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Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with "second-look" laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program.

The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rats' blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B2 (TxB2) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells.

We are reporting a pilot study of total body irradiation in six patients with progressive rheumatoid arthritis, who had previously received gold and penicillamine. Radiation (150 cGy) was administered in ten fractions over 5 weeks. There was a transient pancytopenia following radiotherapy and the total peripheral lymphocyte count remained below pre-treatment levels after 6 months. There were no serious short-term adverse effects. By 6 months, there was no evidence of any change in clinical and laboratory estimates of disease activity. We feel that further studies of this regimen in intractable rheumatoid arthritis are not justified.

Thirty patients, over a 16-year period, treated with whole abdominal irradiation for non-Hodgkin's lymphoma were reviewed. Therapy tolerance, acute toxicity, and long-term outcome were determined. When adequate protection of vital intraabdominal organs was instituted properly, patient tolerance required only conservative medical management. Peripheral hematologic values exhibited mild depressions to nadir values near completion (3,500-4,000 rad) of treatment. Blood count recovery and general functional normalization occurred within the first post-treatment month. Average total weight loss was only 3.5 pounds with a similar pattern of recovery following therapy completion. Sixteen patients with average follow-up of 6 years still survive. Comparative studies involving total abdominal irradiation for human malignancies are also discussed.

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

One of the relevant symptoms of damage due to irradiation are the manifestations of haemorrhagic diathesis. The extravascular effusion of the blood in the course of the course of the irradiation disease may sometimes also be the cause of death of the irradiated individual, it may complicate the course of the arisen disease and sometimes even make any necessary therapeutical help impossible. The postirradiation disorder of haemocoagulation and haemostasis is a process very complicated both in its origin and in its course. Many experimental studies have been devoted to the study of the mechanism of origin of this disorder, of its course and of the possibilities of its therapy and actually we already have some clinical results. For a wider information and for the utilization of the up-to-date findings in practise, we hold it reasonable to summarize, in a certain time period, the information, though of a restricted problem, in order to facilitate an orientation in the contributions research has made up to now and to enable the selection of the adequate direction of the future experimental studies. This was the reason for the compilation of this monograph in which a summary of the up-to-date experience published in the literature and the results of our many-year standing experimental work is presented in the first opening chapter. In the second chapter, the mechanisms of blood clotting in man and the most often used laboratory animals in experiments, i.e. the dog, rabbit, rat and guinea pig, are compared. By a comparison of the platelet counts, of the time of their survival and the modes of reaction to the inductors of aggregation, some differences have been demonstrated between human thrombocytes and those of laboratory animals, which may be partly conditioned by some species specific composition of the glycoproteins of the platelet membrane. Further on, the difficulties in the determination of the levels of the individual coagulation factors are referred to and their values established in man are compared with those found in the examined laboratory animals in which decreased levels of factor VII and markedly elevated levels of factors V and VIII have been demonstrated. Next, the physiological inhibitors of blood clotting in man are compared with similar substances found in the blood of laboratory animals. Some differences in the structure and in the function of these substances slowing down the blood coagulation are stressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Patients with locally advanced cervical cancer have a poor prognosis. The efficacy of radiotherapy is limited by the presence of large tumor volume and nodal disease. As cisplatin is a documented radiosensitizer and has activity in squamous cell carcinomas, a prospective study was designed to evaluate the toxicity and potential synergism of concurrent cisplatin (20 mg/m2 x 5 d every 21 days) and radiotherapy in locally advanced cervical cancer. Forty-three patients were studied, of which 14 were stage IB/IIA (bulky disease) and 29 were stage IIB/IIIB/IVA. Of the 32 evaluable patients, there were 29 complete responders. Of these 29 patients, 27 remain without evidence of disease, with a median follow-up of 12 months. There were no treatment-related deaths. Cisplatin and radiotherapy appear to be a well-tolerated and highly effective regimen for locally advanced cervical cancer.

Ultraviolet-A (UV-A) light penetrates the epidermis, reaches the macrophages and circulating mononuclear cells within the dermis, and has immunoregulatory effects in humans. We examined the effect of UV-A irradiation on disease activity in 26 patients with rheumatoid arthritis (RA) and on immunologic function in these patients and in 11 normal subjects. Ten joules/cm2/day of total body UV-A irradiation, given 5 days each week for 3 weeks, resulted in significant improvement in the duration of morning stiffness, fatigue, joint tenderness, joint swelling, grip strength, patient assessment of disease activity, and physician assessment of disease activity. Platelet counts decreased significantly in the RA patients. Phytohemagglutinin (PHA)-stimulated lymphocyte production of interleukin-2 (IL-2) increased significantly in the combined RA and normal groups. These results suggest that UV-A light may be effective in the treatment of patients with RA, but elucidation of its precise role will require further study including double-blind trials.

Platelet aggregation may be an important factor in the feasibility of transcatheter laser angioplasty. The in vitro effects of increasing doses of CO2 laser irradiation on platelet number, function, and surface ultrastructure were examined. Results indicated a progressive dose-response reduction of both platelet number and function following laser irradiation. By scanning electron microscopy the irradiated platelets showed dose-related changes in pseudopods as well as progressive damage of the cell membrane.

A study was made of the kinetics of thrombocytopoiesis restoration in lethally irradiated mice after transplantation to them of the donor marrow cells. In the initial period, the thrombocytopoiesis restoration is provided by transite cells-precursors of megakaryocytes present in the transplanted bone marrow; the subsequent restoration is due to cells of the self-maintaining population. The level of restoration does not correlate with the number of polypotent cells that form macrocolonies in the spleen of irradiated recipients.

Eleven patients with malignant lymphoma were treated with total body irradiation. This therapy was performed during 3 weeks with a midline dose of 70 to 100 rd. Two patients were treated two times after an internal of 3 months. The authors studied the hematologic side effects of this therapy. The irradiation caused a diminution of leucocytes of 73% of the initial value (range 16,7 to 98,4%), the neutrophilic granulocytes were reduced by 60% (24-95%), the thrombocytes were reduced by 57% (12-73%). The lowest values were seen during the fourth and sixth week of observation or one to three weeks after the end of therapy. In patients with hypoplastic anemia the number of reticulocytes was reduced to zero with a further fall of hematocrit and replacement therapy was necessary. The pool of circulating CFUc was reduced to zero in nine of twelve observations up to six weeks after therapy.