J R Cassady’s research while affiliated with Harvard Medical School and other places

Between April 1969 and December 1980, 329 patients with pathologically staged IA-IIB Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Twenty-five (7.6 per cent) of these patients presented with inguinal-femoral or superficial iliac adenopathy and had disease limited to below the diaphragm. In addition 11 patients presented with intra-abdominal masses and Hodgkin's disease was diagnosed on laparotomy. The median age, histologic subtypes, and actuarial relapse free and overall survival of patients with peripheral adenopathy limited to below the diaphragm were similar to patients with supradiaphragmatic Hodgkin's disease. Patients with disease limited to the pelvic or inguinal-femoral nodes were treated with pelvic and para-aortic irradiation alone. Staging laparotomy identified those patients with para-aortic or splenic involvement and these patients were treated with total nodal irradiation or combined modality treatment. The small group of patients who presented with intra-abdominal disease without peripheral adenopathy was older, had a predominance of lymphocyte depleted histology, and had a worse prognosis than the other patients described.

A 5-day-old female patient was found to have large hereditary retinoblastomas in the posterior pole of each eye. The patient received radiation treatment over a 39-day period, with each retina receiving 4600 rad. Two weeks after the complete treatment the tumours had regressed to approximately one-quarter of their original size. By 14 weeks following completion of radiotherapy the patient had developed in each eye extensive iris neovascularisation with progressive closure of the filtration angles, secondary glaucoma, and retinal detachments resulting from fibrovascular proliferation on the retinal surface. Radiosensitivity studies were from separate conjunctival biopsies obtained before and after radiation. These showed a D0 (calculated survival curve parameters, defined in the Methods section) in the exponential growth phase of 110 prior to radiation and a postirradiation exponential growth phase D0 of 70. Karotype studies showed several chromosomal abnormalities following radiotherapy. The clinical course and pathology findings are thought to represent an unusually severe orbital and ocular response to radiation therapy. These findings are consistent with our hypothesis that some patients with hereditary retinoblastoma may have a defect in the accumulation repair of x-irradiation induced DNA damage.

Primary lymphoma of bone is an unusual extranodal presentation of pediatric non-Hodgkin's lymphoma (NHL). Treatment with radiotherapy alone has resulted in a disease-free survival rate of approximately 50% in most adult series. Between January 1973 and April 1985, 11 children with biopsy-proven NHL of bone were seen and treated at our institutions. The minimal clinical staging included chest and bone radiographs, a radionuclide bone scan, complete blood cell counts and serum chemistries, and a bone marrow aspirate and biopsy. The age range was 9 to 17 years with a median age of 14 years. Histology included diffuse lymphoblastic lymphoma in four patients and diffuse histiocytic lymphoma in seven. Each patient was treated with the Adriamycin/prednisone/Oncovin (APO) protocol and ten patients received concomitant radiation to the whole bone when possible and a boost to the primary lesion(s). The median tumor dose was 5,000 rad (range, 3,600 to 5,600). The median follow-up was 8 years. There have been no relapses, but two patients have developed second bone tumors 5 and 7 1/2 years after beginning therapy. Each second tumor arose directly in the radiation field. The overall 8-year actuarial survival is 83%. We conclude that APO and local radiation results in excellent overall survival for children with primary NHL of bone. The occurrence of two second bone tumors, however, raises questions regarding dose and/or the role of radiation for this disease.

Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. We have reviewed ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981. All patients had biopsy-proven CNS lymphomas without systemic disease at presentation. In our series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.

Radiation therapy (XRT) was used in the treatment of 25 patients with tumors of the pineal and suprasellar locations. A tissue diagnosis was obtained before XRT in 5 patients, and 20 were irradiated without histologic verification. The overall survival rate is 80% (76% with no evidence of disease [NED]). Megavoltage XRT was delivered to the entire neuraxis in 22 patients, and 86% (19/22) are alive from 4 to 88 months (median, 30 months) after treatment. In two of three patients treated only to local fields, tumor recurred in the spine; both are dead of disease. Biopsy-proven germinomas and multiple midline tumors responded favorably to XRT, whereas solitary pineal tumors and teratomas with marker positivity (human chorionic gonadotropin, alpha-fetoprotein) did not respond as well. The endocrinologic presentation, tumor marker status, and early response to radiation measured on computed tomography are useful means for selecting patients for radiation therapy.

Twenty-nine patients with biopsy-proven malignant lymphoma of large-cell "histiocytic" type were treated with the APO protocol (vincristine, adriamycin, and prednisone). Treatment consisted of two years of therapy with a modified adriamycin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and regional radiotherapy (for patients with clinically localized lymphoma). The median age was 13 years (range, two to 20 years). Thirteen patients had localized disease (stage I, II), and 16 had disseminated disease (stage III, IV). The median follow-up is four years (range, seven months to nine years), and Kaplan-Meier estimates of overall and relapse-free survival are 83% and 76%, respectively. No recurrences have been observed in primary or bulk sites of lymphoma in the group of children treated with chemotherapy only. We conclude that the APO protocol, which was modeled after an acute lymphoblastic leukemia regimen, combined with regional radiotherapy can produce long-term remissions for children with malignant lymphoma of large cell "histiocytic" type.

From 1970 to 1982 11 infants with Evans stage IV neuroblastoma who were 11 months of age or less at diagnosis were treated. All but one were treated with intensive multiagent chemotherapy; eight had attempted surgical resection; only one received radiotherapy to the primary tumor. Ten of the 11 infants remain free of disease from 2 1/2 to 13 years (median, four years). Multiagent chemotherapy has clearly improved the outcome for infants with stage IV neuroblastoma.

Twenty-nine patients with biopsy-proven malignant lymphoma of large- cell “histiocytic” type were treated with the APO protocol (vincristine, adriamycin, and prednisone). Treatment consisted of two years of therapy with a modified adriamycin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and regional radiotherapy (for patients with clinically localized lymphoma). The median age was 13 years (range, two to 20 years). Thirteen patients had localized disease (stage I, II), and 16 had disseminated disease (stage III, IV). The median follow-up is four years (range, seven months to nine years), and Kaplan-Meier estimates of overall and relapse-free survival are 83% and 76%, respectively. No recurrences have been observed in primary or bulk sites of lymphoma in the group of children treated with chemotherapy only. We conclude that the APO protocol, which was modeled after an acute lymphoblastic leukemia regimen, combined with regional radiotherapy can produce long- term remissions for children with malignant lymphoma of large cell “histiocytic” type.