Top

Published in:

Open Access 01-12-2023 | Metastasis | Research

Factors affecting local control of bone metastases from radioresistant tumors treated with palliative external beam radiotherapy

Authors: Kenji Makita, Yasushi Hamamoto, Hiromitsu Kanzaki, Kei Nagasaki, Noriko Takata, Shintaro Tsuruoka, Kotaro Uwatsu, Teruhito Kido

Published in: Discover Oncology | Issue 1/2023

Abstract

Background

This study aimed to evaluate the factors that affect the local control (LC) of bone metastases from radioresistant carcinomas (renal cell carcinoma, hepatocellular carcinoma [HCC], and colorectal carcinoma [CRC]) treated with palliative external-beam radiotherapy (EBRT).

Methods and materials

Between January 2010 and December 2020, 211 bone metastases in 134 patients were treated with EBRT in two hospitals (a cancer center and university hospital). Based on follow-up CT, these cases were reviewed retrospectively to evaluate LC at the EBRT site.

Results

The median EBRT dose (BED10) was 39.0 Gy (range, 14.4–66.3 Gy). The median follow-up time of the imaging studies was 6 months (range, 1–107 months). The 0.5-year overall survival and LC rates of the EBRT sites were 73% and 73%, respectively. Multivariate analysis revealed that the primary sites (HCC/CRC), low EBRT dose (BED10) (≤ 39.0 Gy), and non-administration of post-EBRT bone modifying agents (BMAs) and/or antineoplastic agents (ATs) were statistically significant factors that negatively affected the LC of EBRT sites. In the absence of BMAs or ATs, the EBRT dose (BED10) escalation from 39.0 Gy improved the LC of EBRT sites. Based on ATs administration, the LC of EBRT sites was significantly affected by tyrosine kinase inhibitors and/or immune checkpoint inhibitors.

Conclusions

Dose escalation improves LC in bone metastases from radioresistant carcinomas. Higher EBRT doses are needed to treat patients for whom few effective systemic therapies remain available.

Tubiana-Hulin M. Incidence, prevalence and distribution of bone metastases. Bone. 1991;12(Suppl 1):S9-10. https://doi.org/10.1016/8756-3282(91)90059-r.CrossRefPubMed

Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, et al. Distribution of metastatic sites in renal cell carcinoma: a population—based analysis. Ann Oncol. 2012;23:973–80. https://doi.org/10.1093/annonc/mdr362.CrossRefPubMed

Okazaki N, Yoshino M, Yoshida T, Hirohashi S, Kishi K, Shimosato Y. Bone metastasis in hepatocellular carcinoma. Cancer. 1985;55:1991–4. https://doi.org/10.1002/1097-0142(19850501)55:9%3c1991::aid-cncr2820550927%3e3.0.co;2-f.CrossRefPubMed

Santini D, Tampellini M, Vincenzi B, Ibrahim T, Ortega C, Virzi V, et al. Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study. Ann Oncol. 2012;23:2072–7. https://doi.org/10.1093/annonc/mdr572.CrossRefPubMed

Ibrahim A, Scher N, Williams G, Sridhara R, Li N, Chen G, et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res. 2003;9:2394–9.PubMed

van der Velden J, Willmann J, Spałek M, Oldenburger E, Brown S, Kazmierska J, et al. ESTRO ACROP guidelines for external beam radiotherapy of patients with uncomplicated bone metastases. Radiother Oncol. 2022;173:197–206. https://doi.org/10.1016/j.radonc.2022.05.024.CrossRefPubMed

Oldenburger E, Brown S, Willmann J, van der Velden JM, Spałek M, van der Linden YM, et al. ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases. Radiother Oncol. 2022;173:240–53. https://doi.org/10.1016/j.radonc.2022.06.002.CrossRefPubMed

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;7:4–12. https://doi.org/10.1016/j.prro.2016.08.001.CrossRefPubMed

Jung IH, Yoon SM, Kwak J, Park JH, Song SY, Lee SW, et al. High-dose radiotherapy is associated with better local control of bone metastasis from hepatocellular carcinoma. Oncotarget. 2017;8:15182–92. https://doi.org/10.18632/oncotarget.14858.CrossRefPubMedPubMedCentral

10.

Ganju RG, TenNapel M, Mahan N, Zahra A, Shen X. The efficacy of conventionally fractionated radiation in the management of osseous metastases from metastatic renal cell carcinoma. J Oncol. 2018;2018:6384253. https://doi.org/10.1155/2018/6384253.CrossRefPubMedPubMedCentral

11.

Wegner RE, Matani H, Colonias A, Price F, Furhrer R, Abel S. Trends in radiation fractionation for bone metastases: a contemporary nationwide analysis. Pract Radiat Oncol. 2020;10:402–8. https://doi.org/10.1016/j.prro.2020.03.009.CrossRefPubMed

12.

André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383:2207–18. https://doi.org/10.1056/NEJMoa2017699.CrossRefPubMed

13.

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905. https://doi.org/10.1056/NEJMoa1915745.CrossRefPubMed

14.

Tomita Y, Shinohara N, Yuasa T, Fujimoto H, Niwakawa M, Mugiya S, et al. Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma. Jpn J Clin Oncol. 2010;40:1166–72. https://doi.org/10.1093/jjco/hyq146.CrossRefPubMed

15.

Freundt K, Meyners T, Bajrovic A, Basic H, Karstens JH, Adamietz IA, et al. Radiotherapy for oligometastatic disease in patients with spinal cord compression (MSCC) from relatively radioresistant tumors. Strahlenther Onkol. 2010;186:218–23. https://doi.org/10.1007/s00066-010-2110-9.CrossRefPubMed

16.

Rades D, Freundt K, Meyners T, Bajrovic A, Basic H, Karstens JH, et al. Dose escalation for metastatic spinal cord compression in patients with relatively radioresistant tumors. Int J Radiat Oncol Biol Phys. 2011;80:1492–7. https://doi.org/10.1016/j.ijrobp.2010.04.026.CrossRefPubMed

17.

Makita K, Hamamoto Y, Kanzaki H, Kataoka M, Yamamoto S, Nagasaki K, et al. Local control of bone metastases treated with external beam radiotherapy in recent years: a multicenter retrospective study. Radiat Oncol. 2021;16:225. https://doi.org/10.1186/s13014-021-01940-0.CrossRefPubMedPubMedCentral

18.

Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: what are the options, indications, and outcomes? Spine. 2009;34(Suppl):S78-92. https://doi.org/10.1097/BRS.0b013e3181b8b6f5.CrossRefPubMed

19.

Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124. https://doi.org/10.1093/jnci/dju124.CrossRefPubMed

20.

Zhou Xin, Yiping Du, Huang Zebo, Jun Xu, Qiu Tianzhu, Wang Jian, et al. Prognostic value of PLR in various cancers: a meta-analysis. PLOS ONE. 2014;9:e101119. https://doi.org/10.1371/journal.pone.0101119.CrossRefPubMedPubMedCentral

21.

Makita K, Hamamoto Y, Kanzaki H, Kataoka M, Yamamoto S, Nagasaki K, et al. Local control after palliative external beam radiotherapy for bone metastases in patients with favorable prognosis. Mol Clin Oncol. 2022;17:152. https://doi.org/10.3892/mco.2022.2585.CrossRefPubMedPubMedCentral

22.

Hayashi S, Tanaka H, Hoshi H. Palliative external-beam radiotherapy for bone metastases from hepatocellular carcinoma. World J Hepatol. 2014;6:923–9. https://doi.org/10.4254/wjh.v6.i12.923.CrossRefPubMedPubMedCentral

23.

Zeng KL, Myrehaug S, Soliman H, Husain ZA, Tseng CL, Detsky J, et al. Mature local control and reirradiation rates comparing spine stereotactic body radiation therapy with conventional palliative external beam radiation therapy. Int J Radiat Oncol Biol Phys. 2022;114:293–300. https://doi.org/10.1016/j.ijrobp.2022.05.043.CrossRefPubMed

24.

Mathis NJ, Doyle CJ, Rosen DB, Wijetunga NA, Vaynrub M, Bartelstein M, et al. Personalized treatment selection leads to low rates of local salvage therapy for bone metastases. Int J Radiat Oncol Biol Phys. 2022;112:99–105. https://doi.org/10.1016/j.ijrobp.2021.06.025.CrossRefPubMed

25.

Lee E, Kim TG, Park HC, Yu JI, Lim DH, Nam H, et al. Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma. Radiat Oncol J. 2015;33:217–25. https://doi.org/10.3857/roj.2015.33.3.217.CrossRefPubMedPubMedCentral

26.

Smith BW, Joseph JR, Saadeh YS, La Marca F, Szerlip NJ, Schermerhorn TC, et al. Radiosurgery for treatment of renal cell metastases to spine: a systematic review of the literature. World Neurosurg. 2018;109:e502–9. https://doi.org/10.1016/j.wneu.2017.10.011.CrossRefPubMed

27.

All S, Garant A, Hannan R. Stereotactic ablative radiation (SAbR) for oligometastatic RCC. Semin Radiat Oncol. 2021;31:227–34. https://doi.org/10.1016/j.semradonc.2021.02.002.CrossRefPubMed

28.

Ito K, Yamaguchi T, Ogawa H, Nakajima Y, Karasawa K. Stereotactic body radiotherapy for bone metastases in patients with colorectal cancer. Jpn J Clin Oncol. 2020;50:1442–6. https://doi.org/10.1093/jjco/hyaa128.CrossRefPubMed

29.

Umer M, Mohib Y, Atif M, Nazim M. Skeletal metastasis in renal cell carcinoma: a review. Ann Med Surg (Lond). 2018;27:9–16. https://doi.org/10.1016/j.amsu.2018.01.002.CrossRefPubMed

30.

Rades D, Hakim SG, Bajrovic A, Karstens JH, Veninga T, Rudat V, et al. Impact of zoledronic acid on control of metastatic spinal cord compression. Strahlenther Onkol. 2012;188:910–6. https://doi.org/10.1007/s00066-012-0158-4.CrossRefPubMed

31.

Staehler M, Haseke N, Stadler T, Nuhn P, Roosen A, Stief CG, et al. Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer. Urol Oncol. 2012;30:290–3. https://doi.org/10.1016/j.urolonc.2010.02.006.CrossRefPubMed

32.

Kleibeuker EA, Ten Hooven MA, Verheul HM, Slotman BJ, Thijssen VL. Combining radiotherapy with sunitinib: lessons (to be) learned. Angiogenesis. 2015;18:385–95. https://doi.org/10.1007/s10456-015-9476-3.CrossRefPubMedPubMedCentral

33.

Tanaka H, Makita C, Manabe Y, Kajima M, Matsuyama K, Matsuo M. Radiation therapy combined with bone-modifying agents ameliorates local control of osteolytic bone metastases in breast cancer. J Radiat Res. 2020;61:494–8. https://doi.org/10.1093/jrr/rraa020.CrossRefPubMedPubMedCentral

34.

Zołnierek J, Nurzyński P, Langiewicz P, Oborska S, Waśko-Grabowska A, Kuszatal E, et al. Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases. J Cancer Res Clin Oncol. 2010;136:371–8. https://doi.org/10.1007/s00432-009-0664-7.CrossRefPubMed

35.

Asano Y, Yamamoto N, Demura S, Hayashi K, Takeuchi A, Kato S, et al. The therapeutic effect and clinical outcome of immune checkpoint inhibitors on bone metastasis in advanced non-small-cell lung cancer. Front Oncol. 2022;12:871675. https://doi.org/10.3389/fonc.2022.871675.CrossRefPubMedPubMedCentral

Title: Factors affecting local control of bone metastases from radioresistant tumors treated with palliative external beam radiotherapy
Authors: Kenji Makita
Yasushi Hamamoto
Hiromitsu Kanzaki
Kei Nagasaki
Noriko Takata
Shintaro Tsuruoka
Kotaro Uwatsu
Teruhito Kido
Publication date: 01-12-2023
Publisher: Springer US
Keywords: Metastasis
Radiotherapy
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Kidney Cancer
Kidney Cancer
Kidney Cancer
Tyrosine Kinase Inhibitors
Tyrosine Kinase Inhibitors
Checkpoint Inhibitors
Published in: Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-023-00651-0

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods and materials

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment

A modified melanoma-molGPA scoring model: assessment of survival after and efficacy of different radiotherapy modalities in patients with melanoma brain metastases

Advances of exosomal miRNAs in the diagnosis and treatment of ovarian cancer

Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments

Editorial Expression of Concern: Response of human pancreatic cancer cell xenografts to tetraiodothyroacetic acid nanoparticles

Analysis of bacterial diversity and community structure in gastric juice of patients with advanced gastric cancer

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials