Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects

Herskind, Carsten; Ma, Lin; Liu, Qi; Zhang, Bo; Schneider, Frank; Veldwijk, Marlon R.; Wenz, Frederik

doi:10.1186/s13014-016-0750-3

Cited by 43 publications

(38 citation statements)

References 148 publications

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“…However, IORT differs from conventional adjuvant RT in several aspects that may potentially influence the biological effect [reviewed in Ref. (20, 21)].…”

Section: Biological Effects Of Iortmentioning

confidence: 99%

Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases—Implications for Intraoperative Radiotherapy after Resection

2017

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Brain metastases (BM) affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS) while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT) to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions. Furthermore, immune checkpoint blockade (ICB) has proven effective in treating antigenic BM and, thus, combining IORT with ICB might be a promising approach. However, it is not known if a low number of residual tumor cells in the tumor bed after resection is sufficient to act as an immunizing event opening the gate for ICB therapies in the brain. Because immunological data on tumor bed irradiation after resection are lacking, a rationale for combining IORT with ICB must be based on mechanistic insight from experimental models and clinical studies on unresected tumors. The purpose of the present review is to examine the mechanisms by which large radiation doses as applied in SRS and IORT enhance antitumor immune activity. Clinical studies on IORT for brain tumors, and on combined treatment of SRS and ICB for unresected BM, are used to assess the safety, efficacy, and immunogenicity of IORT plus ICB and to suggest an optimal treatment sequence.

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“…However, IORT differs from conventional adjuvant RT in several aspects that may potentially influence the biological effect [reviewed in Ref. (20, 21)].…”

Section: Biological Effects Of Iortmentioning

confidence: 99%

Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases—Implications for Intraoperative Radiotherapy after Resection

2017

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“…These forms of IORT may be delivered using radiation at different energies (37). At the present time, external beam IORT is administered by a dedicated linear accelerator with parallel electron beams of 3–12 MeV kinetic energy or isotropic photon fields with energies between contact and superficial therapy of 50 kV X-rays (38).…”

Section: Modalities For Iortmentioning

confidence: 99%

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer

et al. 2017

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Every year, almost 62,000 are diagnosed with a head and neck cancer (HNC) and 13,000 will succumb to their disease. In the primary setting, intraoperative radiation therapy (IORT) can be used as a boost in select patients in order to optimize local control. Addition of external beam radiation to limited volumes results in improved disease control over surgery and IORT alone. In the recurrent setting, IORT can improve outcomes from salvage surgery especially in patients previously treated with external beam radiation. The use of IORT remains limited to select institutions with various modalities being currently employed including orthovoltage, electrons, and high-dose rate brachytherapy. Practically, execution of IORT requires a coordinated effort and careful planning by a multidisciplinary team involving the head and neck surgeon, radiation oncologist, and physicist. The current review summarizes common uses, outcomes, toxicities, and technical aspects of IORT in HNC patients.

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“…Finally, a good oxygenation status of the tumor bed during surgery could also be a factor for enhanced biological effectiveness, which has not yet been investigated [15]. All these cellular and transcellular reactions of irradiated tissues and their particular impact on clonogenic cell inactivation are the subject of ongoing research [16]. …”

Section: Rationale For a Boost And Biology Of High Single Dosesmentioning

confidence: 99%

Intraoperative Electron Radiotherapy (IOERT) in the Treatment of Primary Breast Cancer

et al. 2018

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IOERT (intraoperative electron radiotherapy) in breast cancer is used either as a boost (10-12 Gy) followed by whole breast irradiation (WBI) or as full-dose partial breast irradiation (PBI, 20-24 Gy) during breast-conserving surgery. IOERT has the longest evidence of all IORT techniques. When administered as a boost, excellent low local recurrence rates were observed in long-term follow-up >5 years. Even in high-risk groups like triple-negative or locally advanced breast cancers, IOERT contributes to long-term local control rates of more than 90%. For selected low-risk groups, IOERT as PBI with 21 Gy seems to be a viable treatment alternative to standard WBI. IOERT has been shown to be advantageous for several reasons: Geographic misses are avoided due to direct visualization of the tumor bed; thus, a high single dose is delivered with utmost precision to small volumes, completely sparing the skin and ensuring good long-term cosmetic outcome. Furthermore, high single doses seem to induce biological mechanisms with verifiable antitumor capability in in-vitro cell-line studies. In addition, IOERT markedly shortens the overall treatment time both in combination with (now mostly hypofractionated) WBI or as a PBI in selected low-risk constellations.

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Biology of high single doses of IORT: RBE, 5 R’s, and other biological aspects

Cited by 43 publications

References 148 publications

Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases—Implications for Intraoperative Radiotherapy after Resection

Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases—Implications for Intraoperative Radiotherapy after Resection

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer

Intraoperative Electron Radiotherapy (IOERT) in the Treatment of Primary Breast Cancer

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