The synergistic effect of SBRT and immunotherapy
Radiation therapy has a vital place in the field of Oncology.
Stereotactic radiation has the ability to precisely deliver the radiation dose to tumors with minimal damage to the surrounding normal tissues. Because of the high intensity doses, treatment duration is also short and is usually completed in 1-5 “fractionated’ sessions.
Stereotactic radiosurgery was introduced as a non-invasive method that involved using multiple beams of radiation incident on a single point to ablate tissue in the brain. This was considered a pioneering approach when compared to the potential complications associated with traditional brain surgery.
The introduction and revisions to the “Gamma knife” used for stereotactic radiosurgery remains limited to intracranial lesions. In contrast, the “Cyber-knife” delivers stereotactic radiation to any part of the body and this type of delivery is known as stereotactic body radiation therapy (SBRT). SBRT has been successfully used in numerous cancers such as those of the lung, pancreas, liver, kidney, vertebral column,spinal cord and central nervous system among.
Recent evidence points that radiation can regulate inflammatory cytokines and chemokines, including IL-1, IL-2, IL-6, TNF-alpha, TGF-beta, CXCL-16, and Type I and Type II Interferons. Because of this, radiotherapy can unmask the cancer and expose it to body’s innate immune function. As a result of this effect, researchers have combined various immunotherapies with radiation to observe whether beneficial clinical responses would be observed to patients receiving high-dose SBRT.
Known as checkpoint blockade immunotherapy (CBI), success was observed especially in controlling metastatic disease in patients who have been previously treated and this led to USFDA approvals. The newer molecules that have been approved include Sipuleucel-T vaccine for minimally-symptomatic metastatic castrate resistant prostate cancer; Ipilimumab and Pembrolizumab for unresectable or metastatic melanoma; Nivolumab for progressive unresectable or metastatic melanoma and metastatic squamous non-small cell lung cancer patients already receiving platinum-based chemotherapy.
In lung cancer, SBRT is the preferred treatment option for medically inoperable patients and early stage operable patients , but with combined immunotherapy, there is a synergistic effect translating to better clinical outcomes than SBRT alone. Essentially, CBI, inhibits negative regulators of immune responses, and enhances the immune system, especially with SBRT. This finding has formed a strong rationale for the ongoing further clinical trials in metastatic cancers.
In conclusion, there appears to be a two-way synergistic benefit in patients with metastatic disease. On the one hand, a high dose radiation via SBRT enhances local tumor cell death and produces a systemic anti-tumor immune response, on the other hand, a synergism is done by combining SBRT with immunotherapy. Further research may direct oncologists to the optimal total dose, fraction size, field size, and scheduling for induction of immune responses. Future trials that are meticulously designed can further expand the understanding of the effects of radiation combined with immunotherapy on local tumor control by SBRT and on systemic metastatic disease by the synergistic response observed with immunotherapy.