting, multifocal, or disseminated germinomas received four to five cycles of ifosfamide, cisplatin, and etoposide (ICE regimen) followed by 24-Gy local radiation therapy. Craniospinal ports were used only in three cases of germinomas with dissemination. Gross-total resection was performed in three patients. Fourteen patients were able to be evaluated for their responses to chemotherapy. All patients achieved a complete response within three cycles. At a median follow-up duration of 24 months, 16 patients (94%) were alive without recurrence. One patient with an HCG-secreting germinoma experienced recurrence 38 months after surgery. That patient underwent successful salvage therapy using the same protocol. Thus, all 17 patients became free of disease with a 70 to 100% Karnofsky Performance Scale status. Toxicities associated with this study's chemotherapy regimen were mostly transient. No patient showed neurological or endocrinological deterioration during the follow-up period. CONCLUSIONS: The EP and ICE regimens were highly effective in treating the central nervous system germinomas and permitted dose and volume reduction of the radiotherapy. Localized 24-Gy irradiation was sufficient for disease control.
Adolescent↗