Cancer of the nasopharynx in childhood

Between 1964 and 1983, 54,304 cases of nasopharyngeal carcinoma (NPC) patients were diagnosed at the Tumor Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou, People's Republic of China. Of the total, 53 (0.1%) cases were younger than 14 years of age, and of these, none were Stage I, four (8%) were Stage II, 36 (68%) were Stage III, and 12 (23%) were Stage IV. Among all cases, 26% had initial symptoms characterized by lesions of the nasopharynx and the majority by cervical mass. Among the children, symptoms involving the cranial nerve were rarely observed. There were significant differences between adults and children on histopathology other than the ratio of carcinoma to sarcoma (4:1 for children; 443:1 for adults). Among the poorly differentiated carcinoma cases, vesicular nucleus carcinoma was observed more frequently in children than adults. The prognosis for children with NPC is poor with a 5-year survival rate of 21% in this series. If NPC is diagnosed early and radiotherapy begun promptly (with doses greater than 5000 cGy), the prognosis may be improved.     

Cancer in relatives of survivors of childhood sarcoma

Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers.     

Cancer in survivors of childhood soft tissue sarcoma and their relatives

One hundred fifty-nine 3-year survivors of childhood soft tissue sarcoma and their relatives were surveyed to determine the frequency of second malignant neoplasms (SMNs) in patients and cancer in their relatives. The cancer experience of the patients, their offspring, siblings, parents, parental siblings, and grandparents was compared to that expected of the general population based on age-, sex- and calendar year-specific rates from the Connecticut Tumor Registry. A significant excess of SMNs was observed in the patients (observed expected = 8:0.38). Among 758 first-degree relatives, a significant cancer excess was observed (34:20.68), attributable largely to cancer of soft tissue and bone (6:0.44) and breast (9:3.39) and to cancers occurring before age 35 years (12:4.14). Overall, a significantly lower than expected cancer incidence was confirmed in the 1,693 second-degree relatives (142:178). To identify patient characteristics associated with higher than expected familial cancer risk, kindreds were partitioned by patient age at diagnosis tumor type, tumor site SMN and other factors. A highly significant cancer excess was observed in the relatives of SMN patients (26:12.78). The tumor types occurring in excess in close relatives were also observed as SMNs in the patients. The findings confirm an association among childhood soft tissue sarcoma and cancers of the breast, bone, joint, or soft tissue as SMN in patients and in close relatives and suggest that the risk of a second tumor is associated with a familial predisposition to cancer.     

Cancer and other causes of childhood mortality in Bombay, India

Mortality from cancer and other diseases from 1964 to 1984 and their contributions in 1984 to premature mortality in Bombay, India, were studied. Cancer was the ninth and tenth cause of death in boys and girls younger than 15 years of age, respectively, in 1984. Prematurity and infectious diseases contributed most to years of potential life lost by children younger than 5 years of age in 1984; cancer, heart disease, and accidents-injury became important in children older than 5 years. When currently high mortality rates in infants and children younger than 5 years of age are reduced, cancer may become a greater childhood health problem. Approximately 5% of male and 3% of female patients with cancer in six hospital and three population-based cancer registries in India were children younger than 15 years of age. Cancer mortality declined from the rate during 1964 to 1972 to the rate during 1973 to 1984 by about 40% in children younger than 5 years old and in girls of 10 to 14 years of age and by 7.5% and 14% in the 5 to 9-year-old boys and girls, respectively. It increased by 12% in the 10 to 14-year-old boys. Early diagnosis and treatment of cancer in children older than 5 years of age may yield increased productive person-years of life.     

Cancer among 1,348 offspring of survivors of childhood cancer

The occurrence of cancer among the 1,348 offspring of 2,441 survivors of childhood cancer, treated before 1978, was investigated. Information was obtained through a questionnaire sent to the general practitioners of these survivors. Twenty-three of 52 offspring born to survivors of heritable retinoblastoma developed retinoblastoma; the heritable form of retinoblastoma is known to be transmitted to offspring as an autosomal dominant. None of the 94 offspring born to the 54 survivors of unilateral retinoblastoma with no family history of the disease have developed the disease. This implies that it is unlikely that more than 9% of survivors of unilateral retinoblastoma with no family history have the germ-cell mutation; consequently it is unlikely that more than 4% of their offspring will be affected. Among the 1,199 offspring born to 629 survivors of other childhood malignant disease, who produced children, one acute monocytic leukaemia and one acute lymphoblastic leukaemia were observed. This is more than expected on the basis of the general population (one-tailed p = 0.04). However, the types of cancer observed in these 2 offspring and their parents conform to a previously described familial aggregation of cancers. Only a small number of children were born to survivors who received therapy that was potentially germ-cell mutagenic, and thus it is not possible to make any accurate estimation of their risk of malignant disease.     

Cancer in the offspring of survivors of childhood leukaemia and non-Hodgkin lymphomas.

Understanding the extent to which childhood leukaemia and non-Hodgkin lymphomas are heritable is important to the survivors of these diseases, their families and clinicians who provide genetic counselling. Such understanding is also relevant to the possibility raised by Gardner et al. (1990, Br. Med. J., 300, 423-429) that paternal preconception irradiation may be an aetiological factor in these diseases. No malignant neoplasm was diagnosed among 382 offspring of survivors of childhood leukaemia and non-Hodgkin lymphoma followed up for a median period of 5.8 years, the largest available cohort of such offspring. These data indicate that it is unlikely that the risk of a malignant neoplasm occurring in the offspring exceeds eight times that expected in the general population. Similarly, the risk of leukaemia and non-Hodgkin lymphoma among offspring is unlikely to exceed 21 times that expected. The proportion of survivors of childhood leukaemia and non-Hodgkin lymphoma with the heritable form of these diseases is unlikely to exceed 5%, assuming an autosomal dominant pattern of transmission, with penetrance of at least 70% and that all heritable cases develop by age 15 years. The best (i.e. at present most likely) estimates of these risks are of course much lower. There was no evidence of an excess of congenital abnormalities among the offspring and the sex ratio was similar to that expected from the general population.     

Cancer risks in childhood and adolescence among the offspring of immigrants to Sweden

We used the nation-wide Swedish Family-Cancer Database to analyse the risk of nervous system tumours, leukaemia and non-Hodgkin's lymphoma in age groups 0-4 and 0-19 years among Swedish-born offspring of immigrants. The study included 850 000 individuals with an immigrant background, including European, Asian and American parents. We calculated standardised incidence ratios for the above three malignancies using Swedish offspring as a reference. Subjects were grouped by region or by selected countries of parental origin. No group differed significantly from Swedes in the occurrence of nervous system neoplasm or leukaemia. Offspring of Yugoslav fathers (SIR 2.27) and Turkish parents were at increased risk of non-Hodgkin's lymphoma. The highest risk was noted for non-Hodgkin's lymphoma among young offspring (0-4 years) of two Turkish parents (6.87). The currently available limited data on rates for childhood non-Hodgkin's lymphoma in these countries do not explain the risk in the offspring of immigrants. Yugoslavs and Turks are recent immigrant groups to Sweden, and their offspring have been subject to much population mixing, perhaps leading to recurring infections and immunological stimulation, which may contribute to their excess of lymphomas.     

Cancer mortality after radiotherapy for a skin hemangioma during childhood.

BACKGROUND AND PURPOSE: A cohort study was performed as part of a European Radiation Protection Program to investigate the carcinogenic effect of treatment with ionizing radiation in early childhood. This paper presents mortality after radiotherapy in this cohort. PATIENTS AND METHODS: The cohort comprised 7037 patients under 15 years of age treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, among whom 4940 received radiotherapy. The vital status and causes of death were obtained as well as the mortality rates in the general French population. External and internal analyses were performed. Standardized mortality ratio (SMR) and relative risk (RR) variations according to exposure to radiotherapy or not and the type of treatment were studied. RESULTS: During the 1969-1997 follow-up period, 16 cohort patients died of cancer, 14 after radiotherapy. A non-significant excess of cancer-related mortality was observed for irradiated patients as compared to the general population (SMR=1.53; 95% CI=0.86-2.48). Treatment with (226)Ra seemed to play a significant role (RR=2.53; 95% CI=0.84-7.07) compared to no radiotherapy. CONCLUSION: This study suggests an excess risk of cancer-related mortality in patients treated during early childhood with radiotherapy for skin hemangioma, and especially with (226)Ra. These patients need to be followed up in the future.     

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995.

Since 1968, the Children's Cancer Group (CCG) has treated more than 16,000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989-1995). Overall, 10-year EFS was 62% +/- 10% for the 1983-1988 series and 72% +/- 1% for the 1988-1995 series (P< 0.0001). Five-year cumulative rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin-Frankfurt-Münster 76/79 study improved outcomes for intermediate and higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cranial irradiation was safely replaced with maintenance intrathecal methotrexate, providing patients received intensified systemic therapy. In the second series, randomized trials showed better outcome with one vs no DI phase for lower risk patients, with two vs one DI phase for intermediate risk patients, and with the CCG 'augmented regimen' for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with additional intrathecal methotrexate for higher risk patients with a rapid day 7 marrow response. In a subsequent study, substitution of dexamethasone in place of prednisone in induction and maintenance improved outcome for standard risk patients. All patients received dexamethasone in DI. These successful treatment strategies form the basis for our current ALL trials.     

Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial

Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity.     

Adult Life after Childhood Cancer in Scandinavia: Diabetes mellitus following treatment for cancer in childhood

AimAn increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting.Materials and methodsFrom the national cancer registries of the five Nordic countries, a cohort of 32,903 1-year survivors of cancer diagnosed before the age of 20 between start of cancer registration in the 1940s and 1950s through 2008 was identified; 212,393 comparison subjects of the same age, gender and country were selected from national population registers. Study subjects were linked to the national hospital registers. Absolute excess risks (AERs) and standardised hospitalisation rate ratios (SHRRs) were calculated.ResultsDM was diagnosed in 496 childhood cancer survivors, yielding an overall SHRR of 1.6 (95% confidence interval (CI), 1.5–1.8) and an AER of 43 per 100,000 person-years, increasing from approximately 20 extra cases of DM in ages 0–19 to more than 100 extra cases per 100,000 person-years in ages ⩾50. The relative risks for DM were significantly increased after Wilms’ tumour (SHRR, 2.9), leukaemia (2.0), CNS neoplasms (1.8), germ-cell neoplasms (1.7), malignant bone tumours (1.7) and Hodgkin’s lymphoma (1.6). The risk for DM type 2 was slightly higher than that for type 1.ConclusionChildhood cancer survivors are at increased risk for DM, with absolute risks increasing throughout life. These findings underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.     

Health insurance coverage in survivors of childhood cancer: the Childhood Cancer Survivor Study.

PURPOSE: To examine the prevalence and predictors of health insurance coverage and the difficulties obtaining coverage in a large cohort of childhood cancer survivors. PATIENTS AND METHODS: This study included 12,358 5-year survivors of childhood cancer and 3,553 sibling controls participating in the Childhood Cancer Survivor Study. Data were collected by surveys distributed in 1994 (baseline) and 2000 (follow-up). RESULTS: At baseline, 83.9% of adult survivors, compared with 88.3% of siblings, had health insurance coverage (P < .01); 6 years later, small but significant survivor-sibling differences remained (88% v 91%; P < .01). Twenty-nine percent of survivors reported having had difficulties obtaining coverage, compared with only 3% of siblings (P < .01). In multivariate analysis of survivors 18 years of age or older, factors associated with being uninsured included younger age at diagnosis (diagnosis age of 0 to 4 years; odds ratio [OR] = 1.7; 95% CI, 1.3 to 2.2), male sex (OR = 1.3; 95% CI, 1.2 to 1.5), age at baseline survey (age 22 to 24 years; OR = 1.6; 95% CI, 1.2 to 2.1), lower level of attained education (less than high school, OR = 2.6, 95% CI, 2.1 to 3.3; high school graduate, OR = 2.1, 95% CI, 1.8 to 2.5), income less than 20,000 dollars (OR = 5.6, 95% CI, 4.5 to 7.1), marital status (widowed/divorced/separated; OR = 1.3; 95% CI, 1.1 to 1.6), smoking status (current smoker, OR = 2.0, 95% CI, 1.7 to 2.3; former smoker, OR = 1.4, 95% CI, 1.2 to 1.8), and treatment that included cranial radiation (OR = 1.3, 95% CI, 1.0 to 1.6). CONCLUSION: Compared with siblings, adult survivors of childhood cancer had significantly lower rates of health insurance coverage and more difficulties obtaining coverage. Since lack of coverage likely has serious health and financial implications for this at-risk population, any disparity in availability and quality of coverage is of great concern.     

Scottish validation study of Cancer Registration data childhood leukaemia 1968-1981--I

This study attempted to validate central registration data on all childhood leukaemia cases in Scotland between 1968 and 1981 in line with the Black Enquiry concerning West Cumbria. Missing files precluded a complete verification, but minor errors of registration were found in 44% of cases. A small number of important mistakes of omission (eight cases), wrong diagnosis (six cases) and postal code errors (nine cases) were found which might affect epidemiological studies of these relatively rare diseases. Precise and verified prospective data collection at the time of diagnosis is essential if the spatial distribution of childhood cancers is being studied.     

Second malignancies after childhood Hodgkin's disease. The Memorial Sloan-Kettering Cancer Center experience

A review of the Memorial Sloan-Kettering Cancer Center experience with second malignancies (SM) after childhood Hodgkin's Disease (HD) identified 17 SM in 320 patients who survived more than 1 year from, and were 15 years old or younger at the time of, HD diagnosis (1949 to 1983). Of 254 previously untreated patients, 12 SM were noticed as compared with 0.606 expected on the basis of rates in the general pediatric population (relative risk, 19.8; 95% confidence interval, 10.2 to 34.6). For patients who received multi-agent chemotherapy, the cumulative probability of developing acute nonlymphocytic leukemia (ANLL) or bone sarcoma was 6.2% and 5.5%, respectively, at 10 years from the initiation of therapy; the cumulative risk of all SM in this group reached 18.7% at 15 years. For patients who received radiation alone or with single-agent chemotherapy, the cumulative risk of SM rose from 0% at 10 years and 2% at 15 years, to 10.7% at 25 years from the initiation of treatment. The risk of ANLL after childhood HD was highest in the first 5 to 10 years after combined modality treatment, and aggressive forms of NHL were associated with excessive immunosuppression. Bone sarcomas predominated in solid SM in the first decade after HD treatment, whereas "adult-type" cancers, for example, breast and colon carcinomas, were more delayed. Our findings, supported by a literature review, point to a therapy-related enhanced risk of approximately age-appropriate solid SM. This possibility mandates careful surveillance of long-term survivors of childhood HD.     

Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

Background:

With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study.

Methods:

Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire.

Results:

Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 5–24 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected.

Conclusions:

Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating clinical follow-up guidelines.     

Cancer surveillance series: recent trends in childhood cancer incidence and mortality in the United States.

BACKGROUND: Public concern about possible increases in childhood cancer incidence in the United States led us to examine recent incidence and mortality patterns. METHODS: Cancers diagnosed in 14540 children under age 15 years from 1975 through 1995 and reported to nine population-based registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were investigated. Age-adjusted incidence was analyzed according to anatomic site and histologic categories of the International Classification of Childhood Cancer. Age-adjusted U.S. mortality rates were calculated. Trends in rates were evaluated by use of standard regression methods. RESULTS: A modest rise in the incidence of leukemia, the most common childhood cancer, was largely due to an abrupt increase from 1983 to 1984; rates have decreased slightly since 1989. For brain and other central nervous system (CNS) cancers, incidence rose modestly, although statistically significantly (two-sided P = .020), largely from 1983 through 1986. A few rare childhood cancers demonstrated upward trends (e.g., the 40% of skin cancers designated as dermatofibrosarcomas, adrenal neuroblastomas, and retinoblastomas, the latter two in infants only). In contrast, incidence decreased modestly but statistically significantly for Hodgkin's disease (two-sided P = .037). Mortality rates declined steadily for all major childhood cancer categories, although less rapidly for brain/CNS cancers. CONCLUSIONS: There was no substantial change in incidence for the major pediatric cancers, and rates have remained relatively stable since the mid-1980s. The modest increases that were observed for brain/CNS cancers, leukemia, and infant neuroblastoma were confined to the mid-1980s. The patterns suggest that the increases likely reflected diagnostic improvements or reporting changes. Dramatic declines in childhood cancer mortality represent treatment-related improvements in survival.