Precision Survivorship Platforms Are Essential for Improved, Equitable Care in Pediatric and AYA Sarcoma

By identifying the biological and systemic drivers of recurrence and late toxicity in pediatric and adolescent/young adult (AYA) survivors of bone sarcomas receiving guideline-concordant care, R. Lor Randall, MD, FACS, hopes that survivorship science will move beyond descriptive frameworks toward models informed by a greater mechanistic understanding, thereby enabling personalized long-term follow-up care.

In an interview with OncLive®, Randall spotlighted research assessing standards for sarcoma survivorship and outcomes as relates to guideline-concordant care, which is being led by his colleague Elysia Marie Alvarez, MD, MPH.Alvarez, who is a pediatric oncologist at UC Davis and member of the Children’s Oncology Group, recently received a K08 award from the National Cancer Institute (NCI) to prospectively examine how sarcoma survivors experience outcomes after receiving similar therapies. This research aims to predict and prevent disparities in outcomes by delineating the mechanistic pathways that influence long-term survivorship, thereby laying the groundwork for more personalized, equitable post-treatment care.

“If the social services around that patient determine that this patient has some disadvantaged socioeconomic situations, we want to really make sure that they get into a formal survivorship clinic” Randall stated. "This [research] will hopefully develop into a predictive survivorship [model], where we know patients who are at risk are going to get different sorts of interventions in their survivorship..."

Randall is the David Linn Endowed Chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at UC Davis Comprehensive Cancer Center in Sacramento, California.

OncLive: What disparities in the quality and equity of sarcoma survivorship remain unaddressed, and how might Dr Alvarez’s work help improve outcomes among pediatric and AYA patients?

Randall: Pediatric bone sarcoma survival has improved, albeit only modestly, over the last few decades; however, the quality and equity of survival has not. Children and AYA [patients] who are cured of things like osteosarcoma and Ewing sarcoma often face decades of cardiopulmonary, endocrine, psychosocial, and musculoskeletal late effects. These burdens fall disproportionately on patients with racial and socioeconomic adverse circumstances, but the treatment exposures are identical across all the populations.

Elysia Marie Alvarez, MD, MPH, a pediatric oncologist with whom I work here at UC Davis Comprehensive Cancer Center, has really spearheaded [research into] guideline-concordant care and improving outcomes in AYA [patients] with bone sarcomas, not just at our institution, but nationally and internationally. She's a lead in the Children's Oncology Group, which is international in its scope.

She recently received an NIH K08 award from the NCI to specifically look at standards for sarcoma survivorship and outcomes as relates to guideline-concordant care for patients with pediatric bone tumors. Her research is starting to look into why those disparities occur at the biologic and systemic levels and see what we can learn from that to really form a platform of precision survivorship care.

What is the overarching vision and methodology of this work?

The vision of this work is to look at the survivorship science, taking it from purely descriptive to mechanistic; identifying biological contextual drivers of late toxicity and recurrence; and using those insights to personalize long term follow up. Even though [patients may] get the same kind of care, [some] patients from her studies experience worse outcomes. By using a multi-pronged approach of population-level analytics, molecular profiling, and health equity frameworks and uniting these 3 disciplines, we can hopefully come up with a precision framework for survivorship.

Firstly, what she's doing is quantifying and characterizing the disparities. Using SEER and other institutional registries from across California and beyond, she's looking at how treatment exposures and social determinants of health affect survival and late-effect outcomes among pediatric and AYA sarcoma patients. She also wants to define the biologic correlates of these late effects. She's integrating molecular and transcriptomic data to discover biological pathways associated with long-term toxicities and recurrence and connecting molecular signatures with clinical and demographic predictors. Finally, her team is looking to develop a predictive survivorship model, combining clinical, biologic, and sociodemographic variables into a data-driven model that stratifies survivors by risk, enabling targeted surveillance and intervention for those patients we know are going to have more compromised survivorship.

Given the competitive research environment, how might the multidisciplinary nature of Dr. Alvarez's research have helped secure funding from the NCI?

This [research] is based upon [previously] published data, but now it's gone through peer review and has resulted in an NCI grant. The reason why [this research, which deals] with socioeconomic disparities, was funded in such a competitive environment and in the current climate of our society was because it was multidisciplinary. [Both myself] and internationally recognized medical oncologist William D. Tapp, MD, of Memorial Sloan Kettering Cancer Center [are part of her mentorship team, and] a cadre of epidemiologists, biostatisticians, computational biologists and molecular biologists, who are very familiar with transcriptomics, [are involved in this project as well]. Dr Alvarez [herself] brings a tremendous amount of expertise [to this project], having done her pediatric and hematology/oncology fellowship at Stanford and getting her MPH at the Harvard Chan School of Public Health.

We are going to take all those aspects into the survivorship arena, which historically has [comprised] only socioeconomic and sort of cultural variable assessments.

What is the main difference between survival and survivorship outcomes for pediatric or AYA patients with sarcoma facing socioeconomic disparity? Why is it important for oncologists caring for these survivors to understand this distinction?

Alvarez is published in [both the Journal of Clinical Oncology and Journal of Adolescent Young Adult Oncology] on guideline-concordant care.1,2 The Journal of Clinical Oncology article [finds] that patients who are facing worse socioeconomic disparity, lower insurance levels, or lower resources survive their cancers pretty much on par with those other patients that are more well-resourced.1 The problem is that they then go on to experience many more lifelong complications.

For anyone taking care of a patient with bone sarcomas, you know that we are winning the battle in roughly 3 out of 4 cases. However, do remember that that's just the beginning of their journey in life. Many pediatric oncologists and even more medical oncologists don't really think about survivorship; they think just about survival. When these [patients] survive, their survivorship can be compromised by, and be sensitive to, [disparities and other factors].

Looking ahead, how might this research on survivorship science reframe our understanding of long-term care needs for sarcoma survivors?

This is exciting stuff, and it's going to be front and center at all the big meetings. We think that the broad impact of this research will be a reframing of survivorship [as a] continuation of cancer biology mixed with socioeconomic variables. [This] will really enable us to predict which patients will need additional interventions when they survive their bone cancers in young adulthood or childhood.

References

1. Abrahão R, Keegan THM, Maguire FB, et al. Receipt of guideline-concordant care is associated with improved survival in patients with osteosarcoma in California: a population-based analysis. JCO Oncol Pract. Published online February 21, 2024. doi:10.1200/OP.23.00591
2. Alvarez E, Malogolowkin M, Frazier AL, et al. Association of Guideline-Concordant Care with Survival in Adolescent and Young Adult Patients with Germ Cell Tumors. J Adolesc Young Adult Oncol. Published online June 11, 2025. doi:10.1089/jayao.2025.0004