Second Cancer Risk in Childhood Cancer Survivors Treated With Intensity-Modulated Radiation Therapy (IMRT): An Updated Analysis of More Than 10 Years of Follow-Up

Background It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. Procedure Patients aged 10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

Risk of developing second malignant neoplasms in patients with neuroblastoma: a population study of the US SEER database

Background Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs). Methods The SEER 18 Regs (1973–2015) and SEER 9 Regs (1973–2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis. Results The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634–2.797, p < 0.001) was the only independent risk factor for developing SMNs. Conclusion This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.

Second Malignant Neoplasms in Patients With Rhabdomyosarcoma

ObjectiveRhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiotherapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN).MethodsThe Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis.ResultsThe 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR=1.95, 95% CI: 1.44 – 2.57, p &lt; 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joints (SIR = 35.25) soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and all nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313 – 0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184 – 0.564. p &lt; 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421 – 0.585, p &lt; 0.001).ConclusionThis study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.

Risk of Developing Second Malignant Neoplasms in Patients with Neuroblastoma: A Population Study of the US SEER Database

Background: Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs).Methods: The SEER 18 Regs (1973-2015) and SEER 9 Regs (1973-2015) data of the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis.Results: The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR=4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR =7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR=2.138, 95%CI=1.634-2.797, p＜0.001) was the only independent risk factor for developing SMNs.Conclusion: This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.

Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms

Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.

Second Malignant Neoplasms in Patients with Rhabdomyosarcoma: A US Population-Based Analysis

Objective Rhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiation therapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN). Methods The Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis. Results The 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR = 1.95, 95% CI: 1.44–2.57, p < 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joint (SIR = 35.25) and soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and brain and other nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313–0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184–0.564. p < 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421–0.585, p < 0.001). Conclusion This study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.