Prospective study of long-term pulmonary manifestations of mantle irradiation.

Given the high cure rate of patients with Hodgkin's disease, the complications related to therapy take on great significance. Mantle irradiation to the thorax is used in virtually all patients with early stage Hodgkin's disease. Prior studies of patients receiving mantle irradiation demonstrated short-term (up to 24 months) abnormalities of pulmonary function. In the present study, we prospectively studied 13 patients for up to 60 months after irradiation only with serial pulmonary function tests, arterial blood gas tests, diffusing capacity of carbon monoxide, chest radiographs, and ventilation-perfusion scans. No respiratory symptoms attributable to therapy were noted. Frequent radiographic changes (62%) were found consisting of apical fibrosis, paramediastinal fibrosis, or pleural thickening. Two patients developed an asymptomatic spontaneous pneumothorax that resolved with conservative management. Ventilation-perfusion scans often (73%) revealed decreased perfusion to the lung apices with associated ventilatory deficits in one-half of these patients. Patients with intrathoracic disease had decreased lung volumes prior to therapy, and lung volumes did not change following irradiation. Lung mechanics were normal throughout the study. Gas exchange at rest was normal in patients with extrathoracic disease. Patients with intrathoracic disease often presented with an abnormal arterial PO2 and widened alveolar-arterial partial pressure gradient for oxygen. However, these parameters normalized by 9 months after therapy. Despite the frequent development of radiographic and V/Q scan abnormalities in the lung apices, patients tolerated mantle radiotherapy remarkably well. In fact, patients with intrathoracic disease demonstrated improved gas exchange at rest following therapy.

Symptomatic radiation-induced pericarditis in Hodgkin's disease.

This is a retrospective review of 193 evaluable patients treated with radiation therapy to the mediastinum for Stages I, II and III-A Hodgkin's disease. Eligible patients were those receiving 3000 rad or more to the mediastinum and no chemotherapy prior to the radiation. During the study period, 13 patients developed symptomatic pericarditis. The interval post treatment to the development of symptoms was six to 34 months. The incidence of pericarditis was studied as a function of: (1) the dose of radiation at a depth of 2 cm, 5 cm and the midplane of the mediastinum; (2) the ratio of anterior to posterior weighting of dose; (3) the presence or absence of intrathoracic tumor; (4) the size of the tumor when present; and (5) the fraction of the heart exposed to the radiation beam. There was a significant increase in the incidence of pericarditis with an increased dose of radiation at 2 cm, 5 cm and midplane depths and also with the presence of a large intrathoracic tumor. A reduction in mediastinal dose is recommended.

Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow.

Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.

Dose rate effects on the survival of normal hematopoietic stem cells of BALB/c mice.

The use of total body irradiation (TBI) to ablate malignant stem cells in leukemia patients prior to bone marrow transplantation and the use of hemibody irradiation (HBI) for treating osseous metastases have focused attention on the dose rate effects, if any, exhibited by normal or malignant hematopoietic stem cells. Using male BALB/c mice 10 to 12 weeks old, we investigated dose rate effects at 103, 45 and 8 rad/min over the dose range from 100 to 500 rad. Bone marrow cells from the femurs of irradiated donor mice were transplanted into lethally irradiated (720 rad) mice of the same age, sex, and strain. Recipient mice were sacrificed 9 days later, their spleens fixed, stained with Bouin's solution, and the macroscopic colonies counted to determine the number of colony forming units (CFU) per femur. Surviving fractions were determined by comparisons to the CFU's of non-treated controls. The logarithms of the surviving fractions, S, versus dose, D, (in rad) were least squares fitted and the extrapolation number, n, and D0 obtained. The extrapolation numbers ranged from 0.65 +/- 0.15 to 0.81 +/- 0.08, and D0 ranged from 61.7 +/- 3.4 to 69.0 +/- 2.8. There are no statistically significant differences between the n's and D0's for these different dose rates over the dose range from 100 to 500 rad, as measured by spleen CFU assay of normal femoral marrow. The D0's are appropriate for this radiosensitive mouse strain. These data are compared to those from other studies using the same method of CFU assay.

Radiation therapy treatment of stage I and II extranodal non-Hodgkin's lymphoma of the head and neck.

We have reviewed the records of 76 patients with Stage I or II extranodal non-Hodgkin's lymphoma who were referred to the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, during the years 1964 through 1974. The histologic slides were reviewed in the 67 cases in which they were available. Forty-three percent of Ann Arbor Stage I and II patients relapsed after primary radiation treatment.Seventy-three percent of these failed in sites distant from the irradiated volume. Failures in the treated volume were infrequent (7%) except in those patients presenting with primary lesions of the brain (4/5). Those patients presenting with lesions of Waldeyer's ring experienced a decrease in survival with increasing tumor size. Because of the high rate of failure in distant sites with tumors in the lingual and palatine tonsils, we are recommending the study of adjuvant chemotherapy in these cases, after primary radiation treatment.

The role of radiation therapy in the management of plasma cell tumors.

A retrospective review is reported of 128 patients presenting with multiple myeloma and 16 patients presenting with solitary plasmacytoma. Ninety-one percent of 116 evaluable patients treated for palliation of painful bone disease received some degree of subjective pain relief. The radiation dose most frequently prescribed was between 1500 and 2000 rad. Of the 278 ports treated, only 17 (6.1%) were re-treated to the same area at a later date. There was no increase in incidence of re-treatment with lower radiation doses. Ten of the 13 patients treated for a solitary plasmacytoma with a minumum follow-up period of three years have local tumor control. The median survival in the solitary plasmacytomas is five and one-half years. Data from the literature on 27 additional solitary plasmacytomas combined with our data suggest an improved local control and a decrease in dissemination with doses greater than 5000 rad. It is concluded that low doses of radiation are usually adequate to treat painful bone lesions of multiple myeloma and doses of 5000-6500 rad in six to seven weeks are recommended for solitary plasmacytomas.

Extended field radiation therapy in Hodgkin's disease: analysis of failures.

A retrospective analysis of 116 primary cases of stage I, II and III-A Hodgkin's disease demonstrated 27 failures, fourteen confirmed by biopsy. Twenty of the 27 (74%) were in lymph node areas only and seven had extranodal extensions. The most frequent site of failure was the hilar nodes and contiguous lung. The majority of failures (78%) occurred within 30 months of treatment and the cause of failure determined in 23 (85%), sixteen of which were due to technical errors of irradiation. Analysis of the dosimetry in the mediastinal, hilar nodes and contiguous lung failures revealed three factors which may have contributed to a low dose. These factors are: 1) the equivalent square, 2) off-axis beam diminution, and 3) the anteroposterior dose profile. Combined radiation therapy and chemotherapy was more effective than either modality alone in the treatment of these failures.

Gonadal shield.

A secondary gonadal shield for use in the pelvic irradiation of males was designed and built using material and apparatus available with the Cerrobend blocking system. The gonadal dose was reduced to approximately 1.5 to 2.5% of the given dose.

Radiation therapy in multiple myeloma.

In this retrospective study of 76 patients with myeloma, the indications for radiation therapy are reviewed and its value analyzed. Eleven patients presented with a "solitary plasmacytoma" and 65 patients presented with disseminated disease. Radiation therapy is successful in both the palliation of pain (81% of cases) and in producing long-term remission and possibly cure in solitary lesions.