Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin

Abstract

Importance: Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography-based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors.

Objective: To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors.

Design, setting, and participants: This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared.

Exposure: Online ART for gynecologic tumors.

Main outcomes and measures: Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum).

Results: The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of -1.5% (90% CI, -31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of -0.02% (90% CI, -3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was -13.1% (90% CI, -47.9% to 1.6%) compared with 0.1% (90% CI, -2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients.

Conclusions and relevance: This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Stuschke reported receiving a research grant (to institution) from AstraZeneca; and serving on the advisory boards for AstraZeneca, Bristol Myers Squibb, Janssen-Cilag, and Sanofi/Aventis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Empirical Distribution Functions

A, Plot of empirical distribution function of percentage minimum dose deviation for interfractional clinical target volume (iCTV) for the adapted and scheduled plans (in comparison with the reference plan on the planning computed tomography [CT] scan). The empirical distributions differed significantly (P < .001; Kruskal-Wallis test). B, Plot of empirical distribution function of generalized equivalent uniform dose (gEUD) deviations for iCTV using the scheduled or adapted plans. The gEUD deviation values were normalized by the gEUD for the CTV in the planning CT scan and calculated from the dose-volume histograms using an exponent a = −20. The empirical distributions differed significantly (P < .001; Kruskal-Wallis test). C, Plot of empirical distribution function of normalized gEUD deviations for interfractional planning target volume (iPTV) using the scheduled dose distribution by the scheduled plan or adapted plans. The empirical distributions differed significantly between the scheduled and adapted plans over the fractions (P < .001; Kruskal-Wallis test). D, Interpatient variability (patients 1-7) of empirical distribution function of normalized gEUD deviations for iCTV using the adapted plan. The normalized interfractional gEUD deviation values were distributed over a small range from −4% to 8% compared with the planned dose distribution on the planning CT scan. E, Interpatient variability of the empirical distribution functions for the paired differences of interfractional normalized gEUD deviation values for iCTV using the adaptive and the scheduled plans. There was a significant interpatient variability in the gains of adaptation (P < .001; Kruskal-Wallis test). ART indicates adaptive radiotherapy; IGRT, image-guided radiotherapy.

Figure 2.. Scatterplot of Normalized Generalized Equivalent Uniform Dose (gEUD) Deviation Values for Interfractional Clinical Target Volume (iCTV) Using the Adapted Plan vs Normalized gEUD Deviation Values Using the Scheduled Plan

The gEUD deviation values for iCTV using the adapted plan remained independent from those using the scheduled plan (r = 0.00). The dashed lines indicate 95% CIs for individual new estimates, the shaded area indicates the 95% CIs for expected estimated values, and the solid line indicates the adaptation line.

Figure 3.. Change in Normalized Generalized Equivalent Uniform Dose (gEUD) for Interfractional Clinical Target Volume (iCTV)

A, Scatterplot highlighting increase in the change in gEUD for iCTV using the adapted plan compared with the scheduled plan vs increase in change in the normalized gEUD for the bladder using the adapted plan compared with the scheduled plan. B, Increase in the change in gEUDiCTV using the adapted plan compared with the scheduled plan vs increase in change in the normalized gEUD for the rectum using the adapted plan compared with the scheduled plan. ART indicates adaptive radiotherapy; IGRT, image-guided radiotherapy. The dashed lines indicate 95% CIs for individual new estimates, the shaded area indicates the 95% CIs for expected estimated values, and the solid line indicates the adaptation line.

Figure 4.. Change in Normalized Generalized Equivalent Uniform Dose (gEUD) for Clinical Target Volume (CTV) Values Comparing the Adaptive Plans With the Scheduled Plan Accumulated Over All Fractions per Series

The change in gEUD for CTV values were obtained from the accumulated dose distributions for the adapted and scheduled plans for each of the 10 delivered treatment series and planning target volume (PTV) margins of 5 mm and 0 mm, respectively. The gain by adaption is larger for a PTV margin of 0 mm compared with 5 mm (P = .004; signed rank test for intraseries comparisons). ART indicates adaptive radiotherapy; IGRT, image-guided radiotherapy.