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  • Letter to the Editor
  • Open Access

Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer; methodological issues to avoid mismanagement of the patients

EJNMMI Research20177:23

  • Received: 5 December 2016
  • Accepted: 21 February 2017
  • Published:


  • Reproducibility
  • PET
  • Methodology
  • Mismanagement

I was interested to read the paper by Grkovski M and colleagues published in the Dec 2016 issue of EJNMMI Res [1]. 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) [1]. 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 [1]. 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 [26]. 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 [26]. Therefore, for quantitative variables, Intra Class Correlation Coefficient single measure is the best statistical test to evaluate reproducibility [26].

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% [1]. 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 [26]. 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.


Competing interests

The author declares that he has no competing interests.



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Authors’ Affiliations

Safety Promotion and Injury Prevention Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R., Iran
Department of Clinical Epidemiology, Shahid Beheshti University of Medical Sciences, Tehran, I.R., Iran


  1. 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.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Szklo M, Nieto FJ. Epidemiology beyond the basics. 2nd ed. Manhattan, New York: Jones and Bartlett Publisher; 2007.Google Scholar
  3. 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.View ArticlePubMedGoogle Scholar
  4. 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.View ArticlePubMedGoogle Scholar
  5. 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.View ArticlePubMedGoogle Scholar
  6. 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.View ArticlePubMedGoogle Scholar


© The Author(s). 2017