nach oben

European Journal of Orthopaedic Surgery & Traumatology

Erschienen in:

05.06.2024 | General Review

Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review

verfasst von: Shinji Tsukamoto, Andreas F. Mavrogenis, Tomoya Masunaga, Hisaki Aiba, Ayano Aso, Kanya Honoki, Hiromasa Fujii, Akira Kido, Yuu Tanaka, Yasuhito Tanaka, Costantino Errani

Erschienen in: European Journal of Orthopaedic Surgery & Traumatology | Ausgabe 6/2024

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs.

Methods

This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies.

Results

Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44–78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7–28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively.

Conclusion

Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures.

Nur mit Berechtigung zugänglich

Haslam A, Prasad V (2019) Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open 2:e192535. https://doi.org/10.1001/jamanetworkopen.2019.2535CrossRefPubMedPubMedCentral

Joseph GJ, Johnson DB, Johnson RW (2023) Immune checkpoint inhibitors in bone metastasis: clinical challenges, toxicities, and mechanisms. J Bone Oncol 43:100505. https://doi.org/10.1016/j.jbo.2023.100505CrossRefPubMedPubMedCentral

Schmid S, Diem S, Li Q et al (2018) Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC). Cancer Immunol Immunother 67:1825–1832. https://doi.org/10.1007/s00262-018-2239-4CrossRefPubMedPubMedCentral

Qin A, Zhao S, Miah A et al (2021) Bone metastases, skeletal-related events, and survival in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors. J Natl Compr Canc Netw 19:915–921. https://doi.org/10.6004/jnccn.2020.7668CrossRefPubMedPubMedCentral

da Silva LM, da Silva GT, Bergmann A et al (2021) Impact of different patterns of metastasis in non-small-cell lung cancer patients. Future Oncol 17:775–782. https://doi.org/10.2217/fon-2020-0587CrossRefPubMed

Landi L, D’Incà F, Gelibter A et al (2019) Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer. J Immunother Cancer 7:316. https://doi.org/10.1186/s40425-019-0793-8CrossRefPubMedPubMedCentral

Selvaggi G, Scagliotti GV (2005) Management of bone metastases in cancer: a review. Crit Rev Oncol Hematol 56:365–378. https://doi.org/10.1016/j.critrevonc.2005.03.011CrossRefPubMed

Jiang W, Rixiati Y, Zhao B et al (2020) Incidence, prevalence, and outcomes of systemic malignancy with bone metastases. J Orthop Surg 28:2309499020915989. https://doi.org/10.1177/2309499020915989CrossRef

Huang J-F, Shen J, Li X et al (2020) Incidence of patients with bone metastases at diagnosis of solid tumors in adults: a large population-based study. Ann Transl Med 8:482. https://doi.org/10.21037/atm.2020.03.55CrossRefPubMedPubMedCentral

10.

Woodward E, Jagdev S, McParland L et al (2011) Skeletal complications and survival in renal cancer patients with bone metastases. Bone 48:160–166. https://doi.org/10.1016/j.bone.2010.09.008CrossRefPubMed

11.

Mavrogenis AF, Pala E, Romagnoli C et al (2012) Survival analysis of patients with femoral metastases. J Surg Oncol 105:135–141. https://doi.org/10.1002/jso.22061CrossRefPubMed

12.

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

13.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026CrossRefPubMed

14.

Hamaoka T, Madewell JE, Podoloff DA et al (2004) Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942–2953. https://doi.org/10.1200/JCO.2004.08.181CrossRefPubMed

15.

Mirels H (1989) Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res 256–264

16.

Del Conte A, De Carlo E, Bertoli E et al (2022) Bone metastasis and immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): microenvironment and possible clinical implications. Int J Mol Sci 23:6832. https://doi.org/10.3390/ijms23126832CrossRefPubMedPubMedCentral

17.

Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71CrossRefPubMedPubMedCentral

18.

Kim SY, Park JE, Lee YJ et al (2013) Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol 66:408–414. https://doi.org/10.1016/j.jclinepi.2012.09.016CrossRefPubMed

19.

Shimizu T, Miyake M, Nishimura N et al (2022) Organ-specific and mixed responses to pembrolizumab in patients with unresectable or metastatic urothelial carcinoma: a multicenter retrospective study. Cancers 14:1735. https://doi.org/10.3390/cancers14071735CrossRefPubMedPubMedCentral

20.

De Giglio A, Deiana C, Di Federico A (2023) Bone-specific response according to MDA criteria predicts immunotherapy efficacy among advanced non-small cell lung cancer (NSCLC) patients. J Cancer Res Clin Oncol 149:1835–1847. https://doi.org/10.1007/s00432-022-04120-zCrossRefPubMed

21.

Asano Y, Yamamoto N, Demura S et al (2023) Novel predictors of immune checkpoint inhibitor response and prognosis in advanced non-small-cell lung cancer with bone metastasis. Cancer Med 12:12425–12437. https://doi.org/10.1002/cam4.5952CrossRefPubMedPubMedCentral

22.

Bongiovanni A, Foca F, Menis J et al (2021) Immune checkpoint inhibitors with or without bone-targeted therapy in NSCLC patients with bone metastases and prognostic significance of neutrophil-to-lymphocyte ratio. Front Immunol 12:697298. https://doi.org/10.3389/fimmu.2021.697298CrossRefPubMedPubMedCentral

23.

Negishi T, Furubayashi N, Nakagawa T et al (2021) Site-specific response to nivolumab in renal cell carcinoma. Anticancer Res 41:1539–1545. https://doi.org/10.21873/anticanres.14913CrossRefPubMed

24.

Nakata E, Sugihara S, Sugawara Y et al (2020) Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Oncol Lett 20:2977–2986. https://doi.org/10.3892/ol.2020.11856CrossRefPubMedPubMedCentral

25.

Angela Y, Haferkamp S, Weishaupt C et al (2019) Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases. Cancer Immunol Immunother 68:1187–1194. https://doi.org/10.1007/s00262-019-02353-5CrossRefPubMedPubMedCentral

26.

Furubayashi N, Negishi T, Sakamoto N et al (2021) Organ-specific tumor response to pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy. Onco Targets Ther 14:1981–1988. https://doi.org/10.2147/OTT.S299724CrossRefPubMedPubMedCentral

27.

Raparia K, Villa C, DeCamp MM et al (2013) Molecular profiling in non-small cell lung cancer: a step toward personalized medicine. Arch Pathol Lab Med 137:481–491. https://doi.org/10.5858/arpa.2012-0287-RACrossRefPubMed

28.

Hoban KA, Downie S, Adamson DJA et al (2022) Mirels’ score for upper limb metastatic lesions: do we need a different cutoff for recommending prophylactic fixation? JSES Int 6:675–681. https://doi.org/10.1016/j.jseint.2022.03.006CrossRefPubMedPubMedCentral

29.

Van der Linden YM, Dijkstra PDS, Kroon HM et al (2004) Comparative analysis of risk factors for pathological fracture with femoral metastases. J Bone Joint Surg Br 86:566–573CrossRefPubMed

30.

Goodheart JR, Cleary RJ, Damron TA, Mann KA (2015) Simulating activities of daily living with finite element analysis improves fracture prediction for patients with metastatic femoral lesions. J Orthop Res 33:1226–1234. https://doi.org/10.1002/jor.22887CrossRefPubMed

31.

Damron TA, Nazarian A, Entezari V et al (2016) CT-based structural rigidity analysis is more accurate than mirels scoring for fracture prediction in metastatic femoral lesions. Clin Orthop Relat Res 474:643–651. https://doi.org/10.1007/s11999-015-4453-0CrossRefPubMed

32.

Sternheim A, Traub F, Trabelsi N et al (2020) When and where do patients with bone metastases actually break their femurs? Bone Joint J 102-B:638–645. https://doi.org/10.1302/0301-620X.102B5.BJJ-2019-1328.R2CrossRefPubMed

33.

van der Wal CWPG, Eggermont F, Fiocco M et al (2020) Axial cortical involvement of metastatic lesions to identify impending femoral fractures; a clinical validation study. Radiother Oncol 144:59–64. https://doi.org/10.1016/j.radonc.2019.10.007CrossRefPubMed

34.

Bellamy EA, Nicholas D, Ward M et al (1987) Comparison of computed tomography and conventional radiology in the assessment of treatment response of lytic bony metastases in patients with carcinoma of the breast. Clin Radiol 38:351–355. https://doi.org/10.1016/s0009-9260(87)80207-6CrossRefPubMed

35.

Ruggieri P, Mavrogenis AF, Casadei R et al (2010) Protocol of surgical treatment of long bone pathological fractures. Injury 41:1161–1167. https://doi.org/10.1016/j.injury.2010.09.018CrossRefPubMed

36.

Wedin R, Bauer HCF (2005) Surgical treatment of skeletal metastatic lesions of the proximal femur: endoprosthesis or reconstruction nail? J Bone Joint Surg Br 87:1653–1657. https://doi.org/10.1302/0301-620X.87B12.16629CrossRefPubMed

37.

Fidler M (1981) Incidence of fracture through metastases in long bones. Acta Orthop Scand 52:623–627. https://doi.org/10.3109/17453678108992157CrossRefPubMed

38.

van der Linden YM, Kroon HM, Dijkstra SPDS et al (2003) Simple radiographic parameter predicts fracturing in metastatic femoral bone lesions: results from a randomised trial. Radiother Oncol 69:21–31. https://doi.org/10.1016/s0167-8140(03)00232-9CrossRefPubMed

39.

Eggermont F, van der Wal G, Westhoff P et al (2020) Patient-specific finite element computer models improve fracture risk assessments in cancer patients with femoral bone metastases compared to clinical guidelines. Bone 130:115101. https://doi.org/10.1016/j.bone.2019.115101CrossRefPubMed

40.

Comito F, Ambrosini V, Sperandi F et al (2018) Osteoblastic bone response mimicking bone progression during treatment with pembrolizumab in advanced cutaneous melanoma. Anticancer Drugs 29:1026–1029. https://doi.org/10.1097/CAD.0000000000000689CrossRefPubMed

41.

Ito S, Tachimori Y, Terado Y et al (2021) Primary malignant melanoma of the esophagus successfully treated with nivolumab: a case report. J Med Case Rep 15:237. https://doi.org/10.1186/s13256-021-02821-6CrossRefPubMedPubMedCentral

42.

Kageyama S-I, Yamaguchi S, Ito S et al (2016) A case report of using nivolumab for a malignant melanoma patient with rheumatoid arthritis. Int Cancer Conf J 5:192–196. https://doi.org/10.1007/s13691-016-0256-8CrossRefPubMedPubMedCentral

43.

Lankes K, Hundorfean G, Harrer T et al (2016) Anti-TNF-refractory colitis after checkpoint inhibitor therapy: possible role of CMV-mediated immunopathogenesis. Oncoimmunology 5:e1128611. https://doi.org/10.1080/2162402X.2015.1128611CrossRefPubMedPubMedCentral

44.

Matull J, Livingstone E, Wetter A et al (2020) Durable Complete response in a melanoma patient with unknown primary, associated with sequential and severe multi-organ toxicity after a single dose of CTLA-4 plus PD-1 blockade: a case report. Front Oncol 10:592609. https://doi.org/10.3389/fonc.2020.592609CrossRefPubMedPubMedCentral

45.

Oliveira LJC, Gongora ABL, Barbosa FG et al (2018) Atypical response with bone pseudoprogression in a patient receiving nivolumab for advanced cutaneous squamous cell carcinoma. J Immunother Cancer 6:130. https://doi.org/10.1186/s40425-018-0444-5CrossRefPubMedPubMedCentral

46.

Kokura K, Watanabe J, Takuma T et al (2023) A case of Avelumab response to multiple bone and lymph node metastases of plasmacytoid variant bladder cancer. Urol Case Rep 47:102358. https://doi.org/10.1016/j.eucr.2023.102358CrossRefPubMedPubMedCentral

47.

Laffi A, Cozzi G, Spada F et al (2022) Metachronous testicular metastases from merkel cell carcinoma (MCC): a case report and literature review. Am J Case Rep 23:e936552. https://doi.org/10.12659/AJCR.936552CrossRefPubMedPubMedCentral

48.

Tamada S, Ikarashi D, Tsuyukubo T et al (2022) Efficacy of combination therapy with pembrolizumab and axitinib for metastatic renal collecting duct cell carcinoma: a report on two cases. IJU Case Rep 5:438–441. https://doi.org/10.1002/iju5.12504CrossRefPubMedPubMedCentral

49.

Yano M, Aso S, Sato M et al (2020) Pembrolizumab and radiotherapy for platinum-refractory recurrent uterine carcinosarcoma with an abscopal effect: a case report. Anticancer Res 40:4131–4135. https://doi.org/10.21873/anticanres.14412CrossRefPubMed

50.

Gefard-Gontier E, Markich R, Zysman M et al (2022) Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors. Cancer Immunol Immunother 71:2609–2618. https://doi.org/10.1007/s00262-022-03180-xCrossRefPubMedPubMedCentral

51.

Lind JSW, Postmus PE, Smit EF (2010) Osteoblastic bone lesions developing during treatment with erlotinib indicate major response in patients with non-small cell lung cancer: a brief report. J Thorac Oncol 5:554–557. https://doi.org/10.1097/JTO.0b013e3181d3e47eCrossRefPubMed

52.

Coleman RE, Croucher PI, Padhani AR et al (2020) Bone metastases. Nat Rev Dis Primers 6:83. https://doi.org/10.1038/s41572-020-00216-3CrossRefPubMed

53.

Yamashita Y, Aoki T, Hanagiri T et al (2012) Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response. Skeletal Radiol 41:409–414. https://doi.org/10.1007/s00256-011-1253-9CrossRefPubMed

54.

Philipp TC, Mikula JD, Doung Y-C, Gundle KR (2020) Is there an association between prophylactic femur stabilization and survival in patients with metastatic bone disease? Clin Orthop Relat Res 478:540–546. https://doi.org/10.1097/CORR.0000000000000803CrossRefPubMed

55.

Ward WG, Holsenbeck S, Dorey FJ et al (2003) Metastatic disease of the femur: surgical treatment. Clin Orthop Relat Res. https://doi.org/10.1097/01.blo.0000093849.72468.82CrossRefPubMed

56.

McLynn RP, Ondeck NT, Grauer JN, Lindskog DM (2018) What is the adverse event profile after prophylactic treatment of femoral shaft or distal femur metastases? Clin Orthop Relat Res 476:2381–2388. https://doi.org/10.1097/CORR.0000000000000489CrossRefPubMedPubMedCentral

57.

Aneja A, Jiang JJ, Cohen-Rosenblum A et al (2017) Thromboembolic disease in patients with metastatic femoral lesions: a comparison between prophylactic fixation and fracture fixation. J Bone Joint Surg Am 99:315–323. https://doi.org/10.2106/JBJS.16.00023CrossRefPubMed

58.

Liu L, Shi Z, Qiu X (2023) Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Clin Transl Oncol. https://doi.org/10.1007/s12094-023-03300-8CrossRefPubMedPubMedCentral

59.

Tsukamoto S, Kido A, Tanaka Y et al (2021) Current overview of treatment for metastatic bone disease. Curr Oncol 28:3347–3372. https://doi.org/10.3390/curroncol28050290CrossRefPubMedPubMedCentral

Titel: Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review
verfasst von: Shinji Tsukamoto
Andreas F. Mavrogenis
Tomoya Masunaga
Hisaki Aiba
Ayano Aso
Kanya Honoki
Hiromasa Fujii
Akira Kido
Yuu Tanaka
Yasuhito Tanaka
Costantino Errani
Publikationsdatum: 05.06.2024
Verlag: Springer Paris
Erschienen in: European Journal of Orthopaedic Surgery & Traumatology / Ausgabe 6/2024
Print ISSN: 1633-8065
Elektronische ISSN: 1432-1068
DOI: https://doi.org/10.1007/s00590-024-04018-1

Intracapsular neck of femur fractures secondary to civilian gunshot injuries: an inter- and intra-observer agreement study on classification and treatment using the AO/OTA classification

Open Access
Original Article

The management of critical bone defects: outcomes of a systematic approach

Open Access
Original Article

The association of hyponatremia and early postoperative complications in aseptic revision total shoulder arthroplasty

Open Access
Original Article

Risk factors for malalignment after intramedullary nail treatment of distal tibia fractures with associated fibula fractures

Open Access
Original Article

Delay to surgery beyond 12 hours is associated with increased hip fracture mortality

Open Access
Original Article

Continuous suture all-inside meniscal repair technique produces excellent functional outcomes and return to play rates with a low rate of failure

Original Article

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie erweitert durch Fallbeispiele, Videos und Abbildungen. Zur Fortbildung und Wissenserweiterung, verfasst und geprüft von Expertinnen und Experten der Gesellschaft für Arthroskopie und Gelenkchirurgie (AGA).

Jetzt entdecken!

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Viele Versäumnisse bei Psoriasis-Arthritis

17.04.2025
Psoriasis-Arthritis
Nachrichten

Menschen mit Psoriasis-Arthritis (PsA) müssen länger auf die Diagnose warten und werden zögerlicher behandelt als an rheumatoider Arthritis (RA) Erkrankte. Diese Defizite hat eine Untersuchung in Großbritannien aufgedeckt.

Yoga gegen Kniearthrose nicht schlechter als Krafttraining

15.04.2025
Gonarthrose
Nachrichten

Menschen mit Gonarthrose profitieren von Yogaübungen nicht weniger als von gezielten Kräftigungsübungen für die lädierten Knie. In einer Vergleichsstudie haben sich für Yogis und Yoginis sogar einige Vorteile ergeben.

Muskelrelaxanzien wohl nur bei akuten Kreuzschmerzen hilfreich

14.04.2025
Rückenschmerzen
Nachrichten

Bei akuten Rückenschmerzen können Muskelrelaxanzien, eventuell in Kombination mit NSAR, zur Schmerzlinderung beitragen. Wegen der Nebenwirkungen wird jedoch empfohlen, die Medikamente nur über wenige Tage einzusetzen.

Thoracic-Outlet-Syndrom nur in Ausnahmefällen operieren!

08.04.2025
DCK 2025
Nachrichten

Das Thoracic-Outlet-Syndrom erfordert nur in ganz bestimmten Fällen ein operatives Vorgehen. Beim DCK wurde vor schwerwiegenden Komplikationen des anspruchsvollen Eingriffs gewarnt.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review