Boost irradiation of breast carcinoma: teletherapy vs. brachytherapy.

BACKGROUND: The results of adjuvant radiotherapy including a boost dose after breast-conserving surgery of mamma carcinoma were retrospectively analysed to relate local tumor control, survival, and cosmetic results to the boost technique. MATERIAL AND METHODS: The study included 229 female patients who were treated in the period 1986--1997. Group A consisted of patients where the primary irradiation was hyperfractionated (two fractions per day) and the boost was applied by reduced portals, also at two fractions per day. In group B the 'boost' was applied interstitially intraoperatively and the 'primary' irradiation followed at one fraction per day. The cosmetic results and the late changes to the mamma were the subjects of follow-up examinations and were assessed using the EORTC score. RESULTS: 129 patients formed group A, median follow-up 4.2 years, and 100 patients with median follow-up of 9.4 years formed group B. 59% of group A and 60% of group B were in stage pT1, 38% and 39% were in pT2, and 25% and 39% were in stage N1 or N2 (no significant differences). Tumors were mostly poorly to moderately differentiated. The upper outer quadrant was most afflicted. Local recurrence occurred in two and five cases, lymph-node recurrence in two cases each, while there were ten and 12 cases of distant metastases. There were no deaths in group A and in group B six with obvious distant metastases and eight with other causes of death. The cosmetic results and late side-effects (induration, teleangiectasis, ulcers) were significantly worse in the interstitial group B. Multivariate analysis revealed that only the total applied dose significantly affected the severity of late radiation side-effects. The cosmetic results worsened with time, the tendency for lymph edemas in the irradiated side increased. Induration decreased continuously after pure teletherapy but increased continuously after interstitial therapy. These trends did not change in either group. CONCLUSIONS: Both therapy schemes resulted in successful local tumor control with good cosmetic results and few side effects, but the interstitial boost therapy was clearly less favourable. Longer-term follow-up is required to compare the late side-effects even further.

Multivariate logistic analysis of dose-effect relationship and latency of radiomyelopathy after hyperfractionated and conventionally fractionated radiotherapy in animal experiments.

PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276 healthy rats was irradiated over 6 weeks hyperfractionally with single doses ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions) and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy (30 fractions). The rats were examined neurologically and sacrificed when paralysis of the hind legs occurred. After fixation, spinal cord was removed and examined histologically. Dose-effect relationship and latency from the beginning of radiotherapy to the onset of paralysis were computed and analyzed using a multivariate logistic regression model. RESULTS: The model fitted the observed data excellently. There were highly significant effects both for the dose level and for the treatment regimen. Latency analysis showed earlier and more intense acute side effects after hyperfractionation but radiomyelopathy occurred markedly later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as predicted by radiobiologists could be confirmed in our experiments. Thus, it seems possible to escalate tumor doses using hyperfractionation without enhanced risk to spinal cord but with higher probability of tumor cure.

Tumor-related prognostic factors for remission of brain metastases after radiotherapy.

PURPOSE: To study CT determined response to external beam radiotherapy as well as influence of tumor-related factors, especially of tumor volume, on remission and to evaluate whether particular subgroups of metastases are controlled by low-dose radiotherapy. METHODS AND MATERIALS: Contrast-enhanced CT scans before and after radiotherapy were analyzed. INCLUSION CRITERIA: brain metastases treated with whole-brain radiotherapy (10 fractions of 3 Gy over 2 weeks) since 1983; no additional treatment, for example, surgery or chemotherapy; at least one follow-up CT. Three hundred thirty-six metastases from 108 patients were evaluated with regard to their volume, extent of necrosis, histology of primary tumor, and interval between radiotherapy and follow-up CT. All parameters were correlated with best local result and progression-free survival by uni- and multivariate tests. Volume-response curves were calculated. RESULTS: In univariate analysis local result was significantly influenced by each of the four parameters mentioned above. Complete remission was observed in 37% of metastases from small-cell carcinoma, 35% of those from breast cancer, 25% of those from squamous-cell carcinoma, and 14% of those from nonbreast adenocarcinoma. The rate was 52% for metastases <0.5 cm3 and 0% for those >10 cm3. In multivariate analysis, small volume and no necrosis were the most important prognostic factors for complete remission. Progression-free survival was influenced by best local result. CONCLUSION: With radiotherapy to a total dose of 30 Gy even small metastases had a complete remission rate of 52% only. Therefore, patients should be treated with locally more effective dose and fractionation schedules when local control is the aim. However, partial remission rate was remarkable even for large and necrotic metastases. This should be considered when palliation is the aim of treatment.

Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.

PURPOSE: In a prospective randomized trial we examined whether radiotherapy of painful bone metastases can be shortened using larger single doses without impairing effectivity. METHODS AND MATERIALS: One hundred patients with painful bone metastases having no prior surgical intervention or treatment with x-ray therapy and had a median follow-up of 12 months were analyzed. The primary tumor was located in the breast in 43%, in the lung in 24%, and in the prostate in 14%. The most frequent sites of metastases were the pelvis (31%), the vertebral column (30%), and the ribs (20%). Further percentages of sites were: lower extremity 11%, upper extremity 6%, and skull 2%. Fifty-one patients received a short course radiotherapy with a total dose of 20 Gy in 1 week (daily dose 4 Gy), and 49 patients received 30 Gy in 3 weeks (daily dose 2 Gy). RESULTS: There were no significant differences in frequency, duration of pain relief, improvement of mobility, recalcification, frequency of pathologic fractures nor survival. There was a light trend favoring 30 Gy in frequency of pain relief and recalcification. Survival was mostly influenced by primary tumor site, Karnofsky performance status, and possibly by the response to radiotherapy (pain relief). CONCLUSIONS: Because of the very short life expectancy of patients with metastatic bone disease, we now use 20 Gy in 1 week as our standard to reduce hospital stay.

Risk factors and dose-effect relationship for osteoradionecrosis after hyperfractionated and conventionally fractionated radiotherapy for oral cancer.

A high frequency of osteoradionecrosis after hyperfractionated radiotherapy (RT) of head and neck tumours led to a detailed analysis of risk factors in the dental, surgical, and radiotherapeutic areas. 168 patients with oral cancer were analysed retrospectively. 19% of them had been irradiated primarily and 81% postoperatively. 116 patients received a total dose mostly ranging from 60 Gy to 70 Gy to the ICRU 29 reference point (daily single dose 2 Gy). 52 patients were treated hyperfractionally with two daily fractions of 1.2 Gy per day, 4 h minimum apart and a total dose 82.8 Gy. Dental findings could be evaluated in 126 patients. Factors were checked for prognostic significance for osteoradionecrosis (ORN). Dose dependency was computed using a PROBIT analysis. Dental status before radiotherapy was generally poor (mean 11/32 teeth present, of these 1 was dead, 2.4 carious, 2.4 loose, 0.3 destroyed). On average, six teeth (range 0-27 teeth) had to be extracted. In one-third of the patients bone surgery was necessary. ORN occurred in 8.6% of the patients treated conventionally but in 22.9% of those treated hyperfractionally (p = 0.029). Biologically effective dose (p = 0.032) and deep paradontitis (p = 0.034) proved to be significant risk factors for ORN. PROBIT analysis showed a steadily rising dose dependency of the ORN frequency after conventional radiotherapy. Using total doses up to 70 Gy the frequency of ORN was 8.6%. Dose escalation using hyperfractionation led to an intolerable ORN frequency (22.9%) where a short interfraction interval was a significant factor. The use of this dose fractionation was therefore discontinued in 1992.

[Primary cerebral non-Hodgkin's lymphomas. The results of radiotherapy]. / Primär zerebrale Non-Hodgkin-Lymphome. Ergebnisse der Strahlentherapie.

BACKGROUND: In the last years many therapeutic attempts were made to improve the poor prognosis of primary cerebral non Hodgkin's lymphoma. The aim of this study was to report on own experiences concerning this rare disease. PATIENTS AND METHODS: In 1986 to 1994 26 patients were treated for primary cerebral non Hodgkin's lymphoma. 15% were HIV-positive. High-grade non-Hodgkin's lymphomas were diagnosed in 62%. 46% of all cases showed multiple lesions. 23% of our patients received a dose less than 25.5 Gy, 27% received 37.5 Gy (whole brain) and 39% were treated with 51 Gy (37.5 Gy whole brain and 13.5 Gy boost dose). Radiation technique included regular and irregular fields (single dose: 1.5 Gy). RESULTS: 62% of patients achieved a complete or partial remission directly after irradiation, in 4% no change or progression was seen. 31% could not be examined due to their bad status or death. The mean follow-up time for all patients was 19.6 months, the median survival was 3.6 months. The 1-year-survival rate was 41%, 3-year survival rate was 28%. Patients who received a tumor dose of 51 Gy had better survival times in comparison to patients who received less (p = 0.01). Prognostic parameters (Cox regression analysis) were: tumor dose, grading and local result after irradiation. The Karnofsky performance status was not an independent parameter (p = 0.12). Side effects were low. Long-term survivors had relatively good quality of life. CONCLUSION: Taking into consideration the small numbers of patients in all studies all results or conclusions have to be made with great reservations. Despite the high proportion of HIV-positive patients our results are in compliance with other authors using similar therapy protocols. Reports dealing with combined radio-chemotherapy have published good results concerning survival time. But long-term morbidity due to these protocols needs further investigation and has to be awaited.

A palliative accelerated irradiation regimen (PAIR) for advanced non-small-cell lung cancer (NSCLC).

In order to avoid overtreatment in advanced NSCLC we developed a palliative accelerated irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a 1-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conventionally irradiated historical controls selected from a pre-existing database according to identical inclusion criteria. Statistical analysis showed that PAIR patients had a significantly longer survival than controls (P = 0.0029). Median survival was 11.8 and 5.8 months, respectively, while 1-year survival was 45.6% vs. 21.2%. Compared to the subgroup of controls who had received the full planned dose of 60 Gy (n = 104) PAIR patients showed no significant difference in survival. In order to adjust for possible imbalances we used a comprehensive blinded prognostic rating design creating one score value per patient out of several known prognostic factors. After adjustment for the resulting prognostic score by means of the Cox proportional hazards model PAIR patients still showed significantly longer survival. We conclude that in advanced NSCLC survival after a palliative short-term regimen appears to be at least equivalent to that following conventional high-dose irradiation.

Relation between local result and total dose of radiotherapy for brain metastases.

PURPOSE: Some studies published recently focused on the improvement of the treatment results of patients with brain metastases who underwent radiation therapy. They evaluated survival as a measure for the expected improvement, but failed to demonstrate a significant benefit from an increased total dose of radiotherapy. This study was targeted to investigate the effect of dose escalation with a different endpoint, the local response. METHODS AND MATERIALS: As a first step, a retrospective analysis of 164 patients treated with a standard regimen of 10 x 3 Gy was performed to find factors correlating with the local result. All patients were systematically followed and underwent regular computed tomography (CT) examinations of the brain after irradiation. The second step was to compare, with respect to local control and survival, 39 patients treated with a total dose of 40-60 Gy with 39 patients treated with the standard regimen selected by means of a matched cohort pairs method. RESULTS: The retrospective analysis showed a dependence of the local result after irradiation on three parameters: diameter of brain metastases, primary tumor, and tumor histology. Small-cell and adenocarcinoma were found to be more radiosensitive than squamous-cell carcinoma. The highest radiosensitivity was found in breast cancer metastases. The matching procedure was performed with respect to those parameters and also the number of brain metastases and total cerebral tumor volume. The resulting groups were absolutely equivalent and differed only with regard to the total dose applied. The local response (complete or partial remission) was 48-52% after 30 Gy vs. 77% after 40-60 Gy (p < or = 0.05). Survival was not significantly different. A further analysis of the dose-response relationships showed the tendency of control probability to increase with total dose. CONCLUSION: This study suggests that there is a rationale for dose escalation in the treatment of brain metastases with radiotherapy, when local control is the aim. However, it seems questionable whether an improvement in survival results.

[Hyperfractionated irradiation of non-small cell bronchial cancer. Final results of a Phase II study]. / Hyperfraktionierte Bestrahlung beim nichtkleinzelligen Bronchialkarzinom. Schlussresultate einer Phase-II-Studie.

The study was performed for the evaluation of hyperfractionated radiotherapy in the treatment of non-small-cell lung cancer. From radiobiological data we expected that the twice daily irradiation with reduced single dose should result in a better sparing of the slowly proliferating healthy lung tissue without any loss in the tumoricidal effect. 34 patients were treated conventionally with 30 daily fractions of 2.0 Gy over six weeks and another 34 patients twice daily with 1.3 Gy over five weeks to a total dose of 65 Gy. The interval between two fractions lasted at least six hours. Life table (Kaplan-Meier estimate) indicated no contrast between the therapy schedules. The treatment groups did not differ in local response of the primary, progression-free interval and occurrence of distant metastases, the hyperfractionated schedule was very well tolerated. Comparison of the posttreatment quality of life showed a better course after the hyperfractionated regimen, without reaching a level of significance.

[The superior vena cava syndrome as an emergency in radiotherapy]. / Die obere Einflussstauung als Notfall in der Strahlentherapie.

Between 1983 and 1988 90 patients with bronchial neoplasms needed emergency irradiation to treat superior vena cava syndrome. Pathohistologically verified were 30 cases with squamous cell carcinoma, twelve with adenocarcinoma, five cases with large cell carcinoma, 30 with a small cell carcinoma, and non-differentiated in five others. No histological examination was carried out in eight cases. Im 30 patients distant metastases were evident at the initial diagnosis. The average duration of follow-up was 118 days. The survival course proved to be independent of histopathological grading, previous treatment, and age. Similarly no influence of the fractionation employed could be seen. Very important to the prognosis however, were the stage of disease, the Karnofsky index, and dependent on that, the total reference dose applied. Patients with a Karnofsky index of 50% or lower survived on average only 17 days.

[A simple method for positioning and fixing the extremities during the radiotherapy of soft-tissue sarcomas]. / Eine einfache Methode zur Lagerung und Fixierung der Extremitäten bei der Strahlentherapie von Weichteilsarkomen.

The exact and reproducible radiotherapy of malignant tumours in the extremities is aided by reliable positioning of the involved limb. In our department individually-formed casts and circular fix up made of two-component polyurethane foam (NEOFRAKT, supplied by Schumacher, Krefeld, FRG) are used. These allow the maintenance of any bending, stretching and torsional positions. The fields to be applied are cut out of the casts, thus preventing any influence on the depth dose of the radiation involved.

[Hyperfractionated irradiation of esophageal cancer. Initial results of a pilot study]. / Hyperfraktionierte Bestrahlung von Osophaguskarzinomen. Erste Ergebnisse einer Pilotstudie.

A group of 21 patients with esophagus carcinomas was submitted to hyperfractionated irradiation with a total reference dose of 65 Gy, applied in 50 fractions over five weeks. Generally, the irradiation was well tolerated. About 49% of the patients are alive one year later.

[Treatment of radiation pneumonitis with curative intent--a review]. / Die Behandlung der Strahlenpneumonitis mit kurativer Intention--ein Uberblick.

Therapeutic assays with medicaments intended for the healing of radiopneumonitis have a long tradition. Numerous medicaments have been assayed in men and animals during the last thirty years without having reached any lasting positive results. In the end, the fibrotic stage of this radiogenic side effect has always been refractory. It was, however, possible with some medicaments to relieve the symptoms of the early exudative phase. This study is supposed to give a general survey of the present state of knowledge in this field.

[Hyperfractionated irradiation of bronchial cancer. Results of a pilot study]. / Hyperfraktionierte Bestrahlung beim Bronchialkarzinom. Ergebnisse einer Pilotstudie.

The results achieved during recent years in experimental radiotherapy of malignant tumors show more and more the benefit provided by the small individual doses applied in fractionated irradiation. The effects and side effects of a hyperfractionated therapy of the bronchial carcinoma were investigated in a not randomized comparative study. The data of 100 patients were available for evaluation; they showed a tendency to local superiority of hyperfractionated irradiation. The value of hyperfractionation shall be examined in detail in a randomized prospective study.

Retroverted impacted gravid uterus with acute urinary retention: report of two cases and a review of the literature.

Two cases of acute urinary retention in association with a retroverted impacted gravid uterus are described. Manual replacement of the uterus into an anterior position resolved the urinary retention in both cases. A review of the literature for retroverted impacted gravid uterus and related disorders is given. Successful treatment of retroverted impacted gravid uterus can usually be performed by initial bladder catheterization followed by manual replacement of the uterus, or by chronic bladder drainage until the uterus ascends out of the pelvis.

[Face masks for radiotherapy of head and neck tumors: comparative tests of different materials]. / Gesichtsmasken zur Strahlentherapie von Kopf-Hals-Tumoren: vergleichende Prüfung verschiedener Materialien.

A most precise immobilisation of the patient's head is indispensable in order to reach a high degree of exactness and reproducibility in radiotherapy of malignant head and neck tumors. Face masks made of different synthetic materials have proved to be a simple and economical solution for this problem. Based on our own experiences with "Baycast Longuettes" (manufacturing firm: Johnson & Johnson, Düsseldorf), eleven substances have been tested in the phantom (compound of plaster and synthetic resin, thermoplast, polyurethane foam, compounds of cotton and synthetic resin, and fibre glass compounds). An appropriate material was "Hexcelite" (manufacturing firm: Medimex, Hamburg), a reticulated thermoplast which after warming up can be easily adapted to the patient's face and which guarantees a very good fixation of the head. As compared to solid masks, there is only a slight superposition of the depth dose of Co-60 gamma radiation by secondary electrons from the mask material, so that an increased rate of radiogenic dermatitides is not to be expected.

[Irradiation of grades III and IV astrocytomas with new types of radiation]. / Bestrahlung von Astrozytomen Grad III und IV mit neuen Strahlenarten.

Until 1983, more than 300 astrocytomas of degree III and IV have been irradiated all over the world with new types of radiation such as neutrons, protons, alpha particles, heavy ions, and pions. Up to now a therapeutic progress could not be achieved. Radiobiologic experimentations suggest that the dense ionisation is unfavorable in the irradiation of malignant cerebral tumors. The clinical radiotherapy research with protons should therefore be intensified and hyperfractionation should be critically reviewed.

[Experience in the use of face masks for radiotherapy of head and neck tumors]. / Erfahrungen bei der Verwendung von Gesichtsmasken zur Strahlentherapie von Kopf-Hals-Tumoren.

By means of positioning and fixation aids, the precision and reproducibility of irradiation fields in radiotherapy of malignant tumors of the head and neck can be considerably improved. Face masks made of different synthetic materials have proved to be a practicable solution of this problem. In our hospital we have developed and tested a simple and not expensive possibility of manufacturing the masks with "Baycast" (producer: Bayer AG Leverkusen). The material is generally well tolerated by the patients, and the head is sufficiently fixed. An increased incidence of radiogenic dermatitides is caused by the overlapping of the depth dose of the Co-60 gamma radiation due to additional secondary electrons emanating from the mask material. This effect can be partly prevented by cutting out the irradiation fields in the masks.

[Radiotherapy of paraplegia caused by extramedullary hematopoietic tissue]. / Zur Radiotherapie der durch extramedulläres hämatopoetisches Gewebe bedingten Paraplegien.

The presentation by computed tomography of an extramedullar epidural intraspinal hemopoisis has only been described sporadically. It has been possible to visualize by CT-scans the regression under radiotherapy of a sensory and motor paraplegia in a 17 years old patient with beta-thalassemia major. The central nervous system (thoracic and lumbar zone as well as os sacrum) was exposed to a total reference dose of 30 Gy which was administered within twenty days by a 60Co unit in single doses of 2 Gy each. From 4 Gy on, the paraplegic symptoms regressed continuously. The control CT taken after 26 Gy- the paraplegia had completely disappeared at this time-showed a significant regression of the intraspinal soft tissue masses. Radiotherapy is very important in the treatment of this disease. A direct correlation is found between clinical symptoms and CT-presentation.