FrederickP. Li

Second malignancies in patients treated for childhood acute lymphoblastic leukemia.

PURPOSE Second malignant neoplasms (SMN) are devastating late complications of childhood acute lymphoblastic leukemia (ALL) and its treatment. We evaluated the incidence and type of SMN diagnosed before leukemic relapse in a large series of patients with ALL. PATIENTS AND METHODS We reviewed the outcome of all patients treated for childhood ALL between 1972 and 1995 on Dana-Farber Cancer Institute (DFCI) and DFCI ALL Consortium protocols. The follow-up time from diagnosis of ALL to induction failure, relapse, remission death, or SMN, whichever occurred first, ranged from 0 to 24.0 years (median, 7.6 years; mean, 6.7 years). RESULTS Thirteen SMNs were diagnosed among 1,597 patients. Eight tumors occurred in a radiation field (five in the CNS and three in the head and neck), two occurred outside of a radiation field (one adenocarcinoma of the sigmoid colon and one epithelioid sarcoma of the chest wall), and three were hematopoietic malignancies. The median time to occurrence was 6.7 years (range, 1.0 to 17.2 years) and the cumulative incidence of second malignancy before another first event was 2.7% (95% confidence interval, 0.7 to 4.7). The risk of a first event, which included induction failure, relapse, or remission death, was 31.0% (95% confidence interval, 28.5 to 33.5). CONCLUSION We found a more than 10-fold risk of other first events when compared with SMN. Thus, we conclude that SMN before first relapse is a relatively uncommon occurrence among survivors of childhood ALL. Future therapeutic regimens must focus on reducing leukemia relapse and enhancing quality of life, as well as preventing SMNs.

Malignant mesothelioma following radiation exposure.

Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered.

Hodgkin's disease in the elderly

47 patients with Hodgkin’s disease presenting after age 60 were analyzed retrospectively for clinical presentation, distribution of disease, and histopathology, and compared to a younger control group. The types of clinical presentation included: local or generalized adenopathy, 50%; ‘B’ symptoms, 25%; ‘unusual manifestations’ and intra-abdominal complications, 13%; and incidentally discovered disease, 12%. In contrast, the younger group presented less often for symptoms (p

FAMILIAL MALE BREAST CANCER

Infiltrating ductal carcinoma of the breast occurred in a total of six men from two families. In one family specimens from three men who had prophylactic mastectomies revealed focal intraductal hyperplasia, suggesting a familial tendency toward proliferation of mammary-duct epithelium. In the other family, benign and malignant breast lesions also developed in several women. Preliminary data suggest elevated urinary oestrogen excretion in three men from these families, implicating a defect in oestrogen production or metabolism in the pathogenesis of male breast neoplasms.

POSSIBLE INHERITED LEUKÆMOGENIC FACTORS IN FAMILIAL ACUTE MYELOGENOUS LEUKÆMIA

Abstract A family with six cases of acute myelogenous leukaemia and two cases of reticuloendothelial malignancy is described. Laboratory tests on surviving family members revealed a greatly increased susceptibility of skin fibroblasts of certain members to in vitro transformation by the oncogenic virus SV40 and abnormal immunoglobulin levels in several members of the kindred. The laboratory data may indicate useful approaches in the study of mechanisms of leukaemogenesis.

Mortality from Second Tumors Among Long-Term Survivors of Retinoblastoma

BACKGROUND Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. PURPOSE We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. METHODS A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. RESULTS Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). CONCLUSIONS These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. IMPLICATIONS Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.