Overlap-Adapted Subvolume Prescription to Reduce Temporal Lobe Injury Risk in T4 Nasopharyngeal Carcinoma: A Prospective Cohort Study With a Contemporaneous Comparator.

PURPOSE: Radiation-induced temporal lobe injury (RTLI) remains a major late toxicity in T4 nasopharyngeal carcinoma (NPC) because primary target volumes frequently overlap the temporal lobe planning risk volume, limiting near-maximum dose constraints. This study evaluated the long-term safety and efficacy of an overlap-adapted subvolume prescription strategy.

METHODS AND MATERIALS: This nonrandomized, single-institution, prospective observational cohort study with a contemporaneous comparator (ClinicalTrials.gov identifier: NCT03539250) enrolled patients with T4N0-3M0 NPC treated between 2018 and 2022 who had planning target volume (PTV)-temporal lobe planning risk volume overlap ≥0.1 cm3. The modified delineation and planning (MD) approach subdivided the primary tumor PTV (PTVnx) into a nonoverlap subvolume (PTVsv1, prescribed 70 Gy) and an overlapping subvolume (PTVsv2, prescribed 66 Gy) using simultaneous integrated boost. The standard delineation and planning (SD) approach prescribed a uniform 70 Gy to the entire PTVnx.

RESULTS

Among 361 patients (MD, n = 104; standard delineation and planning, n = 257), the 5-year cumulative incidence of RTLI was significantly lower in the MD group (23.2% vs 36.2%; P = .019). Multivariable analysis revealed that MD was independently associated with reduced RTLI risk (hazard ratio, 0.56; 95% CI, 0.34-0.94; P = .029). No significant differences were found in 5-year local relapse-free survival (92.3% vs 89.6%; P = .577) or overall survival (84.7% vs 84.4%; P = .896). No marginal recurrences were confined to PTVsv2. After lobe-level propensity-score matching (205 lobes per group), MD achieved significantly lower temporal-lobe maximum dose and dose to 1 cm3 (both P < .001) without differences in volumes receiving 40 to 60 Gy and a borderline reduction in volume receiving ≥65 Gy (P = .053).

CONCLUSIONS

An overlap-adapted subvolume prescription strategy (66 Gy to PTVsv2) significantly reduced the incidence of radiographic RTLI while preserving long-term tumor control in anatomically constrained T4 NPC. The reduction in symptomatic RTLI was numerical but did not reach statistical significance and warrants further validation.