Radiation dose-volume effects in the lung

Abstract

The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold "tolerance dose-volume" levels. There are strong volume and fractionation effects.

Figure 1

Meta-analysis of reported n-values (volume parameter) for the LKB model using an inverse-variance (IV) weighting method. Recovery of variance estimates from the 95% confidence intervals (CI) and use of ~± 2*sigma instead of 1.96*sigma gave rise to small deviations in the derived 95% CI as compared to the literature reported values. Data estimated from (, –41). Abbreviations: n = n-values for the LKB Model, IV = inverse variance, Fixed = fixed effect model CI = confidence interval. The n value reflects the manner in which dose/volume parameters lead to complications. A lower value of n suggests that the tissue is sensitive to hot spots (e.g., an organ structured in “series”), while a higher value of n (closer to 1.0), suggests that the risk is more related to the volume of an organ irradiated (e.g., “parallel” structure).

Figure 2

Rate of RP following fractionated partial lung RT related to: Panel A: Mean lung dose. Confidence intervals shown are ±1 standard deviation. .Mean dose response data from: MSKCC, (10) from Fig 4a; (≥RTOG grade 3, 6 months); Duke, (15) from Table 4; (≥CTC grade 1, 6 months); Michigan, (43) from Table 4 and Fig 2a; (≥SWOG grade 2, 6 months)—bin location and time from authors; MD Anderson, (44) from Fig 2; (≥CTC grade 3, 1 year actuarial—includes concurrent chemo patients); NKI, (9) from Fig 3a; (≥SWOG grade 2, 6 months); Washington University, (11) from Fig 9c; (≥SWOG grade 2—no time limit) with bin locations from authors, increased by 11% to ~account for inhomogeneity corrections; Michigan, (45) from Table 1; (≥SWOG grade 1) with mean doses calculated from relationship between EUD (n=0.87) and mean dose from Kwa et al. (42), Fig 2a); Heidelberg, (46) from Fig 2 and text (≥RTOG acute grade 1); Milan, (47) from Fig 3; (≥SWOG Grade 2—no time limit, patients without COPD – includes induction chemo patients); Gyeonggi, (48) from Table 5; (≥RTOG grade 3, 6 months—includes concurrent chemo patients)—median values of mean dose in each bin provided by the authors. Dashed line is logistic fit: data fit to the form (f/(1+f)), where f=exp(b0+b1*dmean). Best fit values [95% confidence intervals] are b0 = −3.87 [−3.33–−4.49], b1 = 0.126 [0.100–0.153], corresponding to TD₅₀ = 30.75 [28.7–33.9] Gy and γ₅₀ = 0.969 [0.833–1.122], where γ₅₀ represents the increase in response [measured in %] per 1% increase in dose, near the 50% dose response level. Panel B: The rate of RP is shown for different values of Vx. V_x response data from: Yorke V₁₃, V₄₀, (10) from Fig 4d; Willner V₄₀, (68) from Fig 4; Hernando V₃₀, (15) from Table 6; Tsujino V_20, (56) from Fig 1; Kong V₁₃, V₂₀, (43), from Table 4; Armstrong V₂₅, (59) Fig 3; Kim V₂₀, V₃₀, (69) from Table 5; Graham V₂₀, (7) from Table 4; Seppenwoolde V₁₃, (40) from Fig 2; Wang V₅, (44). Some data estimated from published reports.

Figure 2

Rate of RP following fractionated partial lung RT related to: Panel A: Mean lung dose. Confidence intervals shown are ±1 standard deviation. .Mean dose response data from: MSKCC, (10) from Fig 4a; (≥RTOG grade 3, 6 months); Duke, (15) from Table 4; (≥CTC grade 1, 6 months); Michigan, (43) from Table 4 and Fig 2a; (≥SWOG grade 2, 6 months)—bin location and time from authors; MD Anderson, (44) from Fig 2; (≥CTC grade 3, 1 year actuarial—includes concurrent chemo patients); NKI, (9) from Fig 3a; (≥SWOG grade 2, 6 months); Washington University, (11) from Fig 9c; (≥SWOG grade 2—no time limit) with bin locations from authors, increased by 11% to ~account for inhomogeneity corrections; Michigan, (45) from Table 1; (≥SWOG grade 1) with mean doses calculated from relationship between EUD (n=0.87) and mean dose from Kwa et al. (42), Fig 2a); Heidelberg, (46) from Fig 2 and text (≥RTOG acute grade 1); Milan, (47) from Fig 3; (≥SWOG Grade 2—no time limit, patients without COPD – includes induction chemo patients); Gyeonggi, (48) from Table 5; (≥RTOG grade 3, 6 months—includes concurrent chemo patients)—median values of mean dose in each bin provided by the authors. Dashed line is logistic fit: data fit to the form (f/(1+f)), where f=exp(b0+b1*dmean). Best fit values [95% confidence intervals] are b0 = −3.87 [−3.33–−4.49], b1 = 0.126 [0.100–0.153], corresponding to TD₅₀ = 30.75 [28.7–33.9] Gy and γ₅₀ = 0.969 [0.833–1.122], where γ₅₀ represents the increase in response [measured in %] per 1% increase in dose, near the 50% dose response level. Panel B: The rate of RP is shown for different values of Vx. V_x response data from: Yorke V₁₃, V₄₀, (10) from Fig 4d; Willner V₄₀, (68) from Fig 4; Hernando V₃₀, (15) from Table 6; Tsujino V_20, (56) from Fig 1; Kong V₁₃, V₂₀, (43), from Table 4; Armstrong V₂₅, (59) Fig 3; Kim V₂₀, V₃₀, (69) from Table 5; Graham V₂₀, (7) from Table 4; Seppenwoolde V₁₃, (40) from Fig 2; Wang V₅, (44). Some data estimated from published reports.

Figure 3

Whole lung irradiation for diffuse lung or boney metastases, or prophylaxis for occult metastatic disease (, –63). Numbers in parentheses give the incidence of pneumonitis divided by the population at risk for each fractionation scheme in each study. Some data estimated from published reports.