Mantle Irradiation Research Articles

Serum thyroglobulin after mantle irradiation for Hodgkin's disease.

Thyroid function and serum thyroglobulin levels were studied in 66 subjects whose Hodgkin's disease had been previously treated by cervical, mediastinal and axillary lymph node (mantle) irradiation. Three patients were already undergoing treatment for thyroid disorders (one for primary hypothyroidism, two for Graves' disease) and a fourth was found to have euthyroid Graves' disease. 36 (Group I) of the remaining 62 patients had normal free thyroxine indices, normal basal thyrotrophin (TSH) levels and normal TSH response to thyrotrophin releasing factor (TRH). In 20 patients (Group II) free thyroxine indices were normal but either basal TSH levels were raised or normal basal TSH levels were associated with an exaggerated response to TRH. In 6 patients (Group III) free thyroxine indices were subnormal. Although results of thyroid function tests in group I lay within the normal range, the mean free thyroxine index was significantly lower and mean basal and peak TSH levels were significantly higher than those of a group of 35 normal subjects, indicating mild thyroid hypofunction. Elevated thyroglobulin levels were demonstrated in 11 irradiated subjects (18%). Mean thyroglobulin levels were significantly raised in each of the three groups of irradiated subjects. Significant positive correlations were found between log serum thyroglobulin and log basal TSH (r = 0.453, P less than 0.001) and log peak TSH (r = 0.515, P less than 0.001) levels. Mild thyroid hypofunction is common after mantle irradiation for Hodgkin's disease and raised serum thyroglobulin levels are a sensitive indicator of TSH stimulation of the damaged thyroid gland.

The effects of conventionally fractionated, extended portal radiotherapy on the human peripheral blood count

Conventionally fractionated, extended portal radiotherapy (CFEPRT) has been used to treat two diseases in which there was no marrow infiltration (viz. Hodgkin's disease and medulloblastoma). Blood count indices have been monitored during therapy and in the recovery phase. The lymphocytes were the most sensitive and the monocytes the most refractory leucocytes to change; the monocyte count tended to recover during CFEPRT. The platelet count fell gradually and soon after the neutrophil count. The nadir counts for white cells and platelets occurred early or toward the middle of CFEPRT, after which levels were maintained. The hemoglobin slightly and progressively declined. The patterns of change were similar for the two portals analyzed. Absolute eosinophilia occurred in 9 of the 53 CFEPRT patients, often in the recovery period. All patients who maintained their early nadir levels throughout the rest of the CFEPRT demonstrated fast recovery of all indices following completion of radiotherapy; the lymphocyte count recovered fastest. Recent prior CFEPRT or standard MVPP (nitrogen mustard, vinblastine, procarbazine, prednisolone) chemotherapy rendered the blood count more liable to radiation induced cytopenia. A lapse of more than 3 months between MVPP and CFEPRT allowed greater tolerance to the radiotherapy. Recent MVPP may be less myelosuppressive than recent mantle radiotherapy with respect to subsequent tolerance to CFEPRT.

Circulating Lymphocyte Populations in Hodgkin's Disease After Mantle and Paraaortic Irradiation

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T-cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.

Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T- cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.

An evaluation of long-term survival and treatment complications in children with Hodgkin's disease.

Between April 1969 and July 1977, 83 patients, 16 years or younger, with pathologically staged IA-IIIB Hodgkin's disease were seen and treated at the Joint Center for Radiation Therapy. The five-year actuarial relapse-free and overall survivals were 82 and 95%, respectively, with a median follow-up from diagnosis of 65 months. Relapse occurred in 6/50 Stage IA-IIA, 2/9 Stage IIB, 4/9 Stage IIIA, and 3/15 Stage IIIB patients. Of patients who relapsed, 11/15 are currently disease-free following retreatment with chemotherapy. Nine patients with Stage IV disease were also evaluated. Four of seven patients initially treated with chemotherapy remain free of disease. Forty-two patients in this study were treated with mantle and para-aortic irradiation alone, thus avoiding the risk of sterility associated with pelvic irradiation or MOPP chemotherapy while retaining a high probability for long-term disease-free survival. Complications of radiation therapy included growth retardation and thyroid function abnormalities in some patients. Standing height measurements were normal regardless of age at initial treatment, however, 16 of 23 patients 3-12 years old at initial treatment had sitting heights measuring more than one standard deviation below the mean. Intraclavicular distances were shortened in some patients and examples are shown. Thyroid stimulating hormone levels were elevated in 21 of 37 patients evaluated. Radiation therapy, without adjuvant chemotherapy remains an important treatment approach for children with early stage Hodgkin's disease.

Coronary artery disease following mediastinal radiation therapy

Coronary artery disease occurred in four young men (mean age 41 years) who had received curative irradiation therapy for mediastinal malignancies 12 to 18 (mean 15) years previously. None was at high risk for developing coronary artery disease by Framingham criteria. Angiography demonstrated proximal coronary artery disease with normal distal vessels. Distribution of the lesions correlated with radiation dosimetry in that vessels exposed to higher radiation intensity were more frequently diseased. Three patients had coronary bypass grafting for intractable angina and are asymptomatic at 10 to 43 months. A total of 163 patients underwent mediastinal irradiation for lymphoma or thymoma between 1959 and 1980. Among the 29 who survived 10 or more years, five (18%) developed severe coronary artery disease, implicating thoracic radiotherapy as an important risk factor. Because of the importance of mantle irradiation in the treatment of lymphomas, the prevalence of these neoplasms, and the survival patterns following treatment, many long-term survivors may be at increased risk for the development of coronary artery disease. Recognition of the relationship between radiotherapy and coronary artery disease may lead to earlier diagnosis and more timely intervention. Standard surgical treatment may be particularly beneficial because of the relative youth of most of these patients and because the proximal distribution of typical lesions increases the likelihood of complete revascularization.

Follow-Up of Pathological Stage I and IIA Supradiaphragmatic Hodgkin's Disease Primarily Treated with Radiotherapy

One hundred and fifty-five consecutive previously untreated adult patients with supradiaphragmatic pathologic stage IA (71) and IIA (84) Hodgkin's disease treated only with radiotherapy (RT) at the Istituto Nazionale Tumori of Milano from 1970 to 1978 were reviewed. Staging procedures included lymphangiography and laparotomy in all cases. Most patients were irradiated with a conventional cobalt machine. Mantle fields were adopted for 36.8% of cases, mainly at stage I, whereas 63.2% received mantle plus paraaortal irradiation. Doses were above 40 Gy for involved sites and 35-40 Gy for prophylactically irradiated nodes. Minimum and median follow-up were 30 months and 6 years, respectively. All patients achieved complete remission at the end of RT. As of June 1981, 89 of 155 patients (57.5%) were alive and free from progression, 60.6% at stage I, and 54.8% at stage II. Relapses occurred in 54 of 155 cases (35%) after a median free interval of 21 months. Marginal recurrences accounted for 5.8%, true recurrences for 9%, nodal extensions for 8.4%, and extranodal extensions for 11.6%. Males older than 40 years and mediastinal involvement were correlated with higher relapse rates. Salvage treatment consisted of RT alone in 8 patients and chemotherapy plus or minus RT in 44, whereas 2 patients died before a new treatment could start. As of June 1981, 38 of 54 relapsed patients (70.4%) were alive and disease free, whereas 2 were alive with evidence of disease. Actuarial overall survival at 6 years was 90.3% for all cases, 97.1% for stage I, and 84.8% for stage II. Treatment toxicity was analyzed, and problems concerning surgical staging procedures, optimal RT and role of chemotherapy as primary or salvage treatment were discussed.

Radiotherapy as a Cause of Complete Atrioventricular Block in Hodgkin's Disease

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis of the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.

Thyroid Function After Mantle Irradiation in Hodgkin's Disease

We studied the thyroid function of 64 patients with Hodgkin's disease who received mantle irradiation during the period 1966 to 1976. More than two thirds (44 of 64) had some thyroid dysfunction. Twenty had mild dysfunction manifested by an abnormal thyroid-stimulating hormone response to thyrotropin-releasing hormone. Twenty had what could be termed compensated hypothyroidism while four were overtly hypothyroid. The severity of dysfunction was not related to age, sex, or chemotherapy. We found, however, that decreased thyroid function was inversely proportional to the length of time between a diagnostic lymphangiogram and the radiation therapy. These results are consistent with the hypothesis that the iodine load of the lymphangiogram renders the thyroid gland more radiosensitive. Thyroxine suppression of the thyroid gland during the period from the lymphangiogram through the termination of radiation therapy is suggested as a means of avoiding thyroid injury.

Thyroid function after mantle irradiation in Hodgkin's disease

Thyroid function after mantle irradiation in Hodgkin's disease

Complications in the management of the malignant lymphomas (report no 15)

This report reviews the common complications associated with the investigation and treatment of the lymphomas and enumerates the complications recorded so far in the 1410 patients with Hodgkin's disease registered in the British National Lymphoma Investigation. Long-term follow-up of these patients will allow a better understanding of the overall risks of splenectomy. The incidence of leukaemia and other lymphomas in the group of patients studied in the BNLI is extremely low. Two patients developed non-Hodgkin's lymphomas, one having had radiotherapy alone and the other MOPP alone. Two patients developed acute myeloid leukaemia, one after mantle radiotherapy followed by chemotherapy and one after MOPP alone. A fifth patient treated with MOPP alone developed a rapidly fatal acute lymphatic leukaemia three years later. This low incidence of second malignancies may be related to the relatively non-aggressive treatment schedules utilised by the BNLI.

Transient radiation myelopathy (Lhermitte's sign) in patients with Hodgkin's disease treated by mantle irradiation

Transient radiation myelopathy diagnosed by Lhermitte's sign was noted in four of 44 patients with Hodgkin's disease who were treated with 4000 rad/four wks. mantle irradiation from 1969 to 1977. Symptoms appeared four, six, six and twenty weeks after treatment and lasted for four, eight and twenty-four weeks respectively; one patient developed late minor neurological disability two years later. There was no correlation within this group of patients between incidence and time dose fractionation (TDF) or equivalent single dose (ED ret) but a dose response-incidence relationship was noted when this study was compared to others in the literature.

Long-Term Results of Treatment of Children and Adolescents with Hodgkin's Disease

Fifty-four children and adolescents with Hodgkin's disease Stages I--IV were treated with chemotherapy plus radiotherapy from 1967 to 1972. Thirty-eight patients (70%) remain in continuous complete remission. Nine patients have died, four of progressive disease, three of pneumonitis, one with probable pneumococcal sepsis, and one of acute myelocytic leukemia. Significant retardation of height and crown-rump length occurred, particularly in boys who received at least mantle or abdominal radiotherapy when younger than age 16 years. Five women have amenorrhea and no patient has clinical evidence of hypothyroidism. The major long-term effects of therapy in this group of patients has been growth retardation. Future studies to minimize long-term effects of therapy are necessary but must be carefully designed so that present cure rates are not jeopardized.

Chemotherapy--radiotherapy association in Hodgkin's disease, clinical stages IA, II2A: results of a prospective clinical trial with 166 patients.

One hundred sixty-six patients with clinical stages IA, II2A Hodgkin's disease were treated between April 1972 and December 1976 with three courses of multiagent chemotherapy (methylchlorethamine, vincristine, procarbazine, prednisone) followed by mantle irradiation--excluding mediastinum for those with initial upper cervical presentation and absence of mediastinal involvement--or inverted Y radiotherapy. None had staging laparotomy. With a follow-up of 12--84 months, median 40 months, the overall survival is 93.5% and the overall relapse-free survival 89.9%. Eight patients died, three of them with evident disease. Ten patients relapsed; four are now free of disease after retreatment. With chemotherapy-radiotherapy sequence, staging laparotomy is not indicated. Results and side effects of this treatment strategy are compared with those of other treatment policies.

Radiation-induced pericarditis in mantle irradiation: An analysis of causative factors

Radiation-induced pericarditis in mantle irradiation: An analysis of causative factors

Radiation Pneumonia Complicating Adjuvant Cytotoxic Chemotherapy

A patient with Hodgkin's disease developed acute radiation pneumonia four months after completion of mantle radiotherapy and during cyclical adjuvant chemotherapy. Respiratory function tests were useful in the diagnosis of the interstitial abnormality and in monitoring response to prednisone. Serial respiratory function tests in patients receiving bimodal therapy may facilitate early diagnosis of this potentially serious complication.

Hodgkin's Disease

To the Editor. —Though the article by Durkin and Durant in the MarchArchives(139:333-336,1979) may be a worthwhile contribution to the internal medicine literature, their observation concerning residual mass lesions following treatment for Hodgkin's disease is by no means an original realization. Most radiotherapists with substantial experience in the treatment of Hodgkin's disease have learned to anticipate that it is not unusual for a patient to have persistent fibrotic masses in a region of previous massive tumor involvement. As with the two cases reported by Durkin and Durant, this is most usually seen with the nodular sclerosing variety. In view of the relative frequency with which this phenomenon occurs, I would certainly be very skeptical of a recommendation of thoracotomy for a patient with a persistent mediastinal mass four months following mantle irradiation. For a concise and straightforward description of the phenomenon of persistent benign mass lesions following treatment

Pulmonary Reaction to Upper Mantle Radiation Therapy for Hodgkin's Disease

To study the effects of upper mantle radiation therapy on pulmonary function, forced expiratory volume in one second (FEV1), vital capacity (VC), inspiratory capacity (IC), diffusing capacity for CO (DLCO) and diffusion per unit of alveolar volume (DL/VA were determined in 28 patients with Hodgkin's disease, stages 1--3, before therapy and at regular intervals thereafter. Within the first year of follow-up there were significant declines in DLCO, VC, and IC, whereas there were no significant changes in FEV1 or DL/VA. DLCO showed the greatest decline in the largest number of subjects (22/28). Eleven of the 22 had 20 to 60 percent decline of DLCO from baseline. The maximum mean decline in DLCO was -12.7 +/- 3 percent at the 87th +/- 3 days from initiation of therapy postradiation sustained through the 150th day and improving to pretreatment value (+/- 5 percent) by the 8th to 12th month. The changes in DLCO seemed to be independent of the radiation dose ranges evaluated, clinically apparent intrathoracic lymphoma, postradiation radiographic abnormalities and respiratory symptoms. We concluded that impairment in diffusing capacity and loss of vital capacity will develop in most patients receiving upper mantle radiation therapy, indicating that pulmonary reaction occurs despite lung shielding. The functional losses were prolonged and occasionally severe, but were transient and subclinical in most but not all cases. A case of fatal radiation pneumonitis affecting the lung beyond the field of irradiation is reported.

The significance of mediastinal involvement in early stage Hodgkin's disease.

Between April 1969, and December 1974, 111 consecutive surgically staged I A and II A patients with supradiaphragmatic Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Patients received 3600--4400 rad to mantle and para-aortic--splenic pedicle regions. Median follow-up was 56 months (30--96). Fourteen patients developed relapsing Hodgkin's disease and three patients died of possible treatment-related causes, two with acute myocardial infarctions and one with radiation pneumonitis. Patients with mediastinal enlargement greater than one third of the chest diameter have a significantly higher risk (p less than 0.01) of developing relapse (9 of 18) than patients with lesser or no mediastinal disease (5 of 93). Of the 18 patients with large mediastinal disease, six relapsed in the mediastinum and two in the lung. There continue to be no pelvic extensions in the entire group. There is a 92% relapse-free and 97% overall survival in the 93 patients without extensive mediastinal disease. We continue to recommend mantle and para-aortic--splenic pedicle irradiation for these patients. In view of the large number of relapses in patients with extensive mediastinal disease, we are now treating this subgroup of patients with MOPP chemotherapy in addition to mantle and para-aortic irradiation.

Hodgkin's disease: problems of staging.

The preferred histopathological classification of Hodgkin's disease (HD) is that suggested by Lukes and Butler as modified at the Rye Symposium; the histologic subtypes are highly reproducible and correlate well with the anatomic sites of involvement, clinical stage, and survival. The accuracy of the bipedal lymphangiogram, 67gallium scan, and ultrasonography in predicting abdominal involvement by HD is 90% , 50%, and 88%, respectively. Staging laparotomy remains the most accurate method of detecting intra-abdominal disease and has added immensely to new concepts in the management of HD. These concepts suggest that patients with nodal disease limited to the celiac axis or upper para-aortic areas (substage III1) or pathologic stage (PS) IIIS+N-A, when treated with extended field radiotherapy alone have survival rates comparable to PS IIA patients. In contrast, patients in PS IIIA with lower abdominal nodal disease (substage III2), regardless of splenic involvement, have a prognosis comparable to PS IV disease. Thus, there may only be two stages of HD, those curable with extended mantle or smaller radiotherapy fields alone, and those requiring chemotherapy with or without supplemental radiotherapy.