Consideration of time-dose-patterns in 3D treatment planning. An approach towards 4D treatment planning.

PURPOSE: The rendering of the 3D dose distribution together with anatomical information and the volumes of interest (VoI) is essential to get a visual impression of the treatment plan and to find modifications for the optimization of the dose distribution. The integration of biological effects into the 3D treatment planning is of interest for the assessment of different time-dose patterns. MATERIALS AND METHODS: One way of taking into account biological data is to relate the physical dose in critical structures to the corresponding tolerance dose. For that purpose the applied time-dose pattern has to be converted into the standard fractionation scheme being the basis of the tolerance dose. Generally any model can be used for these calculations. Here a modified incomplete repair model is used to calculate the relative biological dose distribution (RBD). The visualization of these biologically isoeffective dose distributions can be performed in the same manner as the physical dose so that the physical and biological dose distributions can by displayed side by side. As this is equivalent to introducing the time as a fourth dimension into 3D treatment planning this is called 4D treatment planning. RESULTS: From 3D dose matrices the biologically isoeffective dose distributions are calculated for the organs at risk. The changes introduced by different time-dose patterns are displayed using the same technique as for rendering 3D treatment plans. The visualisation of the three-dimensional biological dose distributions is shown by means of a patient with an oesophagus carcinoma. The RBD related to the tolerance dose of the organs at risk is displayed for different time-dose fractionations. CONCLUSION: The RBD distribution on a 3D treatment plan can be displayed in the same mode as the physical dose distribution. This offers additionally valuable information in a 3D treatment planning process about the dose to critical organs and the influence of different time-dose patterns.

[How do patients experience radiotherapy?]. / Wie erleben Patienten die Strahlentherapie?

PURPOSE: In the course of a radiotherapy treatment oncological patients--in addition to some physical symptoms--often experience severe psychological distress. This study assesses and analyses the psychological strains emerging throughout a radio-oncological treatment. Specific intervention measures are being suggested to alleviate patient's psychosocial distress. This study is part of a psychosocial intervention project performed in a radio-oncological department. PATIENTS AND METHODS: Using a semi-standardised interviewing technique 30 radio-oncological in-patients were questioned in depth about their psychosocial situation. Subsequently a fully standardised written questionnaire was designed, enabling a further 150 patients to be investigated retrospectively, when presenting themselves for routine radio-oncological follow-up examinations. RESULTS: In particular, the irradiation session itself, the waiting time beforehand, and the relationship to fellow patients were found to be potentially stressful. More than half of all patients reported anxiety during their first irradiation, which usually decreased during subsequent sessions, and in no case increased. One third of the 30 inpatients wished to have more contact and conversations with fellow-patients, e.g. while waiting for their treatment. The 150 retrospectively assessed patients stated a substantially lower wish for further contact. Almost one third of the in-patients apparently gained comfort from a downward comparison to patients who they perceived as being worse off than themselves. CONCLUSION: Psychosocial intervention can help radiotherapy patients to cope with fears and distress, and thus enhance their quality of life. Support should be provided by psychological specialists, as well as by clinical staff in various ways. Anxiety concerning radiotherapy can often be alleviated through a sensitive and empathetic manner while explaining the radiotherapy process. Patient groups and seminars offer patients the opportunity to exchange experiences and to gain further information about their disease and treatment. In situations of extreme distress psychologists can accompany patients, and if necessary perform crisis intervention. Psychological specialists can also provide further education and support for the clinical staff.

Present results of neutron therapy. The German experience.

Results of fast neutron therapy are reviewed with special reference to the main indications for this type of treatment and the experience of five German centers. Neutron therapy seems beneficial compared to conventional radiotherapy in advanced salivary gland tumors, inoperable or unresectable soft tissue sarcomas, some bone tumors, prostate cancer stage C and some rare low-grade tumors. About 3,000 patients with malignancies have been treated with neutrons at the German centers Berlin/Rossendorf, Essen, Hamburg, Heidelberg and Münster. Treatment results and treatment-related morbidity depend on the treatment techniques and the physical selectivity of the neutron machines. A critical appraisal suggests that fast neutrons are of advantage in about 5% of all radiotherapy patients.

[Adjuvant radiotherapy following radical prostatectomy--results, acute and late toxicity]. / Adjuvante Strahlentherapie nach radikaler Prostatektomie--Ergebnisse, Akut- und Spättoxizität.

Between 1975 and 1987, 53 patients with radical retropubic prostatectomy for adenocarcinoma of the prostate (pathological stage C or D1) underwent adjuvant radiotherapy. 26 of these patients additionally underwent subcapsular orchiectomy. Radiation therapy was given to 45 patients as 40 to 50 Gy to the pelvic lymph nodes followed by a boost to the tumor bed to a total of 64 to 70 Gy. Only five of the 45 patients received treatment to prostate and pelvis developed progression, whereas four out of eight patients who were irradiated to the prostate alone showed progression (p < 0.01). The five- and ten-year disease-free survival rates of 33 patients with stage C tumors were 91% and 83%, the local control rate 97% and 94%. 20 patients with stage D1 carcinoma showed a five-year disease-free survival of 79% and a local control rate of 95%. 25/26 patients with subcapsular orchiectomy are living disease-free, 8/27 patients without hormonal manipulation had a progression of disease (p < 0.05). All 13 patients with well or moderate differentiated tumor are alive without evidence of disease, 9/40 patients with poor differentiated carcinoma have shown tumor progression (p < 0.05). Compared to published results, our data suggest, that adjuvant radiotherapy can decrease local recurrence and probably increase disease-free survival in stage C and D1 carcinoma of the prostate.

[The chemoradiotherapy of advanced colorectal carcinoma--the results and toxicity in a pilot study with 44 patients]. / Chemoradiotherapie des fortgeschrittenen kolorektalen Karzinoms--Ergebnisse und Toxizität einer Pilotstudie mit 44 Patienten.

Forty-four evaluable patients with advanced colorectal cancer were treated with simultaneous chemoradiotherapy to the small pelvis. In 34 patients locally recurrent disease and in ten patients primary tumors had been resected. 34 patients had gross and ten patients had microscopic residual tumor after surgical resection, seven of the latter with distant metastases. Radiotherapy was given to a dose of 50 Gy in five weeks. During the first two weeks of treatment simultaneous chemotherapy was applied, using continuous 24 hour intravenous infusion of 5-fluorouracil at 500 mg/m2 on days 1 to 5 and 8 to 12 and bolus injection of mitomycin C at 5 mg/m2 on days 5 and 12. Two-year local control rates in patients with microscopic residual were 76% compared to 36% in patients with gross residual disease. Two-year survival rates were 5/7 patients for microscopical residual tumor and 13/30 patients (44%) with gross residual tumor. Considerable rates of acute and late toxicity were observed, however, these rates were not higher than results reported by others. In view of the increasing interest in chemoradiotherapy for residual and recurrent colorectal cancers, a randomized multicenter study has been opened (ARO I/91). Aim of this clinical trial is to find out, whether patients with advanced colorectal cancer benefit from simultaneous chemoradiotherapy.

Advantage of three-dimensional treatment planning for localized radiotherapy of early stage prostatic cancer.

Conventional two-dimensional (2-d) treatment planning was compared to three-dimensional (3-d) treatment planning for patients with prostatic carcinoma. Both types of treatment planning were performed for all ten patients with five fixed fields. In 3-d planning we used irregular shaped fields. For further evaluation we performed conventional planning in rotation technique in two patients. The target volume included prostate, seminal vesicles and a surrounding security margin of 2 cm. Using the MPR-version of the MEVAPLAN planning system, the three-dimensional dose calculations were performed. For the volumes of interest (VOI's) we discussed quality of the dose distribution concerning homogeneity in the target volume and isodose distribution in the organs at risk, which are the rectum and the urinary bladder. We defined the tumor encompassing reference isodose (ca. 95%) for the calculation of the involved rectum- and bladder volume. Using the five-field technique our results show a reduction of the radiation related rectum- and bladder volume concerning the tumor encompassing reference isodose (ca. 95%) for the rectum in between 9.5 and 36.6% (median: 19%, n = 10) and for the urinary bladder in between 15.7 and 47.8% (median: 28%, n = 10). Calculated for 80% of the reference isodose the difference for the rectum was 15.7 to 31.3% (median: 23%) and for the urinary bladder 24.5 to 56.7% (median: 42%). A significant reduction of radiation related side-effects concerning rectum and urinary bladder can be expected by a reduction of volume involvement and a consecutive dosage limitation.

Visualization of 3-D treatment plans with fast neutrons.

The treatment planning for radiotherapy with fast neutrons requires modifications of the planning systems used for photons. The neutron- and photon-component of the treatment fields must be determined and can then be used for separate calculations. The corrections for inhomogeneities are performed by use of attenuation coefficients and the corresponding corrections for changes in the kerma. The treatment planning system MEVAPLAN (Siemens) was modified to follow these requirements. Thus treatment planning for 14 MeV DT-neutrons could be performed. The multiplanar option is used to calculate 3D-dose distributions based on up to 40 serial CT slices. The generated three-dimensional dose matrix and the CT data are transferred via magnetic tape to the visualization system VOXEL-MAN developed at the University Hospital of Hamburg. This system uses a ray casting algorithm based on the generalized Voxel-model to display detailed 3D-images of human anatomy together with the calculated dose distribution. Different treatment plans for neutrons and photons are calculated and visualized. Various manipulations of the data-sets are displayed to improve the critical examination of the simulated dose distribution and to discern the quality of treatment techniques.

Radiotherapy of local recurrence following radical prostatectomy.

Between 1977 and 1991, 20 patients with radical prostatectomy for adenocarcinoma of the prostate and palpable, biopsy-proven local recurrence without evidence of metastases underwent radiotherapy. Of these patients 16 were treated with orchiectomy combined with irradiation and four patients underwent irradiation alone. Local control, as determined by rectal palpation was achieved in 19/20 patients. Eleven patients are still alive without disease. Disease-free survival (determined since 1987 including PSA) was 68% for five years and 41% for ten years. 6/9 patients have died with cancer, three patients died intercurrent free of disease. Overall survival remained 51% for five years and 31% for ten years. Prevention of local recurrence is of great importance and these data support the adjuvant post-operative irradiation in defined patients at risk.

Biological isoeffect distributions: consideration of the influence of dose per fraction and overall treatment time. A possible tool in future treatment planning.

The biological isoeffect distributions are calculated on the basis of the physical isodose distributions. They consider parameters of biological relevance such as the dose per fraction and the overall treatment time. A clinical example is presented to illustrate the method. The technique presented in this paper only requires minimal modifications in the conventional computer programs for treatment planning and can be updated very easily. The calculation of biological isoeffect distributions is a simple technique to facilitate the transfer of new radiobiological and clinical findings on alpha/beta ratios, tolerance doses and repopulation kinetics, into treatment planning. However, before they can be introduced into clinical practice, more reliable radiobiological data on normal tissues and tumours are required.

[The therapeutic results and early and late toxicities of the treatment of anal canal carcinoma by radiotherapy or chemoradiotherapy]. / Therapieergebnisse, Früh- und Spättoxizität der Behandlung des Analkanalkarzinoms durch Strahlentherapie oder Chemoradiotherapie.

From 1975 to 1989 114 patients with anal canal carcinoma were treated, 81 of these with radiotherapy (RT) alone and 33 with chemoradiotherapy (CRT), 80% respectively 82% of the patients were colostomy-free at the onset of therapy. RT was given to a total dose of 60 Gy in six weeks, for CRT additional simultaneous 5-fluorouracil (500 mg/m2 days 1 to 5 and 8 to 12) and mitomycin C (5 mg/m2 days 5 and 12) was administered. 67% respectively 82% of the patients had UICC stage II to IIIB disease predominantly with G2 and G3 squamous cell carcinomas. Local control after three years was 79% for the RT group vs. 82% for the CRT group. Three-year survival rate was 68% and 71%, respectively. These differences were not significant. Only for G1- compared to G3-tumors there is a significantly higher survival rate. Acute and late damage was slightly lower for the RT treatment group (77% and 25%) compared to the CRT group (79% and 30%). In both treatment groups there was one patient needing a permanent colostomy due to radiation induced proctitis. In conclusion, RT or CRT should be the primary form of treatment in patients with and canal carcinoma and abdominoperineal resection should only be performed in case of local recurrence or tumor persistence. The final decision about the indications for RT or CRT can only be made with the results of a prospective randomized trial.