Combining Heavy-Ion Therapy with Immunotherapy: An Update on Recent Developments

Helm, Alexander; Ebner, Daniel K.; Tinganelli, Walter; Simoniello, Palma; Bisio, Alessandra; Marchesano, Valentina; Durante, Marco; Yamada, Shigeru; Shimokawa, Tetsuya

doi:10.14338/ijpt-18-00024.1

Cited by 23 publications

(16 citation statements)

References 87 publications

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“…Another potential benefit of CIRT may be in combination with immunotherapy. High LET radiation has been shown to have an increased immunogenicity of radiation-induced cell death compared to photon radiation through a variety of mechanisms, thus leading to a hypothesized advantage in the setting of combined immunotherapy (110). High LET radiation, such as CIRT, has been shown to induce immune cell death at lower doses compared to photon irradiation (111).…”

Section: Discussionmentioning

confidence: 99%

“…High LET radiation, such as CIRT, has been shown to induce immune cell death at lower doses compared to photon irradiation (111). In addition, higher doses per fraction have been shown to increase the immune response following radiation, and most patients treated with CIRT are treated with a hypofractionated regimen (110,112). The reader is referred to the review articles by Helm et al and Durante et al for a more detailed discussion of the exact mechanisms of heavy ion therapy and combination immunotherapy (110,113).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, higher doses per fraction have been shown to increase the immune response following radiation, and most patients treated with CIRT are treated with a hypofractionated regimen (110,112). The reader is referred to the review articles by Helm et al and Durante et al for a more detailed discussion of the exact mechanisms of heavy ion therapy and combination immunotherapy (110,113). Although, there is currently a lack of clinical data regarding CIRT in combination with immunotherapies, this will likely be an important frontier, as more patients are treated with immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Carbon Ion Therapy: A Modern Review of an Emerging Technology

et al. 2020

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Radiation therapy is one of the most widely used therapies for malignancies. The therapeutic use of heavy ions, such as carbon, has gained significant interest due to advantageous physical and radiobiologic properties compared to photon based therapy. By taking advantage of these unique properties, carbon ion radiotherapy may allow dose escalation to tumors while reducing radiation dose to adjacent normal tissues. There are currently 13 centers treating with carbon ion radiotherapy, with many of these centers publishing promising safety and efficacy data from the first cohorts of patients treated. To date, carbon ion radiotherapy has been studied for almost every type of malignancy, including intracranial malignancies, head and neck malignancies, primary and metastatic lung cancers, tumors of the gastrointestinal tract, prostate and genitourinary cancers, sarcomas, cutaneous malignancies, breast cancer, gynecologic malignancies, and pediatric cancers. Additionally, carbon ion radiotherapy has been studied extensively in the setting of recurrent disease. We aim to provide a comprehensive review of the studies of each of these disease sites, with a focus on the current trials using carbon ion radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Carbon Ion Therapy: A Modern Review of an Emerging Technology

et al. 2020

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“…During long-term manned missions, both the magnitude and duration of space radiation exposure will increase, subjecting the flight crew to chronic, low doses and low dose rates of secondary neutrons, for which there is limited biological data pertaining to the immune impact. Recently, there has been a growing interest to study the interaction between high-LET radiation and human immunity, to explore the combined use of particle therapy and immunotherapy in cancer treatments [45,46]. However, the exposure conditions in space and particle therapy are quite different.…”

Section: Introductionmentioning

confidence: 99%

Immunological Changes During Space Travel: A Ground-Based Evaluation of the Impact of Neutron Dose Rate on Plasma Cytokine Levels in Human Whole Blood Cultures

et al. 2020

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A better understanding of the combined impact of different space stressors on human health is urgently warranted, considering the upcoming long-duration missions beyond lower Earth orbit. Therefore, a growing number of particle accelerator facilities implement ground-based set-ups to study the effect of simulated space radiation with simulated psychological or physical stressors. The immune system is highly sensitive to these types of stressors and limited information is currently available on the impact of the complex space radiation environment on the astronauts' immune function. This pilot study presents a first step in the implementation of a ground-based set-up with neutron irradiation, which is considered to be an important secondary component in space radiation fields. The effect of dose rate on immune alterations was studied using the in vitro cytokine release assay. Whole blood samples (n = 8) were exposed to 0.125 or 1 Gy of neutron irradiation (fluence-weighted average energy: 29.8 MeV) at a lower dose rate (LDR) of 0.015 Gy/min and a higher dose rate (HDR) of 0.400 Gy/min. Immediately post-irradiation, blood samples were stimulated with lipopolysaccharide (LPS), heat-killed Listeria monocytogenes (HKLM) or lectin pokeweed mitogen (PWM), and incubated for 24 h. Cell-mediated immunity was examined by analysing interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) plasma levels. Stimulants significantly increased all cytokine levels except IL-2, where only PWM induced a significant increase. In general, no statistically significant changes were observed in IL-2, IFN-γ, and TNF-α concentrations at different neutron doses and dose rates when compared to their stimulated, sham-irradiated controls. After PWM-stimulation, IL-10 levels were significantly increased at 0.125 Gy HDR and 1 Gy LDR. In a pooled analysis, the HDR significantly increased IL-2 titres (under PWM-stimulation) and IFN-γ titres (with all stimulants), but significantly decreased TNF-α secretion in unstimulated cultures. Due to the limited sample number, no strong conclusions could be made in this pilot study on the effect of neutron radiation as a single stressor on cytokine secretion in response to different stimuli. However, some interesting trends and dose rate effects were observed, which pave the way for future investigations on the synergistic effects of multiple space stressors on immune cell function.

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“…These findings may be explained by the highly concentrated dose delivery by brachytherapy, SBRT, and CIRT compared with that of EBRT. Evidence suggests that a high, single-fractionated dose induces antitumor immunity efficiently [ 57 ], partially by promoting DNA damage response signaling [ 58 ]. In addition, the properties of carbon ions as high linear energy transfer radiation to efficiently induce antitumor immunity (e.g., induction of HMGB1 [ 59 ], OX40L, CD40, ICAM-1, and MHC-1, and suppression of PD-L1 [ 60 ]) might contribute to the high bounce rate for CIRT.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of PSA Bounce after Radiotherapy for Prostate Cancer: A Meta-Analysis

Darwis

Oike

Kubo

et al. 2020

Cancers

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The rate and characteristics of prostate-specific antigen (PSA) bounce post-radiotherapy remain unclear. To address this issue, we performed a meta-analysis. Reports of PSA bounce post-radiotherapy with a cutoff of 0.2 ng/mL were searched by using Medline and Web of Science. The primary endpoint was the occurrence rate, and the secondary endpoints were bounce characteristics such as amplitude, time to occurrence, nadir value, and time to nadir. Radiotherapy modality, age, risk classification, androgen deprivation therapy, and the follow-up period were extracted as clinical variables. Meta-analysis and univariate meta-regression were performed with random-effect modeling. Among 290 search-positive studies, 50 reports including 26,258 patients were identified. The rate of bounce was 31%; amplitude was 1.3 ng/mL; time to occurrence was 18 months; nadir value was 0.5 ng/mL; time to nadir was 33 months. Univariate meta-regression analysis showed that radiotherapy modality (29.7%), age (20.2%), and risk classification (12.2%) were the major causes of heterogeneity in the rate of bounce. This is the first meta-analysis of PSA bounce post-radiotherapy. The results are useful for post-radiotherapy surveillance of prostate cancer patients.

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Combining Heavy-Ion Therapy with Immunotherapy: An Update on Recent Developments

Cited by 23 publications

References 87 publications

Carbon Ion Therapy: A Modern Review of an Emerging Technology

Carbon Ion Therapy: A Modern Review of an Emerging Technology

Immunological Changes During Space Travel: A Ground-Based Evaluation of the Impact of Neutron Dose Rate on Plasma Cytokine Levels in Human Whole Blood Cultures

Characteristics of PSA Bounce after Radiotherapy for Prostate Cancer: A Meta-Analysis

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