Effect of carbon source and metal toxicity for potential acid mine drainage (AMD) treatment with an anaerobic sludge using sulfate-reduction.

This study compares sulfate-reduction performance in an anaerobic sludge with different carbon sources (ethanol, acetate, and glucose). Also, the toxic effect of copper was evaluated to assess its feasibility for possible acid mine drainage (AMD) treatment. Serological bottles with 1.5 g VSS/L and 150 mL of basal medium (0.67 g COD/g SO42- at a 7-8 pH) were used to determine the percentage of electron equivalents, maximum specific methanogenic (SMA), and sulfide generation activities (SGA). The copper effect was evaluated in a previously activated sludge in batch bioassays containing different concentrations of copper (0-50 mg/L), 3 gVSS/L, and 150 mL of basal medium (0.67 g COD/g SO42-). Carbon source bioassays with glucose obtained the best results in terms of the SGA (1.73 ± 0.34 mg S2-/g VSS•d) and SMA (10.41 mg COD-CH4/g VSS•d). The electron flow in the presence of glucose also indicated that 21.29 ± 5.2% of the metabolic activity of the sludge was directed towards sulfidogenesis. Copper toxicity bioassays indicated that a considerable decline in metabolic activity occurs above 10 mg/L. The 20%IC, 50%IC, and 80%IC were 4.5, 14.94, and 35.31 mg Cu/L. Compared to the other carbon sources tested, glucose proved to be a suitable electron donor since it favors sulfidogenesis. Finally, copper concentrations above 15 mg/L inhibited metabolic activity in the toxicity bioassays.

High-dose definitive concomitant chemoradiotherapy in non-metastatic locally advanced esophageal cancer: toxicity and outcome.

This study is a retrospective analysis of high-dose definitive concomitant chemoradiotherapy in locally advanced esophageal cancer in a single institution. The aim of the study was to identify and quantify the toxicity associated with the high-dose treatment and to analyze the outcome of this treatment. Forty-six patients (41 men and 5 women, median age of 67.5 years) with disease stage IIA-III esophageal cancer were treated with high-dose definitive chemoradiotherapy. Thirty patients had squamous cell carcinomas and 16 had adenocarcinomas. The patients were treated with three courses of chemotherapy. Each chemotherapy course consisted of cisplatin 100 mg/m(2), day 1 and 5-Fluorouracil 1000 mg/m(2)/day, day 1-5. One course was given every 3 weeks. Concurrent radiotherapy (66 Gy/33 fractions) was administered during the last two courses of chemotherapy. Toxicity grades three and four were seen in 47.5% and 40% of the patients, respectively. Treatment related mortality occurred in one patient (2.5%) due to neutropenic septicemia. Follow-up time for surviving patients (2/46) was 45 and 112 months. For the entire study population, the median time to local recurrence in the radiotherapy field was 33 months and the median time to distant metastasis was 8.7 months, whereas median overall survival was 10.8 months and median disease-specific survival 11 months. For responders to chemoradiotherapy, the median time to local recurrence was 76 months, the median time to distant metastasis 16.8 months, the median overall survival and the median disease-specific survival for the responders were both 17 months. The 2, 3 and 5-year survival rates were 22%, 15% and 11% for the entire study population, and 31%, 24% and 17% for the responders to chemoradiotherapy, respectively. By multivariate analysis response to chemoradiotherapy and lower disease stage were positive prognostic factors for survival. The results of our study have shown that concurrent high-dose chemoradiotherapy provides long-term local tumor control in locally advanced esophageal cancer. However, toxicities following this high-dose treatment, while manageable, were significant. Survival rates were not improved by high-dose chemoradiotherapy compared with what is reported in previous studies applying lower doses of definitive chemoradiotherapy.

Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders.

From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 microM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Prediction of treatment temperatures in clinical hyperthermia of locally advanced breast carcinoma: the use of contrast enhanced computed tomography.

PURPOSE: Nineteen patients with locally advanced breast carcinoma were subjected to computed tomography examinations prior to thermoradiotherapy. Pre- and postcontrast computed tomography images were obtained, and tumor contrast enhancement was studied in relation to tissue perfusion, PERF, and steady state temperature, TS, in an attempt to develop an assay for prediction of treatment temperatures in clinical hyperthermia of breast carcinoma. METHODS AND MATERIALS: PERF and TS were calculated from temperature data achieved during the first fraction of the heat treatment regimen. The computed tomography images were subjected to image analysis, and two parameters representing tumor contrast enhancement were calculated from the computed tomography numbers; the absolute increase in mean attenuation, delta N, and the fraction of the postcontrast attenuation values that was higher than the mean precontrast attenuation value, F+C. RESULTS: delta N and F+C were clearly correlated to each other. The two parameters differed considerably among the patients, showing that the accumulation of contrast medium was higher in some tumors than in others. Tumor contrast enhancement increased with increasing PERF, suggesting that the accumulation of contrast medium in the tumors was determined mainly by the effective tissue perfusion. There was also a clear correlation between tumor contrast enhancement and TS. The tumors showing a high accumulation of contrast medium were more difficult to heat than those showing a low accumulation. CONCLUSION: The results indicate that contrast enhanced computed tomography images may give information about the treatment temperatures that can be achieved in clinical hyperthermia of breast carcinoma. The computed tomography images may possibly be used to predict those tumors that can be heated to therapeutic temperatures.

Temperature distribution in locally advanced breast carcinoma during hyperthermic treatment: relationship to perfusion, vascular density, and histology.

Temperature distributions achieved during hyperthermic treatment of 16 patients with locally advanced breast cancer were analyzed in relation to tissue perfusion, vascular density, and histology of treated volume. Temperatures were measured using multi-sensor thermistor probes inserted in the center and periphery of the treatment volume. A steady state temperature, Ts, and a perfusion related parameter, PERF, were determined for each probe location. Vascular density and tissue composition were determined by histologic analysis of biopsies taken from the temperature probe locations before treatment. Both malignant and normal tissue were found in the biopsies, reflecting a diffusive tumor growth pattern. The malignant and normal tissue compartments were analyzed separately using stereologic techniques. Ts, PERF, vascular density, and tissue composition differed significantly between patients. There was a clear relationship between Ts and PERF, showing that the local tissue perfusion was decisive for the temperatures achieved. Ts and PERF showed a clear correlation with the normal tissue vascular density, but not with the malignant tissue vascular density; that is, the treatment temperatures achieved were mainly determined by the vascularization of the normal tissue compartment. Fraction of necrosis was the only tissue compartment parameter that showed a clear relationship to Ts and PERF. Ts increased and PERF decreased with increasing necrotic fraction.

Dosimetric verification of a dedicated 3D treatment planning system for episcleral plaque therapy.

PURPOSE: Episcleral plaque therapy (EPT) is applied in the management of some malignant ocular tumors. A customized configuration of typically 4 to 20 radioactive seeds is fixed in a gold plaque, and the plaque is sutured to the scleral surface corresponding to the basis of the intraocular tumor, allowing for a localized radiation dose delivery to the tumor. Minimum target doses as high as 100 Gy are directed at malignant tumor sites close to critical normal tissues (e.g., optic disc and macula). Precise dosimetry is therefore fundamental for judging both the risk for normal tissue toxicity and tumor dose prescription. This paper describes the dosimetric verification of a commercially available dedicated treatment planning system (TPS) for EPT when realistic multiple-seed configurations are applied. MATERIALS AND METHODS: The TPS Bebig Plaque Simulator is used to plan EPT at our institution. Relative dose distributions in a water phantom, including central axis depth dose and off-axis dose profiles for three different plaques, the University of Southern California (USC) #9 and the Collaborative Ocular Melanoma Study (COMS) 12-mm and 20-mm plaques, were measured with a diode detector. Each plaque was arranged with realistic multiple 125I seed configurations. The measured dose distributions were compared to the corresponding dose profiles calculated with the TPS. All measurements were corrected for the angular sensitivity variation of the diode. RESULTS: Single-seed dose distributions measured with our dosimetry setup agreed with previously published data within 3%. For the three multiple-seed plaque configurations, the measured and calculated dose distributions were in good agreement. For the central axis depth doses, the agreement was within 4%, whereas deviations up to 11% were observed in single points far off-axis. CONCLUSIONS: The Bebig Plaque Simulator is a reliable TPS for calculating relative dose distributions around realistic multiple 125I seed configurations in EPT.

Fractionated thermochemotherapy in vivo of a C3H mouse mammary carcinoma.

The interaction between fractionated heat treatment and fractionated drug treatment with cyclophosphamide (CTX) was investigated in a transplantable C3H mouse mammary carcinoma inoculated into the hind leg of C3D2F1/Bom mice. A tumour core temperature of 43.5 +/- 0.1 degrees C was achieved by immersing the tumour-bearing leg into a water bath thermostatically maintained at 43.7 +/- 0.1 degrees C. CTX was administered i.p. using the maximum tolerated dose (MTD) (LD 1%) for single fraction treatment (100 mg/kg) as the maximum fraction dose. For combined treatment CTX was given 15 min prior to heating. The endpoint was the time to reach a tumour volume of 5 times the volume at first treatment. Specific growth delay was used as effect parameter. In dose-effect experiments using total treatment time at 43.5 degrees C as dose parameter, drug enhancement ratio (DER) was determined as the ratio of the slope of the dose-effect curve for MTD of CTX plus heat to the slope of the curve for heat alone. In dose-effect experiments using total CTX dose as dose parameter, thermal enhancement ratio (TER) was determined as the ratio of the slope of the dose-effect curve for CTX plus 43.5 degrees C for 30 min to the slope of the curve for CTX alone. The regimens investigated were single fraction treatment and 3 and 5 fractions with time intervals of 3 and 5 days. For single fraction treatment DER was 1.4 +/- 0.1 and TER 2.3 +/- 0.2. The drug sensitization of the effect of heat treatment tended to increase with increasing number of fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival curves after X-ray and heat treatments for melanoma cells derived directly from surgical specimens of tumours in man.

X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters.

Clinical correlations of genetic changes by comparative genomic hybridization in Ewing sarcoma and related tumors.

Our previous comparative genomic hybridization (CGH) study of Ewing sarcoma and related tumors showed that DNA sequence copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward poor survival (Armengol et al., Br J Cancer 1997, 75, 1403-1409). These trends were not statistically significant. In the present study, we analyzed 28 primary Ewing sarcomas and related tumors by CGH to study whether these (or other) changes have prognostic value in these tumors. Twenty-one tumors (75%) had changes with a mean of 1.9 changes per tumor. The most frequent aberration was gain of chromosome 8 in 10 tumors (36%). Five tumors (18%) had copy number increases at 1q21-22 and 5 had gain of 7q. Copy number increase of 6p21.1-pter, gain of chromosome 12, and loss of 16q were seen in 11%. Copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward worse outcome, but the differences did not reach statistical significance. A novel finding is the association of copy number increase at 6p with worse distant disease-free (P = 0.04) and overall survival (P = 0.004). To confirm this finding and to see whether copy number increases of 1q21-q22 and of chromosomes 8 and 12 have definite prognostic value, a larger number of cases needs to be studied.

Transillumination for accurate placement of radioactive plaques in brachytherapy of choroidal melanoma.

PURPOSE: To present a technique for accurate plaque placement in episcleral brachytherapy of choroidal melanoma. METHODS: The tumor margins are marked on the scleral surface, and a dummy plaque is temporarily sutured to the globe. A fiber optic light pipe is then wedged into the space between the sclera and the plaque. Because of the reflecting inner surface of the plaque, the perimeter of the plaque can easily be observed during indirect ophthalmoscopy as a circle of light surrounding the tumor. By this method, it is possible to determine the exact position of the entire plaque in relation to the tumor and make the necessary adjustments. When the correct position is found, the dummy plaque is replaced by a radioactive plaque. RESULTS: Since 1993, we have routinely used this procedure in episcleral brachytherapy. CONCLUSION: This modified transillumination technique facilitates a correct positioning of episcleral plaques.

The relevance of tumour and surrounding normal tissue vascular density in clinical hyperthermia of locally advanced breast carcinoma.

It follows from the present work that the vascularization of the normal tissue present in the treatment volume limits the temperatures achieved during heat treatment of invasive ductal breast carcinoma. The temperatures can often be increased by giving fractionated heat treatment because heat treatment may reduce the cooling capacity of the normal tissue vasculature. Significant damage to supplying vessels occurs at the heat doses necessary to cause necrosis in the tumour and surrounding normal tissue, indicating that secondary cell death is an important mechanism for cell inactivation following hyperthermic treatment of breast carcinoma.

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.

Chemotherapy in soft tissue sarcoma. The Scandinavian Sarcoma Group experience.

The first chemotherapy study of soft tissue sarcoma (STS) by the Scandinavian Sarcoma Group was started in 1981 (SSG I). It evaluated the single agent adjuvant doxorubicin in a randomized setting in patients with high-grade STS. No improvement was noted in the overall survival or disease-free survival rate. More intense chemotherapy was thereafter (1991-1994) evaluated in a phase 2 study, introducing ifosfamide and a continuous infusion of etoposide with growth factor (SSG X). The response rate of previously untreated patients was high (42%), but complete remissions were few. Analysis of patients undergoing surgery after preoperative chemotherapy suggested an increased survival. A recent meta-analysis of adjuvant chemotherapy for localized resectable STS in adults, including the SSG I trial, indicated a better disease-free survival and possibly improved overall survival (Thierny et al. 1997). At present, we are studying whether such a benefit can be shown in patients with high-risk prognostic criteria by giving adjuvant ifosfamide and doxorubicin treatment after primary surgery (SSG XIII). In the latter SSG study, started on July 1, 1998, the adjuvant therapy is evaluated in a phase 2 study in selected patients with high-grade STS and other unfavorable prognostic factors.

Prognostic factors in bone sarcomas.

Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].

Posterior uveal melanoma treated with I-125 brachytherapy or primary enucleation.

PURPOSE: To study the incidence, clinical findings, and tumour characteristics of posterior uveal melanoma in Western Norway, and to report the results of a consistent treatment strategy (I-125 brachytherapy or primary enucleation) over a 13-year period. METHODS: The clinical records of all patients with posterior uveal melanoma referred between January 1993 and December 2005 were reviewed. Clinical data, radiation parameters, visual outcome, and mortality were analysed in a dedicated database. RESULTS: The study included 111 consecutive patients. The annual age-adjusted incidence (per million population) of posterior uveal melanoma was 8.5 for women and 8.9 for men. Fifty-six patients underwent I-125 brachytherapy, 52 were enucleated, and three received no treatment. The median follow-up time was 36 months (mean, 52 months; range, 2 months to 13 years). In the brachytherapy group, two eyes were enucleated owing to tumour recurrence and two because of neovascular glaucoma. A visual acuity of 0.1 or better, present in 87% of the patients before brachytherapy, was retained in 40% after a median follow-up of 61 months. After brachytherapy, the 5- and 10-year melanoma-specific mortality rates were 13.4 and 23.8%, respectively. The corresponding mortality rates for patients treated with primary enucleation were 49.5 and 49.5%. CONCLUSION: After brachytherapy, many patients lost useful vision due to radiation-induced complications. The probability of retaining the eye was high and only two patients experienced recurrent tumour growth. The mortality rates compare well with published series, and the differences in tumour size explain the difference in mortality between the two treatment groups.

The amount of treatment versus quality of life in patients formerly treated for head and neck squamous cell carcinomas.

The aim of the present study was to investigate the association between the self-reported quality of life (QoL) versus the initial TNM stage and amount of primary and recurrent tumor therapy given in a population of formerly treated head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL by the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ) C30/H&N35 by structured interview. One hundred and twenty-two patients less than 80 years old, who had been diagnosed with HNSCC in western Norway in the period from 1992 to1997, and who had survived until 2000, were identified. Of these patients, 106 were eligible to be included. Ninety-six of these patients agreed to be interviewed. For TNM stage as well as the type of therapy given (local surgery, neck dissection or radiation therapy), T stage predicted the general QoL scores. Both increased TNM stage and all given tumor therapy seemingly caused lower H&N symptom QoL scores. Of the various tumor treatments employed, neck radiation therapy and neck dissection were indicated to be the most closely associated with the H&N QoL scores. Having neck dissection performed seemingly caused impairment beyond what was explained by the initial TNM stage. In conclusion, tumor therapy to HNSCC should not be restricted due to general QoL considerations. Further study of how and when to perform neck treatment is suggested in order to avoid unnecessary reduced H&N QoL.

Thermochemotherapy in vivo of a C3H mouse mammary carcinoma: thermotolerant tumours.

The ability of cyclophosphamide (CTX) and mitomycin C (MMC) to modify the expression of thermotolerance in vivo at 43.5 degrees C was investigated in a transplantable C3H mouse mammary carcinoma grown s.c. in feet of C3D2F1/Bom mice. Dose-effect curves subjected to linear regression analysis were constructed for single-fraction treatment and for a second treatment 24 h after a priming heat treatment of 43.5 degrees C for 30 min. Tumour volume doubling time during regrowth showed no significant variation among treatment groups, justifying the use of tumour growth time as effect parameter. Thermotolerance ratio for heat alone was 11.6 +/- 2.3. Drug enhancement ratio in thermotolerant tumours was 6.2 +/- 1.4 for CTX (100 mg/kg) and 3.5 +/- 0.9 for MMC (3 mg/kg). These values are about 4 and 3 times larger than the corresponding enhancement ratios found for previously untreated tumours. Thermotolerance ratio for thermochemotherapy was 2.6 +/- 0.3 for CTX and 4.4 +/- 0.7 for MMC, i.e. the degree of thermotolerance was substantially reduced by both drugs, but not completely overcome. Thermal enhancement ratio for CTX and MMC was about equally large in thermotolerant and previously untreated tumours. Thermotolerant tumours showed a tendency for increased resistance to drug treatment alone. Both CTX and MMC may be used clinically to reduce the expression of thermotolerance, particularly in situations with inhomogeneous heating and short fractionation intervals.

Sightsaving therapy in retinoblastoma. Experience with external megavoltage radiotherapy.

In Norway, sightsaving therapy in retinoblastoma has only been given to least affected eyes in bilaterally affected children. The results in 8 eyes given external high energy radiotherapy are reported. Additional focal therapy was given to 3 eyes for residual tumours and to one eye with new tumour at the ora serrata. Cataract was treated in 2 of the 3 eyes in which it developed. Vitrectomy was performed in 2 eyes with vitreous haemorrhage and persisting vitreous haze. Secondary enucleation has been avoided in all eyes 3-9 years after irradiation. One patient developed metastases in the temporal region at the enucleated side. Visual acuity is 6/12-6/6 if the macula has not been destroyed by tumour or focal therapy. Sightsaving therapy is presently also offered to unilateral cases and worst affected eyes in bilateral cases if the eyes belong to Reese-Ellsworth groups I-IV.