Graduation Date

Summer 8-14-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Chi Lin, M.D. Ph.D.

Second Advisor

Zheng Cheng, Ph.D

Third Advisor

Jill C. Beck, M.D.

Fourth Advisor

Donald Coulter, M.D.

Abstract

Background:

The role of immunotherapy in sarcoma treatment remains poorly defined, particularly in pediatric patients where its use has been limited despite a biologic rationale for enhanced immune responsiveness. We evaluated national patterns of immunotherapy utilization and its association with overall survival (OS) among pediatric and adult patients with sarcoma using the National Cancer Database (NCDB).

Methods: 
A retrospective cohort study was performed using the NCDB, including patients diagnosed with rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and other sarcomas between 2004 and 2017 who did not undergo surgical resection. Multivariable logistic regression identified factors associated with receipt of immunotherapy. OS was evaluated using Kaplan–Meier methods and Cox proportional hazards models. Because immunotherapy violated the proportional hazards assumption, a time-dependent Cox model was used with a 14-month landmark.

Results: 
A total of 27,312 patients met inclusion criteria, including 3,680 pediatric patients (1–18 years). Only 483 patients (1.7%) received immunotherapy, of whom just 33 (7%) were pediatric patients. Immunotherapy use increased substantially beginning in 2016, with more than half of treated patients receiving immunotherapy in 2017. On multivariable analysis, receipt of immunotherapy was independently associated with more recent year of diagnosis, stage IV disease, private insurance, non-rhabdomyosarcoma histology, chemotherapy-based treatment, residence in a non-urban area, and treatment at an academic center. Overall survival curves crossed at approximately 14 months. Time-dependent analysis demonstrated an associated improved survival among patients receiving immunotherapy within the first 14 months following diagnosis (HR 0.663, 95% CI 0.578–0.760), whereas immunotherapy administered beyond 14 months was associated with worse survival (HR 1.282, 95% CI 1.068–1.540). Subgroup analyses showed that the early survival benefit was most pronounced in patients older than 39 years and remained consistent across diagnostic eras.

Conclusions: 
Immunotherapy remains infrequently used in sarcoma therapy, particularly among pediatric patients, despite increasing adoption after 2016. Receipt of immunotherapy earlier in the disease course was associated with improved survival, although this association cannot establish a causal benefit because of substantial treatment-selection bias, whereas later use conferred no survival benefit, likely reflecting treatment in relapsed or progressive disease. These findings support prospective evaluation of upfront immunotherapy strategies and combination approaches to better define the role of immunotherapy across sarcoma subtypes, particularly in pediatric populations.

Rights

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Available for download on Wednesday, August 02, 2028

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