Abscopal effect has been mentioned for a long time, but only recently a deeper knowledge about underlying mechanisms supporting the interaction between immune system and radiation therapy became available. Furthermore, the introduction of immune-checkpoint inhibitors makes appealing the idea of combining them with radiotherapy (RT) to elicit abscopal effect and ideally revert an intrinsic or acquired resistance. Herein, we present the case of a non-small-cell lung cancer patient undergoing, during second line nivolumab, palliative RT on thoracic wall lesion, achieving a complete response in the metastatic adrenal site. This case report suggests that the abscopal effect exists in clinical practice of lung cancer care likely due to a synergism between immune-checkpoint and RT, even when administered with a palliative intent.

Lay abstract

Our case report highlights the possible value of adding palliative radiotherapy (RT) to immunotherapy treatment in clinical practice. This combination, which has extensively proved to be well tolerated, could guarantee patients with advanced lung cancer to obtain responses on metastatic lesions not directly treated with RT, based on the activation of the immune system induced by RT/immunotherapy. This finding could allow to improve the immunotherapy-derived benefit, while maintaining a good quality of life.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Mole RH. Whole body irradiation; radiobiology or medicine? Br. J. Radiol. 26(305), 234–241 (1953).
Medline CASGoogle Scholar
2. Abuodeh Y, Venkat P, Kim S. Systematic review of case reports on the abscopal effect. Curr. Probl. Cancer 40(1), 25–37 (2016).
MedlineGoogle Scholar
3. Slone HB, Peters LJ, Milas L. Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J. Natl Cancer Inst. 63(5), 1229–1235 (1979).
MedlineGoogle Scholar
4. Koukourakis MI, Giatromanolaki A. Tumor microenvironment, immune response and post-radiotherapy tumor clearance. Clin. Transl. Oncol. 22(12), 2196–2205 (2020).
Medline CASGoogle Scholar
5. Zhuzhu W, Shuai M, Rui S, Zengqiang L, Yingliang W, Daiying Z. Recent advances and challenges of immune checkpoint inhibitors in immunotherapy of non-small -cell lung cancer. Int. Immunopharmacol. 85, 106613–106613 (2020).
MedlineGoogle Scholar
6. Demaria S, Ng B, Devitt ML et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int. J. Radiat. Oncol. Biol. Phys. 58(3), 862–870 (2004). •• The abscopal effect has been demonstrated to be triggered by a radiation-induced antitumor T-cell response.
MedlineGoogle Scholar
7. Apetoh L, Ghiringhelli F, Tesniere A et al. Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13(9), 1050–1059 (2007).
Medline CASGoogle Scholar
8. Dovedi SJ, Adlard AL, Lipowska-Bhalla G et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 74(19), 5458–5468 (2014).
Medline CASGoogle Scholar
9. Xu J, Escamilla J, Mok S et al. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res. 73, 2782–2794 (2013).
Medline CASGoogle Scholar
10. Guipaud O, Jaillet C, Clément-Colmou K, François A, Supiot S, Milliat F. The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy. Br. J. Radiol. 91(1089), doi:10.1259/bjr.?20170762 (2018) (Epub ahead of print).
MedlineGoogle Scholar
11. Popp I, Grosu AL, Niedermann G, Duda DG. Immune modulation by hypofractionated stereotactic radiation therapy: therapeutic implications. Radiother. Oncol. 120, 185–194 (2016).
Medline CASGoogle Scholar
12. Sharabi AB, Nirschl CJ, Kochel CM et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated anti-tumor immune responses via cross-presentation of tumor antigen. Cancer Immunol. Res. 3(4), 345–355 (2015). • Demonstrates the ability of stereotactic radiotherapy to prime an endogenous antigen-specific immune response.
Medline CASGoogle Scholar
13. Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br. J. Cancer 118(1), 9–16 (2018).
Medline CASGoogle Scholar
14. Fiorica F, Belluomini L, Stefanelli A et al. Immune checkpoint inhibitor nivolumab and radiotherapy in pretreated lung cancer patients: efficacy and safety of combination. Am. J. Clin. Oncol. 41(11), 1101–1105 (2018).
Medline CASGoogle Scholar
15. Antonia SJ, Villegas A, Daniel D et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N. Engl. J. Med. 379(24), 2342–2350 (2018). • The PACIFIC trial shows progression-free survival and overall survival improvement for unresectable stage IIIA-B non-small-cell lung cancer (NSCLC) with the addition of consolidation durvalumab to standard concurrent chemoradiation, a landmark result for locally advanced NSCLC.
Medline CASGoogle Scholar
16. Britschgi C, Riesterer O, Burger IA, Guckenberger M, Curioni-Fontecedro A. Report of an abscopal effect induced by stereotactic body radiotherapy and nivolumab in a patient with metastatic non-small-cell lung cancer. Radiat. Oncol. 13(1), 102 (2018).
MedlineGoogle Scholar
17. Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small-cell lung cancer. Cancer Immunol. Res. 1(6), 365–372 (2013).
MedlineGoogle Scholar
18. Theelen WSME, Chen D, Verma V et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir. Med. 9(5), 467–475 (2021). •• A pooled analysis of PEMBRO-RT and MDACC randomized trials shows that adding radiotherapy to pembrolizumab immunotherapy significantly increases responses in unirradiated lesions and outcomes in patients with metastatic NSCLC.
Medline CASGoogle Scholar
19. OncologyPRO. LBA58 - ORR in patients receiving nivolumab plus radiotherapy in advanced non-small cell lung cancer: first results from the FORCE trial (2020). https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/orr-in-patients-receiving-nivolumab-plus-radiotherapy-in-advanced-non-small-cell-lung-cancer-first-results-from-the-force-trial
Google Scholar

Vol. 13, No. 12

Metrics

Downloaded 145 times

History

Received 16 February 2021

Accepted 11 June 2021

Published online 28 June 2021

Published in print August 2021

Information

Keywords

Financial & competing interests disclosure

M Milella reports personal fees from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. S Pilotto reports honoraria or speakers’ fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Informed consent disclosure

The study was conducted according to the Declaration of Helsinki, the Good Clinical Practice and was reported following case report (CARE) guidelines. The authors obtained the patient’s consent for publication of clinical data, anonymizing her details. The authors state that they have obtained verbal and written informed consent from the patient/patients for the inclusion of their medical and treatment history within this case report

PDF download