142 - Surveying the Valley of Death: How Wide is the Gap between Basic Science and Clinical Application in Radiation/Immunotherapy Research?

Purpose/Objective(s): Effective translation of preclinical insights to clinical trials is essential to advancing cancer research. However, many barriers, often termed the “valley of death,” must be surmounted before preclinical findings lead to successful clinical trials. We aimed to analyze the distribution of grant funding and publication output for studies of radiotherapy (RT) and immunotherapy (IO) combinations.

Materials/Methods: Publicly available databases (NIH RePORTER, PubMed) were used to assess funding allocation and publication volume for preclinical (in vitro or animal studies) versus clinical (human) projects investigating RT/IO. For NIH RePORTER, a search for projects tagged by NIH spending categories of RT/IO was performed for 2019-2024; projects were further subcategorized using specific MeSH terms (e.g., “in vitro”, “mouse”). In PubMed, the MeSH terms (radiation OR radiotherapy) AND (immunotherapy OR “immune therapy”) were used to identify papers published between 2005-2025. Papers were categorized into preclinical and human subject projects then further subdivided into clinical trials versus other publication types.

Results: In NIH RePORTER, 1,091 RT/IO projects from all fiscal years were identified, receiving a total of $483.4 million: 13.7% of projects were preclinical in vitro projects (19.2% of total funding); 58.8% of projects were preclinical animal projects (61.6% of total funding); and 24.5% of projects were clinical human subject research (25.8% of total funding). Proportions of projects and funding per category remained relatively stableyear-over-year. PubMed showed 25,376 articles published on RT/IO; 14.9% preclinical in vitro work, 20.8% preclinical animal research, and 64.3% human subjects research. Of the human subjects papers, 9.8% were clinical trials (6.6% of total publications). Trends over time showed that while all types of publications increased exponentially year-over-year, due to disproportionately high growth rates in human non-clinical work, the percentage of total research output represented by human clinical trials and preclinical in vitro and animal studies decreased (average annual growth of absolute number/average annual change in percentage of total publications; human clinical trials +11.3%/-0.22%, human non-clinical trials +16.4%/+0.44%, preclinical +14.4%/-0.22%, all publications +14.4%/-).

Conclusion: Grant funding and publication interest in preclinical versus clinical projects is unequal with >75% of total grant funding supporting preclinical research. Animal studies alone represented over 60% of NIH-funded research in RT/IO combinations. Despite continued growth in the number of published papers in the RT/IO space, clinical trials represent a small proportion of published studies, suggesting that substantial barriers to successful trial completion and publication remain.