# Rapidly progressive arthropathy identified on imaging of patients treated with Crizotinib for ALK-rearranged/ROS1-positive non small cell lung cancer: A retrospective single-center study

**Authors:** Yael Eshet, Liran Domachevsky, Noam Tau, Gregory Peters Founshtein, Michal Eifer, Jair Bar, Iris Eshed, Avaniyapuram Kannan Murugan, Alejandro Torrado Pacheco, Alejandro Torrado Pacheco, James Mockridge, James Mockridge

PMC · DOI: 10.1371/journal.pone.0333223 · PLOS One · 2026-02-18

## TL;DR

This study found that crizotinib, a cancer drug, can cause joint damage in some patients, as seen on imaging scans.

## Contribution

The study reports a significant association between crizotinib treatment and progressive arthropathy in lung cancer patients.

## Key findings

- 18% of crizotinib-treated patients developed irreversible joint damage.
- Imaging showed synovial proliferation and vertebral endplate destruction.
- Arthropathy occurred up to six years after treatment initiation.

## Abstract

Progressive arthropathy was anecdotally described in patients exposed to crizotinib, a receptor tyrosine kinases inhibitor (TKI) used to treat anaplastic lymphoma kinase (ALK) or ROS Proto-Oncogene 1 (ROS1) positive non-small cell lung cancer (NSCLC). We aimed to evaluate the incidence of this adverse effect.

We retrospectively evaluated imaging studies of all patients in our institution receiving TKI for ALK-rearranged or ROS1-positive NSCLC (crizotinib, alectinib, lorlatinib, brigatinib).

Between February 2012 and August 2023, out of a total number of 71 subjects (51% male, 36−88 years old) who received TKI’s for ALK-rearranged/ ROS1 positive NSCLC, 34/71 (47%) were exposed at least once to crizotinib treatment, while the other 37/71 (53%) patients received other TKI’s. Significantly higher incidence (p = 0.02) of irreversible, progressive arthropathy in one or more joints was detected in 18% (6/34, 95% CI: 0.1–0.26) of crizotinib-treated patients, up to 6 years after treatment initiation. Imaging findings included synovial proliferation and progressive arthropathy in hip and shoulder joints, and vertebral endplate destruction.

We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

## Linked entities

- **Genes:** ALK (ALK receptor tyrosine kinase) [NCBI Gene 238], ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098]
- **Chemicals:** Crizotinib (PubChem CID 11597571), alectinib (PubChem CID 49806720), lorlatinib (PubChem CID 71731823), brigatinib (PubChem CID 68165256)
- **Diseases:** non-small cell lung cancer (MONDO:0005233), arthropathy (MONDO:0006816)

## Full-text entities

- **Genes:** NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}
- **Diseases:** psoas abscess (MESH:D016659), calcifications (MESH:D002114), tumors (MESH:D009369), rearranged (MESH:D002869), shoulder pain (MESH:D020069), bursitis (MESH:D002062), bone marrow edema (MESH:D004487), inflammation (MESH:D007249), respiratory infection (MESH:D012141), pain (MESH:D010146), end plate sclerosis (MESH:D000072042), arthropathy of the hip and shoulder joint (MESH:D000070599), degenerative osteoarthritis (MESH:D010003), arthritic changes (MESH:D015535), humeral head dislocation (MESH:D012784), fever (MESH:D005334), NSCLC (MESH:D002289), cervical or back pain (MESH:D019547), sclerosis (MESH:D012598), osteopenia (MESH:D001851), pneumonitis (MESH:D011014), synovitis (MESH:D013585), Synovial joint arthropathy (MESH:D013581), vertebral osteitis (MESH:D010000), Spinal arthropathy (MESH:D007592), toxicity (MESH:D064420), erosions (MESH:D014077), bone deformity (MESH:D001847), arthritis (MESH:D001168), rheumatoid arthritis (MESH:D001172), death (MESH:D003643), mobility (MESH:D014086), joint destruction (MESH:D008105), subluxation (MESH:D004204), septic arthritis (MESH:D001170), QT interval prolongation (MESH:D008133), bony deformity (MESH:D018213), bacterial infection (MESH:D001424), rotator cuff injury (MESH:D000070636), Neuropathic arthropathy (MESH:D009437), multi-articular disease (MESH:C564969), ILD (MESH:D017563)
- **Chemicals:** Crizotinib (MESH:D000077547), alectinib (MESH:C582670), F18-Fludeoxyglucose (MESH:D019788), PONE-D-25-06712R3 (-), brigatinib (MESH:C000598580), lorlatinib (MESH:C000590786), entrectinib (MESH:C000607349), steroid (MESH:D013256)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12915974/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12915974/full.md

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Source: https://tomesphere.com/paper/PMC12915974