Carbon-ion radiotherapy in accelerated hypofractionated active raster-scanning technique for malignant lacrimal gland tumors: feasibility and safety

Abstract

Introduction: We evaluated treatment outcomes of CIRT in an active raster-scanning technique alone or in combination with IMRT for lacrimal gland tumors.

Methods: A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan-Meier estimates. Toxicity was assessed according to the CTCAE version 5.

Results: Median follow-up was 30 months and overall median LC, OS, and DPFS 24 months, 36 months, and 31 months, respectively. Two-year LC, OS, and DPFS of 93%, 96%, and 87% with CIRT was achieved for all patients. Local failure occurred only in patients with ACC and after a median follow-up of 30 months after the completion of RT (n=5, 21%; P=0.09). We identified a significant negative impact of a macroscopic tumor disease, which was diagnosed on planning CT or MRI before RT, on LC (P=0.026). In contrast, perineural spread (P=0.661), T stage (P=0.552), and resection margins in operated patients (P=0.069) had no significant impact on LC. No grade ≥3 acute or grade >3 chronic toxicity occurred. Late grade 3 side effects were identified in form of a wound-healing disorder 3 months after RT in one patient and temporal lobe necrosis 6 months after RT in another (n=2, 8%).

Conclusion: Accelerated hypofractionated active raster-scanning CIRT for relative radio-resistant malignant lacrimal gland tumors results in adequate LC rates and moderate acute and late toxicity. Nevertheless, LC for ACC histology remains challenging and risk factors for local recurrence are still unclear. Further follow-up is necessary to evaluate long-term clinical outcome.

Keywords: adenoid cystic carcinoma; bimodal RT; carbon-ion radiotherapy; local control; malignant lacrimal gland tumor.

Figure 1

Bimodal treatment plan with IMRT (1) and CIRT (2) for patient 20 with a T4 ACC of the right lacrimal gland. Notes: Native planning CT (A), matched contrast-enhanced planning MRI (B), and coronal reconstruction of the planning CT (C) are depicted from top to bottom. The CTV is delineated in yellow and the PTV in a blue line.

Figure 2

MRI before RT start in patient 20. Notes: In the initial MRI before RT start, you can see an ACC of the right lacrimal gland that infiltrates the right lateral medius muscle and shows perineural spread into the right cavernous sinus. Already at 3 months after primary bimodal RT, PR was diagnosed in the follow-up MRI.

Figure 3

Kaplan–Meier survival curves. Note: (A) LC (median 24 months, range 6–59 months), OS (median 36 months, range 9–102 months), and DPFS (median 31 months, range 6–102 months) for all patients; (B) LC (median 24 months, range 6–59 months), OS (median 31 months, range 11–102 months), and DPFS (median 31 months, range 6–102 months) for ACC patients only. Abbreviation: DPFS, distant progression-free survival.

Figure 4

Kaplan–Meier curves for LC differed in dependence of histology. Notes: Estimated 2-year and 5-year LC for ACC of 80% vs 100% and 21% vs 100% compared with other histology (HR 43.0, 95% CI 0.5–107.8; P=0.09).

Figure 5

Kaplan–Meier curves. Notes: LC for ACC patients only dependent on presence of macroscopic tumor in planning CT and MRI scans before RT (R2 resection + definitive RT). In univariate analysis, we identified a macroscopic tumor before RT as a significant negative prognostic factor for these patients (HR 0.04, 95% CI 0–761.22; P=0.026).