Doubling Time
Published June 2000
Revised July 2004

Doubling Time
One cell divides into two, 2 to 4, 4 to 8, 8 to 16 etc. Exponential growth is found in many primary and metastatic malignancies. Use these calculators to determine doubling time.

Initial Film Date
 Enter dates as dd/mm/yyyy
Final Film Date
Days between studies
Initial Diameter (mm)
Final Diameter (mm)
Time between studies (days)
Doubling Time (days)
Initial Volume (mm3)
Final Volume (mm3)
Time between studies (days)
Doubling Time (days)
Clinical Value of Growth Rate:
  • Differential diagnosis
  • Predictor of longevity
  • Planning screening programs
  • Evaluate therapy
  • Study natural history

Growth rate of malignant tumors generally between 30 and 500 days (median 100 days).

Error rate in measuring growth rate: 7%

Minimal difference observable by CT: 0.3 mm

Smallest nodules that can be reliably seen with CT: 2 mm

Diameter reliable? (from Revel)

  • Intrareader variability 1.32 to 1.7 mm
  • Interreader variability 1.73 mm
  • thus to state wind confidence that a nodule has truly increased in size when measurements are made by 2 radiologists requires that the size increase (or decrease) by 1.73 mm
  • In contrast volume (as determined by computer program) has much less variability

Natural History of Growth
Doublings
Cells
Diameter
0
1
10 um
microscopic
20
1 x 106
1 mm
microscopic
30
1 x 109
1 cm
Detectable CXR
35
1 x 1010.5
3 cm
Average Diagnosis
40
1 x 1012
10 cm
Death
Equation for Doubling time = Ti x log2 / 3 x log(Di/Do) or (ln2 x Ti)/(ln(Vi/Vo)
  • Ti = interval time
  • Di = initial diameter
  • Do = final diameter
  • Vi = initial volume
  • Vo = final volume
    • References:

    Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. AJR 1957; 76:988-1000.

    Geddes DM. The natural history of lung cancer: a review based on rates of tumour growth. Br J Dis Chest 1979; 73:1-17.
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    Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997; 168:325-328.
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    Yankelevitz DF, Gupta R, Zhao B, Henschke CI. Small pulmonary nodules: evaluation with repeat CT--preliminary experience. Radiology 1999; 212:561-6.
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    M. Hasegawa, S. Sone, S. Takashima, F. Li, Z. G. Yang, Y. Maruyama and T. Watanabe. Growth rate of small lung cancers detected on mass CT screening. Br J Radiol 2000; 73:1252.
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    Winer-Muram HT, Jennings SG, Tarver RD, et al. Volumetric growth rate of stage I lung cancer prior to treatment: serial CT scanning. Radiology 2002; 223:798-805.
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    Revel MP, Bissery A, Bienvenu M, et al. Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable? Radiology 2004; 231:453-8.
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    Revel MP, Lefort C, Bissery A, et al. Pulmonary nodules: preliminary experience with three-dimensional evaluation. Radiology 2004; 231:459-66.
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    Kostis WJ, Yankelevitz DF, Reeves AP, Fluture SC, Henschke CI. Small pulmonary nodules: reproducibility of three-dimensional volumetric measurement and estimation of time to follow-up CT. Radiology 2004; 231:446-52.
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