Normal-Tissue Tolerance to IOERT, EBRT, or Both: Animal and Clinical Studies

Vujašković, Željko; Willett, Christopher G.; Tepper, Joel E.; Kinsella, Timothy J.; Gunderson, Leonard L.

doi:10.1007/978-1-61779-015-7_7

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…17,18 Improved physical targeted radiation, such as three-dimensional external beam conformal radiotherapy and intensity-modulated RT, has enabled more precise dose delivery to tumor masses, while limiting the exposure of surrounding normal tissues. 19,20 Nevertheless, the treatment of certain malignancies remains problematic, as malignant tumors are a type of complicated disease that involves the activation and inactivation of different oncogenes during the process of tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Ding

Zhang

et al. 2012

Cancer Gene Ther

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The AND gate functions such that when all inputs are activated the downstream gene will be transcribed and it is off otherwise. To accomplish optimal and targeted gene therapy in solid tumor patients, we have constructed an AND gate genetic circuit and investigated whether it could be activated by low-dose radiation in vitro and in vivo. The enhancement green fluorescent protein (EGFP) expression in different tumor cells transfected with control vector plxsn-EGFP confirmed that 2 Gy of radiation and 1% O 2 for 3 h could activate our AND gate. Besides, the obvious different levels of EGFP expression between 2 and 6 Gy of radiation demonstrated that the AND gate could be regulated by radiation doses. Additionally, through EGFP expression and the codistribution of p53 and HIF-1a in xenografts, we illustrated the targeted activation property of the AND gate and real-time monitoring to hypoxic districts in vivo. Moreover, significant growth inhibition and cell cycle arrest in vitro and apoptosis-inducing effects in vitro and in vivo proved that the AND gate induced ideal antitumor effects. In conclusion, the radiation dose-regulated AND gate genetic circuit could not only effectively monitor the therapeutic process in real-time but also induce ideal antitumor efficacy, and can be further exploited for personal therapy in clinical tumor patients.

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Section: Discussionmentioning

confidence: 99%

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Ding

Zhang

et al. 2012

Cancer Gene Ther

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“…Tolerance of healthy tissue has historically been determined by animal (mostly canine) studies. One paper reporting on animal experiments at the Colorado State University has translated these to estimated tolerated doses when using IOERT and EBRT [30][31][32][33][34]. These studies have shown that the maximum tolerated dose of healthy tissue was quite high.…”

Section: Discussionmentioning

confidence: 99%

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer

Verrijssen¹,

Dries²,

Cnossen³

et al. 2022

jcb

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Purpose: Intra-operative radiotherapy (IORT) has been used as a tool to provide a high-dose radiation boost to a limited volume of patients with fixed tumors with a likelihood of microscopically involved resection margins, in order to improve local control. Two main techniques to deliver IORT include high-dose-rate (HDR) brachytherapy, termed 'intra-operative brachytherapy' (IOBT), and electrons, termed 'intra-operative electron radiotherapy' (IOERT), both having very different dose distributions. A recent paper described an improved local recurrence-free survival favoring IOBT over IOERT for patients with locally advanced or recurrent rectal cancer and microscopically irradical resections. Although several factors may have contributed to this result, an important difference between the two techniques was the higher surface dose delivered by IOBT. This article described an adaptation of IOERT technique to achieve a comparable surface dose as dose delivered by IOBT.Material and methods: Two steps were taken to increase the surface dose for IOERT: 1. Introducing a bolus to achieve a maximum dose on the surface, and 2. Re-normalizing to allow for the same prescribed dose at reference depth.Conclusions: We describe and propose an adaptation of IOERT technique to increase surface dose, decreasing the differences between these two techniques, with the aim of further improving local control. In addition, an alternative method of dose prescription is suggested, to consider improved comparison with other techniques in the future.

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“…Large animal experimental studies have analysed the pathologic response of the pancreas and duodenum [51]. Clinical and experimental data of upper abdominal tissues and organs support good tolerance to a 10-Gy to 20-Gy IOERT boost plus 50-Gy external beam RT (conventional fractionation), including post-resection vascular anastomosis [52,53].…”

Section: Adverse Effectsmentioning

confidence: 99%

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer

Asencio

Roeder

Krempien

et al. 2020

Clinical and Translational Radiation Oncology

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Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer.

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Normal-Tissue Tolerance to IOERT, EBRT, or Both: Animal and Clinical Studies

Cited by 4 publications

References 42 publications

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

The radiation dose-regulated AND gate genetic circuit, a novel targeted and real-time monitoring strategy for cancer gene therapy

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer

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