Conformal avoidance of normal organs at risk by perfusion-modulated dose sculpting in tumor single-dose radiation therapy Journal Article
| Authors: | Greco, C.; Kolesnick, R.; Fuks, Z. |
| Article Title: | Conformal avoidance of normal organs at risk by perfusion-modulated dose sculpting in tumor single-dose radiation therapy |
| Abstract: | Purpose: Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTVHD]), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTVPMDS]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTVPMDS may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose. Methods and Materials: Dose fall-off within the PTVPMDS penumbra of oligometastatic lesions was planned and delivered by intensity modulated inverse dose painting. SDRT- and SDRT-PMDS–treated lesions were followed with periodic positron emission tomography/computed tomography imaging to assess local tumor control. Results: Cumulative baseline 5-year local relapse rates of oligometastases treated with 24 Gy SDRT alone (8% relapses, n = 292) were similar in moderate PTVPMDS dose-sculpted (23-18 Gy, n = 76, 11% relapses, P = .36) and extreme dose-sculpted (<18 Gy, n = 61, 14% relapses, P = .29) lesions, provided the major 24 Gy PTVHD constituted ≥60% of the total PTV. In contrast, 28% of local relapses occurred in 26 extreme dose-sculpted PTVPMDS lesions when PTVHD constituted <60% of the total PTV (P = .004), suggesting a threshold for the PTVPMDS bystander effect. Conclusion: The study provides compelling clinical support for the bystander radiosensitization hypothesis, rendering local cure of tumor lesions despite a ≥25% PTVPMDS dose reduction of the 24 Gy PTVHD dose, adapted to conformally meet OAR dose/volume constraints. The SDRT-PMDS approach thus provides a therapeutic resolution to otherwise radioablation-intractable oligometastatic disease. © 2020 Elsevier Inc. |
| Keywords: | positron emission tomography; radiotherapy; tumors; positron emission tomography/computed tomographies; local tumor control; intensity-modulated; methods and materials; rendering (computer graphics); conformal avoidance; hypothetical models; radio-sensitization; volumetric subdivision |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 109 |
| Issue: | 1 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2021-01-01 |
| Start Page: | 288 |
| End Page: | 297 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2020.08.017 |
| PUBMED: | 32777335 |
| PROVIDER: | scopus |
| PMCID: | PMC8456416 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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