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Review
. 2023 Sep 6;23(1):834.
doi: 10.1186/s12885-023-11360-w.

Osteoblastic bone reaction in non-small cell lung cancer harboring epidermal growth factor receptor mutation treated with osimertinib

Kensuke Kanaoka  1 , Hiromitsu Sumikawa  2 , Shunsuke Oyamada  3 , Akihiro Tamiya  4 , Yuji Inagaki  4 , Yoshihiko Taniguchi  4 , Keiko Nakao  4 , Yoshinobu Matsuda  4 , Kyoichi Okishio  5
Affiliations
Review

Osteoblastic bone reaction in non-small cell lung cancer harboring epidermal growth factor receptor mutation treated with osimertinib

Kensuke Kanaoka et al. BMC Cancer. .

Abstract

Background: Osteoblastic bone reaction (OBR) refers to an increase in bone density at the site of bone metastasis or the appearance of new sclerotic bone lesions after anticancer treatment. OBR can be misunderstood as disease progression. In this study, we aimed to investigate the prevalence and details of OBR and its association with clinical outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with osimertinib.

Methods: This was a single-center, retrospective cohort study. We reviewed patients who were diagnosed with EGFR-mutant NSCLC with bone metastasis and received osimertinib as a first-line treatment between February 2018 and October 2022. The OBR was evaluated by comparing baseline computed tomography (CT) scans with the first CT scan after treatment initiation.

Results: A total of 45 patients were included in this study. Thirty-seven patients (82%) developed OBR. OBR developed in 94% (n = 16) of patients with sclerotic bone lesions (n = 17) at baseline. Similarly, OBR developed in lytic and mixed bone lesions in 76% and 82% of patients with lytic and mixed lesions, respectively. Progression-free survival (PFS) did not differ significantly between patients with (OBR group) and without OBR (non-OBR group) (median PFS, 24 months vs. 17 months; hazard ratio (HR), 0.62; 95% CI, 0.24-1.6; p = 0.31). In univariate analysis, the OBR group showed a trend toward longer skeletal-related events-free survival (SRE-FS) than the non-OBR group (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21-1.33; p = 0.16). Multivariate analysis showed OBR was a significant independent predictor of SRE-FS (HR, 0.35; 95% CI, 0.13-0.92; p = 0.034).

Conclusions: OBR developed in most patients with NSCLC and bone metastasis who received osimertinib treatment. The increased incidence of OBR in patients with EGFR-mutant NSCLC with bone metastasis treated with osimertinib should not be confused with disease progression, and treatment decisions should be made carefully.

Keywords: Bone metastasis; Epidermal growth factor receptor; Non-small cell lung cancer; Osimertinib; Osteoblastic bone reaction; Progression-free survival; Skeletal-related events.

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Conflict of interest statement

Dr. Kanaoka received personal fees from AstraZeneca outside the submitted work. Dr. Oyamada received honoraria from Chugai Co. Dr. Tamiya received grants from AstraZeneca, Beigene, and Daiichi-Sankyo, and personal fees from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, MSD, Taiho, Pfizer, Takeda Pharmaceutical, Nihon Kayaku, Novartis, Merck Biopharma, and Thermo Fisher Scientific outside the submitted work. Dr. Inagaki received personal fees from AstraZeneca, Chugai, Chugaiigakusya, and Pfizer outside the submitted work. Dr. Taniguchi received personal fees from Chugai Pharmaceutical, Ono Pharmaceutical, and AstraZeneca outside the submitted work. The remaining authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Inclusion cohort of the study. CT, computed tomography; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer
Fig. 2
Fig. 2
The typical example of each pattern of osteoblastic bone reaction (OBR). A 58-year-old woman showed sclerotic bone metastasis in the vertebra at baseline (A) and increased bone density after 3 months (B). An 84-year-old woman presented lytic bone metastasis at the pelvis at baseline (C) and conversion to sclerotic lesion after 2 months (D). Another 84-year-old woman presented lytic bone metastasis at the pelvis at baseline (E) and increased bone density after 3 months (F). Arrowheads show the sites in which OBR developed
Fig. 3
Fig. 3
PFS of patients with (OBR group) and without OBR (non-OBR group). PFS was not significantly different between the OBR and non-OBR groups (24 months vs. 17 month; HR, 0.62; 95% CI, 0.24–1.6; p = 0.31). HR, hazard ratio; OBR, osteoblastic bone reaction; PFS, progression-free survival
Fig. 4
Fig. 4
SRE-FS of patients with (OBR group) and without OBR (non-OBR group). The median SRE-FS was not significantly different between the OBR and non-OBR groups (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21–1.33; p = 0.16). HR, hazard ratio; OBR, osteoblastic bone reaction; SRE-FS, skeletal-related events-free survival
See this image and copyright information in PMC

References

    1. Al Husaini H, Wheatley-Price P, Clemons M, Shepherd FA. Prevention and management of bone metastases in lung cancer: a review. J Thorac Oncol. 2009;4:251–259. doi: 10.1097/JTO.0b013e31819518fc. - DOI - PubMed
    1. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(Suppl):1588–1594. doi: 10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G. - DOI - PubMed
    1. Yamashita Y, Aoki T, Hanagiri T, Yoshii C, Mukae H, Uramoto H, et al. Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response. Skelet Radiol. 2012;41:409–414. doi: 10.1007/s00256-011-1253-9. - DOI - PubMed
    1. Riihimäki M, Hemminki A, Fallah M, Thomsen H, Sundquist K, Sundquist J, et al. Metastatic sites and survival in lung cancer. Lung Cancer. 2014;86:78–84. doi: 10.1016/j.lungcan.2014.07.020. - DOI - PubMed
    1. Chen YY, Wang PP, Fu Y, Li Q, Tian JF, Liu T, et al. Inferior outcome of bone metastasis in non-small-cell-lung-cancer patients treated with epidermal growth factor receptor inhibitors. J Bone Oncol. 2021;29:100369. doi: 10.1016/j.jbo.2021.100369. - DOI - PMC - PubMed