Combining immunotherapy with radiation therapy to induce the abscopal response: What clinical and treatment variables matter?

By Jason Liu, BS; Heath B. Mackley MD, FACRO

SA-CME credits are available for this article here.

Ionizing radiation has been used for over a century to treat cancer. Historically, radiation was only thought to improve the local control of cancer. However, a growing body of evidence shows that radiation may induce a regression of tumor cells outside the field of irradiation, a phenomenon known as the abscopal effect. This phenomenon was first described by R.H. Mole in 1953.1 While the mechanism remains unclear, the systemic effect of radiation therapy is believed to be immune related.2-5 It is believed that the radiation damage induced in the tumor cell causes the release of damage-associated molecular patterns (DAMPs) that serve to immunize the host.6-10 This can result in the widespread activation of immune effector cells, which can then attack tumor cells distant to the irradiated target.11-15

While the number of case reports documenting the abscopal response is growing, the abscopal response remains rare and difficult to reproduce clinically with radiation therapy alone. Combining immunotherapy with radiation therapy, however, seems promising for bringing out this rare clinical event. Immunotherapy bolsters the host’s immune system, examples of which include cytokine therapy, adoptive cell transfer, and the new generation of immune checkpoint inhibitors (ICIs). The two major classes of ICIs include PD-1PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab) and CTLA-4 inhibitors (ipilimumab and tremelimumab).

An exciting area of research in radioimmunotherapy is identifying what demographic, clinical, and treatment variables are associated with the abscopal response. Here, we review the current state of knowledge regarding these variables and identify areas requiring further investigation.

Abscopal Response Defined

In the literature, an abscopal effect is defined as a phenomenon in which localized treatment of a tumor causes shrinking not only of the treated tumor, but also of tumors outside the scope of the localized treatment. An abscopal effect may be either partial or complete. For purposes of our review, we define an abscopal response as a complete response resulting from the abscopal effect.

It is difficult to know whether a complete response after radiation and immunotherapy is due to the abscopal response or due to the activity of immunotherapy alone. However, there is evidence that the complete response rate is higher with radiation and immunotherapy than immunotherapy alone, which suggests that a complete response is due to the abscopal effect in patients treated with both radiation and immunotherapy.16-21 A prospective trial in patients with metastatic melanoma treated with radiation and anti-CTLA-4 found the complete response rate to be 13.6%18 compared to a 1.5% complete response rate for patients with metastatic melanoma treated with anti-CTLA-4 only.22 While a fraction of complete responses in patients treated with radiation and immunotherapy may be attributed to immunotherapy alone, the majority of complete responses appear related to the abscopal effect.

Influence of Tumor Type

Tumors are complex environments that contain cancer cells as well as stromal and immune infiltrates. Tumor-infiltrating cells can demonstrate either tumor-suppressive or tumor-promoting effects depending on cell type. Regulatory T-cells and tumor-associated macrophages have been associated with pro-tumor functions, whereas CD8+ T-cells have been associated with anti- tumor functions.23-27A review of case reports reveals a striking feature of the abscopal response in tumor types infiltrated preferentially by CD8+ T-cells.27A pan-cancer analysis of tumors showed that renal cell carcinoma, lung adenocarcinoma, and melanoma had the highest aggregate T-cell infiltration scores.28 Other cancer types with high aggregate T-cell infiltration scores include head and neck squamous cell carcinoma, cervical and endocervical cancer, colon and rectum adenocarcinoma, and lung squamous cell carcinoma.This suggests that an abscopal response would be more likely in one of these cancer types treated with radioimmunotherapy.

Influence of Patient Immune System

Factors that affect a patient’s ability to have an abscopal response include degree of myelosuppression, neutrophil to lymphocyte ratio, and prior exposure to radiation therapy and chemotherapy.29 The ability to have an abscopal response depends on the patient’s ability to mount an immune response. Therefore, patients with decreased lymphocyte counts due to cytotoxic chemotherapy or bone marrow infiltration by tumor are less likely to have an abscopal response. Similarly, patients receiving prolonged fractionation regimens of 30 to 40 fractions are less likely to have an abscopal response due to the decreased availability of effector and memory cells.30 T-cells are highly sensitive to radiation, with a D90 of 0.5 Gy.31 Even with smaller, more conformal radiation therapy fields, protracted radiation therapy regimens may deliver lymphotoxic doses and exhaust T-cells, hindering their ability to produce an abscopal response.32

Although protracted radiation therapy regimens might reduce the incidence of an abscopal response, this does not preclude immunotherapy from being beneficial after fractionated radiation therapy. In the PACIFIC trial, patients with stage III non-small cell lung cancer who received definitive chemoradiation achieved a further response and survival benefit with durvalumab.33 Whether the benefit of the durvalumab was enhanced by the previous chemoradiation because of an abscopal effect, or in in spite of chemoradiation’s temporarily deleterious immune effects, is unknown, but certainly is an ongoing area of interest to researchers.

Influence of Overall Tumor Burden

Patients with significant tumor burden are less likely to achieve an abscopal response than patients with limited disease burden. For example, Kwon and colleagues found that patients with significant metastatic burden from prostate cancer did not benefit from CTLA-4 blockade and radiation therapy, whereas patients with limited disease burden did.34 Similarly, Hiniker and colleagues found that patients with metastatic melanoma treated with anti-CTLA-4 and radiation therapy were more likely to achieve an abscopal response if they had a smaller volume of disease at baseline.18 The 3 patients in their study with an abscopal response had a baseline unirradiated sum of product diameter (SPD) of 4.3 cm2, 8.0 cm2, and 22.8 cm2 compared with a median value of 15.2 cm2 in patients without an abscopal response. Other useful ways of assessing tumor burden in trials include tumor volume, tumor diameter, and number of metastatic areas.

Influence of Radiation Therapy Parameters

Radiation delivery can be altered by changes in dose, fractionation, and duration. Currently, there is no consensus on optimal radiation therapy parameters to induce an abscopal response, and pre-clinical studies have produced conflicting results. Some data suggest that single-fraction radiation is better than multiple fractions. Shen and colleagues, for instance, found that mice bearing B16 melanoma responded more favorably to 800 cGy once a week compared to 200 cGy 5 times a week.35 However, Schaue and colleagues found that mice bearing B16 melanoma had better tumor control and immunity when treated with 2 radiation doses of 7.5 Gy compared to a single dose of 15 Gy.36 Similarly, Dewan and colleagues found that mouse breast carcinoma cells were more likely to respond to 24 Gy in 3 fractions and 30 Gy in 5 fractions than a single fraction of 20 Gy.37 Some studies also report similar results for both single-fraction and multiple fraction radiation.38-40 The variability of these results may be attributed to other factors, including tumor type and radiation techniques.

Regarding the optimal sequencing of radiation therapy with immunotherapy, it is difficult to generalize. For ipilimumab, it is believed that delivering radiation therapy concurrently with immunotherapy is the best approach. Preclinical studies have shown that administering radiation therapy before immunotherapy results in inferior outcomes, supporting the use of concurrent delivery.37 However, other agents such as durvalumab have been effective if administered after chemoradiation.33 Further study is warranted regarding optimal timing of radiation therapy and immunotherapy for each type of immunotherapy agent and cancer type.

One of the few studies examining the relationship between radiation therapy parameters and the abscopal response was a retrospective review of patients with metastatic melanoma treated with radiation therapy and anti-CTLA-4.41 The total dose, number of fractions, dose per fraction, biological equivalent dose (BED), target location, and timing of radiation therapy in relation to immunotherapy were analyzed to determine if they were associated with an abscopal response. It was found in the bivariate analysis that only a higher BED was significantly associated with an abscopal response. The target location seemed to have some effect, but the sample size for each location was not large enough for results to be significant.This potential relationship between BED and abscopal responses was supported by Marconi and colleagues, who reported in a meta-analysis that the occurrence rate of abscopal responses in pre-clinical models increased with BED.42

Additionally, a smaller treatment field is believed to be associated with an abscopal response. Larger treatment fields expose a larger volume of T-cells to radiation, causing them to be exhausted and unable to mount an immune response. Proposed strategies to lower radiation-therapy-induced lymphopenia include hypofractionation, reduced treatment field size (from the elimination of elective nodal coverage or with highly conformal techniques such as stereotactic body radiation therapy or stereotactic radiosurgery), and shortening beam-on treatment times.43

Effect of Radiation Therapy Parameters on the Abscopal Response: Ongoing Trials

Most trials studying the combination of immunotherapy and radiation therapy are examining safety and efficacy. For the purposes of our review, we are focusing on trials studying the specific radiation therapy parameters associated with an abscopal response. We identified 5 trials examining the role of radiation dose, fractionation, and timing on the abscopal response (Table 1). Four of the trials are studying effects of the dose and fractionation on the abscopal response, and one is studying the effect of timing of radiation therapy in relation to immunotherapy on the abscopal response.

A trial by the MD Anderson Cancer Center (NCT02710253) is examining the response rates of patients with metastatic cancer treated with salvage radiation after progression on systemic immunotherapy. The study is recruiting any patient with at least one site of metastatic disease who has been treated with immunotherapy within the last 6 months. Patients will be treated with standard doses of 50 Gy in 4 fractions with stereotactic radiation or 60 to 70 Gy in 10 fractions, 20 to 30 Gy in 5 fractions, 20 to 30 Gy in 5 fractions, or 30 to 45 Gy in 10 to 15 fractions with conventional external-beam radiation to one or more sites of disease amenable to radiation.

A trial by Radiotherapie (NCT02406183) seeks to examine the response rates and maximum tolerated dose of patients with metastatic melanoma treated with anti-CTLA-4 and stereotactic body radiation. Patients are eligible if more than 28 days have passed since their last treatment with anti-CTLA-4 therapy and they have at least 3 extracranial metastatic lesions. Patients will be treated with doses of 24 Gy in 8 fractions, 30 Gy in 10 fractions, or 36 Gy in 12 fractions to one area of disease with concurrent anti-CTLA-4 therapy.

A trial by the University of Texas Southwestern Medical Center (NCT01896271) seeks to examine the response rates of patients with metastatic renal cancer treated with high-dose IL-2 and stereotactic ablative body radiation. The study is currently active for any patient with clear cell renal cell carcinoma and up to 6 sites of metastatic disease with more than one lesion > 1.5 cm. Patients will be treated with stereotactic ablative radiation, with doses varying from 8 to 20 Gy in 1 to 3 fractions followed by high-dose IL-2 treatment.

A trial by Providence Health and Services (NCT01862900) seeks to examine the response rates and maximum tolerated dose of patients with metastatic breast cancer to the liver or lung treated with stereotactic body radiation and an anti-OX40 mAb. Eligible patients have at least one lesion in either the lung or liver, with one site of disease that will not receive radiation. Patients will receive a single dose of 15 Gy, 20 Gy, or 25 Gy to the liver or lung metastasis with concurrent anti-OX40 treatment.

A trial by the Ghent University Hospital (NCT02826564) seeks to examine the response rates of patients with metastatic urothelial cancer receiving stereotactic body radiation with pembrolizumab. The study is active for patients with urothelial cancer and at least one area of metastatic disease, with one site of disease that will not receive radiation. Patients will be treated with stereotactic body radiation prior to or concurrent with systemic pembrolizumab treatment.

To gauge the immunologic response, four of the studies are using biologic correlates, which include absolute lymphocyte count, frequency of Foxp3+Treg cells, shifts in Th1/Th2/Th17, number of plasmacytoid dendritic cells, number of myeloid derived suppressor cells, and IDO expression. The abscopal effect is often considered a medical spectacle without a unifying model, and its exact mechanisms have yet to be elucidated.20 Studying these biologic correlates may shed light on the possible mechanism of the abscopal effect.

Radioimmunotherapy Toxicities

There is some concern that combining immunotherapy with radiation therapy will increase toxicities. Table 2 summarizes the toxicity reports from 6 retrospective studies44-49 for patients treated with ipilimumab and radiation therapy; one retrospective study50 for patients treated with pembrolizumab and radiation therapy; one retrospective study51 for patients treated with nivolumab and radiation therapy; and one retrospective study33 for patients treated with durvalumab and chemoradiation. In general, for patients treated with combined immunotherapy and radiation therapy, there does not seem to be a significant increase in toxicity compared to treatment with immunotherapy alone or radiation therapy alone.


The combination of immunotherapy and radiation therapy is a very promising treatment regimen suggested to increase the occurrence of the previously rare abscopal response. Much uncertainty remains regarding how to best enhance the abscopal response clinically. Understanding the variables that may predict an abscopal response may help determine the necessary steps to unlock a more efficient long-term immune response after radiation therapy and convert this rare phenomenon to an everyday clinical benefit.


  1. Mole RH. Whole body irradiation—radiobiology or medicine? Br J Radiol. 1953;26(305):234-241. doi:10.1259/0007-1285-26-305-234.
  2. Walle T, Monge RM, Cerwenka A, et al. Radiation effects on antitumor immune responses: current perspectives and challenges. Ther Adv Med Oncol. 2018;10. doi:10.1177/1758834017742575.
  3. Brix N, Tiefenthaller A, Anders H, Belka C, Lauber K. Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences. Immunol Rev. 2017;280(1):249-279. doi:10.1111/imr.12573.
  4. Ngwa W, Irabor OC, Schoenfeld JD, et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018. doi:10.1038/nrc.2018.6.
  5. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105(4). doi:10.1093/jnci/djs629.
  6. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31(1):51-72. doi:10.1146/annurev-immunol-032712-100008.
  7. Golden EB, Apetoh L. Radiotherapy and immunogenic cell death. Semin Radiat Oncol. 2015;25(1):11-17. doi:10.1016/j.semradonc. 2014.07.005.
  8. Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860-875. doi:10.1038/nrc3380.
  9. Garg AD, Nowis D, Golab J, et al. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta - Rev Cancer. 2010;1805(1):53-71. doi:10.1016/j.bbcan.2009.08.003.
  10. Garg AD, Galluzzi L, Apetoh L, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:588. doi:10.3389/fimmu.2015.00588.
  11. Hammerich L, Bhardwaj N, Kohrt HE, Brody JD. In situ vaccination for the treatment of cancer. Immunotherapy. 2016;8(3):315-330. doi:10.2217/imt.15.120.
  12. Pierce RH, Campbell JS, Pai SI, Brody JD, Kohrt HEK. In-situ tumor vaccination: bringing the fight to the tumor. Hum Vaccines Immunother. 2015;11(8):1901-1909. doi:10.1080/21645515.2015.1049779.
  13. Derer A, Deloch L, Rubner Y, et al. Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses - pre-clinical evidence and ongoing clinical applications. Front Immunol. 2015;6:505. doi:10.3389/fimmu.2015.00505.
  14. Vanpouille-Box C, Pilones KA, Wennerberg E, Formenti SC, Demaria S. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine. 2015;33(51):7415-7422. doi:10.1016/j.vaccine.2015.05.105.
  15. Weichselbaum RR, Liang H, Deng L, Fu Y-X. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017;14(6). doi:10.1038/nrclinonc.2016.211.
  16. Barker CA, Postow MA. Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys. 2014;88(5):986-997. doi:10.1016/j.ijrobp.2013.08.035.
  17. Ishihara D, Pop L, Takeshima T, Iyengar P, Hannan R. Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment. Cancer Immunol Immunother. 2017;66(3). doi:10.1007/s00262-016-1914-6.
  18. Hiniker SM, Reddy SA, Maecker HT, et al. A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Radiat Oncol Biol. 2015;93(3):S95. doi:10.1016/j.ijrobp.2015.07.228.
  19. Theurich S, Rothschild SI, Hoffmann M, et al. Local tumor treatment in combination with systemic ipilimumab immunotherapy prolongs overall survival in patients with advanced malignant melanoma. Cancer Immunol Res. 2016;2997:1-12. doi:10.1158/2326-6066.CIR-15-0156.
  20. Teng F, Kong L, Meng X, Yang J, Yu J. Radiotherapy combined with immune checkpoint blockade immunotherapy: achievements and challenges. Cancer Lett. 2015;365(1):23-29. doi:10.1016/j.canlet.2015.05.012.
  21. Koller KM, Wang W, Schell TD, et al. Malignant melanoma—the cradle of anti-neoplastic immunotherapy. Crit Rev Oncol Hematol. 2016;106:25-54. doi:10.1016/j.critrevonc.2016.04.010.
  22. Hodi FS, Lee S, McDermott DF, et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014;312(17):1744-1753. doi:10.1001/jama.2014.13943.
  23. Nishikawa H, Sakaguchi S. Regulatory T-cells in cancer immunotherapy. Curr Opin Immunol. 2014;27(1):1-7. doi:10.1016/j.coi.2013.12.005.
  24. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41(1):49-61. doi:10.1016/j.immuni.2014.06.010.
  25. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23(3):277-286. doi:10.1016/j.ccr.2013.02.013.
  26. Gajewski TF, Schreiber H, Fu Y-X. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014-1022. doi:10.1038/ni.2703.
  27. Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015;41(6). doi:10.1016/j.ctrv.2015.03.011.
  28. Şenbabaoğlu Y, Gejman RS, Winer AG, et al. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17(1):231. doi:10.1186/s13059-016-1092-z.
  29. Golden EB, Chhabra A, Chachoua A, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: A proof-of-principle trial. Lancet Oncol. 2015;16(7):795-803. doi:10.1016/S1470-2045(15)00054-6.
  30. Chi K-H, Liu S-J, Li C-P, et al. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother. 2005;28(2):129-135. doi:10.1097/01.cji.0000154248.74383.5e.
  31. Nakamura N, Kusunoki Y, Akiyama M. Radiosensitivity of CD4 or CD8 positive human T-lymphocytes by an in vitro colony formation assay. Radiat Res. 1990;123(2):224-227. doi:10.2307/3577549.
  32. Yovino S, Grossman SA. Severity, etiology and possible consequences of treatment-related lymphopenia in patients with newly diagnosed high-grade gliomas. CNS Oncol. 2012;1(2):149-154. doi:10.2217/cns.12.14.
  33. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017:NEJMoa1709937. doi:10.1056/NEJMoa1709937.
  34. Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700-712. doi:10.1016/S1470-2045(14)70189-5.
  35. Shen RN, Hornback NB, Shidnia H, et al. A comparison of lung metastases and natural killer cell activity in daily fractions and weekly fractions of radiation therapy on murine B16a melanoma. Radiat Res. 1988;114(2):354-360.
  36. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 2012;83(4):1306-1310. doi:10.1016/j.ijrobp.2011.09.049.
  37. Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15(17):5379-5388. doi:10.1158/1078-0432.CCR-09-0265.
  38. Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8 + T-cells: Changing strategies for cancer treatment. Blood. 2009;114(3):589-595. doi:10.1182/blood-2009-02-206870.
  39. Sharabi AB, Lim M, DeWeese TL, Drake CG. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015;16(13):e498-e509. doi:10.1016/S1470-2045(15)00007-8.
  40. Filippi AR, Fava P, Badellino S, et al. Radiotherapy and immune checkpoints inhibitors for advanced melanoma. Radiother Oncol. 2016;120(1). doi:10.1016/j.radonc.2016.06.003.
  41. Mackley HB, Liu J, Zhu J. Improved infield response rates and overall survival in patients with metastatic melanoma receiving higher biological equivalent doses of radiation with ipilimumab. J Radiat Oncol. 2017;6(2):215-223. doi:10.1007/s13566-017-0305-8.
  42. Marconi R, Strolin S, Bossi G, Strigari L. A meta-analysis of the abscopal effect in preclinical models: is the biologically effective dose a relevant physical trigger? PLoS One. 2017;12(2). doi:10.1371/journal.pone.0171559.
  43. Kang J, Demaria S, Formenti S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016;4(1). doi:10.1186/s40425-016-0156-7.
  44. Kiess AP, Wolchok JD, Barker CA, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015;92(2):368-375. doi:10.1016/j.ijrobp.2015.01.004.
  45. Patel KR, Shoukat S, Oliver DE, et al. Ipilimumab and stereotactic radiosurgery versus stereotactic radiosurgery alone for newly diagnosed melanoma brain metastases. Am J Clin Oncol Cancer Clin Trials. 2017;40(5):444-450. doi:10.1097/COC.0000000000000199.
  46. Qin R, Olson A, Singh B, et al. Safety and efficacy of radiation therapy in advanced melanoma patients treated with ipilimumab. Int J Radiat Oncol. 2016;96(1):72-77. doi:10.1016/j.ijrobp.2016.04.017.
  47. Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2013;2(6):899-906. doi:10.1002/cam4.140.
  48. Tazi K, Hathaway A, Chiuzan C, Shirai K. Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery. Cancer Med. 2015;4(1):1-6. doi:10.1002/cam4.315.
  49. Koller KM, Mackley HB, Liu J, et al. Improved survival and complete response rates in patients with advanced melanomatreated with concurrent ipilimumab and radiotherapy versus ipilimumab alone. Cancer Biol Ther. 2016;0(0):1-7. doi:10.1080/15384047.2016.1264543.
  50. 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;18(7):895-903. doi:10.1016/S1470-2045(17)30380-7.
  51. Ahmed KA, Stallworth DG, Kim Y, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol. 2016;27(3):434-441. doi:10.1093/annonc/mdv622.


Liu J, Mackley HB. Combining immunotherapy with radiation therapy to induce the abscopal response: What clinical and treatment variables matter?. Appl Radiat Oncol. 2019;(1):14-19.

March 18, 2019