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. 2018 Oct;13(10):1549-1559.
doi: 10.1016/j.jtho.2018.06.007. Epub 2018 Jun 27.

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy

Kevin Shiue  1 , Alberto Cerra-Franco  1 , Ronald Shapiro  2 , Neil Estabrook  1 , Edward M Mannina  1 , Christopher R Deig  1 , Sandra Althouse  3 , Sheng Liu  4 , Jun Wan  4 , Yong Zang  5 , Namita Agrawal  1 , Pericles Ioannides  1 , Yongmei Liu  1 , Chen Zhang  6 , Colleen DesRosiers  1 , Greg Bartlett  1 , Marvene Ewing  1 , Mark P Langer  1 , Gordon Watson  1 , Richard Zellars  1 , Feng-Ming Kong  1 , Tim Lautenschlaeger  7
Affiliations

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy

Kevin Shiue et al. J Thorac Oncol. 2018 Oct.

Abstract

Introduction: It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC.

Methods: The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed.

Results: At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/β = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005-1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively).

Conclusions: In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Keywords: Histology; NSCLC; Stereotactic ablative radiotherapy; Stereotactic body radiation therapy.

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Conflict of interest statement

Declaration of Interests

KS, none; AC, none; RS, none; NE, none; EMM, none; CRD, none; SA, none; SL, none; JW, none; YZ, none; NA, none; PI, none; YL, none; CZ, none; CD, none; GB, none; ME, none; MPL, none; GW, none; RZ, none; FK, none; TL, none.

Figures

Figure 1
Figure 1
Involved lobe control for the dosimetric cohort (A) overall, (B) stratified by histology; in-field control for the dosimetric cohort (C) overall, (D) stratified by histology.
Figure 1
Figure 1
Involved lobe control for the dosimetric cohort (A) overall, (B) stratified by histology; in-field control for the dosimetric cohort (C) overall, (D) stratified by histology.
Figure 1
Figure 1
Involved lobe control for the dosimetric cohort (A) overall, (B) stratified by histology; in-field control for the dosimetric cohort (C) overall, (D) stratified by histology.
Figure 1
Figure 1
Involved lobe control for the dosimetric cohort (A) overall, (B) stratified by histology; in-field control for the dosimetric cohort (C) overall, (D) stratified by histology.
Figure 2
Figure 2
In-field control stratified by prescription dose (biologically effective dose, α/β=10, cutoff 110 Gy, no minimum limit) and (A) median gross tumor volume, or (B) adenocarcinomas vs squamous cell carcinomas.
Figure 2
Figure 2
In-field control stratified by prescription dose (biologically effective dose, α/β=10, cutoff 110 Gy, no minimum limit) and (A) median gross tumor volume, or (B) adenocarcinomas vs squamous cell carcinomas.
Figure 3
Figure 3
In-field control for adenocarcinomas vs squamous cell carcinomas in the study cohort, stratified by (A) 4- and 5-fraction and (B) 3-fraction schedules, (C) 12 Gy x 4 and 10 Gy x 5 schedules and (D) 18 Gy or 20 Gy x 3 schedules.
Figure 3
Figure 3
In-field control for adenocarcinomas vs squamous cell carcinomas in the study cohort, stratified by (A) 4- and 5-fraction and (B) 3-fraction schedules, (C) 12 Gy x 4 and 10 Gy x 5 schedules and (D) 18 Gy or 20 Gy x 3 schedules.
Figure 3
Figure 3
In-field control for adenocarcinomas vs squamous cell carcinomas in the study cohort, stratified by (A) 4- and 5-fraction and (B) 3-fraction schedules, (C) 12 Gy x 4 and 10 Gy x 5 schedules and (D) 18 Gy or 20 Gy x 3 schedules.
Figure 3
Figure 3
In-field control for adenocarcinomas vs squamous cell carcinomas in the study cohort, stratified by (A) 4- and 5-fraction and (B) 3-fraction schedules, (C) 12 Gy x 4 and 10 Gy x 5 schedules and (D) 18 Gy or 20 Gy x 3 schedules.
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