Letter to the Editor | Open | Published:
Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer; methodological issues to avoid mismanagement of the patients
EJNMMI Researchvolume 7, Article number: 23 (2017)
I was interested to read the paper by Grkovski M and colleagues published in the Dec 2016 issue of EJNMMI Res . They aimed to assess the reproducibility of 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) as a non-invasive, quantitative imaging technique, spatiotemporal intratumour distribution in patients with non-small cell lung cancer (NSCLC) . The Pearson correlation coefficient r was calculated for mean standardized uptake values (SUV) within investigated volumes of interest and for voxels within tumour volumes (r TV). The reproducibility of FMISO voxelwise distribution, SUV- and tumour-to-blood ratio (TBR)-derived indices was assessed using correlation and Bland-Altman analyses . Although they correctly used Bland-Altman, they reported Pearson’s correlation r which in reproducibility (precision, repeatability, reliability, or interchangeability) is one of the common mistakes [2–6]. Pearson’s correlation r only assesses the linearity between two continuous variables. Any shift in the location and/or scale of the regression line which leads to non-reproducibility cannot be detected by this correlation coefficient [2–6]. Therefore, for quantitative variables, Intra Class Correlation Coefficient single measure is the best statistical test to evaluate reproducibility [2–6].
Based on their results, the SUVmax, SUVmean, TBRmax, and TBRmean were highly correlated (r ≥ 0.87, p < 0.001) and were reproducible to within 10–15% . It is good to know that in reliability analysis, individual based approach should be considered instead of global average which Pearson’s correlation r cannot do. It means we can simply get strongly positive and significant Pearson r (r = 0.95, p value < 0.001) with no reproducibility at all. Moreover, statistically significant should not be considered in reproducibility analysis [2–6]. They concluded high reproducibility of FMISO intratumour distribution in NSCLC patients, facilitating its use in determining the topology of the hypoxic tumour sub-volumes for dose escalation, in patient stratification strategies for hypoxia-targeted therapies, and in monitoring response to therapeutic interventions. Such conclusion may be a misleading message due to inappropriate use of statistical test to assess reproducibility. Briefly, for reliability analysis, appropriate tests should be applied; otherwise, misdiagnosis and mismanagement of the patients cannot be avoided.
Grkovski M, Schwartz J, Rimner A, Schöder H, Carlin SD, et al. Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer. EJNMMI Res. 2016;6(1):79. Epub 2016 Nov 7.
Szklo M, Nieto FJ. Epidemiology beyond the basics. 2nd ed. Manhattan, New York: Jones and Bartlett Publisher; 2007.
Sabour S. Reliability assurance of EML4-ALK rearrangement detection in non-small cell lung cancer: a methodological and statistical issue. J Thorac Oncol. 2016;11(7):e92–3. doi:10.1016/j.jtho.2016.04.022.
Sabour S, Ghassemi F. Comments on Reproducibility of digital measurements of lower-limb deformity on plain radiographs and agreement with CT measurements by Sorin G, Pasquier G, Drumez E, Arnould A, Migaud H, Putman S published in Orthop Traumatol Surg Res 2016;102:423-28. Common mistake and methodological issue to avoid mismanagement. Orthop Traumatol Surg Res. 2016;102(6):827–8. doi:10.1016/j.otsr.2016.07.001. Epub 2016 Aug 12.
Sabour S. Reproducibility of semi-automatic coronary plaque quantification in coronary CT angiography with sub-mSv radiation dose; common mistakes. J Cardiovasc Comput Tomogr. 2016;10(5):e21–2. doi:10.1016/j.jcct.2016.07.002. Epub 2016 Jul 9.
Sabour S. Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation. Common mistakes and methodological issue. Atherosclerosis. 2016;251:490–1. doi:10.1016/j.atherosclerosis.2016.05.035. Epub 2016 May 20.
The author declares that he has no competing interests.