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Published in: Journal of Radiation Oncology 3/2018

01-09-2018 | Original Research

Tolerability of sequential immune therapy and palliative radiotherapy to the cervical and thoracic spine

Authors: W. Tristram Arscott, Abigail Doucette, Pallavi Kumar, John P. Plastaras, Amit Maity, Joshua Jones

Published in: Journal of Radiation Oncology | Issue 3/2018

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Abstract

Background

Use of immune therapy in metastatic cancers is rapidly expanding; however, its combination with commonly prescribed palliative radiation fields and doses is not well studied. To investigate this, we evaluated the toxicity of combined immune therapy and palliative cervical or thoracic spine radiotherapy.

Methods

Patients receiving cervical or thoracic spine radiation were evaluated based on administration of immune therapy within 30 days of radiation, use of 3D conformal or simpler techniques, and minimum 1 follow-up from end of treatment.

Results

Thirty patients were evaluable. Median survival following radiotherapy was 87 days. Pembrolizumab was most commonly combined with radiation (11 patients), then nivolumab (10), ipilimumab (3), and atezoliumab (2). Four patients (13.3%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis) and 12 patients (40%) had grade 2 toxicity (esophagitis, dysphagia). Ten patients (33.3%) had no toxicity. Three of the 4 patients with grade 3 toxicity received concurrent ipilimumab and nivolumab. Median dose was 30 Gy (range, 20–39) and fractions were 10 (range, 5–15). There was a trend toward increased grade 2+ toxicity with greater number of vertebral levels irradiated, 5.7 ± 3.4, vs. 4.0 ± 1.6 for none/grade 1 (P = .086). Seven of 7 patients exposed to ipilimumab developed grade 2+ toxicity vs 39% in the remaining patients (P = .007 for interaction). Radiation dose, fractionation, and timing of immune therapy were not significant contributors.

Conclusions

Combined immune therapy and radiotherapy for palliation of spine metastases suggests increased toxicity when a greater number of vertebral bodies are irradiated, or when combined immune therapy agents are utilized.
Literature
1.
go back to reference Sharpe AH (2017) Introduction to checkpoint inhibitors and cancer immunotherapy. Immunol Rev 276:5–8CrossRef Sharpe AH (2017) Introduction to checkpoint inhibitors and cancer immunotherapy. Immunol Rev 276:5–8CrossRef
2.
go back to reference Postow M, Wolchok J (2017) Toxicities associated with checkpoint inhibitor immunotherapy. UpToDate Postow M, Wolchok J (2017) Toxicities associated with checkpoint inhibitor immunotherapy. UpToDate
3.
go back to reference Ahmed MM, Guha C, Hodge JW, Jaffee E (2014) Immunobiology of radiotherapy: new paradigms. Radiat Res 182:123–125CrossRef Ahmed MM, Guha C, Hodge JW, Jaffee E (2014) Immunobiology of radiotherapy: new paradigms. Radiat Res 182:123–125CrossRef
4.
go back to reference Weichselbaum RR, Liang H, Deng L, Fu YX (2017) Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol 14:365–379CrossRef Weichselbaum RR, Liang H, Deng L, Fu YX (2017) Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol 14:365–379CrossRef
5.
go back to reference Kang J, Demaria S, Formenti S (2016) Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer 4:51CrossRef Kang J, Demaria S, Formenti S (2016) Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer 4:51CrossRef
6.
go back to reference Qian JM, Yu JB, Kluger HM, Chiang VL (2016) Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 122:3051–3058CrossRef Qian JM, Yu JB, Kluger HM, Chiang VL (2016) Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 122:3051–3058CrossRef
7.
go back to reference Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377CrossRef Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377CrossRef
8.
go back to reference Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, Saha S, Shura L, Knox SJ (2016) A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Int J Radiat Oncol Biol Phys 96:578–588CrossRef Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, Saha S, Shura L, Knox SJ (2016) A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Int J Radiat Oncol Biol Phys 96:578–588CrossRef
9.
go back to reference Patel KR, Shoukat S, Oliver DE, Chowdhary M, Rizzo M, Lawson DH, Khosa F, Liu Y, Khan MK (2017) Ipilimumab and stereotactic radiosurgery versus stereotactic radiosurgery alone for newly diagnosed melanoma brain metastases. Am J Clin Oncol 40:444–450CrossRef Patel KR, Shoukat S, Oliver DE, Chowdhary M, Rizzo M, Lawson DH, Khosa F, Liu Y, Khan MK (2017) Ipilimumab and stereotactic radiosurgery versus stereotactic radiosurgery alone for newly diagnosed melanoma brain metastases. Am J Clin Oncol 40:444–450CrossRef
10.
go back to reference Bang A, Wilhite TJ, Pike LRG, Cagney DN, Aizer AA, Taylor A, Spektor A, Krishnan M, Ott PA, Balboni TA, Hodi FS, Schoenfeld JD (2017) Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiation therapy. Int J Radiat Oncol Biol Phys 98:344–351CrossRef Bang A, Wilhite TJ, Pike LRG, Cagney DN, Aizer AA, Taylor A, Spektor A, Krishnan M, Ott PA, Balboni TA, Hodi FS, Schoenfeld JD (2017) Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiation therapy. Int J Radiat Oncol Biol Phys 98:344–351CrossRef
11.
go back to reference Pike LRG, Bang A, Ott P, Balboni T, Taylor A, Catalano P, Rawal B, Spektor A, Krishnan M, Cagney D, Alexander B, Aizer AA, Buchbinder E, Awad M, Gandhi L, Hodi FS, Schoenfeld JD (2017) Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol 124:98–103CrossRef Pike LRG, Bang A, Ott P, Balboni T, Taylor A, Catalano P, Rawal B, Spektor A, Krishnan M, Cagney D, Alexander B, Aizer AA, Buchbinder E, Awad M, Gandhi L, Hodi FS, Schoenfeld JD (2017) Radiation and PD-1 inhibition: favorable outcomes after brain-directed radiation. Radiother Oncol 124:98–103CrossRef
12.
go back to reference Hoskin P, Misra V, Hopkins K, Holt T, Brown G, Arnott S, Shibu Thomas S, Reczko K, Beare S, Lopes A, Forsyth S (2017) SCORAD III: randomized noninferiority phase III trial of single-dose radiotherapy (RT) compared to multifraction RT in patients (pts) with metastatic spinal canal compression (SCC). J Clin Oncol 35:LBA10004-LBACrossRef Hoskin P, Misra V, Hopkins K, Holt T, Brown G, Arnott S, Shibu Thomas S, Reczko K, Beare S, Lopes A, Forsyth S (2017) SCORAD III: randomized noninferiority phase III trial of single-dose radiotherapy (RT) compared to multifraction RT in patients (pts) with metastatic spinal canal compression (SCC). J Clin Oncol 35:LBA10004-LBACrossRef
13.
go back to reference Peyraga G, Caron D, Lizee T et al (2017) Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases. Support Care Cancer Peyraga G, Caron D, Lizee T et al (2017) Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases. Support Care Cancer
14.
go back to reference Fairchild A, Harris K, Barnes E, Wong R, Lutz S, Bezjak A, Cheung P, Chow E (2008) Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol 26:4001–4011CrossRef Fairchild A, Harris K, Barnes E, Wong R, Lutz S, Bezjak A, Cheung P, Chow E (2008) Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol 26:4001–4011CrossRef
15.
go back to reference Granton PV, Palma DA, Louie AV (2017) Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation. Radiat Oncol 12:27CrossRef Granton PV, Palma DA, Louie AV (2017) Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation. Radiat Oncol 12:27CrossRef
16.
go back to reference Thompson R (2014) RadOnc: an R package for analysis of dose-volume histogram and three-dimensional structural data. J Radiat Oncol Inform 6:98–110 Thompson R (2014) RadOnc: an R package for analysis of dose-volume histogram and three-dimensional structural data. J Radiat Oncol Inform 6:98–110
17.
go back to reference Kroeze SG, Fritz C, Hoyer M et al (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev 53:25–37CrossRef Kroeze SG, Fritz C, Hoyer M et al (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev 53:25–37CrossRef
18.
go back to reference Aboudaram A, Modesto A, Chaltiel L, Gomez-Roca C, Boulinguez S, Sibaud V, Delord JP, Chira C, Delannes M, Moyal E, Meyer N (2017) Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination. Melanoma Res 27:485–491CrossRef Aboudaram A, Modesto A, Chaltiel L, Gomez-Roca C, Boulinguez S, Sibaud V, Delord JP, Chira C, Delannes M, Moyal E, Meyer N (2017) Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination. Melanoma Res 27:485–491CrossRef
19.
go back to reference Barker CA, Postow MA, Khan SA, Beal K, Parhar PK, Yamada Y, Lee NY, Wolchok JD (2013) Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma. Cancer Immunol Res 1:92–98CrossRef Barker CA, Postow MA, Khan SA, Beal K, Parhar PK, Yamada Y, Lee NY, Wolchok JD (2013) Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma. Cancer Immunol Res 1:92–98CrossRef
20.
go back to reference Chandra RA, Wilhite TJ, Balboni TA, Alexander BM, Spektor A, Ott PA, Ng AK, Hodi FS, Schoenfeld JD (2015) A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology 4:e1046028CrossRef Chandra RA, Wilhite TJ, Balboni TA, Alexander BM, Spektor A, Ott PA, Ng AK, Hodi FS, Schoenfeld JD (2015) A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology 4:e1046028CrossRef
Metadata
Title
Tolerability of sequential immune therapy and palliative radiotherapy to the cervical and thoracic spine
Authors
W. Tristram Arscott
Abigail Doucette
Pallavi Kumar
John P. Plastaras
Amit Maity
Joshua Jones
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Radiation Oncology / Issue 3/2018
Print ISSN: 1948-7894
Electronic ISSN: 1948-7908
DOI
https://doi.org/10.1007/s13566-018-0352-9

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