Abstract
BackgroundDespite the advances in oncology, patients with bulky tumors have worse prognosis and often receive only palliative treatments. Bulky disease represents an important challenging obstacle for all currently available radical treatment options including conventional radiotherapy. The purpose of this study was to assess a retrospective outcome on the use of a newly developed unconventional stereotactic body radiation therapy (SBRT) for PArtial Tumor irradiation of unresectable bulky tumors targeting exclusively their HYpoxic segment (SBRT-PATHY) that exploits the non-targeted effects of radiotherapy: bystander effects (local) and the abscopal effects (distant).Materials and methodsTwenty-three patients with bulky tumors received partial bulky irradiation in order to induce the local non-targeted effect of radiation (bystander effect). The hypoxic tumor segment, called the bystander tumor volume (BTV), was defined using PET and contrast-enhanced CT, as a hypovascularized-hypometabolic junctional zone between the central necrotic and peripheral hypervascularized-hypermetabolic tumor segment. Based on tumor site and volume, the BTV was irradiated with 1–3 fractions of 10–12 Gy prescribed to 70% isodose-line. The pathologic lymph nodes and metastases were not irradiated in order to assess the distant non-targeted effects of radiation (abscopal effect). No patient received any systemic therapy.ResultsAt the time of analysis, with median follow-up of 9.4 months (range: 4–20), 87% of patients remained progression-free. The bystander and abscopal response rates were 96 and 52%, respectively. Median shrinkage of partially irradiated bulky tumor expressing intensity of the bystander effect was 70% (range 30–100%), whereas for the non-irradiated metastases (intensity of the abscopal effect), it was 50% (range 30–100%). No patient experienced acute or late toxicity of any grade.ConclusionsSBRT-PATHY showed very inspiring results on exploitation of the radiation-hypoxia-induced non-targeted effects that need to be confirmed through our ongoing prospective trial.Present study has been retrospectively registered by the local ethic committee under study number A 26/18.
Highlights
Despite the tremendous oncological developments, patients with bulky tumors still have poor prognosis, and often receive only palliative treatments [1,2,3,4,5]
stereotactic body radiation therapy (SBRT)-PATHY showed very inspiring results on exploitation of the radiation-hypoxia-induced non-targeted effects that need to be confirmed through our ongoing prospective trial
In order to improve the role of radiotherapy as an inductor of non-targeted effects (NTE), we have previously proved for the first time that the irradiation of hypoxic tumor cells resulted in effective radiation-hypoxia-induced bystander (R-H-IBE) and abscopal effects (R-H-IAE) [7]
Summary
Despite the tremendous oncological developments, patients with bulky tumors still have poor prognosis, and often receive only palliative treatments [1,2,3,4,5]. The incorporation of NTE in routine clinical practice is still scarce several studies have proven their existence and their potential beneficial outcome [6] These studies provided an immune based explanation to the NTE phenomenon and rebuked skepticism on the ability of radiotherapy to one lesion to induce tumor shrinkage in a distant non-irradiated lesion. At a certain radiation dose, radiation-induced tumor cells damage activates antitumor immune response through the release of tumor antigens and damage-associated molecular pattern, which, in turn, results in increased activation of antigen-presenting cells and T-lymphocytes This activation of the immune system triggers antigen-specific, adaptive immunity, a phenomenon referred to as “in situ” radio-vaccination [6]. The purpose of this study was to assess a retrospective outcome on the use of a newly developed unconventional stereotactic body radiation therapy (SBRT) for PArtial Tumor irradiation of unresectable bulky tumors targeting exclusively their HYpoxic segment (SBRT-PATHY) that exploits the non-targeted effects of radiotherapy: bystander effects (local) and the abscopal effects (distant)
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