Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus

Turchan, William Tyler; Pitroda, Sean P.; Weichselbaum, Ralph R.

doi:10.1158/1078-0432.ccr-21-0145

Cited by 12 publications

(8 citation statements)

References 75 publications

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“…Turchan et al suggested that elective nodal irradiation in head and neck cancer may elicit an immunosuppressive effect and thus potentially explain the lack of benefit so far for SITAR in head and neck cancer. 81 Many current clinical SITAR studies are phase 2 studies, having been sequentially developed after the relatively recent phase 3 confirmation of efficacy of immunotherapy in many settings. However, there is a wealth of preclinical work in this area.…”

Section: Combining Cellular Immunotherapies With Radiation Therapymentioning

confidence: 99%

“…The RAPPORT study has been quick to adopt this approach by offering SITAR treatment, either SABR or fractionated radiotherapy to all visible metastases in oligometastatic renal cancer patients, and this study demonstrated a relatively high local control and 2-year survival. 40,56 Turchan et al 81 also promote this approach, suggesting that immunotherapy may be more effectivewhen there is a lower volume of residual tumour burden.…”

Section: Combining Cellular Immunotherapies With Radiation Therapymentioning

confidence: 99%

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Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

et al. 2022

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Previous preclinical and clinical trials have shown promising antitumour activity and toxicity profile when employing the 'Synergy between Immunotherapy and Radiotherapy' (SITAR) strategy. Approximately, one in seven radiation therapy studies currently recruiting is investigating SITAR. This article reviews the range of cancers known to respond to immunotherapy and publications analysing SITAR. It sets the background for work that needs to be done in future clinical trials. It also reviews the potential toxicities of immunotherapy and discusses areas where caution is required when combining treatments.

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Section: Combining Cellular Immunotherapies With Radiation Therapymentioning

confidence: 99%

Section: Combining Cellular Immunotherapies With Radiation Therapymentioning

confidence: 99%

Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

et al. 2022

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“…Many therapeutic approaches have been combined with RT with the hope of increasing abscopal effect to elicit potent systemic antitumor efficacy. [13] Immunosuppressive properties of TMEs prevent effective lymphocyte priming and reduce immune cell infiltration, thus dampening the effects of cancer immunotherapy. [75] For example, hypoxia is frequently associated with increased T cell exhaustion.…”

Section: Remodeling the Tme To Reinforce Radiation-induced Immune Res...mentioning

confidence: 99%

Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy

2023

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or intra-arterial administration of therapeutic radionuclides or by direct implantation of radioisotope-embedded beads into tumors. [3] In external RT, therapeutic doses of ionizing radiation are delivered to tumors using external beams of photo ns, electrons, and protons. [4] Both types of RT can directly induce local apoptosis, autophagy, necrosis, or replicative senescence of cancer cells [5] by producing reactive oxygen species (ROS) [6] to cause DNA damage. [7] Advances in hardware and software technologies have provided conformal radiation techniques, [8] which are aided by advanced imaging systems to deliver a desired dose of radiation to the precise location of a tumor, thus maximizing therapeutic effects while minimizing radiation damage to normal organs. [9] Radiosensitizers can be introduced during RT to enhance the radiotherapeutic effects of ionizing radiation. The radiosensitizers can be classified as: 1) chemotherapies such as cisplatin, 5-fluorouracil, and taxanes; 2) gaseous molecules such as O 2 , NO, and H 2 S; and 3) high-Z elements such as Au, Ba, Bi, Pt, Hf, and W. Chemotherapies presumably enhance RT by arresting cancer cells in the most radiation-sensitive phases of the cell cycle and eliminating radioresistant cells in late S phase but often cause debilitating side effects to cancer patients. Gaseous radiosensitizers enhance RT by increasing ROS production and/or reducing the expression of hypoxia-inducible factor-1α (HIF-1α). It is, however, challenging to ensure therapeutic efficacy due to the difficulty in controlling their concentrations, diffusion rates, and tumor retention. High-Z elements enhance RT by increasing biological reactions and depositing more radiation energy in tumors, via their stronger interactions with secondary photons and electrons, than in normal tissues. [10] In addition to increasing local antitumor effects of RT, the holy grail of radiosensitizer design is to improve the killing of tumor cells outside of the irradiated fields (abscopal effect). An ideal radiosensitizer would enhance RT to produce systemic antitumor effects by inducing immunogenic cell death (ICD), enhancing the presentation of tumor-associated antigens (TAAs), and activating cytotoxic T cells to mount host immune responses.Although RT is widely used to treat many different types of tumors, it has several limitations. First, radio-resistance is a key impediment to both curative and palliative RT. Previous research on enhancing the effectiveness of RT has mainly focused on cancer cells while neglecting the complicated Radiotherapy (RT) uses ionizing radiation to eradicate localized tumors and, in rare cases, control tumors outside of the irradiated fields via stimulating an antitumor immune response (abscopal effect). However, the therapeutic effect of RT is often limited by inherent physiological barriers of the tumor microenvironment (TME), such as hypoxia, abnormal vasculature, dense extracellular matrix (ECM), and an immunosuppressive TME. Thus, it is critical to develop new RT strategies tha...

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“…As previously reviewed, currently reported trials of radio-immunotherapy in the treatment of patients with metastatic disease vary in a number of important ways, which along with the potentially immunosuppressive effects of radiotherapy may contribute to the negative results of the majority of these studies [ 30 , 31 ]. However, given that the aforementioned prospective studies include patients with extensive metastatic burden with at least one metastasis not treated with local therapy, it is likely that, as is the case when radiotherapy and immunotherapy are used as monotherapies, combined radio-immunotherapy is most effective as a treatment for metastatic cancer in patients with low-volume disease, thus explaining the negative results of currently reported studies.…”

Section: Immunotherapy May Increase the Therapeutic Ratio Of Radiothe...mentioning

confidence: 99%

“…Further investigations are also needed to identify novel means of maximizing the efficacy of radio-immunotherapy in patients with oligometastatic disease. Currently, a number of factors including the ideal radiotherapy dose, immunotherapy agents, and sequencing of radiotherapy and immunotherapy in patients with metastatic disease remain poorly defined [30] . Additionally, a number of ongoing studies are investigating immunomodulatory agents capable of overcoming ICB resistance; given that the majority of currently utilized immunotherapies are forms of ICB, these agents may help maximize the therapeutic ratio of radio-immunotherapy in patients with oligometastatic cancer [47] .…”

Section: Radio-immunotherapy In the Treatment Of Cancer: Future Direc...mentioning

confidence: 99%

Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy

2022

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Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus

Cited by 12 publications

References 75 publications

Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy

Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy

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