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The case of a three-year-old girl with fibrosarcoma of the right orbit is presented. She was initially treated with surgery and later with radiotherapy. After an interval of thirty-three years she developed a suprasellar epidermoid cyst and two years later a right frontal meningioma. The two benign tumors fulfill the usual criteria for irradiation induced tumors and the possible role of radiotherapy in their induction is discussed.
A man developed breast cancer 30 years after chest radiation for metastatic osteogenic sarcoma. At least eight previous cases of radiation-associated breast cancers have been reported in males, but this man represents the first to develop breast cancer following a childhood malignancy.
Sarcoma of the chest wall following postoperative radiation therapy (2500 rads) for breast carcinoma is presented; it appeared 16 years after the initial radiation, and had light and electron microscopic features of malignant fibrous histiocytoma (MFH). Unique ultrastructural finding was the presence of Langerham cell granules in some of the tumor cells. This appears to be the first documented instance of a soft tissue MFH containing such granules in the tumor cells.
Six hundred and thirteen consecutive patients with Hodgkin's disease (HD), with a follow-up of two to ten years, were reviewed with the aim of establishing the type and frequency of second malignancies. Acute non-lymphoid leukemia developed in 2 of 152 patients treated by chemotherapy (CHT), and in 5 of 344 patients treated by CHT and radiotherapy (RT). Leukemia developed 12 to 83 months after diagnosis of HD, was always preceded by a preleukemic phase (3 to 25 months), and was always fatal (after 1 to 12 months). The karyotype of leukemic cells was studied in 4 of 7 patients and was always abnormal. Solid tumors developed in 1 of 152 patients treated by CHT, and in 4 of 344 patients treated by CHT and RT. The tumors appeared 10 to 63 months after diagnosis of HD and killed all 5 patients after 10 to 16 months. For patients treated by CHT, the actuarial frequency of leukemia and other tumors seven years after diagnosis of HD was 2.0% and 1.26%, respectively. For patients treated by CHT and RT, the figures were 2.04% and 2.26%, respectively. Second malignancies were not recorded among 117 patients treated by RT alone. These data are consistent with a relationship of acute leukemia to therapy for HD.
A kindred with the familial cancer syndrome is reported in which every confirmed affected member of the pedigree had at least one primary carcinoma of the colon. The average age at which cancer appeared was 38 years, and multiple primary neoplasm occurred in 23% of the cancer patients. Transmission of the cancer trait is consistent with an autosomal dominant mode of inheritance. Colonoscopy eliminated the presence of any unsuspected cancers in family members at risk. HLA typing was done, and by direct typing or inference, data were available on 66 living and deceased individuals. There were four informative matings in the kindred, the offspring of which showed only three crossovers of a possible 17. The lod score totaled 1.06 at a recombination fraction of 0.20. The need for cooperative efforts of many investigators in HLA linkage studies is emphasized, along with the potential value of such an approach.
Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. Care must be exercised in associating previous therapy and a subsequent malignancy. "Naturally" occurring second cancers must be separated from those which are iatrogenic. Associations in the literature have been made involving malignancies as a sequelae of prior gynecologic therapy. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. Irradiation therapy, however, has not yet been shown to be related to leukemia in cervical cancer patients. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified.
The incidence of second malignant neoplasms (SMN) was assessed in 248 patient with Hodgkin's disease (HD) treated by radiotherapy alone (XRT) or in combination with chemotherapy (XRT + C) between January/1960 and June/1977. Radiation therapy was categorized as less than extended field (less than EF), extended field (EF) or total nodal irradiation (TNI). Chemotherapy was scored as single agent (SAC) or multiagent (MAC). MAC consisted primarily of either nitrogen mustard, vincristine, prednisone and procarbazine (MOPP) or cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP). Ten metachronous malignancies occurred 1-21 years (median 10 years) after the diagnosis of HD. With a median follow-up of 6 years the observed-to-expected ratio (O/E) was 4.2 for XRT alone and 7.6 for XRT + MAC. For 46 patients with greater than or equal to 10 years follow-up (median 13 years) the O/E ratio was 16.1 for XRT and 26.5 for XRT + MAC. All SMN occurred in patients who had not had a splenectomy at or prior to the time of HD diagnosis. Only four of nine solid SMN were within treatment portals or near portal margins. The diagnosis of another malignant neoplasm was made prior to or simultaneous with the diagnosis of HD in four additional patients. This observation, and the occurrence of five of six SMN outside of the treatment field in the XRT alone group, suggest that there may be factor(s) associated with the incidence of SMN in HD in addition to treatment itself.
Among 910 survivors of childhood cancer, four developed infiltrating carcinoma of the breast and another had noninfiltrating breast tumor. Expected frequency was 0.3 cases of breast cancer in the series. The affected women developed breast carcinoma at ages 20, 25 and 38 years, and the men at ages 38 and 39 years, respectively. Each patient had received orthovoltage chest irradiation for treatment of Wilms' tumor or bone sarcoma between seven and 34 years previously, and estimated radiation dose to the breast exceeded 300 rad in each instance. Four patients also received diverse forms of chemotherapy. Survivors of childhood cancer have increased risk of developing breast cancer and should undergo periodic screening, particularly after breast tissue had been irradiated. Individualized radiotherapy planning can help exclude the breasts from treatment fields for some thoracic neoplasms.
The pathologic findings are described in three patients who developed second intracranial neoplasms after irradiation for central nervous system malignancy. The second neoplasms were an astrocytoma, an ependymoma, and multiple meningiomas. All were histologically different from the first neoplasms and appeared in the field of irradiation between 3 and 15 years later. It is suggested that therapeutic irradiation was a causative factor in the development of these tumors.
This article describes four cases of non-Hodgkin's lymphomas occurring after successful treatment of Hodgkin's disease (HD). The clinical symptoms consisted of digestive disorders, and the histology confirmed an intestinal involvement in these four patients. In all cases patients had diffuse large cell types (intermediate or high grade). The respective role of HD treatment (combination chemotherapy in 3 of 4 patients with irradiation in 3 of 4 patients) and of other pathogenic hypotheses, are discussed.
Malignant neoplasms known to develop following external beam radiation include squamous cell carcinoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, mixed mullerian tumors, malignant schwannoma, myelogenous leukemia and angiosarcoma. Latency periods of many years characterize the onset of these tumors following the exposure. Cutaneous angiosarcoma following radiotherapy for breast carcinoma has been rarely documented, occurring up to 13 years postirradiation. Two cases of this entity are reported occurring 37 months postradiotherapy at the site of mastectomy performed for mammary duct carcinoma.
As more children are now being cured of cancer, increasing attention needs to be focused on the long-term sequelae of cancer therapy, principally late-appearing second cancers and damage to organ systems. To this end, the authors have established an oncology follow-up clinic specifically designed to examine former pediatric cancer patients who are likely to be cured. Patients receive a physical examination and appropriate organ function studies based upon initial diagnosis, pre-existing conditions, treatment received, and any complications experienced during the course of therapy. The late effects noted among the first 200 such survivors examined reveal a high proportion of severe sequelae secondary to radiation therapy in early childhood. Second malignant neoplasms may also be related to alkylating agent chemotherapy and to genetic conditions. Although certain therapeutic practices have improved the outlook for these patients, and, in some cases, reduction in intensity of therapy has been found to be effective, increased survival and newer treatment modalities have made extended follow-up increasingly necessary in order to detect and possibly prevent the occurrence of such late effects.
Peritoneal mesothelioma in a 61-year-old man, occurred 26 years after abdominal radiotherapy for a testicular seminoma. The patient had no history of asbestos exposure. After asbestos, radiation is the second most frequent defined cause of mesothelioma in North America, but the number of well-documented cases is small; this case represents only the fifth example of peritoneal mesothelioma after therapeutic irradiation of the abdomen.
The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.
The clinicopathologic features of 53 cases of postradiation soft tissue sarcoma (PRS) were correlated with the physical characteristics of the administered radiation. All but three patients received radiation for malignant processes. Of the secondary sarcomas, malignant fibrous histiocytoma (MFH) accounted for 36 cases (68%), followed by seven extraskeletal osteosarcomas (13%), six fibrosarcomas (11%), two malignant Schwannomas (4%), one extraskeletal chondrosarcoma, and one angiosarcoma. The sex incidence, age of the patient at time of diagnosis, and location of the PRS correlated only with the clinical characteristics of the initial treated condition. The latency period (mean 10 years) showed an indefinite relationship to patient survival but no definite relationship to the patient's age at the time of the initial radiation. There was no difference between patients treated with megavoltage radiation (39 patients) and with orthovoltage radiation (seven patients) in the type of sarcoma, location, or survival, although the orthovoltage group received a lower mean radiation dose (3880 rads) than the megavoltage group (4446 rads). Megavoltage radiation, however, produced deeper tissue radiation changes and was associated with a shorter latency period. Most PRS were poorly differentiated, produced abundant collagen, and had a dismal prognosis.
The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.
There is a known increased risk for the co-occurrence of both breast cancer and colorectal cancer in the same women, presumably as a result of either shared reproductive hormonal or environmental risk factors. Using data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, the authors investigated whether there is a similar relationship between breast cancer, colorectal cancer, and prostate cancer in men. The observed-expected ratio was not significantly elevated for either colorectal cancer after breast cancer or for breast cancer after colorectal cancer in men. There was an increased incidence of prostate cancer after colorectal cancer, but this relationship was not present in the opposite direction and is believed to result from detection bias. There was an increased incidence of breast and colorectal cancer in women. These results suggest that the observed breast and colorectal cancer relationship in women may be a result of shared reproductive hormonal factors.
BACKGROUND: Hereditary ovarian cancer may be site specific or may appear in combination with breast cancer or other cancers in a family. The most common hereditary form is the breast-ovarian cancer syndrome. It is estimated that in 100% of these families, there is linkage to a cancer susceptibility gene on chromosome 17q, BRCA1. METHODS: A positive family history of breast or ovarian cancer was reported for 71 of 450 unselected cases of ovarian cancer identified in Southern Ontario. Detailed pedigrees were completed by telephone interview for 48 of the 71 subjects. RESULTS: Nine families were identified with five or more cases of breast or ovarian cancer, 14 families with four cases of cancer, and eight families with three cases. Breast cancer appeared in 80% of the ovarian cancer families. There were 81 healthy first-degree female relatives of the cancer cases considered to be at high risk for ovarian cancer. CONCLUSIONS: It is feasible to use a simple questionnaire on all incident cases of ovarian cancer in a population to identify families with potential hereditary breast-ovarian cancer. Two point nine percent to 6.9% of cases of ovarian cancer appear to be inherited; the majority of the families also will have an excess number of cases of breast cancer.