[Prevention of heterotopic ossification by radiotherapy following total hip prosthesis]. / Verhinderung ektoper Ossifikationen nach Totalendoprothese des Hüftgelenks durch Strahlentherapie.

BACKGROUND: Clinically relevant heterotopic bone formation (HBF) following total hip arthroplasty (THA) occurs in about one third of all high risk patients. HBF can reduce the functional result of surgery by pain and limited range of motion. The experience with patients treated with postoperative radiation therapy after THA with or without removal of HBF is reported. PATIENTS AND METHOD: Between November 1986 und June 1993, postoperative irradiation was performed on 238 hips of 216 patients (117 men, 99 women, median age 66 years, range 38-86 years) with defined risk factors using 10 Gy in 5 fractions (n = 176) or 7 Gy in one fraction (n = 62) with a cobalt unit. In general, irradiation was performed during the first four postoperative days after primary THA alone in 182 hips or removal of HTB in 56 hips with (n = 28) or without (n = 28) revision surgery. Risk factors for HBF were preexisting ipsi- or contralateral HBF in 105 hips (group 1) or hypertrophic osteoarthritis, previous operative procedures of the hip and others in 134 hips (group 2). After a follow-up of at least 6 months patients were examined and radiographs of the hip were performed to classify HBF. RESULTS: New or progressive ossifications had developed in the interval in 15 of 104 hips of group 1 (14.4%), compared with 19 of 134 hips in group 2 (14.2%). Clinically significant new HBF (grade 3 or 4) occurred in none of group 2, and in 3 hips of group 1 (2.9%). After radiation with 10 Gy HBF of all grades occurred in 23 of 176 hips (13.1%), and in nine of 62 hips after 7 Gy (14.5%). The lowest number of treatment failures was found in patients irradiated during the first 4 postoperative days. CONCLUSION: These results demonstrate that immediate postoperative radiation is efficacious for prevention of clinically relevant HBF following THA and removal of HBF.

[Video technology and the personal computer in the therapy simulator]. / Videotechnik und Personalcomputer am Therapiesimulator.

PURPOSE: Technical progress in the development of radiation therapy simulators provided valuable addition of electronically stored images and monitor indicators for individual radiation parameters. One can store as well as print these data as a treatment plan. The possibility of supplementing older simulators with these technical options will be reported in the following paper. METHODS: The modification of our simulator installation was done simply. The new equipment needed to expand our simulator facility was almost exclusively derived from the fields of entertainment and home electronics (Visualizer/video camera, video tape recorder, video mixer, additional monitor; personal computer and printer). RESULTS: With these modifications we reached the technical standards of the latest simulator generation. In addition, we succeeded in implementing additional technical options: e.g. image inversion with contrast alignment to diagnostic displays, complete magnetic tape recording of the entire x-ray process with possible repetition, electronic overlapping of the simulator image and the diagnostic image (e.g. NMR; angiograms) to determine the treatment volume, automation in x-ray documentation. CONCLUSION: Increased precision and rational work steps employing readily available equipment will lead to further improvement in the quality of radiotherapy.

Tumor inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. Part II: Biological evaluation-in vitro studies on the P 388 D1 leukemia cell line.

Experiments on the P 388 D1 cell line (48 h exposure) demonstrate that [1,2-bis-(fluorophenyl)ethylenediamine]platinum(II) complexes are comparably active on the cell number and 3H-thymidine incorporation, irrespective of the position of the fluorine atom (ortho, meta, or para) and the nature of the "leaving group" (Cl- or H2O). However, the compounds of the R,R/S,S series are more active than those of the R,S series and comparable to cisplatin. In the "tumor colony forming assay" the R,R/S,S configurated compounds are about ten times as active as cisplatin. The R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts reach their half maximum effect more readily (t1/2 approximately equal to 1.6 h) than their R,S configurated analogues (t1/2 approximately equal to 20 h). A time limited contact of the cells with R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts (-1h) leads to a similar inhibition like a permanent drug exposure indicating a fast uptake of the complex by the tumor cell. In experiments on the Ehrlich ascites tumor of the mouse and on the L 1210 leukemia cell line R,R/S,S-[1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) turns out to be equipotent with cisplatin.

[In vitro studies of the antitumor effect of melphalan and analogous aniline mustard derivatives]. / In vitro-Untersuchungen zur tumorhemmenden Wirkung von Melphalan und analogen Anilin-Lost-Derivaten.

Melphalan and analogous aniline mustard derivatives were tested on antitumor activity in vitro. All compounds showed similar antiproliferative effects against melanoma B16, sarcoma 180 and leukemia P388D1. Thus, the singular clinical efficiency of melphalan may not simply be explained by a selective uptake employing amino acid carrier systems of tumor cells.

Is there any clinical relevance of serial determinations of serum carcinoembryonic antigen in small cell lung cancer patients?

Carcinoembryonic antigen (CEA) serum concentrations were serially determined by an enzyme immunoassay before, during, and after chemotherapy and radiotherapy in 129 male patients with small cell lung cancer (SCLC). Pretherapeutic CEA concentrations were as follows: 2.5 ng/ml or less for 37% of the patients; greater than 2.5 but less than or equal to 5 for 27%; and greater than 5 for 36%. Before therapy, CEA levels in patients with extensive disease (median value, 5.8 ng/ml) were higher than those in patients with limited disease (3.0 ng/ml; P less than 0.01). Median survival in patients with pretherapeutic CEA titers of 5 ng/ml or less (median survival, 14.3 months) was significantly longer than in patients with CEA levels greater than 5 but less than or equal to 10 and CEA levels greater than 10, respectively (8.3 and 9.7 months; P less than 0.01). Patients with pretherapeutic CEA levels greater than 10 ng/ml showed a significant decrease (P less than 0.01) of CEA while reaching partial remission (PR) or complete remission (CR). In five of 16 evaluable patients, a continuous increase of CEA titers was seen starting at least 3 months before relapse could be defined by clinical, radiologic, or endoscopic means. However, the number of patients for whom CEA serum determinations reliably indicate stage of disease and outcome of therapy is small (at best, 10% of all SCLC patients), and pretherapeutic CEA level cannot be used for individual prognosis. Moreover, it is still uncertain whether earlier detection of relapse in SCLC can improve the therapeutic results. So far, the clinical relevance of serial CEA serum determinations in SCLC patients is rather low.

A simple method of delayed processing of tumor tissue in a soft agar clonogenic assay.

Sarcoma 180 tumor tissue from C57 mice was processed in a soft agar clonogenic assay immediately after removal from the animal and after various methods of storage. The sensitivity to the antineoplastic drug cis-platinum was not affected by different storage methods. The highest yield of colony forming cells per 100 mg tumor tissue was 2.3 X 10(4) cells following immediate processing of fresh tumor material. A 24-h storage of solid tumor tissue at 4 degrees C as well as cryopreservation of solid tumor tissue or cryopreservation of a single cell suspension prepared from fresh tumor specimens were found to reduce this value to 24%-37%. Storage of a tumor single cell suspension for 24 h at 4 degrees C however, proved to be a useful and simple method of delayed processing of tumor in a soft agar clonogenic assay. The observed cell yield was 1.91 X 10(4) colony forming cells, 83% of the immediately processed value. If this procedure is suitable for use with human tumor material obtained from biopsies and surgery, the 24 h time interval would be useful for transport from hospital to an appropriate special laboratory. This would result in the broader application of the human soft agar clonogenic assay in predictive testing and drug screening.

Vindesine/cisplatin chemotherapy in relapsed or primarily resistant small-cell carcinoma of the lung.

Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3-4 mg/m2) and cisplatin (60-100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the "less-than-complete-remission" group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.

4'-Epi-Doxorubicin -- a clinical phase-II trial in solid tumors.

4'-Epi-doxorubicin is a new anthracycline analog with reduced cardiac toxicity in animal studies. A phase-II study was performed in 17 patients predominantly with non-small-cell lung cancer. All suffered from recurrent or advanced tumors and 7 of 16 evaluable patients had been pretreated with an alternative chemotherapy. 4'-Epi-doxorubicin was applied at a dose of 75 mg/m2 every 3-4 weeks. The median total dose was 280 mg (range: 130-250 mg). Only one patient with epidermoid lung cancer (overall response rate: 6%) showed a minor response and stable disease was observed in six other patients with bronchogenic carcinoma. Myelosuppression was rare and moderate: leukocytopenia of less than 2,000/mm3 occurred in 25% of patients and thrombocytopenia of less than 100,000/mm3 in 8% of patients. The frequency of alopecia and gastrointestinal side effects was 88% and 80%, respectively. Persistent electrocardiographic alterations were recorded in 2 of 14 (14%) patients. One of four patients revealed a marked reduction of left ventricular ejection fraction in radionuclide cardiography. It is concluded that 4'-epi-doxorubicin is not superior to adriamycin in this low-prospect treatment area, but studies with increased doses appear necessary in adriamycin-sensitive tumors because of recent reports from phase-III trials showing reduced cardiac and gastrointestinal toxicity with 4'-epi-doxorubicin in comparison with adriamycin.

[Short-term induction and cyclic maintenance therapy in inoperable small cell bronchial cancer]. / Untersuchungen zur kurzzeitigen Induktions- und zylischen Erhaltungstherapie beim inoperablen kleinzelligen Bronchialkarzinom.

Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p less than 0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p less than 0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600-900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.