Radiotherapy for retinoblastoma. Treatment strategies.
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Brachytherapy↗
Biomedical subjects
W Sauerwein
Publications and source records attributed to W Sauerwein.
Clinical and technical requirements for proton treatment planning of ocular diseases. The SERAG (South Europe Radiotherapy Group).
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Conjunctival Neoplasms↗
Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).
BACKGROUND: The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. METHODS: Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox's proportional hazard model. RESULTS: In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). CONCLUSIONS: In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.
Adenocarcinoma, Follicular↗
Comet assay study of DNA damage and repair of tumour cells following boron neutron capture irradiation with fast d(14) + Be neutrons.
We compared the amount of radiation-induced DNA damage and the extent of DNA repair in human melanoma cells (MeWo) using the 'comet assay' after neutron, boron neutron capture and X-irradiation. Using a colony-forming assay it was shown earlier that lethal effects in tumour cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The effectiveness of boron neutron capture in killing tumour cells depends on the number of 10B atoms delivered to the tumour, the subcellular distribution of 10B and the thermal neutron fluence at the side of the tumour. Using the 'comet assay' the DNA damage of fast neutrons (mean energy 5.8 MeV) was shown to be significantly greater than for the same absorbed dose of X-rays. The presence of 600 ppm 10B (boric acid H5 10BO3) in the cell medium during irradiation with d(14) + Be neutrons in a phantom enhances the DNA damage by 20% compared with neutron irradiation alone. After DNA damage induction by neutrons and neutron capture of boron, the DNA repair capacity of the MeWo cells is significantly reduced in comparison with X-irradiation resulting in proportionally more residual DNA damage after 180 min of repair time.
Boron Neutron Capture Therapy↗
[Long-term outcome of radiotherapy of choroid hemangioma].
The usual therapeutic approach to circumscribed choroidal hemangiomas of the posterior pole consists of scatter photocoagulation of the tumor surface. This may often require repetitive treatment or additional invasive measures prior to coagulation due to massive exudative detachment of the retina. In this study, external beam irradiation with high-energy photons (total absorbed dose: 20 Gy) was applied to 36 symptomatic patients. The indication for treatment was exudative retinal detachment including or threatening the fovea. The mean duration of follow-up was 4.5 years (4 months to 24 years, median 4 years). In 23 cases (63.8%) complete resolution of the subretinal fluid could be achieved; 13 cases (36.2%) showed residual serous detachment at some distance from the fovea. The visual acuity improved by two or more lines in 14 cases (38.9%), remained stable in 14 cases and decreased in only 8 cases (22.2%). The functional success was dependent on the interval between onset of first subjective symptoms and treatment. External beam irradiation is a successful form of treatment for choroidal hemangiomas.
Adult↗
Monte Carlo simulation of the biological effects of boron neutron capture irradiation with d(14)+Be neutrons in vitro.
It was shown that radiation effects in tumor cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The classic approach for macroscopic dosimetry in fast-neutron therapy cannot be applied to the dose in boron neutron capture therapy (BNCT). The effectiveness of BNCT in killing tumor cells depends on the number of 10B atoms delivered to the tumor, the subcellular distribution of 10B and the thermal neutron fluence at the site of the tumor. Monte Carlo calculations of the energy depositions of short-range particles with high LET coming from 10B disintegrations were performed and compared to the observed biological effects. The simulation allows us to study the influence of the localization of intracellular 10B in the nucleus, cytoplasma, plasma membrane or extracellular space. The biological response function which describes the probability of the lethal effect produced by a single particle track through the cell nucleus was found by comparing the calculated microscopic dose distribution spectra for single events with the survival observed experimentally. Calculations for a human melanoma cell population treated as a monolayer in the presence or absence of boron with d(14)+Be neutrons will be demonstrated. Two different boron compounds enriched in 10B were investigated in this study: boric acid (H3 10BO3) and p-dihydroxyboryl phenylalanine (BPA). The study shows that a high fraction of BPA enters the cytoplasm while boric acid was found only in the extracellular space. The computer simulations indicate that BPA yields a higher potential effectiveness for inactivation of melanoma cells than boric acid.
Boron Neutron Capture Therapy↗
Histopathologic findings in large uveal melanomas after brachytherapy with iodine 125 ophthalmic plaques.
Eyes of 25 patients among a series of 100 consecutive patients who underwent iodine 125 brachytherapy for extremely large uveal melanomas measuring more than 7-8 mm in height had to be enucleated after an average interval of 1.4 years. The dose delivered to the tumor apex was 120-150 Gy. Indications for enucleation were most frequently radiation-induced alterations in the anterior segment with loss of fundus visibility. Eight cases showed insufficient tumor regression, and two cases were suspicious for growth. Microscopically complete tumor necrosis was found in ten eyes. Six cases were classified as "uncertain tumor regression." Apparently "viable" tumor cells were seen in nine eyes. This group of eyes showed a significantly shorter interval between therapy and enucleation. One specimen showed extraocular tumor extension. Brachytherapy with iodine 125 may result in complete tumor necrosis, even in large uveal melanomas. The morphologic extent of tumor necrosis seems to be positively correlated with the interval after therapy.
Aged↗
Pulmonary and cerebral irradiation for hyperleukocytosis in acute myelomonocytic leukemia.
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Adult↗
Prognosis and treatment of disseminated uveal melanoma.
BACKGROUND: The clinical course of uveal melanoma differs greatly from that of cutaneous melanoma. METHODS: Twenty-four patients with metastatic uveal melanoma (13 men and 11 women; median age at diagnosis, 56 years [range, 17-67 years]) were evaluated retrospectively. RESULTS: Main sites of metastases were liver (87%), lung (46%), bone (29%), and skin (17%). Median relapse-free survival time was 36 months (range, 5-240 months). Median survival time after clinical detection of metastases was 9 months (range, 1-54 months). Relapse-free survival time was significantly greater in patients 50 years of age or younger. After manifestation of metastases, the clinical course was more favorable in patients in whom the liver was either not involved at all or not among the first sites of dissemination. These patients had a median survival time of 19 months, compared with 7 months for patients in whom the liver was involved initially. First-line systemic treatment of metastatic disease yielded three cases of stable disease lasting 6-14 months, but no complete or partial response. Three patients received intraarterial liver perfusion as first- or second-line treatment, resulting in one partial response, which lasted 6 months. CONCLUSION: Treatment and prognosis results of patients with metastatic uveal melanoma were poor, especially when the disseminated to the liver; survival time of approximately 9 months can be expected.
Adolescent↗
Principles and history of neutron capture therapy.
Neutron capture therapy (NCT) is a form of radiation therapy using nuclides having a high propensity for capturing thermal neutrons and reacting with a prompt nuclear reaction (i.e. disintegration). If these nuclides are introduced selectively into tumor cells it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. The principles of this modality were described in 1936. First clinical trials in the USA from 1951 to 1961 using 10B resulted in failure. Since 1968 patients suffering from glioblastoma have been successfully treated in Japan by NCT with 10B and since 1987 another Japanese group has treated melanoma using NCT. The Japanese experiences and recent advances in the evaluation of tumor-affinitive boron-containing drugs have spurred interest in NCT. This article presents some basic physical notions and a historic overview of NCT that emphasizes the well documented early trials as well as some recent developments. Problems which occurred in the past now demand special efforts for a better understanding of the effects of NCT before starting new clinical trials in the next few years.
Boron Neutron Capture Therapy↗
Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy.
Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth-dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep-seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non-boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%.
Boron Neutron Capture Therapy↗
[The special aspects in the planning and use of an electron linear accelerator facility for intraoperative radiotherapy (IORT)].
Limiting conditions for the planning of the installation of an electron linear accelerator in an operating theatre are described taking into account the radiotherapeutical and surgical requirements based on the example of the Essen facility for intraoperative radiotherapy (IORT) with electrons. Special features of the facility like a non-contact electron applicator system with television monitoring, table-top trolley, which is used also during irradiation, are explained in detail. Measured isodose curves for all tubes and all electron energies serve for the radiotherapist as criteria for decision on tube size and electron energy selection during surgical operation. The influence of misalignments of the tube on dose distributions is investigated. Limit values of alignment tolerances are deduced. Daily constancy tests for monitor calibration, electron energy, and tube alignment system are to be performed for quality assurance. Tables of the planned and realized treatments and of a representative time schedule of an IORT give a survey on the indications and the necessary time effort and staff. Completion of the set of tubes as well as optimization of the tube fixation accessory and of the table-top trolley are main subjects for future developments.
Anesthesiology↗
Long-term treatment effects in patients with bilateral retinoblastoma: ocular and mid-facial findings.
A total of 99 patients with bilateral retinoblastoma who had been treated between 1965 and 1982 were reexamined in April 1988 to study the late effects of treatment. Their median age at the follow-up visit in 1988 was 16 years (range, 6-27 years), and the median follow-up was 15 years (range, 6-26 years). All patients underwent a full eye examination, morphometric measurements of the mid-face and genetic counselling. Each eye or orbit and the corresponding side of the patient's mid-face were evaluated separately, resulting in 198 data sets from 99 individuals. Subjects were divided into four treatment groups according to whether photo- and cryo-coagulation, enucleation, radiation therapy or various combinations thereof were used. In all, 81 eyes had a visual acuity of greater than 0.4 (in 23 of these, however, only with low-vision aids). Within a dose range of 36-51 Gy, the location of the tumor (36%) or cataract (15%) were the main factors responsible for poor visual acuity, whereas radiation retinopathy and/or optic neuropathy occurred in only three cases. Cataracts were more frequently observed following orthovoltage as compared with megavoltage therapy (P = 0.012). A total of 72 eyes had been enucleated and had not received radiation therapy at any time. Cosmetic results (as measured by several parameters) in these cases were significantly better then those in 28 subjects who underwent combined radiation therapy and enucleation. As defined by various subjective as well as objective findings, mid-facial hypoplasia occurred significantly more often following orthovoltage as compared with megavoltage therapy.
Adolescent↗
Dosimetry and fluence measurements with a new irradiation arrangement for neutron capture therapy of tumours in mice.
Incorporation of 10B in human tumours treated with fast neutrons would increase the local dose in the tumour. In tissue the neutrons are thermalized mainly causing the neutron capture reaction 10B (n,a) 7Li. The dose enhancement can be calculated using the thermal neutron fluence measured by activation of gold foils in a phantom. At a phantom depth of 5 cm a dose enhancement of (0.056 +/- 0.0028)% for each microgram of 10B per gram of tissue was determined in the tumour. A therapeutic gain by this dose enhancement in fast neutron therapy should be examined for a solid tumour in a mouse. The feasibility for neutron capture therapy of tumours in mice depends on the distribution of the tumour dose and on the effective shielding of the bodies of the mice. Therefore, a special holding device for simultaneous irradiation of four tumours was developed. The dose distribution in the tumours and in the surrounding bodies of mice was measured with TLD-300 in a special mouse phantom.
Animals↗
Risk factors for metastases in patients with retinoblastoma.
The study is based upon a review of data from 583 consecutive patients with retinoblastoma over the years 1956 to 1986. Mean follow-up was 8 years, and median was 5.5 years. In 41 patients, metastases developed within 5 years. The influence of clinical and histopathologic risk factors on the occurrence of metastases was first analyzed by univariate tests. Significant variables were then reevaluated using the Cox proportional hazards method. Four factors were found to be independently associated with the development of metastases: optic nerve invasion with and without involvement of the resection line, choroidal invasion and enucleation of an affected eye more than 120 days after initial diagnosis. The 5-year metastatic risks associated with these factors were 67%, 13%, 8%, and 4%, respectively. The relative risk estimate, calculated from the Cox model, was used for a score classification with groups of low, medium, and high metastatic risk. The 5-year incidence of metastases was 4%, 43%, and 68%, respectively.
Adolescent↗
[Risk of metastasis in retinoblastoma].
580 patients with retinoblastoma were analysed retrospectively. Median follow up was 5.5 years. 41 patients developed metastases within 5 years. Clinical and histopathological risk factors were analysed by univariate tests with regard to the occurrence of metastases. Significant variables were then reevaluated using Cox proportional hazards method. Four factors correlated independently with the development of metastases: optic nerve invasion with involvement of the resection line, optic nerve invasion without involvement of the resection line, choroidal invasion and enucleation of an affected eye more than 120 days after initial diagnosis. The regression coefficient beta of the Cox-model was used for a score classification with groups of high, medium and low metastatic risk. The 5-year incidence of metastases was 68%, 43% and 4% respectively.
Adolescent↗
Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy.
Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck (mostly 40-60 Gy) before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance (P less than 0.09). In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated.
Adenocarcinoma↗
New and recurrent tumor foci following local treatment as well as external beam radiation in eyes of patients with hereditary retinoblastoma.
The study is based on a retrospective analysis of data from 200 patients with hereditary retinoblastoma. Apart from four unilateral cases with a positive family history all patients had bilateral disease; 229 appeared suitable for conservative treatment while 167 eyes had to be enucleated. Primary local treatment was performed in 102 eyes, while 127 eyes received primary external beam radiation using a linear accelerator. Follow-up was adjusted by life tables, with 75% of the patients being observed longer than 2 years. Using life-table statistics new and recurrent tumors were found in 41% of all patients and in 95% of these cases they were noted within 26 months after initiation of therapy. Among eyes treated with primary external beam radiation new and recurrent tumors were observed significantly less frequently when 50 Gy (22% compared with 49% after 40 Gy) and a highly accurate beam alignment technique (22% compared with 48% after alignment to the outer bony canthus) were applied. The incidence of recurrent tumors following primary local treatment did not differ significantly with regard to the application of either photo- or cryocoagulation (28% vs 33%), while no recurrence was observed among tumors that were suitable for primary treatment using ruthenium or cobalt plaques.
Brachytherapy↗