Henrik Hertz

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

PURPOSEnTo assess the risk of subsequent malignant neoplasms among Hodgkins disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden).nnnPATIENTS AND METHODSnThere were 1,641 Hodgkins disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated.nnnRESULTSnA total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkins lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkins disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkins disease in the 1980s.nnnCONCLUSIONnPatients who survive Hodgkins disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkins disease in the teenage years calls for enhanced activity for early diagnosis.

SECOND MALIGNANT NEOPLASMS AFTER CANCER IN CHILDHOOD AND ADOLESCENCE: A POPULATION-BASED CASE-CONTROL STUDY IN THE 5 NORDIC COUNTRIES

Our purpose was to assess the risk of developing a second malignant neoplasm (SMN) after cancer in childhood and adolescence associated with different treatment modalities. Our investigation was performed as a nested case‐control study within a Nordic cohort of 25,120 patients younger than 20 years old at first malignant neoplasm (FMN) diagnosed in 1960 through 1987. SMNs were diagnosed in 1960 through 1991. For each case of SMN, 3 controls were sampled, matched by sex, age, calendar year of diagnosis and length of follow‐up. For the final analysis, there were 234 cases and 678 controls. Relative risks (RRs) of various exposures were estimated by means of conditional logistic regression, with non‐exposed as the reference. The RR of developing SMN in the radiated volume was 4.3 (95% confidence interval 3.0–6.2). The risk was highest in children diagnosed before the age of 5 years; it increased with the dose of radiation and with increasing follow‐up time after FMN. Chemotherapy alone was not associated with an increased RR, but it significantly potentiated the effect of radiotherapy. RRs were unchanged between the periods 1960–1973 and 1974–1987, and since the use of chemotherapy increased in the latter period, the number of SMNs may increase. Hereditary factors were important for the occurrence of SMN independently of therapy. We conclude that radiation was the most important treatment‐related risk factor for the development of SMN. Chemotherapy appeared to play only an accessory role during the study period, potentiating the carcinogenic effect of radiotherapy. Int. J. Cancer 88:672–678, 2000.

Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood

Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0–10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1–17.6) at bone marrow transplantation and 21.5 years (11.6–25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to −2.6 standard deviation scores (SDS) (−6.3 to −0.6), P = 0.002, and −2.6 SDS (−4.8 to −0.5), P = 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated.

Bone Mass After Treatment for Acute Lymphoblastic Leukemia in Childhood

PURPOSETo study bone mass after childhood acute lymphoblastic leukemia (ALL) and determine if reduced bone mass is related to previous therapy or endocrine status at follow-up.PATIENTS AND METHODSWe studied 95 survivors of childhood ALL who were in first remission a median of 11 years (range, 3 to 23 years) after diagnosis and who had never been irradiated outside a cranial field. The bone mass was measured by dual-energy x-ray absorptiometry. The results were compared with data on 396 local controls.RESULTSAdjusted for sex and age, the mean whole-body bone mineral content (BMC) and bone mineral areal density (BMDA) were both significantly reduced (0.4 SDs less than the predicted mean value). This was mainly caused by reduced bone mass in the 33 participants who were aged 19 years or older at follow-up. In these young adults, the mean height for age, bone area for height, and BMC for bone area were all significantly reduced. This indicated that the reduced whole-body bone mass was caused by both reduced b...

Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: A population-based case-control study in the five Nordic countries

The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960 – 1987. SMSTs were diagnosed in 1960–1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

Bone mass and body composition after cessation of therapy for childhood cancer

Our aim was to review current information on body composition and bone mass after cessation of therapy for childhood cancer and to present preliminary data on body composition and bone mass in a group of Danish survivors of childhood leukaemia or lymphoma. Elevated body‐mass index (weight/height2; BMI) is frequent after treatment for childhood acute lymphoblastic leukaemia. BMI increases during therapy or within the first year after therapy and remains abnormal thereafter. Treatment with corticosteroids, abnormal growth‐hormone secretion after treatment with cranial irradiation (CI) or corticosteroids, younger age at diagnosis, or female gender were risk factors for elevated BMI in earlier studies. We evaluated 185 survivors of childhood leukaemia or lymphoma by dual‐energy X‐ray absorptiometry scanning. We found elevated whole‐body relative fat mass, which was associated with CI. Other studies found reduced bone mass in the radius, the lumbar spine and the whole body after treatment for childhood cancer. Growth‐hormone deficiency that is not adequately corrected, CI, reduced height or reduced weight were risk factors for reduced bone mass. In our 185 participants, the whole‐body bone mass was also reduced significantly compared with reference values. CI and older age at follow‐up were risk factors for reduced bone mass. We conclude that the elevated relative fat mass and reduced bone mass seen after treatment for childhood leukaemia or lymphoma is associated mainly with CI. Int. J. Cancer Supplement 11: 40–43, 1998.

Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma.

Excess fatness is frequent after childhood ALL treated without BMT. We measured the whole-body percent fat by dual-energy X-ray absorptiometry and the body-mass index (weight/height2 (kg/m2), BMI) in 25 survivors of childhood leukaemia or lymphoma (21 with ALL) who had received TBI and allogeneic BMT a median of 8 years ago (range 4–13). Adjusted for sex and age, the mean BMI was slightly but significantly reduced (0.4 s.d. below predicted) and the whole-body percent fat was significantly increased compared with healthy controls (1.1 s.d. above predicted). Eleven of 25 patients had a percent fat above the 90 percentile of the reference values, which indicates excess fatness. Adjusted for sex and age, a higher percent fat was related to additional cranial irradiation. Controlled for this, the whole-body percent fat seemed to be unrelated to age at BMT, length of follow-up, and previous chemotherapy. Compared with untransplanted ALL survivors treated with cranial irradiation, BMT survivors had significantly reduced BMI but similar whole body percent fat. BMI was a poor measure of body fatness in these patients. In conclusion, survivors of BMT for childhood leukaemia or lymphoma are adipose and slightly underweight and consequently have a substantially reduced lean body mass. Bone Marrow Transplantation (2001) 27, 817–820.