Radiotherapy And the Immune Response

//Radiotherapy And the Immune Response

Radiotherapy And the Immune Response

Selective immunotherapy with checkpoint inhibitors has been showing significant improvement in cancer treatment and the quality of life of patients.

According to the latest study findings, radiation therapy further increases the effect of checkpoint inhibitors. “This new data confirms the enormous added value of Radiotherapy in cancer treatment. Radiotherapy can improve the effectiveness of modern medicines – a potential that is in the interest of the patients and must by no means go unused,” emphasises Prof. Dr. med. Jürgen Dunst,

President of the DEGRO Annual Conference 2017

Recently, in the renowned journal “Lancet Oncology” an analysis of the “KEYNOTE-001-study”[1], which describes the importance of radiotherapy for the effectiveness of the checkpoint inhibition with pembrolizumab. Forty two patients in this study (43%) had received radiation therapy prior to pembrolizumab therapy, Thirty eight of these were patients undergoing radiation therapy outside the brain (mainly in the chest). Results showed a significant advantage in progression-free survival (duration of the progression of the tumour disease) and in overall survival in patients who had previously undergone radiation therapy. In the analysis, a previous Radiotherapy is an even more important predictive factor for survival! The underlying hypothesis is that radiation therapy spontaneously suppresses the immune response. Thus immunological therapies can be supported. Such synergistic effects have already been discussed and described for several years [2].

A significant increase in the immune response after radiotherapy was observed for the first time laboratory chemical five years ago in a case report on melanoma-Patients[3].

According to the experts from the German Society at their annual meeting, which took place in Berlin thiese findings expand the field of application of radiation therapy. Because it will not only be successful in destroying tumour cells, but also to reduce the effects of the immunotherapy. “The data now available underscores the high level of the importance of radiotherapy in cancer therapy.

However, radiotherapy serves as more than simply a “catalyst” and “booster” for immunotherapy. Various targeted drugs can also be used that increase the efficiency of radiotherapy. As a working group from Dresden showed, the localised tumour control after a combined treatment of radiotherapy with the simultaneous administration of the antibody cetuximabof showed better results than with radiotherapy alone. Two years ago, the working group, together with colleagues from Hamburg, were able to show an increased radiosensitivity of tumour cells by EGFR inhibition in patients with non-small cell lung cancer.

Lung cancer in a p53-dependent tumour was arrested the cell cycle in the G1- Phase [5].

Parameters have also been identified which determine the effect of the therapy in experiments which can now be further clinically tested. As Professor Mechthild Krause, head of the study, explains, the future of cancer therapy lies in the exploitation of such synergistic treatments. “The tumour cells are altering their genetic signature.”

Monotherapy can only be effective for a certain period of time. To ensure the survival of the patients, we must focus on new combination therapies for efficiency and safety.

Referenzen

[1] Shaverdian N, Lisberg AE, Bornazyan K et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 2017 May 24.. [Epub ahead of print][2] Sharabi AB, Lim M, DeWeese TL et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015 Oct; 16(13): e498-509

[3] Postow MA, Callahan MK, Barker CA et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012; 366(10): 925-31

[4] Koi L, Löck S, Linge A et al. EGFR-amplification and gene expression as potential biomarkers for a combined EGFR-directed radiotherapy in HNSCC-tumour-xenografts. (in press/unpubliziert)

[5] Kriegs M, Gurtner K, Can Y et al. Radiosensitization of NSCLC cells by EGFR inhibition is the result of an enhanced p53-dependent G1 arrest. Radiother Oncol 2015; 115(1): 120-

2018-08-16T12:34:13+00:00 June 7th, 2017|