Effect of Favorable Pathologic Response After Neoadjuvant Radiation Therapy Alone in Soft-tissue Sarcoma

Palm, Russell; Liveringhouse, C.; Gonzalez, Ricardo J.; Binitie, Odion; Yang, Guang; Naghavi, A.O.

doi:10.1016/j.adro.2022.101086

Cited by 6 publications

(1 citation statement)

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“…This isotoxic approach is hypothesized to result in acceptable normal tissue dosing for the GARD-optimized RT dose, focally escalating radiation dose levels with the use of modern radiation techniques (e.g., simultaneous integrated boost [SIB]). The hypofractionation offers a higher biological effect on these low α/β regions, providing an avenue for safely improving FPR rates without significantly increasing toxicity, which is associated with improved local control, distant control, and overall survival [ 24 – 26 , 37 ]. With improved understandings of tumor heterogeneity, radiosensitivity, and radiomics, our goal is to personalize radiation treatment for each patient.…”

Section: Introductionmentioning

confidence: 99%

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma

Naghavi,

Bryant,

Kim

et al. 2024

BMC Cancer

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Background Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. Methods Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. Discussion This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. Trial registration NCT05301283. Trial status The trial started recruitment on March 17, 2022.

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Section: Introductionmentioning

confidence: 99%