Second malignant tumours in childhood Hodgkin's disease

This study was undertaken to determine the treatment-specific incidence of second malignant tumours (SMT) in childhood Hodgkin's disease. The institutional databases at The Hospital for Sick Children, the Princess Margaret Hospital, and the Toronto-Bayview Regional Cancer Centre were reviewed for the years 1958–1993. Three hundred and forty-three consecutive newly diagnosed children were evaluated. The overall 30 year cumulative SMT incidence was 31%. The 20 year SMT incidence was greater for patients who relapsed (n = 129), 27%, compared with patients who remained relapse free (n = 214), 13%. For patients with stage 1–3B disease who remained relapse free, the 10 year SMT rate was 7% for patients who were surgically staged and treated with extended field radiation treatment (EF RT) (35 G), compared with 3% in clinically staged patients treated with MOPP (six cycles) and EF RT (25–30 G). To date there is no significant difference in the oncogenicity of these treatment protocols. However, EF RT alone was less effective in disease control. For stages 1–3B, 62% of patients relapsed after EF RT alone compared with 18% after bimodal treatment. Therefore treatment intensification due to relapse was more frequent in the former group. The overall 10 year SMT incidence for patients treated with these protocols was 11% and 3%, respectively. The 20 year SMT incidence following EF RT alone was 24%. We conclude that SMTs were a common late complication in childhood Hodgkin's disease and are a limiting factor in the achievement of cure. The incidence of SMTs was increased in children who required retreatment and was minimal in children who remained in a first complete remission. Therefore the initial treatment strategy in childhood Hodgkin's disease must be to minimize the risk of relapse, in order to avoid the morbidity and mortality associated with both relapse and SMT induction, and to achieve this objective with a primary treatment protocol of low oncogenicity. © 1996 Wiley-Liss, Inc.     

Second intracranial neoplasms following treatment of childhood acute lymphoblastic leukaemia

We report a boy with acute lymphoblastic leukaemia (ALL) treated with chemotherapy and prophylactic cranial irradiation to a dose of 24 Gy. Six years after diagnosis he developed a glioma and died. Prior to 1979, four cases of second malignant neoplasm (SMN) of the brain had been reported in children treated for ALL. These SMNs occurred within 2 years of the original diagnosis (median 1.3 years) and at least two of four patients had not received prior radiotherapy. Since 1979, 28 cases of SMN of the brain have been reported including nine of 468 (1.9%) long-term survivors in one study. All occurred more than 3.7 years from diagnosis (median 6.5 years; range 4-13 years) and all received cranial irradiation (median 24 Gy; range 20-48 Gy). These data indicate a change in the pattern of SMNs which is most likely due to the introduction of cranial irradiation. As well, the frequency of SMNs in children treated for ALL appears to have increased, although it is still no greater than the risk of SMNs developing following the treatment of any other primary childhood neoplasm.     

Thirty-year population-based review of childhood renal tumours with an assessment of prognostic features including tumour DNA characteristics

We have reviewed all paediatric kidney tumours seen in the West Midlands Health Authority Region over a 30-year period. There were 205 cases confirmed after a review of the pathology by three paediatric pathologists. Seven were cases of bone metastasising renal tumour (clear cell sarcoma), 5 were rhabdoid tumours, 2 were renal cell carcinomas, and 13 were mesoblastic nephromas. In 3 cases, it was not possible to define further the histological diagnosis. The remaining 175 cases were considered to be Wilms' tumour (86%), which is equivalent to an incidence of 5.7/10⁶/year. In the cases of Wilms' tumour, there were 91 boys and 84 girls (1.1:1). The majority of patients were Caucasian with only 7% of non-Caucasian origin. At presentation, 78% of the patients were less than 5 years old. All of these patients except 9 had surgery as part of their treatment, 154 children had total nephrectomy, 3 had partial nephrectomy, and 9 had other surgical procedures. The majority also received chemotherapy and radiotherapy. Sex, chemotherapy, and stage all had prognostic significance in univariate analysis. The actuarial survival at 10 years increased from 17% for patients treated in the first decade of the study to 78% for patients treated in the third. DNA characteristics were investigated using flow cytometry in paraffin-embedded material and adequate information was obtained in 73 cases of Wilms' tumour. Only 7 had aneuploid tumours. Univariate survival analysis of these 73 results showed that stage, sex, the percentage of cells in the synthetic phase and the proliferative index from the DNA investigations had predictive value. © 1993 Wiley-Liss, Inc.     

Second malignant neoplasms in patients treated on SIOP Wilms tumour studies and trials 1, 2, 5, and 6

The incidence of second malignant neoplasms (SMNs) was investigated among 1,988 patients with complete data, enrolled in the SIOP Wilms tumor trials and studies 1, 2, 5, and 6, treated between September 1971 and October 1987. By the end of 1992, eight SMNs were documented, whereas only 1.3 were expected (standardized incidence ratio [SIR] = 4.15; 95% CI = 1.79, 8.17). The risk increases in the first 10 years from diagnosis, while no apparent excess of risk is observed in the subsequent periods. This finding however is difficult to interpret due to the low statistical power. The cumulative incidence of a second cancer observed at 15 years after Wilms tumor diagnosis was 0.65%. Six SMNs were registered in the cohort of patients treated in the SIOP studies 1,2 and 5 (999 cases) compared to the two cases observed in the SIOP6 cohort (989 cases). If the suggested reduced incidence of second cancers between SIOP1-5 and SIOP6 patient cohorts is confirmed by longer follow-up, it might reflect changes in the treatment protocols. Med. Pediatr. Oncol. 29:239–244, 1997. © 1997 Wiley-Liss, Inc.     

Second neoplasms after treatment of childhood cancer in Slovenia

BACKGROUND: The number of long time survivors of childhood cancer treatment is constantly increasing over the last decades as a result of advances in diagnosis and treatment. The occurrence of second neoplasms is one of most serious late effects observed in cancer survivors. METHODS: The risk of secondary neoplasm was studied in a cohort of 1,577 patients treated for childhood cancer registered in the Cancer Registry of Slovenia (CRS) between 1961 and 2000. The time at risk was defined from the date of diagnosis of first malignancy to the time of death or the end of the study. RESULTS: The most frequent primary malignancies were: acute leukemia 28.5%, central nervous system (CNS) tumors 21.3%, and lymphomas 16.6%. Median observation time was 7.8 years. Forty-eight patients developed second neoplasms. CNS tumors, acute leukemias, and thyroid carcinoma were most frequent second neoplasms. The cumulative risk for second neoplasm in the entire cohort was 0.06% at 5 years, 5.1% at 15 years, and 12.6% at 25 years after diagnosis of first cancer. The overall survival after second neoplasm was 65% 10 years after the diagnosis of second neoplasm. CONCLUSIONS: Patients after treatment of childhood cancer are at special risk for subsequent neoplasms and long-term follow-up is mandatory.     

Quality of life in a cohort of patients diagnosed with renal failure in childhood and who received renal transplant

Tozzi AE, Mazzotti E, Di Ciommo VM, Dello Strologo L, Cuttini M. Quality of life in a cohort of patients diagnosed with renal failure in childhood and who received renal transplant. Abstract: Studies on HRQOL on kidney‐transplanted young adults who had a diagnosis of chronic renal failure (CRF) in the pediatric age are uncommon. We studied HRQOL and its predictors in a sample of young adults with CRF in childhood who underwent a renal transplant. We recruited patients ≥18 yr old with renal transplant. We measured HRQOL by a standardized questionnaire on lifestyle, Short Form‐36 (SF‐36; including a PCS and a MCS; scale: 0–100), the GHQ (for short‐term changes in mental health; scale: 0–36), and the MSPSS (with scales for family, friends, and significant others; scale: 0–100). We assessed the association of potential predictors of HRQOL through multiple linear regression models. We studied 66 patients aged 18–34 yr. The average PCS score was 76.4, and the average MCS score was 73.9. The mean GHQ total score was 14.8, and the total scale MSPSS mean score was 70. Severe comorbidities significantly affected the PCS score. Individuals with severe comorbidities had lower PCS scores.     

Secondary neoplasms after radiotherapy for a childhood solid tumor

This study was conducted to determine the outcome of patients who develop a second neoplasm after radiotherapy (RT) for a childhood solid tumor. From 1956 to 1998, 429 children with a malignant solid tumor were treated at a single radiation oncology facility. The medical records and radiotherapy charts were reviewed to determine if the patient developed a secondary neoplasm after treatment for malignancy. Twenty-three (5.4%) patients developed a second neoplasm. There were 12 males and 11 females with a median age at RT of 6.6 years (range, 2 months to 20 years). There were 14 malignant neoplasms in 13 (3.0%) and 14 benign neoplasms in 11 patients (2.6%). The types of initial solid tumors treated with RT were Ewing sarcoma in 6, Wilms tumor in 6, medulloblastoma in 5, neuroblastoma in 3, and other in 3. Median RT dose was 45 Gy (range, 12.3 to 60 Gy) using 4 MV in 9, 1.25 MV in 8, 250 KV in 4, and 6 MV photons in 1 patient. One child was treated using 15-MeV electrons. Fourteen had chemotherapy. Median follow-up was 23.2 years (range, 5.3 to 44.4 years). For the 14 malignant neoplasms, the median time interval from initial tumor to second malignancy was 10.1 years. The 14 second malignant neoplasms (SMN) were osteosarcoma in 3, breast carcinoma in 2, melanoma in 2, malignant fibrous his- tiocytoma in 1, dermatofibrosarcoma in 1, leiomyosarcoma in 1, mucoepidermoid carcinoma in 1, colon cancer in 1, chronic myelogenous leukemia in 1, and basal cell carcinoma in 1. Ten of the 14 SMN (71%) were at the edge or inside the RT field. The 5- and 10-year overall survival rate after diagnosis of an SMN was 69.2%; it was 70% for children with a SMN at the edge or inside the RT field and 66.7% for those outside of the RT field. The 14 benign neoplasms appeared at a median time of 16.9 years and included cervical intraepithelial neoplasia in 3, osteochondroma in 3, thyroid adenoma in 1, duodenal adenoma in 1, lipoma in 1, cherry angioma in 1, uterine leiomyoma in 1, ovarian cystadenofibroma in 1, and giant cell tumor in 1. Only 5 (36%) of the 14 benign tumors occurred in the RT field, with osteochondroma being the most common. Of 189 deaths occurring in 429 patients, only 3 (1.6%) were secondary to radiation-induced malignancy. Not all SMN in children receiving RT occur in the irradiated field. More than two-thirds of children with a radiation-induced malignancy are alive 10 years after the diagnosis of a SMN.     

Imaging of liver tumours in childhood

Primary liver tumours account for 6% of all paediatric neoplasms. In a child with a clinical abdominal mass, imaging (in consultation with a paediatric surgeon) aims to confirm the intrahepatic site, determine its likely resectability, exclude metastatic abdominal disease, and characterise the mass. The imaging in 44 patients with primary liver tumour over a 33-year period was reviewed and correlated with surgical/pathological findings. Characterising hepatic masses with ultrasound, computed tomography, nuclear medicine, and angiography is less important than determining its resectability and alerting the surgeon to vascular anomalies and the presence of metastatic disease. We conclude that a chest X-ray and ultrasound study are the primary methods for evaluation of a child with suspected hepatic mass. With careful attention to technique, the mass can be evaluated and an assessment made of tumour resectability preoperatively. Based on this review, we propose a schema for the initial evaluation of suspected hepatic masses in children. Offprint requests to: J. F. de Ocampo     

The outcome of solid tumours occurring in the neonatal period

Sixty-six solid neoplasms occurring in neonates treated at the Red Cross Childrens Hospital over a 34-year period (1957–1991) were reviewed and recalled for long-term follow-up (mean 10.4 years). Associated congenital abnormalities were rare, but chromosomal abnormalities were detected in 3 patients, one of which was familial. Teratomatous germ-cell tumours predominated, followed by neuroblastomas and soft-tissue tumours; 23 had malignant morphologic appearances and 43 were morphologically non-malignant. Seventy-nine per cent presented within the 1st week of life, 41% of these within the first 24 h. Although most sacrococcygeal teratomatous germ-cell tumours were benign, malignancy was present in 2 patients (1 of these presented during the 1st week of life). A further 11 sacrococcygeal teratomas were found on light microscopy to include immature elements and had unpredictable clinical behaviour; 2 of these later metastasized despite adequate surgical clearance.All 4 patients with mesoblastic nephromas and 1 with a neonatal Wilm's tumour survived. In addition, 6 of the 10 patients with a neuroblastoma survived long-term. One of 3 patients with a rhabdomyosarcoma survived as well as 1 of 2 with a hepatoblastoma. Congenital fibrosarcomas, although morphologically aggressive, had an excellent outcome. Surgical excision was performed in all cases, and overall patient survival on long-term follow-up was 66% (44 patients). These survivors included 10 (41%) of those with malignant tumours and 24 (84%) with potentially malignant tumours. Metastatic spread or secondary tumours were shown to occur at variable stages, and early, frequent, and regular follow-up is recommended. Complications of extensive surgery resulted in 3 temporary and 2 long-term problems. Other adverse effects of therapy were observed in survivors of chemo- or radiation therapy, where poor growth was noted in 9 (82%), behavioural disturbances in 3 (27%), and intellectual impairment in 4 (36%).     

Second primary myogenic sarcoma in a patient with bilateral retinoblastoma

Retinoblastoma is the primary ocular malignancy affecting children under 6 years of age. The development of second malignant tumors in survivors of hereditary retinoblastoma is a well-known clinical entity and a major cause of morbidity and mortality. Rhabdomyosarcomas as second primary tumors have been only rarely described. The authors report a patient with bilateral retinoblastoma who developed a myogenic sarcoma of the orbit after 5.5 years of diagnosis. The short latency period may be explained by tumor histology with the contribution of radiotherapy and chemotherapy. The prognosis of second tumors is poor despite aggressive treatment.     

Leukemia in a Child with a History of Medulloblastoma

Leukemia of mixed lineage, was diagnosed in a 6.5-year-old boy with a history of medulloblastoma, 38 months after his initial cancer diagnosis. Therapy had included craniospinal radiation and nitrosourea-based chemotherapy. In addition, onset of leukemia was preceded by therapy with recombinant growth hormone for short stature. Although rare, leukemia is a treatment-related complication for patients with past brain tumors whose follow-up should therefore include surveillance with complete blood counts.     

Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence

The standardized incidence ratios (SIR) and cumulative incidence rates were determined for developing second malignant neoplasms (SMNs) after primary central nervous system (CNS) malignancies occurring during childhood using registry data. A total of 4553 cases of primary CNS malignancies were identified. Forty-six cases developed SMNs, 19 occurring in a previously radiated field. The SIRs of developing second malignant neoplasms were 6.3 and 3.1 for those cases receiving and not receiving radiation therapy, respectively. The 20-year cumulative incidences for developing SMNs were 3.3 and 1.2% for cases receiving and not receiving radiation therapy, respectively. Children surviving CNS malignancies have an increased susceptibility for SMNs.     

Second malignant neoplasms in childhood malignant brain tumour: A long‐term population‐based study

Aim: To provide a profile of second malignant neoplasms (SMN) in patients with childhood primary malignant brain tumour originating from neuroepithelial tissues with latest data in a population‐based study. Methods: Surveillance, Epidemiology, and End Results (SEER) database (1973–2007) was used to identify above‐stated patients. SMN patients were further identified, and standardised incidence ratios (SIRs) and excess absolute risks (EARs) for risk‐factor‐decided subgroups were calculated. Univariate and multivariate analyses of the association between cumulative incidence of SMN and the risk factors were performed in the whole population. Results: A total of 106 patients were identified as having SMNs. EARs peaked at age at primary diagnosis of 10–14. Males had higher SIRs and EARs than females. Both SIRs and EARs increased after 1990. Age was statistically significant in both univariable and multivariable analyses for cumulative incidence of SMN and RT was not significant in both the analyses, in the whole population of 9075 patients. After follow‐up recalculation, matched patients in the ≥1990 group had slightly shorter median interval between primary and secondary cancer than those in the <1990 group, but with no significance. Conclusion: The risk of SMN in children with primary malignant brain tumours in a more advanced treatment era might have changed. During making further advances in the treatment of these neoplasms, minimising toxicities while maintaining promising prognostic outcomes will keep being our goal.     

Improving outcome of malignant brain tumours in very young children: a population-based study in Finland during 1975-93

Abstract Sixty-four children with malignant brain tumours diagnosed at less than 3 years of age were reported to the Finnish Cancer Registry from 1975 to 1993. The survival rate has improved significantly: the 5-year survival rate was 26% for all children, 13% for children diagnosed during 1975-85 ( n = 30) and 40% for those diagnosed during 1986-93 ( n = 4). Of the surviving children in 1986-93, 43% were categorized in Bloom's group I or II and could lead active lives without major disabilities. The remaining children had severe neurologic late complications, such as hemiplegia, intractable seizures, and mental retardation.     

Second malignancies in patients treated for Ewing sarcoma: A systematic review

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.     

Risk factors for obesity in childhood survivors of suprasellar brain tumours: a retrospective study

Aim: To characterize postdiagnosis changes in body mass index (BMI) among childhood survivors of suprasellar brain tumours, and to determine the risk factors associated with obesity. Methods: We conducted a retrospective analysis of 46 children (16 boys and 30 girls) with median (IQR) age of 7.49 (3.47–11.59) years at tumour diagnosis, and followed up for 3.93 (1.68–7.27) years. Survival analyses were used to identify risks of developing obesity. Results: There were no sex differences in age at tumour diagnosis, duration of follow‐up, tumour types, endocrinopathies, treatment modalities or baseline BMI SDS. In the first year after tumour diagnosis, ΔBMI SDS (median; IQR) was greater in girls (1.32; 0.07–2.08) than in boys (0.48; ?0.40 to 0.89) (p = 0.01). At diagnosis, 3/46 children (6%) were obese; this increased to 20/46 (43%) by last follow‐up (p < 0.001) and was more common in girls (17/30; 57%) than in boys (3/16; 19%). Female gender (hazard ratio 5.0, 95% CI 1.2–21.7; p = 0.04) and greater than average baseline BMI (hazard ratio 4.7, 95% CI 1.1–20.8; p = 0.02) were risk factors for subsequent obesity. Conclusion: Accurate prediction of obesity risk is important and would allow early targeted intervention in high‐risk patients.     

Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007

Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC‐3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: Two thousand four hundred and eighty‐seven children (<15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow‐up have improved significantly when comparing the two time periods, 1983–1995 and 1995–2007 (76 vs. 82%; p < 0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow‐up were 80, 79 and 76%, respectively.     

Bilateral primary renal lymphoma with orbital metastasis in a child

Primary renal lymphoma (PRL) is a rare condition and bilateral PRL even rarer. Most of these bilateral PRL have been reported in adults. We describe a 3‐year‐old male with bilateral primary renal B cell lymphoma with orbital metastases. We discuss the difficulties in diagnosis and management of this rare presentation of lymphoma. Pediatr Blood Cancer 2009;52:539–541. © 2008 Wiley‐Liss, Inc.