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The moving-strip irradiation of the total peritoneal region plays an important role in the adjuvant therapy of the ovarian carcinoma. TLD dosimetric and mathematic investigations of this radiotherapeutic method show that 1. the best dose homogeneity in the longitudinal profile is achieved by 60Co units, if the patients are not too stout, 2. a higher relative depth dose has to be estimated than for an open field of the same total field size, 3. an additional 2,5 cm strip has to be inserted in order to achieve an abrupt drop on the border of the total irradiation field, 4. this method offers a good guarantee against false adjustment, if this is not too grave, 5. the conformity between the dose distribution curves calculated and those measured by TLD is excellent.

The serum protein spectrum of a PAGE separation shows characteristic and permanent modifications in patients of premenopausal age submitted to a curative or postoperative irradiation by high dose rate afterloading method or percutaneous telecobalt therapy for carcinoma of the cervix. In older patients, the serum protein spectrum remains nearly unchanged during and after radiotherapy.

Between February 1977 and February 1981, 55 patients with ovarian cancer (45 at stage III and 10 at stage IV) underwent simultaneous radio-/chemotherapy and early therapeutic second-look operation. The overall response rate amounts to 94%, 63% of which are complete and 31% are partial remissions. Stage III comprises 74% complete and 26% partial remissions. Patients with complete remission at stage III have a significantly longer tumor-free survival time than patients with partial remission (median 16 vs. 8 months). A longer overall survival time (median 30 vs. 16 months) is also significant. At stage III there have been 74% successful therapeutic second operations. In all patients with residual tumors above 2 cm in diameter after primary operation a response rate of 92% could be achieved, 52% showed complete remissions. The survival time proved to be independent of both histological parameter and age. The remaining residual tumor above or under 2 cm in diameter in any single location is, however, a significant prognostic factor for long-time survival. Possible curative chances for patients with stage III disease are only to be expected through interdisciplinary oncological cooperation.

On a small selection of patients examinations have been conducted how far proliferation of the tumor and metastasis can be pursued with the statement of TPA combined with the LDH-isoenzymes. By this proceeding it proves that a control of therapy and the respective state of the tumor is possible without great display by simultaneous determination and continuous examination of both the parameters.

During a radiotherapy of ovarial carcinomas and other gynecologic tumors, special attention must be given to the reaction of the organs of urinary excretion as well as of the small and large intestine, especially if the irradiation is applied by the moving strip method or as an abdominal bain with an irradiation field comprising the whole abdominal and diaphragmatic region. The early and late radiogenic reactions of our great number of patients were routinely examined. A continuous control of the urinary excretion conditions before, during and after radiotherapy is absolutely necessary. These examinations are also of high relevance with regard to the early recognition of recurrences. An additional control of the rectum and sigmoid region is necessary with respect to late lesions. Regular ultrasonic or CT examinations are important in order to early recognize metastases in the preferred regions of formation of metastases which are hardly accessible by other methods (intraperitoneal dissemination with ascites, surface of the diaphragm, local extension, retroperitoneal lymph nodes, and transdiaphragmatic extension to the interpleural lymph nodes). Finally the authors present their first experiences with the NMR technique in radio-oncology and discuss the value of tumor markers in case of ovarial carcinomas.

A report is given on 160 patients suffering from ovarian carcinomas the stages which were exactly determined by TNM classification. 32 patients had tumors of the stages T1-T3, 128 patients had tumors of the stage T4. All T3 subgroups showed favorable results after radical surgery and a postoperative combination of radiotherapy and selective cytostatic chemotherapy. The therapy plans including radiotherapy had more advantages than those without radiotherapy. Furthermore, the cytostatic treatment was more successful after a chemotherapy resistance test than after blind administration of cytostatic drugs.

Evidence for an overall improvement in survival for patients with cancer of the ovary is presented. This improvement is from approximately 30% to 40% with a long term survival compatible with cure. The discussion then focuses on how treatment has contributed to that improvement, and in particular the use of radiation therapeutically. The results of the prospective randomized clinical trials at The Princess Margaret Hospital, Toronto, indicate that the use of pelvic and abdominopelvic irradiation for patients other than Stage IA, well differentiated, who have no or small residuum following surgery is curative for a large proportion and is the reason for the improvement in overall survival. Comparison of these results with others in the literature is done and shown not to disprove the findings of the PMH study. Mention is made of newer developments in multifactorial analysis to better define the patients for whom radiation is the treatment of choice currently.

Pretherapeutic informations furnished by surgery and histopathology are of special importance for the local high voltage therapy of the operated ovarial carcinoma. The intraoperative state does not only confirm the diagnosis, but also reveals the full biologic extension of the tumor and, thus, the correct staging. Extensive supplementary radiodiagnostic examinations are necessary if the informations furnished by the surgeon are not complete. Between February 1977 and February 1981, we treated 55 patients suffering from ovarial carcinomas with a combined simultaneous radio-chemotherapy (45 patients with stage III and 10 with stage IV). The first operations had been performed at gynecologic departments of other hospitals in 60% of all cases, at surgical departments of other hospitals in 20% of all cases and at the II. Gynecologic Clinic of the University of Vienna in only 20% of all cases. The definitive staging was established by postoperative analyses of X-ray views of the chest, liver-spleen scintigrams, ultrasonic examination, computed tomography, lymphoscintigraphy and lymphography. 36 women were submitted to an early therapeutic second operation. It turned out that in most of all cases the retroperitoneal manifestations were correctly recognized by the different radiodiagnostic methods; histopathology was superior in only 8% of all cases. The rate of retroperitoneal metastases is 45% out of the total collective and 40% out of patients in stage III. With the therapy method applied, the survival time does not depend upon the retroperitoneal state as long as there are no tumor manifestations with a maximum diameter of more than 2 cm. The liver metastases described after the first operation do not necessarily correspond to such manifestations; often they are rather tumorous peritoneal layers. More attention should be given to the state of the subdiaphragmatic region, because manifestations in this region are an unfavorable diagnostic factor. Patients in stage III have possibly still curative chances. A careful surgical exploration and a close co-operation between surgery, histopathology, radiodiagnosis and clinical examination are not only a basis for a rational treatment but will also exempt patients from unnecessary or cumbersome examinations.

An investigation was conducted in order to determine the effect of combined high voltage irradiation and the sensitizing drug misonidazole (Ro-07-0582) on human gynecologic carcinomas transplanted into nu/nu mice with thymic aplasia. Two carcinomas of the endometrium, two carcinomas of the ovaries, and one carcinoma of the cervix were submitted to Co-60 irradiation with and without misonidazole. The tumor growth was compared to that of control groups. The dosage and fractionation of the high voltage irradiation (2 x 5 Gy/week, total dose 60 Gy) were adapted to clinical data. Misonidazole (1 mg/kg body weight) was administered by intraperitoneal injection 15 minutes before the irradiation. Compared with the control animals, the locally irradiated tumors showed a slower growth or even a regression. The administration of misonidazole, however, did not produce significant differences in our five cases. Some reasons for this absence of the radiosensitizing effect of misonidazole are briefly discussed.

Human tumor transplants were grown in a thymus defective nude mouse mutant (nu/nu BALB/c/A/Bom). Procedures for local irradiation of the tumor with 60Co-radiation are described. An introductory test of the usefulness of these transplants in studies of radiation effects on human tumors is performed by investigation of the time course of regression of adenocarcinoma transplants in six mice following single exposures of 375, 750, 1180 and 1575 rd, respectively, and malignant melanoma transplants in two mice following single exposures to 1475 and 2420 rd, respectively. The higher radioresistance of the malignant melanomas relative to that of the ovarian tumor is expected on the basis of clinical experience and indicates that radiation effects on human tissue implants in nude mice mirror some of the fundamental features of the in situ situation.

Due to improved graduated surgery techniques and large-field radiotherapy applied in all cases, the ovarial dysgerminoma has become a disease showing a high rate of recoveries. Under consideration of their own medical records, the authors present the relevant epidemiologic and clinical parameters, establish a diagnosis programme and develop a therapeutic concept which also wants to take into account the individual requirements of patients regarding their age and their prognosis.

A report is given on 683 cases of ovarian cancer, who underwent postoperative radiation therapy at the Radiation Department of the 1st University-Clinic of Obstetrics and Gynecology in Vienna. An uniform staging and histological classification is complicated by the fact, that in recent years the rate of cases operated elsewhere and subsequently admitted to our clinic went up to 76%. Of all 683 cases, 193 (28,3%) reached a five-year survival time. Because of these still unsatisfying results of postoperative radiation treatment in ovarian cancer the importance and necessity of randomised studies with different therapeutic programs is emphasized.

Not only the effect of cytostatic drugs and hormones, but also that of ionizing radiation can be tested after transplantation of human tumoral tissue into nu/nu mice with thymic aplasia. In this study, the effects of high voltage irradiations dosed up to 60 Gy (fractionation 2 X 5 Gy per week) to three carcinomas of the endometrium, three carcinomas of the cervix, three ovarian carcinomas, and one mammary metastasis of an immunoblastic sarcoma were observed during a period of 120 days. This irradiation plan could be performed without problems in eight cases, in two cases it had to be stopped after 50 Gy. Nine tumors decreased significantly in size, reaching sizes which were below those measured before irradiation. In six among the nine cases, the tumors grew again after different periods of observation. In case of rather long periods of observation, those points within the curves of development can be taken as efficacy indices which are representing the lowest or the initial values of tumor sizes. In another study, the effects of high voltage irradiation to tumors of the nude mouse are correlated to those found in the corresponding patients.

Percutaneous abdominal radiotherapy leads to an obligatory simultaneous stress of the kidneys. This partial stress of the kidneys can be reduced to a bearable minimum if the medicophysical irradiation planning methods, already developed nowadays. are used. The improved irradiation technique basing on these methods was examined, by administering abdominal irradiation, in a corresponding collective of patients. Clinical, laboratory-chemical, roentgenologic, and nucleo-medical examinations were carried out in different intervals. The significant control results certified the kidney protecting method of our radiotherapy.

A new technique for radiation therapy in stage I and II carcinoma of the ovary is presented, intended to cover as homogeneously as possible the paraaortic, subdiaphragmatic and intradiaphragmatic areas of the direct lymphatic pathways as well as the small pelvis. This technique permits to deliver a dose of up to 46 Gy to this target volume, adjuvant chemotherapy being regarded as a convenient complement of such localized radiation therapy. Using a modern interactive system for treatment planning, a combination of 2 a.-p./p.-a. and 2 lateral fields is developed. Individually shaped circular satellites and rectangular satellites serve for protection of the liver and small intestine. Good reproducibility is obtained by means of the simple geometrical form of the fields and satellites.

A report is given on the utilization of computer tomography for the irradiation planning. Owing to international cooperation it was possible to use the obtained pictures as a basis for a computerized irradiation planning. The authors give some practical examples of optimized isodose plans for individual cases which have been elaborated by using the computer-tomographic cross-section pictures and the computerized system for irradiation planning and which give a good idea of the efficiency of the system.

Prior to intraabdominal radiogold therapy of the ovarian carcinoma, at the gynecologic clinic of the university of Göttingen and at the gynecologic and obstetric center at Giessen a peritoneography is made. If the distribution of the contrast solution is homogeneous within the abdomen, a homogeneous distribution of activity can also be expected after the radiogold instillation. By means of the peritoneography it is possible to see incorrect punctures into the abdominal walls, into the intestine, into the retroperitoneal space, or into peritoneal conglutinations before the radiogold instillation. Peritoneography, therefore, contributes to a reduction of the early complications of the radiogold therapy. The method used in peritoneography at Göttingen and the method of Giessen are described. The first one (Göttingen) is more comfortable for the patient, as it necessitates less changes of position; the other (Giessen) is a little more economical. A suitable cannula for puncture is described.

A report is given on 57 patients with pseudomucinous ovarian carcinomas. The prognosis of the disease depends on two decisive factors, if the FIGO stages are not taken into consideration: 1. the operation which should be executed as radically as possible, 2. the intraperitoneal instillation of radiogold which shall be repeated two times. The following therapeutic results were realized under this treatment: a five-year survival rate of 76,9% and a ten-year survival rate of 72.7%. There were no serious side-effects of the radiogold therapy since the introduction of routine peritoneographies before instillation of 198Au.

From 1960 to 1972, 276 out of 330 cases of ovarian cancer were treated by different techniques of postoperative radiation therapy; 54 advanced cases underwent prospective chemotherapy. Radiogold intraabdominally administered (190 to 300 mCi), telecobalt (5000 rd) or the combination of radiogold and telecobalt was chosen for postoperative radiation therapy. Cyclophosphamide (Endoxan), prednisolone, and gestagenes (Prothil) were given as a long-term chemotherapy. The most successful technique of radiation therapy is confronted with long-term chemotherapy after three years (five years) of survival: Stage I a, b, c: Radiogold = 91.7% (66.7%), chemotherapy (only I c) = 100%. Stage II a, b: Radiogold + telecobalt = 47% (35%), chemotherapy = 85%. Stage III: Radiogold + telecobalt = 25% (0%), chemotherapy = 52%. Stage IV: Radiotherapy = 0%, chemotherapy = 25%. The absolute five-year survival without chemotherapy amounted to 23%. The mortality curve under chemotherapy shows a four-year survival rate of 88%, if tumor cells had been detected microscopically (ascites, omentum), but of only 30% after macroscopical verification of the tumor. Therefore, the maximally possible partial resection of the tumor is recommended in inoperable stages before the beginning of chemotherapy. "Prophylactic" long-term chemotherapy following macroscopically complete surgical treatment is recommended, whenever microscopical spread of tumor cells appears to be possible. In inoperable stages, chemotherapy ought to be applied prior to radiation therapy. In stages I a, b, c, and II a, postoperative irradiation with radiogold (100 mCi) and in stage II b additionally radiation teletherapy of the pelvis (6000 rd) is recommended.

The authors have analysed the influence exercised by the combined therapy of the ovary carcinoma on the plasma ribonuclease activity in Wistar rats. The medicaments "Proresid", "VM-26", and "Methotrexat" together with a percutaneous irradiation of the abdomen did not alterate perceptibly the enzyme activity during the experiment, but there was a considerable reduction of the enzyme activity after an application of "Endoxan", "Adriblastin" and "Methotrexat" with subsequent administration of "Leukovorin". The most violent ribonuclease suppression, however, was obtained by an intraperitoneal instillation of radiogold and a fractioned percutaneous irradiation of the abdomen with intercalated administration of "Endoxan".

By treating eleven patients with an individual large field therapy adapted to the single stage and subsequent chemotherapy (Leukeran), we obtained an average survival time of 42,6 months (living patients) and 37,6 months (patients died), respectively. Late complications of this therapy were not observed, the tolerance was good. In case of recurrence after this treatment, the reserves of bone marrow seem to be too small to allow an aggressive chemotherapy.

During the period between January 1956 and July 1974, 102 patients with malignant ovarian tumors were submitted to post-operative radiotherapy. In two cases only, a pre-operative radiotherapy was applied, too. In spite of the relatively small group of patients, the therapy results of 38 patients of stage Ia seem to be particularly remarkable. The five-year survival rate was 86.8% including the proliferative tumors. Considering these results together with the problems of the clinical classification of stage I according to FIGO, it seems reasonable to apply radiotherapy even in this stage.

A method is reported which permits an assessment of the effect of radiation, especially with 198Au, upon primary cultures. Thus, a statement of the individual radiation sensitivity of a tumor can be made, which is not possible with conventional methods. The tumors investigated by us exhibited a dependence of their cells in vitro upon the activity of the radiogold, and different tumors revealed a different radiosensitivity to the same dose.

At the Allgemeine Krankenhaus St. Georg, Hamburg, 240 patients with ovarian carcinomas were submitted to an adjuvant treatment between 1961 and 1973. The external therapy with telecobalt or by an 18 MeV betatron was dosed from 3000 to 4000 rads. Most of the patients received an additional single intraperitoneal application of 150 mCi gold-198. The five-year survival rate of all patients was 45%, whereas it was 71% for stage I, 47% for stage II, 21% for stage III, and 4% for stage IV. In 3% out of all cases, surgical procedure was necessary because of complications. Today, an indication for intraperitoneal therapy by radioactive isotopes is only adopted in case of a ruptured malignant ovarian tumor.

A report is given of the treatment of three patients with advanced malignant tumors. Combined percutaneous irradiation and application of adriamycine produced severe side effects which, in one case, took a lethal end. A combination of relatively good tolerance consisting of an irradiation therapy and stosstherapy with cyclophosphamide is presented as an alternative treatment of the advanced ovarian carcinoma. The authors express a warning of simultaneous application of radiation and adriamycine therapy.