Letter to the editor: Computed tomography Hounsfield unit values as a treatment response indicator for spinal metastatic lesions in patients with non-small-cell lung cancer: a retrospective study in Japan

Article information

Asian Spine J. 2025;19(4):675-676
Publication date (electronic) : 2025 August 5
doi : https://doi.org/10.31616/asj.2025.0237.r1
1Shaikh Khalifa Bin Zayed Al-Nahyan Medical and Dental College, Lahore, Pakistan
2Sheikh Zayed Hospital, Lahore, Pakistan
3Nursing Department, Communicable Disease Centre, Hamad Medical Corporation, Doha, Qatar
Corresponding author: Javed Iqbal, Nursing Department, Communicable Disease Center, Hamad Medical Corporation, Doha, Qatar, P.O Box 3050 Tel: +974-5595-1635, E-mail: jiqbal3@hamad.qa
Received 2025 April 24; Revised 2025 May 3; Accepted 2025 May 19.

To the Editor,

We have thoroughly engaged with the article “Computed tomography Hounsfield unit values as a treatment response indicator for spinal metastatic lesions in patients with non-small-cell lung cancer: a retrospective study in Japan” by Taniwaki et al. [1]. We congratulate the team and commend the efforts they put into this important and understudied area—quantitative evaluation of treatment response in spinal metastases using Hounsfield units (HU) in patients with non-small-cell lung cancer. However, despite the promising findings, we would like to suggest important methodological pointers that can further strengthen the findings of future studies with similar data.

First, the exclusion of 61 patients—33 of whom died within two months with rest lacking sufficient followup imaging—introduces survivorship bias. These patients likely had more aggressive disease and may have influenced HU trends, reducing generalizability of the results. Including them through imputation or sensitivity analysis can help mitigate bias [2].

Second, HU measurements were taken from single-slice manual regions of interests (ROIs) without assessing inter- or intra-observer variability. Given known HU variability due to ROI size, positioning, and scanner calibration, reproducibility is uncertain [3,4]. Future work should adopt reliability metrics such as intraclass correlation coefficients and consider automated volumetric analysis [5].

Third, defining HU “responders” using a median cutoff of 124 HU lacks biological justification. Dichotomizing a continuous variable without validation (e.g., receiver operating characteristic curve analysis) risks misclassification and limits interpretability. Future studies should seek to find and confirm best HU thresholds for survival prediction in separate groups [6].

Fourth, the multivariate model included only age, sex, and the modified Katagiri score, omitting critical prognostic factors such as visceral metastases, epidermal growth factor receptor/anaplastic lymphoma kinase status, programmed death-ligand 1 expression, and Eastern Cooperative Oncology Group performance status, which may confound results [7,8]. Their absence reduces the validity of the inferences made.

Finally, the retrospective, single-center design, small sample (n=85), and varied treatments limit generalizability. Prospective, multicenter studies with standardized imaging and treatment protocols would improve external validity and statistical power [9].

In conclusion, although the study identifies a potentially useful imaging biomarker, methodological improvements, more extensive prognostic modeling, and outside validation would support its findings. The treatment of spinal metastases may benefit from quantitative imaging like HU, but strict standardization and contextual interpretation are necessary.

Notes

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Author Contributions

Conceptualization: JI. Methodology: MHA, JI. Data curation: MHA, JI. Writing–the original draft: MHA, SMU, MHL, JI. Writing–reviewing and editing: MHA, JI. Supervision: JI. Final approval of the manuscript: all authors.

References

1. Taniwaki H, Dohzono S, Sasaoka R, Takamatsu K, Hoshino M, Nakamura H. Computed tomography Hounsfield unit values as a treatment response indicator for spinal metastatic lesions in patients with non-small-cell lung cancer: a retrospective study in Japan. Asian Spine J 2025;19:46–53.
2. Hernan MA, Robins JM. Causal inference: what if. Boca Raton (FL): Chapman & Hall/CRC; 2020.
3. Schreiber JJ, Anderson PA, Rosas HG, Buchholz AL, Au AG. Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Joint Surg Am 2011;93:1057–63.
4. Ahern DP, McDonnell JM, Riffault M, et al. A meta-analysis of the diagnostic accuracy of Hounsfield units on computed topography relative to dual-energy X-ray absorptiometry for the diagnosis of osteoporosis in the spine surgery population. Spine J 2021;21:1738–49.
5. Raunig DL, McShane LM, Pennello G, et al. Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment. Stat Methods Med Res 2015;24:27–67.
6. Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol 2010;5:1315–6.
7. Katagiri H, Okada R, Takagi T, et al. New prognostic factors and scoring system for patients with skeletal metastasis. Cancer Med 2014;3:1359–67.
8. Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA 2019;322:764–74.
9. Sheikh A, Smeeth L, Ashcroft R. Randomised controlled trials in primary care: scope and application. Br J Gen Pract 2002;52:746–51.

Article information Continued