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BMC Cancer

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Open Access 01-12-2021 | Systemic Therapy | Study protocol

Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy

Authors: Glenn S. Bauman, Mark T. Corkum, Hatim Fakir, Timothy K. Nguyen, David A. Palma

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease.

Methods

Up to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes.

Discussion

This study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies.

Trial registration

This trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.

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Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMed

Urruticoechea A, Alemany R, Balart J, Villanueva A, Vinals F, Capella G. Recent advances in Cancer therapy: an overview. Curr Pharm Des. 2010;16(1):3–10. https://doi.org/10.2174/138161210789941847.CrossRefPubMed

St. James S, Bednarz B, Benedict S, Buchsbaum JC, Dewaraja Y, Frey E, et al. Current status of radiopharmaceutical therapy. Int J Radiat Oncol 2020;0. doi:https://doi.org/10.1016/j.ijrobp.2020.08.035, 109, 4, 891, 901.

Bauman G, Charette M, Reid R, Sathya J. Radiopharmaceuticals for the palliation of painful bone metastases - A systematic review. Radiother Oncol. 2005; 75: 258.E1–258.E13. doi:https://doi.org/10.1016/j.radonc.2005.03.003.

Tsao MN, Rades D, Wirth A, Lo SS, Danielson BL, Gaspar LE, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis (es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210–25. https://doi.org/10.1016/J.PRRO.2011.12.004.CrossRefPubMedPubMedCentral

Lutz S, Balboni T, Jones J, Lo S, Petit J, Rich SE, et al. Palliative radiation therapy for bone metastases: update of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2017;7(1):4–12. https://doi.org/10.1016/J.PRRO.2016.08.001.CrossRefPubMed

Rodrigues G, Videtic GMM, Sur R, Bezjak A, Bradley J, Hahn CA, et al. Palliative thoracic radiotherapy in lung cancer: an American Society for Radiation Oncology evidence-based clinical practice guideline. Pract Radiat Oncol. 2011;1(2):60–71. https://doi.org/10.1016/J.PRRO.2011.01.005.CrossRefPubMedPubMedCentral

Corkum MT, Rodrigues GB. Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer. Lung Cancer Manag. 2017;6(2):47–53. https://doi.org/10.2217/lmt-2017-0006.CrossRefPubMedPubMedCentral

Hellman S, Weichselbaum R. Oligometastases. J Clin Oncol. 1995;13(1):8–10. https://doi.org/10.1200/JCO.1995.13.1.8.CrossRefPubMed

10.

Palma DA, Salama JK, Lo SS, Senan S, Treasure T, Govindan R, et al. The oligometastatic state-separating truth from wishful thinking. Nat Rev Clin Oncol. 2014;11(9):549–57. https://doi.org/10.1038/nrclinonc.2014.96.CrossRefPubMed

11.

TAC K, Corkum MT, Louie AV. Stereotactic radiotherapy in oligometastatic cancer. Chinese Clin Oncol. 2017;6:S16. https://doi.org/10.21037/cco.2017.06.20.CrossRef

12.

Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol. 2020;38(25):2830–8. https://doi.org/10.1200/JCO.20.00818.CrossRefPubMed

13.

Gomez DR, Tang C, Zhang J, Blumenschein GR, Hernandez M, Lee JJ, et al. Local consolidative therapy Vs. maintenance therapy or observation for patients with Oligometastatic non–small-cell lung Cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol. 2019;37(18):1558–65. https://doi.org/10.1200/JCO.19.00201.CrossRefPubMedPubMedCentral

14.

Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, et al. Consolidative radiotherapy for limited metastatic non–small-cell lung Cancer. JAMA Oncol. 2018;4(1):e173501. https://doi.org/10.1001/jamaoncol.2017.3501.CrossRefPubMed

15.

Ruers T, Van Coevorden F, Punt CJA, Pierie J-PEN, Borel-Rinkes I, Ledermann JA, et al. Local treatment of Unresectable colorectal liver metastases: results of a randomized phase II trial. JNCI J Natl Cancer Inst. 2017;109(9). https://doi.org/10.1093/jnci/djx015.

16.

Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019;19(1):816. https://doi.org/10.1186/s12885-019-5977-6.CrossRefPubMedPubMedCentral

17.

Al-Shafa F, Arifin AJ, Rodrigues GB, Palma DA, Louie AV. A review of Ongoing trials of stereotactic ablative radiotherapy for Oligometastatic cancers: where will the evidence Lead? Front Oncol. 2019;9:543. https://doi.org/10.3389/fonc.2019.00543.CrossRefPubMedPubMedCentral

18.

Palma DA, Bauman GS, Rodrigues GB. Beyond Oligometastases. Int J Radiat Oncol Biol Phys. 2020;107(2):253–6. https://doi.org/10.1016/j.ijrobp.2019.12.023.CrossRefPubMed

19.

Ritter TA, Matuszak M, Chetty IJ, Mayo CS, Wu J, Iyengar P, et al. Application of critical volume-dose constraints for stereotactic body radiation therapy in NRG radiation therapy trials. Int J Radiat Oncol Biol Phys. 2017;98(1):34–6. https://doi.org/10.1016/j.ijrobp.2017.01.204.CrossRefPubMedPubMedCentral

20.

Berg RS, Yilmaz MK, Høyer M, Keldsen N, Nielsen OS, Ewertz M. Half body irradiation of patients with multiple bone metastases: a phase II trial. Acta Oncol (Madr). 2009;48(4):556–61. https://doi.org/10.1080/02841860802488128.CrossRef

21.

Murrell DH, Karnas SJ, Corkum MT, Hipwell S, Palma DA, Rodrigues G, et al. Radical radiotherapy for locally advanced non-small cell lung cancer—what’s up with arm positioning? J Thorac Dis. 2019;11:2099–104. https://doi.org/10.21037/jtd.2019.05.40.CrossRefPubMedPubMedCentral

22.

Salazar OM, Da Motta NW, Bridgman SM, Cardiges NM, Slawson RG. Fractionated half-body irradiation for pain palliation in widely metastatic cancers: comparison with single dose. Int J Radiat Oncol. 1996;36(1):49–60. https://doi.org/10.1016/S0360-3016(96)00248-9.CrossRef

23.

Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter Radium-223 and survival in metastatic prostate Cancer. N Engl J Med. 2013;369(3):213–23. https://doi.org/10.1056/NEJMoa1213755.CrossRefPubMed

24.

Wills C, Cherian S, Yousef J, Wang K, Mackley HB. Total body irradiation: a practical review. Appl Radiat Oncol. 2016;5(2):11–7.

25.

Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet (London, England). 2018;392:2353–66. https://doi.org/10.1016/S0140-6736(18)32486-3.CrossRef

26.

Chen M, You R, You-Ping L, Huang P-Y, Zou X, Shen G-P, et al. Chemotherapy plus local-regional radiotherapy versus chemotherapy alone in primary metastatic nasopharyngeal carcinoma: A randomized, open-label, phase III trial. Ann Oncol. 2019;30(Supplement_5):v449. https://doi.org/10.1093/annonc/mdz252.CrossRef

27.

Paluri RK, Li P, Anderson A, Nandagopal L, McArdle T, Young M, et al. First-in-human phase 1 clinical trials – a single-Center experience in the era of modern Oncotherapeutics. Sci Rep. 2020;10(1):1–7. https://doi.org/10.1038/s41598-020-64906-4.CrossRef

Title: Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy
Authors: Glenn S. Bauman
Mark T. Corkum
Hatim Fakir
Timothy K. Nguyen
David A. Palma
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Systemic Therapy
Radiotherapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08020-2

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Abstract

Background

Methods

Discussion

Trial registration

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