Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma.
dc.contributor.author | Patel, Rutulkumar | |
dc.contributor.author | Mowery, Yvonne M | |
dc.contributor.author | Qi, Yi | |
dc.contributor.author | Bassil, Alex M | |
dc.contributor.author | Holbrook, Matt | |
dc.contributor.author | Xu, Eric S | |
dc.contributor.author | Hong, Cierra S | |
dc.contributor.author | Himes, Jonathon E | |
dc.contributor.author | Williams, Nerissa T | |
dc.contributor.author | Everitt, Jeffrey | |
dc.contributor.author | Ma, Yan | |
dc.contributor.author | Luo, Lixia | |
dc.contributor.author | Selitsky, Sara R | |
dc.contributor.author | Modliszewski, Jennifer L | |
dc.contributor.author | Gao, Junheng | |
dc.contributor.author | Jung, Sin-Ho | |
dc.contributor.author | Kirsch, David G | |
dc.contributor.author | Badea, Cristian T | |
dc.date.accessioned | 2023-03-27T13:12:28Z | |
dc.date.available | 2023-03-27T13:12:28Z | |
dc.date.issued | 2023-01 | |
dc.date.updated | 2023-03-27T13:12:26Z | |
dc.description.abstract | This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti-PD-1), or RT + anti-PD-1 to surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). We generated a high mutational load primary mouse model of STS by intramuscular injection of adenovirus expressing Cas9 and guide RNA targeting Trp53 and intramuscular injection of 3-methylcholanthrene (MCA) into the gastrocnemius muscle of wild-type mice (p53/MCA model). We randomized tumor-bearing mice to receive isotype control or anti-PD-1 antibody with or without radiotherapy (20 Gy), followed by hind limb amputation. We used micro-CT to detect lung metastases with high spatial resolution, which was confirmed by histology. We investigated whether sarcoma metastasis was regulated by immunosurveillance by lymphocytes or tumor cell-intrinsic mechanisms. Compared with surgery with isotype control antibody, the combination of anti-PD-1, radiotherapy, and surgery improved local recurrence-free survival (P = 0.035) and disease-free survival (P = 0.005), but not metastasis-free survival. Mice treated with radiotherapy, but not anti-PD-1, showed significantly improved local recurrence-free survival and metastasis-free survival over surgery alone (P = 0.043 and P = 0.007, respectively). The overall metastasis rate was low (∼12%) in the p53/MCA sarcoma model, which limited the power to detect further improvement in metastasis-free survival with addition of anti-PD-1 therapy. Tail vein injections of sarcoma cells into immunocompetent mice suggested that impaired metastasis was due to inability of sarcoma cells to grow in the lungs rather than a consequence of immunosurveillance. In conclusion, neoadjuvant radiotherapy improves metastasis-free survival after surgery in a primary model of STS. | |
dc.identifier | 711999 | |
dc.identifier.issn | 1535-7163 | |
dc.identifier.issn | 1538-8514 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | American Association for Cancer Research (AACR) | |
dc.relation.ispartof | Molecular cancer therapeutics | |
dc.relation.isversionof | 10.1158/1535-7163.mct-21-0991 | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Sarcoma | |
dc.subject | Soft Tissue Neoplasms | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Disease-Free Survival | |
dc.subject | Neoadjuvant Therapy | |
dc.subject | Radiotherapy, Adjuvant | |
dc.subject | Retrospective Studies | |
dc.subject | Tumor Suppressor Protein p53 | |
dc.subject | Progression-Free Survival | |
dc.title | Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma. | |
dc.type | Journal article | |
duke.contributor.orcid | Mowery, Yvonne M|0000-0002-9839-2414 | |
duke.contributor.orcid | Everitt, Jeffrey|0000-0003-0273-6284 | |
duke.contributor.orcid | Jung, Sin-Ho|0000-0002-1473-7236 | |
duke.contributor.orcid | Badea, Cristian T|0000-0002-1850-2522 | |
pubs.begin-page | 112 | |
pubs.end-page | 122 | |
pubs.issue | 1 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pratt School of Engineering | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Biostatistics & Bioinformatics | |
pubs.organisational-group | Pharmacology & Cancer Biology | |
pubs.organisational-group | Biomedical Engineering | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | Radiation Oncology | |
pubs.organisational-group | Radiology | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Head and Neck Surgery & Communication Sciences | |
pubs.organisational-group | Regeneration Next Initiative | |
pubs.publication-status | Published | |
pubs.volume | 22 |
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