Late complications after radiotherapy for prostate cancer.

BACKGROUND: The aim of the present study was to analyze in detail the time course of the incidence of radiation-induced late effects. For this purpose, unpublished data of patients treated by radiation therapy in Hamburg in the late 1980s were analyzed. Relatively large volumes were exposed to comparatively high doses, thus leading to a high rate of treatment-related side effects. PATIENTS AND METHODS: A total of 180 consecutive patients received radiotherapy for prostate cancer. The median age was 66 years (range 41-88 years). The median of the maximum dose was 77.5 Gy (range 56.3-95 Gy) and overall treatment time was 51 days (range 28-128 days). Endpoints analyzed were late complications of grade 3 or higher, overall and disease-free survival, local tumor control, and distant metastases. Data analysis was actuarial and the log-rank test was used to compare the various subgroups. RESULTS: After 2 years, 80.5 ± 3.2% of the patients were without any complications of grade 3 or higher, and after 5 years a constant level of 70.3 ± 4.0% was approached. When multiple lesions occurred per patient, the later events were disregarded. A total of 66 complications occurred in 42 patients. The percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by an exponential function and a constant fraction. Complications approached a constant level of 70.3% at a rate of 5.3% per month. This means that patients who will develop a complication do so at exponential kinetics and at a relatively high rate, whereas about 70% of the patients will never experience a late effect even over long observation periods. After subdividing the maximum dose into three equal dose groups of 55 patients each (< 73.3 Gy, 73.3-80 Gy, > 80 Gy), the constant fraction decreased from 85.7 to 72.8% and 52.2%, whereas the incidence rate was 4.3%, 7.7%, and 5.6% per month and, thus, almost independent of radiation dose. CONCLUSION: For a given group of patients, the rate of the incidence of late complications appears to be independent of radiation dose and (from analyzing data in the literature) independent of the grade of lesions, whereas the fraction of patients without late effects depends on both parameters.

Prognostic value of haemoglobin levels during concurrent radio-chemotherapy in the treatment of oesophageal cancer.

AIMS: To evaluate the prognostic value of haemoglobin levels during radio-chemotherapy for overall survival, metastases-free survival (MFS) and locoregional control in patients with locally advanced oesophageal cancer. MATERIALS AND METHODS: Age, gender, performance status, tumour location, tumour length, histology, histologic grading, T-stage, N-stage, UICC-stage and weekly haemoglobin levels during concurrent radio-chemotherapy were retrospectively investigated and related to outcome in 108 patients, who received radio-chemotherapy for stage II/III oesophageal cancer. Radio-chemotherapy consisted of 59.4-60 Gy irradiation, two to four courses of cisplatin (75 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 on days 1-5). Haemoglobin levels during radio-chemotherapy were compared among the following three groups: patients with over 60% of haemoglobin levels less than 12 g/dl; patients with over 60% of haemoglobin levels at 12-14 g/dl; and patients with over 60% of haemoglobin levels greater than 14 g/dl. RESULTS: On univariate analysis, haemoglobin levels of 12-14 g/dl and greater than 14 g/dl during concurrent radio-chemotherapy provided better outcomes than haemoglobin levels less than 12 g/dl. The 2-year overall survival rates were 34%, 35% and 16%, respectively (P = 0.002). The 2-year MFS survival rates were 23%, 46% and 21%, respectively (P = 0.06). The 2-year locoregional control rates were 44%, 58% and 19%, respectively (P < 0.001). ECOG performance status (1 better than 2-3) was significantly associated with overall survival (P = 0.013), tumour length (<7 cm better than > or = 7 cm) with overall survival (P = 0.002) and MFS (P = 0.002), N-stage (N0 better than N1) with overall survival (P = 0.004) and MFS (P < 0.001), and UICC-stage (stage II better than III) with overall survival (P = 0.025) and MFS (P = 0.010). On multivariate analysis, haemoglobin levels during radio-chemotherapy maintained significance for overall survival (P = 0.002) and locoregional control (P < 0.001), tumour length for overall survival (P = 0.002) and MFS (P = 0.008), and N-stage for MFS (P = 0.003). CONCLUSIONS: Haemoglobin during radiotherapy and concurrent radio-chemotherapy is an independent prognostic factor in oesophageal cancer treatment. To improve outcome, it seems important to maintain the haemoglobin at 12-14 g/dl.

Results of radiotherapy of subfoveal neovascularization with 16 and 20 Gy.

PURPOSE: In a nonrandomized, prospective study the efficacy of radiotherapy with 16 and 20 Gray (Gy) for subfoveal neovascularization in age-related macular degeneration (ARMD) was analysed. MATERIAL AND METHODS: From 1996 to 1998, 63 eyes were irradiated with 16 Gy and 38 eyes with 20 Gy for exudative ARMD. A total of 12 eyes had classic ARMD, 89 eyes occult ARMD, median baseline visual acuity (VA) was 6/30 (range: 3/60-6/9.5), median age was 78 years. Risk factors (type of ARMD, baseline VA) were evenly distributed in both groups. Median follow-up was 1.3 years (range: 4 months-4.7 years). VA of +/-1 line or better and unchanged size and activity of the membrane in fluorescein angiography were defined as stable. Actuarial methods were used. RESULTS: Median loss of VA was -3 lines (range: -14 to +5), neovascularization remained unchanged or decreased in size and activity in 35 eyes. At 18 months, the probability of stabilized VA was 0.4 (95% confidence interval (CI): 0.3-0.5), at 24 months 0.3 (95% CI: 0.2-0.4). Radiation dose, type of ARMD or baseline VA had no significant impact on outcome of VA and membrane size and activity (P>0.05). Side effects were mild and transient increased tearing. CONCLUSION: In this study, the results after radiotherapy were comparable to the natural course of the disease. An impact of radiation dose (16 vs 20 Gy) on stabilizing visual acuity and subfoveal neovascularization could not be shown. The results of studies on dose escalation using very small fields and high radiation doses should be awaited.

Time benefit in the assessment of recurrences following fractionated radiotherapy in an experimental tumour system using positron-emission tomography with 18F-fluorodeoxyglucose.

PURPOSE: To determine the sensitivity and specificity of 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) in the diagnosis of R1H tumours after fractionated radiotherapy, and the dependency of sensitivity and specificity on time after therapy. In addition, the time benefit of FDG-PET concerning early recognition of recurrences after fractionated radiotherapy was assessed. MATERIAL AND METHODS: Subcutaneously growing rat rhabdomyosarcoma R1H tumours were irradiated by applying total doses of 80 or 85 Gy after reaching a start volume of 0.8 cm3. Twenty animals were treated. Tumour volume was determined twice a week. FDG-PET was performed weekly before, during and for 6 months after therapy using a conventional full-ring whole-body PET scanner. In total, 600 PET results were evaluated qualitatively using a six-scale score. PET results and actual tumour volumes were compared. The sensitivity and specificity of tumour detection by PET was calculated for different times after the onset of therapy. The optimal score for tumour detection and the influence of time after therapy on the quality of PET (time benefit) was evaluated using receiver-operating characteristics. RESULTS: After irradiation, 8/20 tumours (40%) were locally controlled, while 12/20 recurred. In this tumour model, evidence of relapse is assured when a volume of 0.1 cm3 is reached. Sensitivity of tumour diagnosis by PET increases with time, i.e. with the volume of recurrent tumours after the onset of therapy, mounting to > 0.95 after 100 days. Specificities of 0.95-1.0 were determined after therapy, showing no increase with time. Tumour diagnosis by PET is highly accurate when performed 80 days after the start of treatment. On average, tumours were recognized by PET on 31, 62, 74 and 81 days (median) before approaching volumes of 0.2, 0.5, 0.8 or 1.0 cm3, respectively. CONCLUSION: An experimental system was implemented that allows reproducible detection of recurrent R1H tumours after radiotherapy using FDG-PET. The usefulness of PET as a diagnostic test for R1H tumours is very good and a reliable resolution for PET is demonstrated for volumes < 1 cm3. The results indicate that FDG-PET enables early recognition of recurrences after fractionated radiotherapy.

Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG).

A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2-97.4) and 99.6% (95% CI: 99.2-100%) at 5 years and 94.9% (95% CI: 92.5-97.4%) and 99.6% (95% CI: 99.2-100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any 'in-field' relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated.

Quantification of late complications after radiation therapy.

BACKGROUND: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. METHODS: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15 x 2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. RESULTS: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p(a) was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p(a) remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p(a)=10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). DISCUSSION: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time; Type 3, curves composed of two components, a fast initial decline followed by an exponential decrease. For each kind of kinetics, provided that the dose distribution is not too heterogeneous, the incidence of late effects appears to occur at exponential or approximately exponential kinetics, even many years after treatment. This implies that a random process might be involved in the occurrence of late radiation sequelae. CONCLUSIONS: There might be a lifelong risk of developing late complications, of which patients and clinicians should be aware. It appears worthwhile to try to identify, in follow-up examinations of patients after radiation therapy, what kind of processes might be involved in triggering subclinical residual injury to develop into a clinically manifest late effect.

Impact of pulmonary metastases of the R1H-tumour on radiation tolerance of rat lung.

PURPOSE: The aim was to investigate the influence of pulmonary metastases of the rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat. MATERIAL AND METHODS: Three groups of animals were investigated: metastases-free animals treated with fractionated irradiation of the lungs; metastases-bearing animals receiving no irradiation; and metastases-bearing animals treated with fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases were thus treated at various well-defined sizes. Total doses of 20-60Gy were applied in fractions of 2 Gy within 11 days. Complication rate and survival time were used as endpoints. RESULTS: About 2 months after onset of irradiation treatment, animals had to be sacrificed because of severe respiratory distress either caused by irradiation-induced lung damage (median 57 days, range 36-77 days), or because of development of lung metastases (65, 20-160 days). A decrease of the ED(50) (dose required to induce lethal lung damage in 50% of irradiated animals) was determined for metastases-bearing animals. This effect increased with metastatic volume. CONCLUSIONS: The results suggest that the presence of tumours in the lung decreased the lung tolerance to radiation. This effect can hardly be explained by a reduction in functional lung volume by metastatic volume.

Impact of treatment acceleration and its timing on the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.

BACKGROUND AND PURPOSE: In clinical practice a concomitant boost is usually given as a second daily dose to a reduced field. The question arises which part of treatment should be accelerated to achieve optimal tumor control. An experiment was performed on tumor bearing rats to determine the optimal timing of treatment acceleration for this experimental tumor system. MATERIAL AND METHODS: Rhabdomyosarcoma R1H of the rat were treated applying 30 fractions in an overall treatment time of 40-42 days, up to total doses ranging from 67.5 to 97.5 Gy were administered. For control a standard treatment was given as continuous treatment applying one fraction per day. A boost of five additional fractions was given as a second fraction during 5 days. Three experimental arms received a boost either in the 1st, 4th, or in the last week of treatment. Treatment outcome was assessed using tumor control as endpoint. RESULTS: All experimental arms proved more effective than the standard treatment. Treatment was most effective when the boost was administered in the 1st week of treatment. A TCD37% of 87.1 Gy (95% CI: 82.8 ... 92.7 Gy), 96.5 Gy (89.9 ... 107.1), and 107.3 Gy (97.2 ... 131.0) was determined, when the boost was given in the 1st, 4th, or last week of treatment, respectively. The observed difference between the experimental arms was statistically significant (p = 0.004). CONCLUSIONS: Initially accelerated treatment schedules were found to be more effective for tumor control in an experimental tumor system.

Tandem application of sodium lauryl sulfate and n-propanol does not lead to enhancement of cumulative skin irritation.

Irritant contact dermatitis has a broad spectrum of clinical features and is a leading cause of occupational disease worldwide. It has been shown previously that a combination of chemically different irritants may cause an additive effect compared to single application of these substances. In this study, tandem application of sodium lauryl sulfate and n-propanol was investigated in 20 human volunteers using non-invasive bioengineering methods, such as measurement of transepidermal water loss and chromametry. N-propanol did not enhance cumulative skin irritation when used with sodium lauryl sulfate, as has been reported for toluene. As n-propanol is the active ingredient in many disinfectants, this is of particular interest regarding occupational skin irritation in health care workers.

Influence of dose per fraction and overall treatment time on the response of pulmonary micrometastases of the R1H-tumour to fractionated irradiation.

BACKGROUND AND PURPOSE: Macroscopic subcutaneously growing R1H-tumours have been shown to respond almost independently of the dose per fraction when treated under ambient conditions. In addition decelerated repopulation during fractionated irradiation has been shown for this experimental tumour. The aim of the present study was to investigate whether this is also the case for pulmonary micrometastases which are assumed to be fully oxygenated or whether differences in the oxygenation status of the tumour possibly alters its response to fractionation. The influence of the dose per fraction and overall treatment time on the response of micrometastases to fractionated irradiation was studied. MATERIALS AND METHODS: Pulmonary metastases were induced by i.v. injection of viable tumour cells. Treatment was started 14 days later, when metastases reached an average size of four cells. Total doses of 16 to 28 Gy were administered within an overall treatment time of 11 or 25 days, using doses per fraction of 1, 2, or 4 Gy. Tumour response was quantified by metastatic control (MCD(37%)). RESULTS: Fractionation had a significant influence on local control (P=0.009). After application of 1, 2, or 4 Gy and an overall treatment time of 11 days the MCD(37%) was 25.4 (95% C.I.: 21.5-32.0) Gy, 20.7 (17. 0-24.0) Gy, and 18.5 (14.9-21.6) Gy, respectively. When overall treatment time was prolonged to 25 days the MCD(37%) increased to 25. 5 (21.3-33.5) Gy when fractions of 2 Gy where applied, but this difference was not significant (P=0.13). The doubling time of 12.8 days determined for the metastatic clonogenic tumour cells during fractionated irradiation was significantly longer than the 4.1 days observed for untreated metastases (P=0.006). CONCLUSIONS: The results show a strong influence of fractionation on treatment outcome and a decelerated repopulation during fractionated irradiation treatment for well oxygenated pulmonary metastases of the R1H-tumour.

Loss of wild-type p53 function is responsible for upregulated homologous recombination in immortal rodent fibroblasts.

PURPOSE: A correlation between mutations in the tumour suppressor gene p53 and high rates of homologous recombination were previously found in immortal rodent fibroblasts. In the current study, direct evidence was sought that loss of p53 function is mainly responsible for upregulated levels of homologous recombination. MATERIALS AND METHODS: Homologous recombination was assessed in vitro using DNA plasmid substrates that stably integrated into the genome of mouse and rat embryonic fibroblasts. RESULTS: Primary fibroblasts with wild-type p53 displayed a recombination rate of about 1 x 10(-4). This number increased by 33- to 93-fold after spontaneous cellular immortalization, accompanied by loss of p53 function. To exclude potential bias from other gene mutations, wild-type p53 was experimentally disrupted in primary fibroblasts leading to an increase in recombination by one order of magnitude. Conversely, re-introduction of wild-type p53 into p53-null immortal cells reconstituted suppressed recombination rates. Finally, early-passage fibroblast cultures from p53-knock-out mice showed elevated recombination rates, which did not increase further following immortalization. CONCLUSIONS: Loss of wild-type p53 is the major genetic determinant of increased homologous recombination frequencies in immortal rodent fibroblasts. Cellular p53 status will be an important factor to consider when performing functional analysis of the increasing number of mammalian proteins that are found to be involved in homologous recombination.

Comparison of biological effects of DNA damage induced by ionizing radiation and hydrogen peroxide in CHO cells.

PURPOSE: Free OH radicals are considered to be the common mediator of DNA damage after ionizing radiation and oxidative stress. In particular, double-strand breaks (dsb) have a major impact on cell killing after irradiation, while the mechanism of cell killing is less clear for oxidative injury. The latter not only affects DNA, but also equally other cell compartments, such as membranes and mitochondria, which may trigger cell death. This study intended to clarify the relationship between DNA damage induction, repair and cell inactivation for hydrogen peroxide and ionizing radiation. MATERIALS AND METHODS: Chinese hamster ovary (CHO) cells were treated with H2O2 in serum-free medium in combination with/ without X-irradiation. DNA damage was measured using the alkaline unwinding method or neutral constant-field gel electrophoresis. Cell survival was recorded using the colony-formation assay. RESULTS: Hydrogen peroxide induced a large number of single-strand breaks (ssb>36000/cell) without impairing cell survival. This number reached a maximum (36 Gy-equiv. at 3 x 10(-4) mol/dm3) without further increase after higher concentrations. Repair kinetics of ssb were similar to those after irradiation. Dsb were found only after very high concentrations of H2O2 (>3 x 10(-2) mol/dm3), which is different from irradiation which generated ssb and dsb in the same dose range. A linear-quadratic increase of dsb was found with increasing concentrations of H2O2 suggesting a single or a pairwise action of OH radicals to form a dsb. After either irradiation or peroxide treatment cell killing was observed only after doses which also allowed dsb detection. The number of dsb calculated per lethal event was in the same range but slightly higher after irradiation (1.7-fold) than after H2O2 treatment. CONCLUSIONS: Cell killing after irradiation or hydrogen peroxide appears to be due to dsb, whereas cells withstand large numbers of single-strand lesions and other types of non-DNA damage occurring at lower concentrations of hydrogen peroxide. The number of ssb saturates at intermediate concentrations of H2O2 suggesting that a limited amount of chromatin-bound metal ions is available for OH radical generation.

[Giant condylomata acuminata (Buschke-Löwenstein tumor)]. / Condylomata gigantea Buschke-Löwenstein.

HISTORY AND ADMISSION FINDINGS: A 59-year-old woman had for 3 weeks been suffering from painful, moist skin changes on the external genitals, for 3 months having noticed vegetations in the anogenital and perineal region. She had been fatigued and lacking in energy since then. Her last gynecological examination had been 20 years ago. Examination of the skin on admission revealed extensive plaque and cauliflower-like warts and large areas of maceration in the anogenital region, the labia and perineum, with large areas of maceration. Nodules were clearly palpable in the left labium majora: the inner aspects were markedly reddened and had some cutaneous erosions. These findings suggested giant condyloma (GC; Buschke-Löwenstein tumour). INVESTIGATIONS: Biopsy showed marked condylomatous epithelial proliferations which, with the formation of markedly thickened epithelial cones, had reached the stage of a verrucous carcinoma. TREATMENT AND COURSE: Under local anti-inflammatory and adstringent medications the inflammatory reaction quickly subsided. Vulvectomy was performed to remove the tumour. CONCLUSION: Giant condyloma (Buschke-Löwenstein tumour) is a rare pseudocancereous lesion. If human papilloma viruses of type 16 or 18 is demonstrated in the lesions, malignant degeneration should be considered. Histological examination is essential to differentiate it from squamous cell carcinoma.

[Results of radiotherapy for vertebral hemangioma]. / Ergebnisse der Strahlentherapie von Wirbelkörperangiomen.

PURPOSE: Assessment of treatment results of symptomatic vertebral hemangiomas and review of the literature (Table 3). PATIENTS AND METHODS: Ten patients treated between 1974 to 1997 were retrospectively analyzed. Efficacy of treatment was determined according to improvement of pain and/or neurological symptoms (Table 1). RESULTS: Improvement was achieved in 8 of 10 patients. The initially existing neurological symptoms of 3 patients disappeared completely in 2 cases and improved in 1 case. Acute side effects were slight. Late side effects were not seen. A dose-effect relationship could not be assessed. There was no relapse. CONCLUSION: Radiotherapy with 30 Gy for symptomatic vertebral angioma as primary therapy is indicated. In case of neurological symptoms a radiotherapy after operative therapy is recommendable even if the patient is free of symptoms to prevent progress or relapse.

Interstitial high dose rate brachytherapy in locally progressive or recurrent head and neck cancer.

In a retrospective study, 19 patients with progressive or recurrent head and neck cancer which had been treated with interstitial high dose rate brachytherapy were analysed. All of them had been previously treated with external radiation. Initial therapy further included surgery in 9 cases and chemotherapy in 3 patients. Staging according to the TNM system revealed advanced stage tumors in the majority of patients. Interstitial brachytherapy was carried out with the isotope Iridium-192. The applied total dose at the reference isodose varied between 10 and 30 Gy. Application was fractionated once a week. A complete tumor remission was achieved in 5 patients and partial remission in 10 patients. In 4 patients the tumor continued to grow despite brachytherapy. The mean follow-up in our collective was 21 months. The calculated local control rate was 34% at 24 months. The survival rate was 49% at 12 months and 35% at 24 months. Interstitial brachytherapy is recommended as a palliative treatment in preirradiated squamous cell carcinoma with local recurrence or progression.

[Melatonin in dermatology. Experimental and clinical aspects]. / Melatonin in der Dermatologie. Experimentelle und klinische Aspekte.

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Serum melatonin levels exhibit a circadian rhythm with low levels during the day, rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin participates in the regulation of several physiological processes such as seasonal biological rhythm, daily sleep induction, aging and modulation of immunobiological defence reactions. Furthermore, melatonin has a highly lipophilic molecular structure facilitating penetration of cell membranes and serving as an extra- and intracellular free radical scavenger. Melatonin seems to quench mainly hydroxyl radicals, the most damaging of all free radicals. Melatonin may play a role in the etiology and treatment of several dermatoses e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin on hair growth is another aspect. Topical application of melatonin inhibits the development of UV-erythema. Penetration through skin after topical application and oral bioavailability auxit further investigations on the pharmacokinetic and pharmacodynamic actions of melatonin.

Late complications after a combined pre and postoperative (sandwich) radiotherapy for rectal cancer.

BACKGROUND AND PURPOSE: The purpose of this study was to analyse the treatment related side effects, the outcome and the prognostic significance of clinical parameters in two groups of patients with rectal cancer receiving either preoperative or pre and postoperative radiotherapy after radical resection. The authors of this study were not involved in the radiation treatments. PATIENTS AND METHODS: From 1986 to 1990, 63 patients received a combined pre and postoperative (sandwich) radiotherapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days. Postoperative irradiation consisted mostly of 15 x 2 Gy (31 patients) but the range was 20-40 Gy. The results were compared with those on 73 patients who only received preoperative radiotherapy in the same time period. The distribution of prognostic factors was not very different between treatment groups. Out of 63 patients in the sandwich group, 22 received concurrent chemotherapy and 18 also received radiotherapy to the liver. Radical surgery usually followed on the day after the last preoperative radiotherapy session. Median follow-up of survivors was 6 years. RESULTS: Local tumour control was 88% after 5 years and 84% after 8 years in the sandwich group, and 90 and 85%, respectively, in the preoperative radiotherapy group. Thus, tumour control was similar for the two radiotherapy regimens applied. However, the percentage of patients suffering from one or more complications after 5 years was 84% in the sandwich and 17% in the preoperative radiotherapy group. The incidence of severe late complications (grade > or = 3) was recorded as a function of time after start of treatment. In the sandwich group the actuarial rates of late complications at 5 years (and the median time to diagnosis) were 53% (27 months) for anorectum, 43% (37 months) for bladder, 28% (51 months) for bone, 19% (36 months) for dermis, 47% (48 months) for ileum, 41% (32 months) for lymphatic and soft tissue, and 44% (53 months) for ureters. CONCLUSIONS: Severe late reactions did not occur within a certain period of time, but continued to appear for at least 10 years after radiotherapy. Sandwich therapy, as given in this series, did not appear to give a greater tumour control than preoperative radiotherapy alone, whereas the rate of complications was drastically enhanced. Thus, the rationale of a sandwich therapy with a long time interval between surgery and postoperative irradiation appears questionable.

[Radiotherapy of soft tissue sarcomas]. / Strahlentherapie der Weichteilsarkome.

Soft tissue sarcomas are uncommon neoplasms that represent approximately 1% of all malignancies. It is clear that sarcomas require a therapeutic approach that establishes local control and thereby eliminates the potential of metastasis for patients with truly limited disease. Localized sarcomas are generally treated by surgery. Excision must be complete, with a wide margin of normal tissue, and along anatomic planes, or recurrence will almost certainly follow. Amputations are still occasionally required, although limb salvage procedures are being used increasingly, particularly in the context of multimodality therapy with irradiation or chemotherapy. Radiotherapy can be highly effective for improving local control and is used as adjuvant therapy, either preoperatively or postoperatively. In case of non-in-sano-resection a salvage surgery is indicated. Use of adjuvant postoperative radiotherapy allows for more conservative surgery without compromising local control, and therefore often may allow limb salvage where amputation might otherwise be necessary, e.g. in case of R1- or R2-resection without a new resection, a close margin or large tumors with histologic G2 or G3 grading and in case of local relapses. Local control rate of 90% are reported for the combination of pre- and postoperative radiotherapy. Prognosis is still limited by distant metastases. In case of unresectable tumors neutron radiotherapy results in 50% local control. New approaches e.g. hyperfractionated-accelerated radiotherapy, interoperative radiotherapy and chemoradiotherapy are promising perspectives, which are being evaluated in clinical studies. Desmoid tumors benefit of postoperative radiotherapy in case of R1-resection or relapse.

[Fluorescence with Wood's light. Current applications in dermatologic diagnosis, therapy follow-up and prevention]. / Fluoreszenz im Wood-Licht. Aktueller Einsatz in der dermatologischen Diagnostik, Therapiekontrolle und Prävention.

The invisible long-wave ultraviolet radiation (340-450 nm, max.365 nm) produced by a Wood lamp can help to diagnose dermatoses with a characteristic fluorescence (tinea capitis, erythrasma, tinea versicolor, Pseudomonas infections, porphyrians, and pigmentary alterations). It is also used in the detection of medications that are taken systemically (tetracycline) or that are applied to the skin. Recently, a fluorescence technique with Wood light has been used as a preventive measure to monitor and quantify skin protection at the workplace and to teach workers in high-risk occupations the proper use of protective creams.