The treatment of diffuse undifferentiated non-Hodgkin's lymphoma in children: the Childrens Cancer Study Group experience.
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Biomedical subjects
Publications and source records attributed to R D Jenkin.
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Between April 1977, and August 1980, the Children's Cancer Study Group (CCSG) conducted a clinical trial of childhood non-Hodgkin's lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4-drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP] ) was compared with a 10-drug regimen (regimen 2, modified LSA2-L2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitt's tumor (BT), 40; "undifferentiated" non-Burkitt's type (NB), 67; large cell or "histiocytic" lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.
Investigators of the Children's Cancer Study Group entered 73 children with previously untreated localized non-Hodgkin's lymphoma on a prospective randomized trial of systemic treatment with either a four-drug program (cyclophosphamide, vincristine, methotrexate, prednisone [COMP]) or a 10-drug (LSA2-L2 modified) program of 18 months duration. All patients received central nervous system prophylaxis with intrathecal methotrexate and most received local or regional radiation treatment. The three-year relapse-free survival rate for all patients (N = 73) was 84%; for COMP (N = 42) was 85%, and for LSA2-L2 (N = 31) was 84%. Of the 12 patients who suffered adverse events eight relapsed and four died of toxicity. Histopathology was reviewed centrally. Of 32 patients with nonlymphoblastic disease treated with COMP only one relapsed. Of 26 patients treated with LSA2-L2, four relapsed. Patients with localized lymphoblastic disease were uncommon. None of three patients treated with LSA2-L2 relapsed compared with three of nine treated with COMP. COMP is an excellent treatment for patients with localized disease of nonlymphoblastic type, but the relative value of the two regimens for patients with localized lymphoblastic disease is uncertain.
Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rad in five days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 15 years. In premenopausal patients who received ovarian irradiation, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (p = 0.04) and prolonged survival (p = 0.02). No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.
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Single-dose half-body irradiation (HBI), introduced for the palliation of pain from widespread bone metasases in adults, has proved to be successful. Relief is obtained in a high proportion of patients, with upwards of two-thirds experiencing complete relief. Onset of response is fast and clinically valuable duration varies from 5 to 20 weeks. Objective evidence of tumor regression is found less frequently. The dose-limiting toxicity has proved to be acute radiation pneumonitis, with bone marrow tolerance of lesser importance, in spite of the fact that many patients received previous local irradiation and/or chemotherpy. Palliative HBI has not become a valuable treatment in pediatric malignancies, because of a shorter metastatic phase. Pediatric tumors usually have shorter cell cycle times and are more responsive to systemic agents. Results are described in selected institutions, where HBI has been used in the treatment of pediatric malignancies. A single institution pilot study was undertaken at the Princess Margaret Hospital involving 17 patients with Ewing's sarcoma of bone, without overt metastases at diagnosis. Results to date have not been obviously different from overall survival in the first intergroup Ewing's sarcoma study. Overall, the treatment has been shown to be well tolerated and can be given entirely on an out-patient basis. When compared on a historical basis with a previous single dose total body irradiation study, the one year survival rate was increased. HBI appears to be a tolerable treatment, when given concurrently with or sequential to local and systemic treatment.
This article is a review of 22 cases of Ewing's sarcoma peripheral to the elbow and knee treated with moderate dose radiotherapy, with special reference to local control, functional result and risk of irradiation induced sarcoma. Eleven patients (50%) are alive two to 16 years following radiotherapy. Two of these had local recurrences, one being salvaged by reirradiation and the other by amputation. The functional results of treatment were assessed in the nine survivors who did not have a recurrence . Eight had normal limb function and one had a 3 cm leg-length discrepancy. Nine patients in the total experience of the hospital who survived more than ten years after radiotherapy were assessed for evidence of postirradiation sarcoma and none were found. The excellent results of radiotherapy in terms of local control, function and lack of irradiation induced sarcomas is attributed to the use of moderate doses of irradiation.
Forty cases of young patients with embryonal rhabdomyosarcoma or undifferentiated sarcoma in parameningeal sites of the head and neck were reviewed. All 40 were treated with radiation therapy in conjunction with surgery and 16 were also treated with adjuvant chemotherapy. The overall five year survival rate was 35%. A primary tumor dose of at least 5000 rad resulted in a significantly greater survival rate compared with lesser doses. Meningeal involvement at diagnosis was present in 20 patients (50%) and the 30% five year survival rate for this group was no different than that for patients without initial meningeal involvement (41%). At first or second relapse, meningeal involvement was present in six of 37 patients and in two patients this occurred as an isolated event with distant meningeal seeding; in four other patients, meningeal involvement was a manifestation of local recurrence. As of the time of the last follow-up examination, control of the primary tumor had been achieved in 22 of the 40 (55%). It is considered that primary tumor radiation treatment parameters may be critical in determining the incidence of subsequent meningeal relapse.
Data from 119 patients with nasopharyngeal carcinoma who were under 30 years of age were retrospectively analyzed by the investigators of the Children's Cancer Study Group. The overall five-year survival and relapse-free survival rates from diagnosis were 51 and 36%, respectively. When the tumor was confined to the nasopharynx (1 + T2, 41 patients), the five-year survival was 75%. No significant correlation was found between survival or local recurrence and the radiation dose to the primary site. The five-year survival from relapse was 37% for 21 reirradiated patients with local and/or regional relapse compared with 11% for 45 patients with other forms of relapse. It is concluded that the optimal radiation dose for tumor eradication in young patients is now known.
One hundred and twenty-two patients with medulloblastoma received postoperative irradiation at the Princess Margaret Hospital, Toronto, from 1958 to 1978, inclusive. The surgical procedure in these patients was total resection (44 patients), subtotal resection (66 patients), or biopsy alone (12 patients). Twenty-five patients received adjuvant chemotherapy. Overall 5- and 10-year survival rates were 56% and 43%, respectively. Improved survival rates were associated with an increased degree of resection and with posterior fossa radiation doses of 5200 rads or more. The posterior fossa was the common site of first relapse (in 56 patients, 46%). Systemic metastases at first relapse occurred in 18 of 52 patients (35%), and were associated with the use of ventriculosystemic shunts. Millipore filters did not prevent systemic relapse in shunted patients. A subset of 15 patients who received a posterior fossa dose of 5200 rads or more after a total resection had a 5-year survival rate of 77%, which remained constant to 10 years. This result is considered to be the upper limit that can be achieved by current treatment methods.
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Osteosarcoma or chondrosarcoma developed as a second malignant neoplasm (SMN) in 40 of 188 individuals with SMN whose first neoplasm occurred in childhood. A genetic susceptibility to cancer was found in 23; the SMN developed in an irradiated field in 32; both factors wer present in 16; neither in one. When a genetic predisposition was present, radiation shortened the interval to SMN. The intervals between tumors and the age at which the bone sarcomas developed in relation to genetic disease and therapy were analyzed by a two-mutation hypothesis. Studies of SMN in childhood permit us to make observation about the role of genetic factors and environmental mutagens in cancer etiology.
A pilot study of the toxicity and efficacy of a new treatment schedule for childhood non-Hodgkin's lymphoma was conducted by members of the Children's Cancer Study Group (CCSG) prior to its use in a randomized phase III trial. Chemotherapeutic agents used were cyclophosphamide (CPM), vincristine (VCR), and prednisone, together with intravenous (IV) and intrathecal methotrexate (IT MTS). Radiation therapy was also employed. From September 1976 to April 1977, 27 eligible, newly diagnosed patients with non-Hodgkin's lymphoma were entered onto this pilot study. Toxicity was acceptable with minor adjustments in dosage and timing of the myelosuppressive agents. Fourteen of the 22 patients entered onto maintenance remain entirely disease-free, and all have completed the prescribed course of chemotherapy. None of the 12 patients characterized as having a "favorable" prognosis has relapsed, with a median follow-up of 27 months from on study.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rads in 5 days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 10 years. In premenopausal patients who received ovarian irradiation the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (P = 0.02) and prolonged survival (P = 0.02); the survival expectancy of these patients was similar to that of the general population of the same age from the third year after the cancer operation. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.