The effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease.

To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified.

Treatment of early--stages I and II--nodular, poorly differentiated lymphocytic lymphoma.

Twenty-nine patients with Stages I and II nodular, poorly differentiated lymphocytic lymphoma were treated with radiation therapy or radiation therapy plus chemotherapy. Twenty-two patients with Stage I received radiation to the involved field, the other seven with Stage II received total lymphoid radiation. Complete remission was achieved in all 29. There were no differences in remission duration or survival according to treatment modality. Five of 29 (17%) patients relapsed. No relapses were observed after 5 years. Ten patients died; one patient died of lymphoma, and nine others died in continuous complete remission of various other causes. Sixty-six percent of the patients were alive at 74-160 months (median 118 months). Involved field radiation with or without chemotherapy was well tolerated, producing acceptable toxicity. Substantially more toxicity was observed after total lymphoid irradiation and although cures were also achieved, less toxic treatment programs should be investigated. The low rate of relapse observed in early stages of this lymphoma in this and in other studies is suggestive that cures might be achieved in nearly one-half of the patients presenting in early stage.

Simultaneous low-dose radiation and low-dose chemotherapy in the treatment of advanced Hodgkin's disease.

Simultaneous combination chemotherapy (CT) (BCNU 40 mg/m2, procarbazine 50 mg/m2, prednisone 40 mg/m2, and vincristine 1.4 mg/m2) with low-dose radiation therapy [(RT) 2000 rad] delivered to all areas of tumor involvement aside from the bone marrow was given to 28 patients with advanced Hodgkin's disease. Upon completion of RT and CT, the BCNU and procarbazine was increased by 100% until a total of six cycles of CT (with and without RT) were given. Eleven patients had received prior CT and had not achieved complete remission (CR) or had relapse from CT-induced CR within 1 year. Seventeen others had not had prior CT (7 had prior RT). Among the previously treated patients, one patient died in autopsy-proven CR during treatment. The other 10 patients achieved CR. Eight had relapsed at 4-36 months (median time to relapse, 6 months). Five patients died of Hodgkin's disease, three others died of status asthmaticus and pneumonia, radiation pneumonitis, and acute nonlymphocytic leukemia, respectively. Three patients are still alive (2 in continuous CR) at 28, 89, and 90 months. Among the previously untreated patients, four died during treatment, one of acute myocardial infarction, two of liver failure, and one of radiation pneumonitis. Twelve of the other 13 patients achieved CR. One of the CR died of pneumonia and sepsis 3 months after completion of treatment; two other patients relapsed at 10 and 15 months. Nine remain in continuous CR at 42-89 months of follow-up, (median follow-up, 81 months). Of 107 tumor areas treated with RT, in-field relapse occurred in two areas (1.9%). Hematologic tolerance to this treatment was good in both groups of patients. Radiation pneumonitis occurred in 50% of the patients whose lungs were irradiated, and it was fatal in two. By design or for other reasons, the median and mean doses of BCNU and procarbazine given to previously treated patients were 62% and 65.2%, respectively. In untreated patients, the median and mean doses of these two agents were 66.6% and 61.4%, respectively. There were no differences in dosage of these two agents between patients who remain alive in CR and those who relapsed and died. The potential of similar programs of radiation and chemotherapy is discussed.

Staging laparotomy and splenectomy in early Hodgkin's disease. No therapeutic benefit.

In a prospective randomized study of treatment for early-stage Hodgkin's disease presenting above the diaphragm, 76 patients had staging by laparotomy (Group I) and 28 had staging by closed techniques (Group II). Treatment consisted of involved-field radiotherapy alone (44 patients), involved-field radiotherapy followed by chemotherapy (38 patients), total nodal radiotherapy alone (15 patients), or total nodal radiotherapy followed by chemotherapy (seven patients). On presentation, both groups had similar clinical features and similar treatment distribution. With similar follow-up (87 months), no significant differences in remission or survival were observed between Groups I and II: remission 59 versus 68 percent; survival 74 versus 92 percent; p value 0.27 and 0.09, respectively. Multiple areas of relapse were more frequently observed in Group I (11 of 32 had relapse) as compared with Group II (none of nine had relapse, p less than 0.082). In Group I, relapse in the abdomen was observed as an isolated event or as part of disseminated relapse in 12 percent of patients compared with 3 percent (one patient) in Group II with abdominal relapse alone. Seven patients in Group I and two patients in Group II died with Hodgkin's disease. Six other patients in Group I died with complete remission of non-Hodgkin's lymphoma (one patient), leukoencephalopathy (one patient), sepsis during chemotherapy (two patients), myocardial infarction (one patient), and cerebrovascular accident (one patient). Three other patients in this group had other secondary malignancies successfully controlled (histiocytic lymphoma, squamous cell carcinoma of the cervix, and malignant schwannoma). No second primary lesions or death with complete remission were observed in Group II. Staging laparotomy with splenectomy in early-stage Hodgkin's disease did not improve the duration of remission or survival or decrease the number of abdominal relapses compared with closed staging.

Seminoma at Roswell Park, 1970 to 1979. An analysis of treatment failures.

A retrospective study of all cases of seminoma treated at Roswell Park Memorial Institute from 1970 through 1979 was conducted. Fifty-six evaluable patients treated initially with radiation therapy were seen during this period, and the overall survival rate at an average follow-up period of 52 months was 82%. The survival rate in patients with bulky abdominal or supradiaphragmatic metastases was only 33% (4 of 12 patients). Treatment failures were analyzed to determine their apparent causes and the implication of such failures to the future management of seminoma. The use of combination chemotherapy as the initial treatment modality in advanced seminoma is discussed in light of these results.

Large mediastinal mass in Hodgkin's disease. Results of two treatment modalities.

Sixty-eight untreated patients with Hodgkin's disease (HD), stages I-III, presenting with a large mediastinal mass were treated as follows: patients with "good-risk HD" (lymphocyte predominant or nodular sclerosis and no "B" symptoms) stages I and II were treated by randomization with involved field radiotherapy (IF RT) or IF RT plus six cycles of combination chemotherapy (CT). Those with "poor-risk HD" (presence of B symptoms or with other histologic types) stages I and II and all patients with stage III were treated by randomization with total nodal radiation (TNR) or TNR + CT. Complete remission (CR) was achieved in 66/68 patients (97%) with the initial RT. A significantly longer duration of remission (p = 0.001), but not of survival (p = 0.08) was observed in patients treated with RT + CT compared to RT alone. Significantly longer duration of remission (p = 0.01), but not of survival, was observed in patients with good-risk stages I-II treated with RT + CT. In this category, remission and survival was better with RT + CT than with RT alone in stage III, but these differences were not statistically significant. In poor-risk patients stages I-II, a trend for longer remission and survival (not significant) was observed in patients treated with RT + CT; in stage III, both treatment modalities gave similar poor results. Both treatment modalities were well tolerated by most patients. One patients died with radiation pneumonitis shortly after completion of TNR. One patient developed a malignant schwannoma after treatment with IF RT, and another one developed acute nonlymphocytic leukemia after TNR + CT. Decrease in the transverse diameter of the heart without overt manifestations of cardiac disease was observed in 59% of the patients evaluated for this parameter.

Heart size and function after radiation therapy to the mediastinum in patients with Hodgkin's disease.

Changes in the transverse heart diameter and cardiothoracic ratio were determined by comparing the pretreatment and last follow-up posteroanterior chest x-rays of 96 patients with stage I-III Hodgkin's disease who had received radiation therapy (RT) to the mediastinum, with the same parameters observed in 20 similar patients whose mediastinum was not irradiated. A significantly higher proportion of patients who had received RT to the mediastinum had a decrease in transverse heart diameter and cardiothoracic ratio. Among patients presenting with a large mediastinal mass, these changes were more pronounced as compared to the other groups; however, this difference was not of statistical significance. First-pass left ventricular ejection fraction (LVEF) performed with 99mTc pertechnetate (obtained in 55 of these patients 30-120 months after RT to the mediastinum) was compared with the LVEF of 20 normal controls. The control group had a significantly higher LVEF than the group of patients who had received RT to the mediastinum. No correlation was observed between changes in these parameters and the use of adjuvant, salvage, or no chemotherapy after mediastinal RT. None of these patients presented congestive heart failure or constrictive pericarditis, but our findings indicate a subclinical cardiomyopathy in more than one-half of the patients who received RT to the mediastinum, suggesting that the incidence of heart damage after mediastinal RT might be higher than expected. Prospective studies are necessary to elucidate the incidence and implications of this potentially serious complication.

Second malignant tumors detected by needle aspiration cytology.

Between 1967-1980, 14 second primary cancers were detected by needle aspiration cytology in patients treated for malignant tumors. The interval between the first cancer and the occurrence of the second cancer varied from six months to 21 years. In all 14 cases, the cytologic diagnosis of the second cancer was later confirmed by histopathologic examinations. In 13 patients, the second cancer was dissimilar from the first one, and in one patient the two cancers were subtypes of lymphoproliferative tumors. In three patients the cytologic diagnosis falsely defined the subtype of the second cancer. Malignant lymphoma was the predominant tumor either as the first cancer (50%) or as the second cancer (43%). Thyroid cancer occurred as the second cancer in three patients. Needle aspiration cytology of all newly appearing lesions can be performed routinely during follow-up examinations to discriminate between relapsed disease and new malignant tumors.

Gastrointestinal involvement in non-Hodgkin's lymphoma.

A total of 813 patients admitted to Roswell Park Memorial Institute from 1963--1972 with non Hodgkin's lymphoma (NHL) were reviewed for gastrointestinal (GI) involvement. Primary involvement was found in 71 and secondary involvement in 31 patients. Occult GI involvement was detected in 46% of the autopsy cases. The median survival time after the diagnosis of secondary GI involvement was nine months. The occurrence of primary GI-NHL was: 33 in the stomach, 18 in the small intestine, 14 in the ileocecal area including appendix, and 6 in the large intestine. Retrospective staging according to the Ann Arbor staging classification showed 24 to have presented as Stage I, 30 as Stage II, 4 as Stage III, and 13 as Stage IV. The primary diagnostic and therapeutic approach was operative, except in 2 patients with rectal lymphoma. Resection of the principally involved site was carried out in 42 patients. The remainder had palliative procedures or biopsy examinations only. Postoperative radiation therapy was given to 38 patients. Prognostically important features for primary GI-NHL were: stage; histologic type; site of the primary disease; and whether or not radiotherapy was administered. The age of the patient, size or degree of local extension, and type of operative procedure were prognostically of no importance. The results of this study would indicate that in Stage I and II primary GI-NHL, elective resection is not necessary prior to radiation therapy and that resection alone cannot be considered adequate treatment. A modified staging classification is proposed.

Acute transient radiation hepatitis following whole abdominal irradiation.

Sporadic cases or radiation hepatitis have been reported following doses above 3500 rad delivered in 3-4 weeks to the liver. The authors report their experience of radiation hepatitis in two out of 117 consecutive lymphoma cases treated with total abdominal irradiation. These two patients developed clinically overt manifestations which lasted for a short period of time and fully recovered. The dose delivered to the whole liver was 3000 rad in six weeks, but in one an additional 1000 rad in five fractions were delivered to the left lobe in an attempt to boost the dose to the central axis lymphatic system up to 4000 rad. The low incidence of radiation hepatitis and its reversible course, when 3000 rad in six weeks are delivered to the whole liver, is emphasised.

Spinal cord compression in malignant lymphoma. Treatment and results.

The natural history, treatment, and results of 73 spinal cord compressions caused by malignant lymphomas are analyzed. It is found that the spinal cord compression caused by malignant lymphomas is generally a late manifestation of the illness, although primary or early involvements are occasionally seen. In our study, reticulum cell sarcoma is the most frequently variety followed by Hodgkin's disease and lymphosarcoma. The dorsal spinal cord is the most frequently involved segment and pain, weakness, and paresthesia are cardinal symptoms. Radiation treatment delivered in the early phase of the compression is commonly successful in reversing the neurologic symptoms and a dose above 2500 rads appears to be optimal for local control of disease. The low incidence of cerivcal cord compression in Hodgkin's disease patients may be related to frequent manifestation and irradiation of the neck nodes in these patients. Early detection of disease in the deep seated areas along the spinal cord and irradiation of these areas may prevent progression of tumor to the epidural space.