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Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control.

Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, Robinson W, Chidel M, Glode M, Raben D - Radiat Oncol (2011)

Bottom Line: On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05).In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.

ABSTRACT

Background: Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.

Methods: The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUVmax) were analyzed.

Results: The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.

Conclusions: An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.

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Local Control. Actuarial local control for both melanoma and RCC lesions
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Figure 1: Local Control. Actuarial local control for both melanoma and RCC lesions

Mentions: The actuarial rate of LC for all patients was 88% at 18 months (Figure 1). Several factors were analyzed by univariate analysis in an effort to identify predictors of LC. In general, for quantitative parameters, the median value was chosen as an arbitrary cut-off for univariate analysis to maximize the comparison cohorts. Log rank comparison revealed number of fractions (3 vs 5, p < 0.01) as well as dose per fraction (> 11 Gy/fraction vs <11 Gy/fractions, p < 0.01) and BED ( > 100 Gy vs < 100 Gy, p < 0.01) to be significant predictors of LC. Histology (RCC vs melanoma, p = 0.06) total dose (≥50Gy vs <50Gy, p = 0.09) SFED (≥ 45 Gy vs < 45 Gy, p = 0.06) and GTV (>7cc vs <7cc, p = 0.06) showed a strong trend towards significance. Site treated (lung vs other) and disease burden (oligometastatic vs widely metastatic) were not predictors of local control. Given the small number of events available to analyze, a multivariate analysis was not performed.


Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control.

Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, Robinson W, Chidel M, Glode M, Raben D - Radiat Oncol (2011)

Local Control. Actuarial local control for both melanoma and RCC lesions
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094365&req=5

Figure 1: Local Control. Actuarial local control for both melanoma and RCC lesions
Mentions: The actuarial rate of LC for all patients was 88% at 18 months (Figure 1). Several factors were analyzed by univariate analysis in an effort to identify predictors of LC. In general, for quantitative parameters, the median value was chosen as an arbitrary cut-off for univariate analysis to maximize the comparison cohorts. Log rank comparison revealed number of fractions (3 vs 5, p < 0.01) as well as dose per fraction (> 11 Gy/fraction vs <11 Gy/fractions, p < 0.01) and BED ( > 100 Gy vs < 100 Gy, p < 0.01) to be significant predictors of LC. Histology (RCC vs melanoma, p = 0.06) total dose (≥50Gy vs <50Gy, p = 0.09) SFED (≥ 45 Gy vs < 45 Gy, p = 0.06) and GTV (>7cc vs <7cc, p = 0.06) showed a strong trend towards significance. Site treated (lung vs other) and disease burden (oligometastatic vs widely metastatic) were not predictors of local control. Given the small number of events available to analyze, a multivariate analysis was not performed.

Bottom Line: On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05).In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.

ABSTRACT

Background: Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.

Methods: The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUVmax) were analyzed.

Results: The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUVmax was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.

Conclusions: An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.

Show MeSH
Related in: MedlinePlus