Long-term results of patients with clinical stage C prostate cancer treated by phototherapy and early orchiectomy. A retrospective analysis of 169 cases.

BACKGROUND: To evaluate the value of radiotherapy and immediate hormonal therapy in the treatment of stage C prostate cancer. PATIENTS AND METHOD: From 1977 to 1986, 169 patients with clinically stage C prostate cancer underwent irradiation with curative intent following early orchiectomy. Sixty-four patients had a transurethral resection, 22 patients a prostatectomy and 83 patients had only a biopsy. In 38 patients a grade Ia/b tumor was found, in 78 patients a grade IIa/b tumor and in 43 patients a grade IIIa/b tumor using the German grade of malignancy. Treatment fields included the prostate, the seminal vesicles and the locoregional lymphatics. Until 1979 the dose was 60 Gy for the tumor encompassing isodose and from then on 65 Gy with a single dose of 2 Gy. RESULTS: With a median follow-up of 98 months, the overall survival rate for 8 and 10 years was 51% and 37% and the cause specific survival rate was 84% and 77%, respectively. Thirty-two patients (19%) developed distant metastases. Patients with local tumor control (n = 148) had a significantly better overall survival rate of 45% for 10 years compared to patients with clinical local progression of disease (n = 21) of 22% (p < 0.05). Multivariate analysis showed the grade of malignancy and local control as independent factors for overall survival and cause-specific survival (p < 0.05). Twenty-three patients (14%) had at least one late side effect for the rectum or the bladder, in almost all cases grade I or II. Five patients (3%) showed severe late side effects RTOG grade III (n = 2) or IV (n = 3). One patient had a colostomy, in 2 patients a severe haemorrhagic cystitis was seen. CONCLUSIONS: Radiotherapy with photons and early orchiectomy for patients with stage C prostate cancer achieves high local control rates and a 30% to 40% 10-year survival rate with a low incidence of late side effects. The value of the radiotherapy of the locoregional lymphatics remains controversial.

[Indications for radiotherapy of rectal cancer]. / Indikationen zur Strahlentherapie bei Rektumkarzinom.

Surgery and radiotherapy complete each other in local control of suffering from rectal carcinoma. A radiotherapeutic effect on tumor is secured often. The adjuvant radiotherapy is the most interesting indication, though the most controversial as present too. Analysing all data and with experiences of an own irradiation study we have not any doubt that the indication is qualified for a combined therapy, if the therapeutic aim with priority is to prevent a local relapse as the most frequent and complained of form of therapeutic failure. In this problem, radical irradiation forms, as pre- and accumulating irradiation (sandwich-technique) and after-irradiation, render superior to an exclusive pre irradiation. In result of this study we practise a preirradiation of 25 Gy with immediately following operation and an accumulating irradiation to 50 Gy in proved high-risk-stage (T greater than or equal to 3 NoMo,Tx N1-3 Mo). If there is a primary local incurability by tumor invasion into the neighbourhood a pre-irradiation is done with 50 Gy and following explorative laparatomy within 4-6 weeks. Nearly 60% of these tumors become operable after that. Likewise we practise in unirradiated patients with locoregional tumor recurrence. Also here the extirpation quota of patients with general or systemic incurability, that a stoma construction is required in, we carry out a transanal tumor reduction and irradiate with 50 Gy after that. Especially this therapeutic principle has proved its worth in patients that are past eighty. Here with acceptable living quality and avoiding a stoma construction a survival can be reached that corresponds to the statistical survival of this stage of life.

[Perioperative radiotherapy of bone and soft tissue tumors]. / Perioperative Radiotherapie von Knochen- und Weichgewebetumoren.

The goal of pre- and/or postoperative irradiation of soft tissue sarcoma combined with conservative surgery is to reduce the local failure rate comparable to that of radical surgery but with substantial less morbidity and loss of function; this is realized, so that local control and survival rates following combined therapy are comparable to those achieved by radical surgery alone. The high effect of fast neutrons is mentioned especially in large tumors. In osteosarcoma fast neutron therapy may give better chance for inactivation of tumor cells resistant against chemotherapy.

Clinical results after therapy with fast neutrons (DT, 14 MeV) since 1976 in Hamburg-Eppendorf.

In Hamburg since 1976 to 1980 we have treated 328 patients with fast neutron (DT, 14 MeV) and after reconstruction of the generator further 69 patients in 1984. The therapy with DT-neutrons had the best curative effect on high differentiated tumors. With the standard dose of 16 Gy in four weeks or--treating tumors in radiosensitive organs like brain and intestine--with a photon-neutron schedule, we have seen no necroses in normal tissues. The rate of medium or slight subcutaneous fibroses is not more than 10%. The local effect on tumors in our pilot study has been better than with megavoltage therapy in invasive thyroid cancer, prostate cancer stage C, soft tissue sarcoma and also in rectum-carcinoma. The best results have been achieved with neutrons only, but a photon-neutron schedule may be more effective as megavoltage therapy only. With our DT-neutrons we find some indications for better results than with megavoltage therapy if we use sophisticated treatment planning and if we strictly observe the tolerance dose of the different tissues and organs. The therapeutic index of our monoenergetic DT-neutrons is higher than with cyclotron-produced neutrons.

Clinical results with fast neutrons (DT, 14 MeV).

In Hamburg, the therapy with DT-neutrons had the best curative effect on highly differentiated tumors. With the standard dose of 15.6 Gy in four weeks with fast neutrons only or--in treating tumors in radiosensitive organs such as brain and intestine--with a photon-neutron schedule, we have seen no necroses in normal tissues. The rate of medium or slight subcutaneous fibroses has been no more than 10%. The local effect on tumors in our pilot study has been better than with megavoltage therapy in invasive thyroid cancer, prostate cancer stage C, soft tissue sarcoma, and rectal carcinoma. The best results have been achieved with neutrons only, but a photon-neutron schedule may be more effective as megavoltage therapy only. With our DT-neutrons we find some indications for better results than with megavoltage therapy if we use sophisticated treatment planning and if we strictly observe the tolerance dose of the different tissues and organs. The therapeutic index of our DT-neutrons is higher than with cyclotron-produced neutrons.

[Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy]. / Kombinierte Chemotherapie-Radiotherapie-Studie des kleinzelligen Bronchuskarzinoms (CCR-Studie): Chemo-/Radiotherapie gegen Radio-/Chemotherapie.

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.

[ALL-study series of Hamburg (author's transl)]. / Hamburger ALL-Studien.

From 1971 through 1979 145 newly diagnosed patients with ALL have been treated within a series of consecutive studies. Study I corresponds to branch A of the 1972 DAL study. In the following studies the induction therapy has been escalated stepwise with the continuation therapy remaining mostly unchanged. Thereby the disease free survival rates increased from 75 to 94% after one year and from 32 to 60% after 4 years respectively. CNS-relapse mainly occurred during the second year of treatment. Their incidence rose from 5% to more than 10% in connection with a change in the radiation portal. Since another correction of the portals with special consideration of the paramedian lower border of the skull base no more CNS-relapses have been observed until now. The actual cooperative ALL-study follows a modified BFM-protocol with postponed asparaginase in hoping to achieve reduced initial morbidity and at least equal good survival times.

The effect of an analyzed deuterium ion beam on the lifetime of TiT targets used at the fast neutron therapy facility (DT, 14 MeV) Hamburg-Eppendorf.

Report on experiments performed with mixed or analyzed deuterium ion beams incident on TiT targets at the neutron therapy facility Hamburg-Eppendorf. Bombarding a TiT target area with all separated atomic and molecular ions of an analyzed deuterium ion beam at different beam spots, the "initial" half-life of the used tritium target increases with a factor of more than three as against the half-life obtained with a mixed deuterium ion beam at a single beam spot. In this case, the effective target current is not reduced and in the same order as that for a mixed deuterium ion beam. Using the atomic deuterons only, the increase of the "initial" half-life is far longer yet, but the loss in target current is about 50% dependent on the reduction of molecular deuterium ions. These facts are most important for the economy of this type of neutron therapy facilities clinical work.

[Spleen irradiation and splenectomy for treatment of hypersplenism in chronic myeloid leukemia and chronic lymphatic leukemia (author's transl)]. / Milzbestrahlung uns Splenektomie zur Behandlung des Hyperspleniesyndroms bei chronischer myeloischer und chronischer lymphatischer Leukämie.

Hypersplenism is characterized by cytopenia, splenomegaly (possibly hyperplastic bone-marrow), and lienal hypersequestration. It is necessary, in view of the rather important surgical risks of splenectomy, to clarify if the hypersplenism may be influenced by splenic irradiation in case of chronic myeloid leukemia (CML) or chronic lymphatic leukemia (CLL). References in literature are rare and do not present a reliable differentiation of the syndrome, according to its present definition. Of our patients, three cases with hypersplenism verified by radioiron studies are reported: in one patient with chronic myeloid leukemia, irradiation of the spleen had no effect, whereas pancytopenia was completely repaired by means of splenectomy. The same results were seen in a patient with chronic lymphatic leukemia. In the last patient, however, who had chronic lymphatic leukemia, fractionated irradiation of the spleen led to a distinct improvement of anemia and thrombopenia, but the recovery lasted only six months. This effect is due to transient normalization of the lienal hypersequestration.

Response of mouse intestine to 14 MeV neutrons.

At the Hamburg-Eppendorf Hospital neutron facilities the relative biological effectiveness (r.b.e.) of d,T-neutrons was determined with respect to survival of mouse intestinal crypts. (CBA/Rij x C57BL/Rij)F1 mice were irradiated to the whole body at different depths inside a tissue-equivalent phantom. Irradiations were carried out with a collimated neutron beam at about 6 rad/min given in single doses ranging from 450 to 1000 rad. For reference, gamma-rays from a 60Co therapy unit were used. The number of surviving intestinal crypts per circumference of the jejunum was determined 3 1/2 days after irradiation according to the method of Withers and Elkind. The number of surviving stem cells was calculated on the basis of Poisson statistics. The doses necessary to reduce survival to ten crypt stem cells per circumference amounted to 689 +/- 19 rad for neutrons and 1449 +/- 29 rad for 60Co gamma-rays. From these figures an r.b.e. of 2 . 1 +/- 0 . 1 is obtained. Measurements at different depths in the phantom did not show any variation of r.b.e. with depth along the axis of the neutron beam.

[Radiation effects in brain and spinal cord (author's transl)]. / Strahlenbedingte Reaktionen des Gehirns und des Rückenmarks.

Radiation sensitivity of both the brain and spinal cord in prenatal and postnatal stages, in infancy and adult age is represented also in consideration of a combined treatment with methotrexate. In adults, application of important doses of high-energy radiation increases the risk of injurious effects to the central nervous system. If the spinal cord is involved, more than 60% of the radiolesions have a progredient course ending with death. The pathogenesis and disposing factors are referred to, and the incidence of radiation necrosis with regard to age and sex, the degrees of injury and their frequence within different ranges of dosage are analyzed on the basis of data from universal literature. An examination of "tolerance doses" for the spinal cord is made by means of Strandquist-diagrams and of the Ellis-formula. The slopes of regression lines are reported for various "degrees of response" in skin, brain and spinal cord following radiation therapy. In the Strandquist-diagram, slopes of regression lines are dependent on the "degree of response", flattening if skin and spinal cord are affected by radiation in the same degree, necroses having the same slope for both the organs.

The neutron therapy facility (DT, 14 MeV) at the radiotherapy department of the university hospital Hamburg-Eppendorf.

The neutron therapy facility at the Radiotherapy Department of the University Hospital Hamburg-Eppendorf is described. This unit has been developed for clinical purposes according to the initiative and conception of the radiotherapist by AEG/Fed. Rep. of Germany and RDI/USA since 1969. The installation was completed at the beginning of 1974. Special treatment head and bed systems allow isocentric treatment and arc or multiple port therapy. For routine work operation conditions of 8 to 12 mA total beam current and 500 kV accelerating voltage are used. The neutron output at 12 mA is about 3.5 x 10(12) n/s giving a phantom dose rate of more than 20 rad/min for a field size of 17.8 x 17.8 cm2 at 80 cm source-skin distance. Technical installations for improvement of dose rate and half-life of the target are planned. Results of physical measurements about neutron energy distributions, contributions from neutrons and gamma-rays to the total absorbed dose, build-up effect, axial and lateral dose distributions as well as isodose profiles for different field sizes in a homogeneous phantom are presented. Bewteen February 1976 and November 1977 up to 180 patients have been treated.

[Morphological and clinical results after combined hormone and radiation therapy for carcinoma of the prostate (author's transl)]. / Morphologische und klinische Behandlungsergebnisse nach kombinierter Hormon- und Strahlentherapie des Prostatakarzinoms

83 prostatic carcinomas were analysed morphologically and clinically before and after combined therapy. The classification of these tumors is based on the proliferation pattern resulting in a group with only one and a group with a variety of growth patterns. The largest groups were carcinomas with glandular structures. On the basis of multiple biopsies the histologic regression of the tumors was determined. In 71% of the cases there was good agreement of morphological results and local palpation findings. Further analyses revealed a correlation between histological growth pattern of the carcinomas and degree of regression: prostatic carcinomas with glandular pattern showed more often a good regression after combined therapy than solid and(or) cribriform tumors. In the groups with a variety of structural pattern the degree of regression was dependent on the prevailing tumor structure. According to these results the organoid-glandular carcinomas of prostate are prognostically more favourable than all the other proliferation patterns. Nevertheless in a single case a prognosis of the therapeutic effect based only on the tumor differentiation can not be made.

Aspects of timing and selection of cases in radioiodine therapy and percutaneous irradiation of well differentiated carcinoma of the thyroid.

142 patients with well differentiated carcinoma of the thyroid were treated postoperatively by radioiodine and percutaneous irradiation according to a fixed schedule. Institution of radioiodine treatment and percutaneous irradiation within 6 months after surgery resulted in a low incidence of local tumor recurrences or of newly formed metastases, and in a high survival rate. Criteria are given, by which postoperative percutaneous irradiation may be omitted without risking impairment of therapeutical results.