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The effect of radiotherapy on anti-tumor immunity is bidirectional, immunotherapy, especially the combination of immune checkpoint inhibitors (ICIs) and radiotherapy, can produce synergistic effects on anti-tumor immunity. Compared with conventional radiotherapy, stereotactic ablative body radiotherapy (SABR) can achieve high-precision and high-dose irradiation on target lesions, and has stronger anti-tumor immune activation effect. At the same time, due to the steep dose gradient, SABR can better protect the surrounding normal tissues, which is an effective means for the rapid control of local lesions in advanced non-small cell lung cancer (NSCLC). ICIs are an important component of standard treatment for advanced NSCLC. There is growing evidence that SABR in combination with ICIs can benefit patients with advanced NSCLC. This article reviews the biological basis and clinical research progress on the combination of these two therapies, aiming to provide reference for the domestic counterparts to better use this new treatment model.
ABSTRACT
Radiotherapy is a pivotal method in cancer treatment harbouring immunomodulatory effects. Radiotherapy combined with immunotherapy has been proven to yield promising preliminary results in certain types of tumors. Most studies have concentrated on the dose fractionation of radiotherapy and timing of radiotherapy and immunotherapy. With the development of related studies, attention has been gradually paid to the influence of target volume upon circulating lymphocytes and tumor microenvironment. The interaction between target volume and immunotherapy has been valued. For tumors not suitable for hypofractionated radiotherapy, such as advanced esophageal cancer, conventional fractionated radiotherapy has been adopted. The volume and planning of target volume play a pivotal role in radiotherapy combined with immunotherapy. This article illustrates the feasibility of radiotherapy combined with immunotherapy, theory and conception of optimizing target volume.
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Pancreatic cancer is technically divided into surgically resectable, borderline resectable or unresectable disease according to the relationship between tumor mass and adjacent blood vessels. Upon diagnosis, most of the lesions have been locally advanced or had distant metastases, and only 20% of the patients have the opportunity for tumor resection. Radiotherapy and chemotherapy are essential for pancreatic cancer. In this article, the literatures published in recent years were reviewed to focus on the research progress on the clinical trials of neoadjuvant radiochemotherapy, stereotactic body radiation therapy (SBRT), radiochemotherapy combined with immunotherapy for localized pancreatic cancer.
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Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.
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Radiotherapy (RT) is one of the three prevailing therapeutics for tumors. With rapid development of immunotherapy (IM), the combination of IM and RT has gainned increasingly widespread attention. Cytotoxic T lymphocyte associated protein-4(CTLA-4) inhibitor is an important checkpoint target in immune activation and regulation, which exerts significant anti-tumor effects in melanoma and non-small cell lung cancer, etc. Accordingly, the combination of RT and anti-CTLA-4 antibody has become a hot spot. This article reviews research progress on pre-clinical and clinical evidences of RT combined with anti-CTLA-4 antibody, which provides evidence for further exploration in this field.
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In recent years, heavy ion beams have received great attention in the field of malignant tumor radiotherapy due to their radiation physics and biological characteristics. The high rate of local tumor control is one of its advantages, but the control rate of metastatic lesions is still crucial in the treatment of most malignant tumors. Clinical studies on the combined conventional radiotherapy and immunotherapy suggest that the combination of the two can not only control the primary lesions, but may also reduce or completely eliminate distant metastatic lesions. High linear energy transfer radiation, especially heavy ion beams, may have stronger potential in combined immunotherapy. Therefore, this article focuses on the basic research progress of heavy ion beams regulating anti-tumor immune effects and their combined application with immunotherapy.
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In recent years, increasing evidence has shown that hyperthermia is safe, effective and causes low toxicity. Hyperthermia can exert synergistic effect with other treatments, such as radiotherapy and chemotherapy. It has become an important adjuvant anti-tumor treatment secondary to surgery, chemotherapy, radiotherapy and biological treatment. Hyperthermia can improve the efficacy of radiotherapy and chemotherapy by directly inhibiting tumor cells and heat-induced radiosensitizing effect. Hence, hyperthermia is gradually applied in the multimodality treatment of tumors. In this article, we intend to review the research progress on the application of tumor hyperthermia in conventional radiotherapy, chemotherapy, immunotherapy and new biomaterials.
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Objective@#To preliminarily compare the efficacy and safety of Pembrolizumab and Nivolumab in the treatment of advanced malignant tumors.@*Methods@#Clinical data of 50 patients diagnosed with advanced malignant tumors treated with Pembrolizumab and Nivolumab from January 2017 to August 2018 in our hospital were retrospectively analyzed. All patients were divided into the Pembrolizumab (n=26) and Nivolumab groups (n=24). The incidence of adverse reactions was statistically compared between two groups by using χ2 test. The survival analysis was performed by using Kaplan-Meier method.@*Results@#The median progression-free survival in the Pembrolizumab group was 213 d, and 146 d in the Nivolumab group (P>0.05). The incidence of aminotransferase elevation and hypothyroidism in the Nivolumab group was significantly higher than that in the Pembrolizumab group (63% vs. 23%, 12% vs. 0%, both P<0.05), whereas the incidence of oral mucositis in the Nivolumab group was 0%, significantly lower than 15% in the Pembrolizumab group (P<0.05). The median overall survival time in the Pembrolizumab group was 579 d, and 238 d in the Nivolumab group (P>0.05).@*Conclusion@#Clinical efficacy does not significantly differ, whereas the incidence of adverse reactions slightly differs between the Pembrolizumab and Nivolumab groups.
ABSTRACT
Objective To preliminarily compare the efficacy and safety of Pembrolizumab and Nivolumab in the treatment of advanced malignant tumors.Methods Clinical data of 50 patients diagnosed with advanced malignant tumors treated with Pembrolizumab and Nivolumab from January 2017 to August 2018 in our hospital were retrospectively analyzed.All patients were divided into the Pembrolizumab (n =26) and Nivolumab groups (n =24).The incidence of adverse reactions was statistically compared between two groups by using x2 test.The survival analysis was performed by using Kaplan-Meier method.Results The median progression-free survival in the Pembrolizumab group was 213 d,and 146 d in the Nivolumab group (P＞0.05).The incidence of aminotransferase elevation and hypothyroidism in the Nivolumab group was significantly higher than that in the Pembrolizumab group (63％ vs.23％,12％ vs.0％,both P＜0.05),whereas the incidence of oral mucositis in the Nivolumab group was 0％,significantly lower than 15％ in the Pembrolizumab group (P＜0.05).The median overall survival time in the Pembrolizumab group was 579 d,and 238 d in the Nivolumab group (P＞0.05).Conclusion Clinical efficacy does not significantly differ,whereas the incidence of adverse reactions slightly differs between the Pembrolizumab and Nivolumab groups.
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@#Objective To investigate the antitumor immunity induced by tumor derived mixed heat shock protein/peptide(mHSPs),interleukin-12(IL-12)and Cyclophosphamide(Cy).MethodsPurified mixed HSP was prepared from tumor by S180 protein extraction and purification,SDS-PAGE,Western blot and animal experiment were applied for mixed HSPs analysis.ResultsThe proliferation of cytotoxic T lymphocyte(CTL)cocultured in the mHSPs+Cy+IL-12 group was significantly remarkable and the content of CD8+ CTLs was significantly more in comparison with the other groups(P<0.01).To the tumor bearing mice,mHSPs+Cy+IL-12 group showed partial therapeutic efficacy,the averaged survival period was over 60 d,and 90% of the mice in this group got long period tumor free survival(>90d),obvious difference(P<0.05)from the other groups.ConclusionTumor derived mixed HSPs can induce powerful antitumor immune efficacy and show favorable therapeutic efficacy.