Date of Award

Spring 2021

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Mandy Seymour

Abstract

Introduction: Ewing sarcoma (ES), a rare bone cancer, most commonly affects the pediatric population and typically originates in bones of the legs and pelvis but can occur in or metastasize to any bone. There is no cure for ES, however, current treatment includes a fusion of both systemic and localized therapies. This evidence-based review article analyzes the use of topotecan or irinotecan, systemic therapies, combined with standard chemotherapy, a localized therapy, and the corresponding recurrence rates and prognosis in patients under 30 years of age as compared to standard chemotherapy alone.

Methods: An extensive literature review consisting of 18 articles from various sources including EBSCOhost, PMC, PubMed, and Web of Science was conducted in November 2019. Retrospective chart reviews and case studies were selected based on publication date, intervention technique, and sample population. The design, outcomes, and results of these reviews and studies were then analyzed and compared.

Results: While the evidence demonstrates improvements in overall survival and event-free survival of patients with ES, the reviews and studies lacked sufficient rigor to confirm or deny the efficacy of the addition of topotecan or irinotecan in combination with standard chemotherapy as an alternative treatment with statistical significance.

Discussion: Prognosis and long-term survival of ES varies considerably from person to person based on several factors including size, location, presence or lack of metastases, age, and overall health – with the location being the strongest predictive factor. Primary pelvic ES was linked with the greatest mortality, while primary extremity ES the lowest.

As ES is a rare disease, research is limited and consists predominately of studies with small sample sizes. Additionally, several limitations including lack of randomization, double-blinding, and the utilization of chart reviews, which can introduce bias and sampling error, making it difficult to conclude the effectiveness of the treatment. However, as indicated by the evidence, several of the alternative treatment regimens proved promising in the treatment of non-metastatic, refractory, or relapsed ES. In contrast, the evidence also suggests little to no improvement in the survival rates of metastatic, refractory, or relapsed ES.

Conclusion: Although there is not sufficient evidence to fully support the incorporation of irinotecan or topotecan with standard chemotherapy in the treatment of ES, there is enough evidence to encourage further research evaluating its efficacy as an alternative treatment to the standard of ES. It is imperative that both researchers and healthcare providers continue to search for a treatment regimen for ES that is not only associated with better overall survival and event-free survival in patients with primary, non-metastatic ES, but also metastatic, refractory, or relapsed ES. The existing evidence does not justify changing the current treatment of ES at this time but encourages us to continue researching the treatment regimens that have proved effective and explore how we can make them more effective for a broader patient presentation of ES.

Additional Files

Hurst Capstone_Prsentation__Zoom.mp4 (12702 kB)

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The efficacy of the combination of topotecan or irinotecan with standard chemotherapy versus chemotherapy alone in patients with Ewing Sarcoma

Introduction: Ewing sarcoma (ES), a rare bone cancer, most commonly affects the pediatric population and typically originates in bones of the legs and pelvis but can occur in or metastasize to any bone. There is no cure for ES, however, current treatment includes a fusion of both systemic and localized therapies. This evidence-based review article analyzes the use of topotecan or irinotecan, systemic therapies, combined with standard chemotherapy, a localized therapy, and the corresponding recurrence rates and prognosis in patients under 30 years of age as compared to standard chemotherapy alone.

Methods: An extensive literature review consisting of 18 articles from various sources including EBSCOhost, PMC, PubMed, and Web of Science was conducted in November 2019. Retrospective chart reviews and case studies were selected based on publication date, intervention technique, and sample population. The design, outcomes, and results of these reviews and studies were then analyzed and compared.

Results: While the evidence demonstrates improvements in overall survival and event-free survival of patients with ES, the reviews and studies lacked sufficient rigor to confirm or deny the efficacy of the addition of topotecan or irinotecan in combination with standard chemotherapy as an alternative treatment with statistical significance.

Discussion: Prognosis and long-term survival of ES varies considerably from person to person based on several factors including size, location, presence or lack of metastases, age, and overall health – with the location being the strongest predictive factor. Primary pelvic ES was linked with the greatest mortality, while primary extremity ES the lowest.

As ES is a rare disease, research is limited and consists predominately of studies with small sample sizes. Additionally, several limitations including lack of randomization, double-blinding, and the utilization of chart reviews, which can introduce bias and sampling error, making it difficult to conclude the effectiveness of the treatment. However, as indicated by the evidence, several of the alternative treatment regimens proved promising in the treatment of non-metastatic, refractory, or relapsed ES. In contrast, the evidence also suggests little to no improvement in the survival rates of metastatic, refractory, or relapsed ES.

Conclusion: Although there is not sufficient evidence to fully support the incorporation of irinotecan or topotecan with standard chemotherapy in the treatment of ES, there is enough evidence to encourage further research evaluating its efficacy as an alternative treatment to the standard of ES. It is imperative that both researchers and healthcare providers continue to search for a treatment regimen for ES that is not only associated with better overall survival and event-free survival in patients with primary, non-metastatic ES, but also metastatic, refractory, or relapsed ES. The existing evidence does not justify changing the current treatment of ES at this time but encourages us to continue researching the treatment regimens that have proved effective and explore how we can make them more effective for a broader patient presentation of ES.