Howard B. Latourette

Early menopause in long-term survivors of cancer during adolescence

Objective: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. Study Design: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. Results: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. Conclusions: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Radiation dose and second cancer risk in patients treated for cancer of the cervix

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkins lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkins disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Economic status and survival of cancer patients.

The relation of economic status to survival was studied for 39 kinds of cancer representing all types for which 60 or more indigent patients were seen in University of Iowa Hospital for primary care during the years 1940–1969. For every type the indigent patients had poorer survival than non‐indigent patients. Quality of care would be eliminated as a major variable since a second group of “ward” patients of higher economic status was available for comparison and the differences were substantially greater between the two groups of teaching patients than between the “clinic pay” and “private” patients. Age differences and differences in stage of disease accounted for less than half of the survival deficits in the indigents. The two important problems were high mortality from causes other than cancer and excess cancer mortality not accounted for by stage differences, particularly among patients who should have had 5‐year survival rates between 40 and 70%. In these patients cancer recurred more often and earlier among the indigent. We postulate host differences associated with poverty that could also account for much of the observed Black‐White differences as well as some international differences in cancer survival rates.

CANCER IN OFFSPRING OF LONG-TERM SURVIVORS OF CHILDHOOD AND ADOLESCENT CANCER

A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person-years of follow-up in the second decade of life, when most cases of cancer developed, was small.

Bony metastases from carcinoma of cervix Occurrence, diagnosis, and treatment

Fifty‐five patients treated for cervical carcinoma developed bony metastases between January 1, 1961 and December 31, 1973. Roentgenograms were diagnostic in all but 2 of the patients. In 15 patients, a combination of radioactive scans and roentgenograms was used to establish the diagnosis. The most common mechanism of bony involvement from carcinoma of the cervix was extension of the neoplasm from para‐aortic nodes, with involvement of the adjacent vertebral bodies. The earliest metastases were discovered at the time of the primary diagnosis. Thirteen years was the longest interval from the primary diagnosis until the discovery of bony metastases. Sixty‐nine percent of the patients were diagnosed within 30 months. Ninety‐six percent of the patients died within 18 months. Seventy‐six percent of the patients received some form of therapy for their metastases. Thirty‐six of these patients were treated with radiation therapy. Four of these patients received complete relief of symptoms, 24 some relief, and 8 patients received no relief.

Radiation therapy in carcinoma of the vulva.A review of 53 patients

Fifty‐three patients were treated with radiation therapy for carcinoma of the vulva. Twenty‐four of these patients received primary radiation therapy, and the absolute 5‐year survival for this group was 8.3% (2/24). Twenty patients were treated for post‐surgicl recurrence with an absolute 5‐year survival of 20% (4/20). Surgery is considered the treatment of choice in this disease entity. However, radiation therapy may be indicated when localized cancer, either primary or recurrent, has extended beyond the limits of surgicalresection; when distant metastases are present; when the patients general condition precludes surgery, or when surgery is refused. Following is a discussion f our experience in the treatment of carcinoma of the vulva and the problems encountered with the use of radiation therapy.

Management of Recurrent Carcinoma of the Cervix

Abstract Early diagnosis and management of recurrent cervical carcinoma are the most difficult problems encountered by physicians. In this study there were 145 patients with recurrent disease who were re-treated by additional radiation and 17 patients were treated by radical operation. In the patients treated by reirradiation, there were 4 patients who survived 5 years (3.1 per cent). Satisfactory palliation was achieved in 54 per cent of the patients without an excessive number of serious complications. The unanswered question is: How can operable recurrence be detected earlier in our Stage I and Stage II cases?

Central nervous system changes complicating the use of radiotherapy for the treatment of a nasopharyngeal neoplasm in a diabetic patient.

A case is reported of a diabetic patient with a nasopharyngeal neoplasm who developed radiation induced brainstem damage even though irradiated at a conventional time‐dose‐volume relationship. The clinical course was correlated with autopsy findings which revealed radiation changes in the brain‐stem consisting primarily of vascular hyalinization with foci of infarction, edema, and demyelination. Atherosclerotic changes were conspicuously absent and therefore not the case of the alterations. The changes occurred three months after completion of therapy, which was more rapid than expected for radiation injury. It is hypothesized that diabetes may have predisposed the patient to this severe complication of standard therapy. More needs to be learned concerning the relationship between diabetes mellitus and radiation complications. Perhaps a modified time‐dose relationship should be considered.

Para‐aortic lymph node irradiation in carcinoma of the uterine cervix

Patients with advanced carcinoma of the uterine cervix, Stages III and IV, received extensive pretreatment evaluations to assess the incidence of para‐aortic lymph node spread for this disease. A total of 40 patients was subjected to exploratory laparotomy for para‐aortic node biopsy. Involved para‐aortic nodes were found in 13/37 Stage III patients (35%) and 2/3 Stage IV patients. Of these 15 patients, 4 had other intraperitoneal spread, making them unsuitable for extended field radiation. Eleven patients received radiation to extended fields to cover para‐aortic lymph nodes. Anterior‐posterior Co.,60 ports were used, with a daily fraction of 180 rad, to a total of 5400 rad. This therapy was tolerated fairly well. Gastrointestinal problems were the most frequent immediate and late side‐effects. Of these patients, 10 completed all prescribed therapy. Five of these have died, at an average of 6.6 months following treatment; 5 are alive at 30, 21, 15, 15, and 5 months.

Infantile Hepatic Hemangioendothelioma: A Surviving Case

A surviving case of infantile hepatic hemangioendothelioma is presented. The patient was treated with a combination of radiation therapy, cytotoxan, and prednisone, resulting in regression of the tumor.