12 min

Fine Tuning Therapy for Intermediate-Risk Neuroblastoma Using Clinical Response and Tumor Biology Journal of Clinical Oncology (JCO) Podcast

    • Science

This JCO Podcast provides observations and commentary on the JCO article “Maintaining Outstanding Outcomes Using Response and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531” by Twist et al. My name is Javed Khan, and I am Deputy Chief and Senior Investigator at the Genetics Branch and an Attending for the Pediatric Oncology Branch of the National Cancer Institutes of the NIH in Bethesda, Maryland. My oncologic specialty is Pediatric Hematology Oncology.
Childhood cancer is a life-threatening disease where survival rates have increased exponentially to over 75% over the past three decades. However, this has come at a considerable cost with significant incidence of late effects including hearing loss, scoliosis, hypothyroidism, growth and development delay, infertility, psychological, emotional, cognitive and neurological sequelae, and secondary malignancies. Most of these late effects have been attributed therapy including chemotherapy, surgery and radiation.
In the manuscript that accompanies this podcast, Twist et al report on the results of the Children’s Oncology Group study ANBL0531, whose primary aim was to reduce therapy for subsets of children aged =95% for the entire cohort.
Neuroblastoma is an extracranial pediatric malignancy of neural crest origin that has often been described as an enigmatic cancer due to its significant clinical, molecular and biological heterogeneity. For example, some patients with widely metastatic disease are cured with minimal or no therapy whereas others have relentless progression to death despite intensive therapies.  There has been considerable progress in dissecting out the causes of this heterogeneity and developing prognostic biomarkers to stratify the risk based on several clinical, histological and molecular markers. At the time this clinical study was performed, and the manuscript written, the authors stratified patients using several clinical and biologic parameters including age, the International Neuroblastoma Staging System, MYCN amplification status, the International Neuroblastoma Pathology Classification of histopathology, and tumor DNA index. An additional marker utilized in this study was loss of heterozygosity determination of the tumors at chromosome bands 1p36 and 11q23. This stratification strategy has led to the identification of low and high-risk groups where therapy is more clearly defined and patients with low risk have excellent outcome for most patients with surgery alone and watchful waiting. For high-risk disease, significant strides have been made using a combination of surgery, aggressive chemotherapy, radiation followed by Chimeric Antibody 14.18 anti GD2 therapy, GM-CSF, IL-2 and Isotretinoin, however the five-year survival remains guarded at 40-50%. In the intermediate-risk group, the subject of this study, although the 5-year survival rates of 90-95% have been achieved, this group is significantly heterozygous raising the possibility of reducing therapy for subsets of patients within this group. This was the motivation for this study.
Thus, the goal of this clinical protocol, ANBL0531, was to refine the minimal therapy needed to achieve excellent outcomes for patients with intermediate-risk neuroblastoma, with the aim to maintain an overall 3-year OS rate of > 95% for the entire cohort. Patients were stratified into Groups 2, 3, or 4, who were assigned to receive a minimum of 2, 4, or 8 cycles of chemotherapy, respectively. Chemotherapy was identical to that used on a previous study A3961.
Reduction of therapy was planned to be achieved for patients with biologically favorable tumors (Groups 2 and 3) by using the achievement of Partial Response (PR) to chemotherapy +/- surgery to be the endpoint of therapy, rather than the achievement of Very Good Partial Response (VGPR) as was previously used on A3961. If the treatment endpoint was not achieved after completion of the sc

This JCO Podcast provides observations and commentary on the JCO article “Maintaining Outstanding Outcomes Using Response and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531” by Twist et al. My name is Javed Khan, and I am Deputy Chief and Senior Investigator at the Genetics Branch and an Attending for the Pediatric Oncology Branch of the National Cancer Institutes of the NIH in Bethesda, Maryland. My oncologic specialty is Pediatric Hematology Oncology.
Childhood cancer is a life-threatening disease where survival rates have increased exponentially to over 75% over the past three decades. However, this has come at a considerable cost with significant incidence of late effects including hearing loss, scoliosis, hypothyroidism, growth and development delay, infertility, psychological, emotional, cognitive and neurological sequelae, and secondary malignancies. Most of these late effects have been attributed therapy including chemotherapy, surgery and radiation.
In the manuscript that accompanies this podcast, Twist et al report on the results of the Children’s Oncology Group study ANBL0531, whose primary aim was to reduce therapy for subsets of children aged =95% for the entire cohort.
Neuroblastoma is an extracranial pediatric malignancy of neural crest origin that has often been described as an enigmatic cancer due to its significant clinical, molecular and biological heterogeneity. For example, some patients with widely metastatic disease are cured with minimal or no therapy whereas others have relentless progression to death despite intensive therapies.  There has been considerable progress in dissecting out the causes of this heterogeneity and developing prognostic biomarkers to stratify the risk based on several clinical, histological and molecular markers. At the time this clinical study was performed, and the manuscript written, the authors stratified patients using several clinical and biologic parameters including age, the International Neuroblastoma Staging System, MYCN amplification status, the International Neuroblastoma Pathology Classification of histopathology, and tumor DNA index. An additional marker utilized in this study was loss of heterozygosity determination of the tumors at chromosome bands 1p36 and 11q23. This stratification strategy has led to the identification of low and high-risk groups where therapy is more clearly defined and patients with low risk have excellent outcome for most patients with surgery alone and watchful waiting. For high-risk disease, significant strides have been made using a combination of surgery, aggressive chemotherapy, radiation followed by Chimeric Antibody 14.18 anti GD2 therapy, GM-CSF, IL-2 and Isotretinoin, however the five-year survival remains guarded at 40-50%. In the intermediate-risk group, the subject of this study, although the 5-year survival rates of 90-95% have been achieved, this group is significantly heterozygous raising the possibility of reducing therapy for subsets of patients within this group. This was the motivation for this study.
Thus, the goal of this clinical protocol, ANBL0531, was to refine the minimal therapy needed to achieve excellent outcomes for patients with intermediate-risk neuroblastoma, with the aim to maintain an overall 3-year OS rate of > 95% for the entire cohort. Patients were stratified into Groups 2, 3, or 4, who were assigned to receive a minimum of 2, 4, or 8 cycles of chemotherapy, respectively. Chemotherapy was identical to that used on a previous study A3961.
Reduction of therapy was planned to be achieved for patients with biologically favorable tumors (Groups 2 and 3) by using the achievement of Partial Response (PR) to chemotherapy +/- surgery to be the endpoint of therapy, rather than the achievement of Very Good Partial Response (VGPR) as was previously used on A3961. If the treatment endpoint was not achieved after completion of the sc

12 min

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