Spatially fractionated radiation therapy: History, present and the future

Yan, Weisi; Khan, Mohammad K.; Wu, Xiaodong; Simone, Charles B.; Fan, J; Gressen, Eric; Zhang, Xin; Limoli, Charles L.; Bahig, Houda; Tubin, S.; Mourad, W.F.

doi:10.1016/j.ctro.2019.10.004

Cited by 86 publications

(91 citation statements)

References 57 publications

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“…First experimental evidence on BEs appeared in 1990s [ 20 ]. Since then, exclusively unconventional, “spatially-fractionated” approaches like SBRT-based PArtial Tumor irradiation targeting HYpoxic tumor segment (SBRT-PATHY), GRID or LATTICE brought BEs to the clinic [ 21 , 22 , 23 , 24 ]. Particularly, these techniques expose only some parts of the tumor (and not total tumor) to the high-ablative radiation dose sparing the peritumoral tissue which is compatible with triggering the mechanisms responsible for BE-induction.…”

Section: Introductionmentioning

confidence: 99%

Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY)

Tubin

Gupta

Grusch

et al. 2020

Cancers

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Radiation-induced immune-mediated abscopal effects (AE) of conventional radiotherapy are very rare. Whole-tumor irradiation leads to lymphopenia due to killing of immune cells in the tumor microenvironment, resulting in immunosuppression and weak abscopal potential. This limitation may be overcome by partial tumor irradiation sparing the peritumoral immune-environment, and consequent shifting of immune-suppressive to immune-stimulatory effect. This would improve the radiation-directed tumor cell killing, adding to it a component of immune-mediated killing. Our preclinical findings showed that the high-single-dose irradiation of hypoxic tumor cells generates a stronger bystander effect (BE) and AE than the normoxic cells, suggesting their higher “immunogenic potential”. This led to the development of a novel Stereotactic Body RadioTherapy (SBRT)-based PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) for induction of the immune-mediated BE and AE. Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopal-tumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects. This review discusses the current evidence on the safety and efficacy of SBRT-PATHY in the treatment of unresectable hypoxic bulky tumors and its bystander and abscopal immunomodulatory potential.

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Section: Introductionmentioning

confidence: 99%

Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY)

Tubin

Gupta

Grusch

et al. 2020

Cancers

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“…Hence, it will be important to be aware of the absolute positioning of the minibeams within these organs at risk. In contrary to organs at risk, the positioning of minibeams can also be used to efficiently target aggressive cancer cells within high-risk tumor subregions 60 .…”

Section: Discussionmentioning

confidence: 99%

Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival

Sammer

Girst

Dollinger

2021

Sci Rep

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Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directions are calculated to minimize side effects. In particular, heterogeneous dose distributions applied to the tumor are investigated to evaluate optimized sparing capabilities of normal tissues at the close tumor surrounding. A 5 cm thick tumor is considered at 10 cm depth within a 25 cm thick water phantom. Pencil and planar minibeams are interlaced from two (opposing) directions as well as planar beams from four directions. An initial beam size of σ0 = 0.2 mm (standard deviation) is assumed in all cases. Tissue sparing potential is evaluated by calculating mean clonogenic cell survival using a linear-quadratic model on the calculated dose distributions. Interlacing proton minibeams for homogeneous irradiation of the tumor has only minor benefits for the mean clonogenic cell survival compared to unidirectional minibeam irradiation modes. Enhanced mean cell survival, however, is obtained when a heterogeneous dose distribution within the tumor is permitted. The benefits hold true even for an elevated mean tumor dose, which is necessary to avoid cold spots within the tumor in concerns of a prescribed dose. The heterogeneous irradiation of the tumor allows for larger ctc distances. Thus, a high mean cell survival of up to 47% is maintained even close to the tumor edges for single fraction doses in the tumor of at least 10 Gy. Similar benefits would result for heavy ion minibeams with the advantage of smaller minibeams in deep tissue potentially offering even increased tissue sparing. The enhanced mean clonogenic cell survival through large ctc distances for interlaced pMBRT with heterogeneous tumor dose distribution results in optimum tissue sparing potential. The calculations show the largest enhancement of the mean cell survival in normal tissue for high-dose fractions. Thus, hypo-fractionation or even single dose fractions become possible for tumor irradiation. A widened therapeutic index at big cost reductions is offered by interlaced proton or heavy ion minibeam therapy.

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“…While the optimal spacing for such LRT treatments is unknown, the spacing used in this study provides a reasonable trade-off between the conflicting considerations. 20 All simulations and dose calculations were completed using the Geant4 Gate Monte-Carlo photon and electron transport algorithms. 21 The average energy of Cobalt-60 beams, 1.25 MeV, was used as the initial energy of each photon.…”

Section: Methodsmentioning

confidence: 99%

“…In general, a denser shot spacing will increase the integral dose delivered in each fraction at the cost of a lower peak‐to‐valley dose difference and potentially higher toxicity. While the optimal spacing for such LRT treatments is unknown, the spacing used in this study provides a reasonable trade‐off between the conflicting considerations 20 …”

Section: Methodsmentioning

confidence: 99%

Technical Note: Dosimetric feasibility of lattice radiotherapy for breast cancer using GammaPod

Kopchick

Niu

et al. 2020

Medical Physics

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Purpose: Studies on Lattice radiotherapy (LRT) for breast cancer have been largely lacking. This study investigates the dosimetric feasibility of using Gamma Pod, a stereotactic radiotherapy apparatus originally designed for breast SBRT, to deliver LRT to large, bulky breast tumor as a noninvasive treatment option. Methods: The GammaPod-based LRT was simulated using Geant4 Gate Monte Carlo software. The simulated GammaPod was equipped with 5 mm diameter non-coplanar circular beams that span 28°l atitudinally from 18°to 43°off the horizontal plane. Two degrees longitudinal intervals were used to simulate rotating sources. To simulate the treatments to different breast sizes, three water-equivalent hemisphere volumes with diameters of 10, 15, and 20 cm were analyzed. The lattice was planned by spacing focal points 2 cm apart in the transverse and sagittal planes and 2.5 cm in the coronal plane. This resulted in 22-172 shots for full breast treatment. The maximum dose for each individual shot was 20 Gy. The peak-to-valley dose differences and skin dose were analyzed. To verify the feasibility of delivering LRT, a test plan was created and delivered to a commercial diode array dose verification device using a clinical GammaPod system with 15 mm collimators. Results: The dose profiles showed the average peak-to-valley dose percent differences of 94.10% in the 10 cm hemispherical volume, 88.95% in the 15 cm hemispherical volume, and 83.60% in the 20 cm hemispherical volume. Average skin dose was 1.27, 1.72, and 2.13 Gy for the 10, 15, and 20 cm irradiation volumes, respectively. The LRT plan delivered using a clinical GammaPod system with larger collimators verified the feasibility of LRT plan delivery. Conclusion: GammaPod-based lattice radiotherapy is a viable treatment option and its application can be extended to treating large bulky breast tumors.

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Spatially fractionated radiation therapy: History, present and the future

Cited by 86 publications

References 57 publications

Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY)

Shifting the Immune-Suppressive to Predominant Immune-Stimulatory Radiation Effects by SBRT-PArtial Tumor Irradiation Targeting HYpoxic Segment (SBRT-PATHY)

Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival

Technical Note: Dosimetric feasibility of lattice radiotherapy for breast cancer using GammaPod

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