ABSTRACT
Objetivo: analisar as reações adversas nos pacientes oncológicos em uso de inibidores de checkpoint e sua prevalência. Método: revisão integrativa da literatura, utilizando a combinação de descritores "Imunoterapia" AND "Reação adversa" AND "Neoplasias", no recorte temporal de cinco anos, incluindo as bases CINAHL (Cumulative Index to Nursing and Allied Health Literature), CINAHL (Cumulative Index to Nursing and Allied Health Literature) e Cochrane. Resultados: foram encontrados 17 artigos, sendo 14 da base de dados MEDLINE e três da base de dados CINAHL, todos na língua inglesa. As principais reações adversas identificadas foram diarreia, colite, pneumonite, fadiga, rush, alterações hepáticas e endócrinas. Os artigos revelaram maiores prevalências dessas reações quando o tratamento está associado às medicações Nivolumabe e Ipilimumabe juntas, sendo observadas em cerca de 42% a 57% dos pacientes. Conclusão: com a rápida expansão do uso dos inibidores de checkpoint, uma terapêutica que aumenta a sobrevida desses pacientes, conhecer seus eventos adversos torna-se primordial para um cuidado de qualidade.
Objective: to examine for adverse reactions and determine their prevalence in cancer patients using checkpoint inhibitors. Method: this integrative literature review used a combination of the descriptors: "immunotherapy" AND "adverse reaction" AND "Neoplasms", in a five-year time frame, in the MEDLINE and Cochrane databases. Results: seventeen articles, all in English, were found (14 in MEDLINE and three in CINAHL). The main adverse reactions identified were diarrhea, colitis, pneumonitis, fatigue, rush, hepatic, and endocrine changes. The articles revealed that, when the treatment involved Nivolumab and Ipilimumab together, prevalence of these reactions was higher (from 42% to 57% of patients). Conclusion: with the rapid expansion of the use of checkpoint inhibitors, a therapy that increases survival, knowing their adverse events becomes essential for quality care.
Objetivo: analizar reacciones adversas en pacientes con cáncer, utilizando inhibidores de checkpoint y su prevalencia. Método: revisión integradora de la literatura, utilizando la combinación de descriptores "Inmunoterapia" y 'Reacción adversa" y "Neoplasias", en un recorte temporal de cinco años, incluyendo las bases de datos CINAHL (Cumulative Index to Nursing and Allied Health Literature y Cochrane. Resultados: se encontraron 17 artículos, siendo 14 de la base de datos MEDLINE y 3 de la base de datos CINAHL, todos en inglés. Las principales reacciones adversas identificadas fueron diarrea, colitis, neumonitis, fatiga, erupción cutánea, alteraciones hepáticas y endocrinas. Los artículos revelaron una mayor prevalencia de estas reacciones cuando el tratamiento se asocia con los medicamentos Nivolumab e Ipilimumab juntos, observándose en alrededor del 42% al 57% de los pacientes. Conclusión: con la rápida expansión del uso de inhibidores de checkpoint, una terapia que aumenta la sobrevida de esos pacientes, conocer sus eventos adversos se vuelve fundamental para una atención de calidad.
ABSTRACT
In recent years, immunotherapy has become the hottest topic in the field of oncology. Both the Keynote189 study and the Keynote407 study have confirmed that progression-free survival is significantly prolonged in patients who have been benefited from immune checkpoint blockades in lung cancer. In an article published in The New England Journal of Medicine in 2012, a case report of radiation abscopal effects caused by immunization combined with conventional radiotherapy has attracted great attention in the field of oncology. The Pacific study, published in 2017, expanded the indications for immunotherapy from advanced to locally-advanced non-small cell lung cancer. The second analysis of Keynote001, published in the Lancet Oncology in the same year, suggested that radiation therapy may mediate the immune memory effects, whereas the mechanism and time window are still unclear. With the publication of PEMBRO-RT study and several pieces of work by our team in recent years, various details of radiotherapy combined with immunotherapy (iRT) have become more mature. In clinical practice, iRT is involved in the full treatment of lung cancer. However, iRT is not a hodgepodge or stew that needs further refinement and sorting. In this article, the principles, efficacy in clinical practice, and exploration of the details of iRT were discussed.
ABSTRACT
Surgery,radiotherapy and chemotherapy are three traditional treatments for malignant tumors.With the development of medicine,immunotherapy has been gradually adopted as an emerging therapy of malignancies.Recent clinical studies have demonstrated that the combination of radiotherapy and immunotherapy can induce the abscopal effect and improve the prognosis of patients.Compared with the conventional radiotherapy,stereotactic radiotherapy has a larger single dose and higher accuracy,which is more likely to induce the bystander effect and anti-tumor response.The combination of stereotactic radiotherapy and immunotherapy has been proven to be a more promising therapy in certain clinical trials.However,not all types of tumors can benefit from such combined therapy in clinical practice.The optimal dose,fraction pattern and lesion of radiotherapy,immune enhancement and safety remain to be further clarified.In this article,the research progress,related controversies and future research direction of stereotactic radiotherapy combined with immunotherapy for malignancies were reviewed.
ABSTRACT
Remarkable advances have been made in immunotherapy,especially immune checkpoint inhibitors.However,only less than 30％ patients would respond to single checkpoint inhibitors.Radiotherapy can augment the anti-tumor immune responses elicited by immunotherapy,either by way of synergy or complementation.This article reviews the mechanisms,the advances and challenges in combination therapy.
ABSTRACT
Radiotherapy ( RT) is used as primary treatment for numerous cancers. Although it is usually described as an immunosuppressive modality,there are new preclinical evidences suggesting that RT could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. Some studies established the proof of concept that combining RT with strategies modifying immunology could enhance antitumor effects.
ABSTRACT
The application of precision medicine in cancer treatment is becoming increasingly common as a result of the continuous advancement in basic research and physical techniques.The revolution of radiotherapy techniques, development of multimodal imaging technology, application of biological target dose carving and adaptive radiotherapy, availability of big data-based radiotherapy planning systems, and selection of chemotherapy regimen have all made the treatment of nasopharyngeal carcinoma increasingly precise.The growing interaction between laboratory research and clinical practice not only underscores the importance of translational medicine, but also prompts the development of biological immunotherapy and screening of prognostic factors.As a result, these changes mark the beginning of a new era for the diagnosis and treatment of nasopharyngeal carcinoma.This review provides a summary from 61 articles on the current progress in translational study and clinical application of precision medicine in nasopharyngeal carcinoma.
ABSTRACT
Radiotherapy can not only kill tumor cells directly, but also accelerate tumor regression by mediating systemic and local anti-tumor immune response. Regulatory T cells(Tregs)are known as a subset of T cells which suppress the immune system. Therefore, Tregs become one of the therapeutic targets for cancer. Recently,much attention has been paid to combination therapy with radiotherapy and anti-Tregs therapy. This article reviews the biological characteristics of Tregs and the interaction between Tregs and radiotherapy.
ABSTRACT
In recent years,a large number of pre-clinical and clinical investigations have indicated that stereotactic body radiation therapy(SBRT)can not only kill cancer cells directly,but also induce the immunogenic death of cancer cells through releasing numerous tumor-associated antigens and damage-associated molecular patterns to form in situ tumor vaccine. CD8(+)T cells in lymph nodes are cross-sensitized by activated antigen-presenting cells. SBRT initiates local and systemic anti-tumor immune response. Moreover, SBRT can induce the abscopal effect if combined with immunotherapy. In addition, SBRT improves the microenvironment for tumor immunosuppression and enhances the sensitivity of tumors to immunotherapy. This article reviews the research advances in the synergistic mechanisms for combination therapy with SBRT and immunotherapy.
ABSTRACT
Radiotherapy ( RT) is used as primary treatment for numerous cancers. Although it is usually described as an immunosuppressive modality,there are new preclinical evidences suggesting that RT could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. Some studies established the proof of concept that combining RT with strategies modifying immunology could enhance antitumor effects.
ABSTRACT
Radiotherapy not only acts as an important local treatment of cancer, but also plays a key role in regulation of immune function. Radiotherapy regulates anti?tumor immune responses by promoting the generation of neoantigens, regulating the release of cytokine, and enhancing the sensitivity of tumor to cell?mediated immunity. Recently, several studies and clinical practice reported the abscopal effect in some patients undergoing radiotherapy combined with immunotherapy, which showed partial or complete response of metastases outside the irradiation field, suggesting the combination therapy as a promising strategy. However, further studies are needed for the understanding of the mechanism and influencing factors for immunity such as radiation dose and fractionation scheme. This paper reviews the research advances in the mechanism of radiotherapy?immunotherapy interaction and the combination therapy for cancer.
ABSTRACT
Modern immunology has established that tumor immune escape is associated with hidden or missing tumor-specific antigens and tumor-associated antigens,as well as immune suppressors that are released from tumor cells to inhibit the immune cytotoxicity and antigen-presenting cells (APCs).The changes in tumor microenvironment have an impact on tumor immunity and treatment outcomes.The immune effects finally depend on activation and inhibition of T cell receptors and other co-regulated receptors (CD28,CD80/CD86,and CTLA-4) in spite of the existence of APCs and cytotoxic T lymphocytes in tumor microenvironment.Recent studies have revealed that radiotherapy induced not only DNA damage but also immunogenesis in tumor cells.Both conventionally fractionated radiotherapy and hypofractionated radiotherapy can induce immunogenesis in tumor cells.Immunogenic regulation makes many tumor antigens expressed in cells exposed to irradiation,which induces immune recognition and cytotoxicity;cell content (DNA,HMGB1,etc.) released from dead immunogenic cells can trigger immune effects and in situ tumor vaccination,which further induce an abscopal effect of radiotherapy.A lot of anti-tumor immunotherapy fails to achieve satisfactory treatment outcomes.Therefore,how to combine radiotherapy,especially stereotactic body radiotherapy,with anti-tumor immunotherapy has recently become a new challenge for researchers.
ABSTRACT
Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.