Objective: This study aims to investigate the characteristics and related high risk factors of second neoplasms after chemotherapy and radiotherapy in children with solid tumors.
Methods: The detailed clinical data of seven children with malignant solid tumors, who were treated in our department, were retrospectively analyzed, in order to summarize the clinical characteristics of the secondary onset of second neoplasms, and determined the risk factors related to the occurrence of second neoplasms.
Results: (1) Clinical characteristics: Among the seven children with malignant solid tumors, three children had rhabdomyosarcoma (3/132, 2.27%), two children had hepatoblastoma (2/313, 0.64%), one child had neuroblastoma (1/305, 0.33%), and one child had inflammatory myofibroblastoma (1/3, 33.33%). Furthermore, among these children, four children were boys and three children were girls, and their onset age ranged within 5-34 months, with a median onset age of 27 months. Moreover, among these children, three children were ≤1 year old. All second neoplasms exhibited symptoms, and the diagnosis was made after the complete remission of the first primary tumor. The time interval between these two tumors was within 17-78 months, and the median time was 38 months. Three of seven children with rhabdomyosarcoma were treated with chemotherapy in combination with radiotherapy, while four children only received the chemotherapy. The chemotherapy cycles were 6-39 times, and the median chemotherapy cycles were 10 times. Among these children, one child with relapsed stage IV rhabdomyosarcoma and one child with stage IV retroperitoneal neuroblastoma had 39 cycles and 33 cycles of chemotherapy respectively. (2) Characteristics of the accumulated doses of high-risk chemotherapy drugs: The accumulated dose of cyclophosphamide in six patients was within 2.47-44.45 g/m2, with a median of 6.14 g/m2. The accumulated dose of ifosfamide in five patients was within 13.63-96.41 mg/m2, with a median of 31.23g/m2. The accumulated dose of etoposide in six patients was within 1,237.35-3,754.95 mg/m2, with a median of 1,548.67 mg/m2. The accumulated dose of anthracyclines in seven patients was within 150.68-843.78 mg/m2, with a median of 329.73 mg/m2. The accumulated dose of vincristine in seven patients was within 3.11-18.89 mg/m2, with a median of 15.92 mg/m2. The accumulated dose of cisplatin in seven patients was within 271.23-1,681.59 mg/m2, with a median of 733.07 mg/m2. Children with abdominal inflammatory myofibroblastic tumors did not apply cyclophosphamide, ifosfamide and etoposide regimens. The main chemotherapy drugs consisted of methotrexate, pirarubicin, cisplatin and vincristine. (3) Radiotherapy doses. (4) Characteristics of second neoplasms: Among the seven children with second neoplasms, five children had leukemia, 3 patients with rhabdomyosarcoma were combined with radiotherapy. The doses of radiation were 40 and 45GY" after "(3) Radiotherapy doses (four children had acute myeloid leukemia and one children had acute B-lymphoblastic leukemia), one child had myelodysplastic syndrome, and one child had myeloid sarcoma. Furthermore, among these seven children, four children (4/7) had abnormal chromosomes, two children were normal, and one child gave up the treatment and underwent the chromosome test after the diagnosis of second neoplasms.
Conclusion: The incidence of secondary onset of second neoplasms in children with malignant solid tumors is not high, considering that this is correlated to the use of alkylating agents, topoisomerase II inhibitors, platinum-based chemotherapy drugs and radiotherapy, and associated with the chromosomal abnormalities of children.
Key words: Chemotherapy, Children, Radiotherapy, Second malignant neoplasm, Solid tumor.
Questo studio ha lo scopo di studiare le caratteristiche e i relativi fattori ad alto rischio delle seconde neoplasie dopo chemioterapia e radioterapia nei bambini con tumori solidi. Sono stati analizzati retrospettivamente e dettagliatamente i dati clinici di sette bambini con tumori solidi maligni, che sono stati trattati nel nostro reparto, al fine di riassumere le caratteristiche cliniche all’inizio dell’insorgenza delle seconde neoplasie e determinare i fattori di rischio correlati al verificarsi di questa insorgenza. CARATTERISTICHE CLINICHE: tra i sette bambini con tumori solidi maligni, tre bambini avevano rabdomiosarcoma (3/132, 2,27%), due bambini avevano epatoblastoma (2/313, 0,64%), un bambino aveva neuroblastoma (1/305, 0,33%) e un bambino presentava miofibroblastoma infiammatorio (1/3, 33,33%). Inoltre si trattava di quattro bambini e tre bambine, e la loro epoca di insorgenza era compresa tra 5-34 mesi, con una mediana di 27 mesi; tre bambini avevano età non superiore ad 1 anno. Tutte le seconde neoplasie erano sintomatiche e la diagnosi era stata fatta dopo la completa remissione del primo tumore primario. L’intervallo di tempo tra questi due tumori era compreso tra 17 e 78 mesi e il tempo mediano era di 38 mesi. Tre su sette bambini con rabdomiosarcoma sono stati trattati con chemioterapia in combinazione con radioterapia, mentre quattro bambini hanno ricevuto solo la chemioterapia. I cicli di chemioterapia erano ripetuti da 6 a 39 volte e i cicli di chemioterapia in media 10 volte. Un bambino con rabdomiosarcoma in stadio IV recidivo e un bambino con neuroblastoma retroperitoneale in stadio IV hanno avuto rispettivamente 39 cicli e 33 cicli di chemioterapia. Caratteristiche delle dosi accumulate di farmaci chemioterapici ad alto rischio: la dose accumulata di ciclofosfamide in sei pazienti era compresa tra 2,47 e 44,45 g/m2, con una mediana di 6,14 g/m2. La dose accumulata di ifosfamide in cinque pazienti era compresa tra 13,63 e 96,41 mg/m2, con una mediana di 31,23 g/m2. La dose accumulata di etoposide in sei pazienti era compresa tra 1.237,35-3.754,95 mg/m2, con una mediana di 1.548,67 mg/m2. La dose accumulata di antracicline in sette pazienti era compresa tra 150,68- 843,78 mg/m2, con una mediana di 329,73 mg/m2. La dose accumulata di leurocristina in sette pazienti era compresa tra 3,11 e 18,89 mg/m2, con una mediana di 15,92 mg/m2. La dose accumulata di cisplatino in sette pazienti era compresa tra 271,23-1,681,59 mg/m2, con una mediana di 733,07 mg/m2. I bambini con tumori miofibroblastici infiammatori addominali non hanno ricevuto regimi di ciclofosfamide, ifosfamide ed etoposide. I principali farmaci chemioterapici sono stati il metotrexato, la pirarubicina, il cisplatino e la vincristina. Dosi di radioterapia. CARATTERISTICHE DELLE SECONDE NEOPLASIE: tra i sette bambini con seconde neoplasie, cinque bambini avevano la leucemia (quattro leucemia mieloide acuta e un bambino la leucemia linfoblastica B acuta), un bambino aveva la sindrome mielodisplastica e un bambino aveva sarcoma mieloide. Inoltre, tra questi sette bambini, quattro (4/7) avevano cromosomi anomali, due bambini erano normali e un bambino ha rinunciato al trattamento e ha subito il test cromosomico dopo la diagnosi di seconde neoplasie. CONCLUSIONE: L’incidenza dell’insorgenza secondaria di seconde neoplasie nei bambini con tumori solidi maligni non è elevata, considerando che ciò è correlato all’uso di agenti alchilanti, inibitori della topoisomerasi II, farmaci chemioterapici a base di platino e radioterapia e associati alle anomalie cromosomiche.