We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T‐MTV) or T classification would be a better predictor of laryngectomy‐free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T‐MTV cut‐off value was determined by time‐dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T‐MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T‐MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T‐MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97–8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47–6.69; P = 0.004) compared with small T‐MTV (≤28.7 mL). The T‐MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three‐year LFS and OS rates for patients with small versus large T‐MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2‐T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99–1.00). Given the excellent interobserver reliability, T‐MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

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Background: Boron neutron capture therapy is a radiotherapy utilizing the neutron capture reaction. The commonly used boron agent, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumors. In this study, to propose a novel strategy of selective boron delivery targeting peptide transporter, we developed BPA-containing dipeptides (BPA-Tyr and Tyr-BPA) and examined their interaction with peptide transporters and their uptake into tumor cells. Methods: We established HEK293 cells stably expressing PEPT1 or PEPT2, and examined their interaction with BPA-Tyr and Tyr-BPA. Dipeptide transport activity was compared among tumors with varied PEPT1 and PEPT2 expression levels. We evaluated the boron accumulation in tumors after the treatment of BPA-Tyr and Tyr-BPA in vitro and in vivo. Results: BPA-Tyr and Tyr-BPA are transported by PEPT1 and PEPT2. The peptide transport activity in tumor cells correlated with PEPT1 expression level. BPA-Tyr and Tyr-BPA were delivered into PEPT1-expressing tumor cells via a PEPT1-mediated mechanism in vitro. In vivo, intravenous administration of BPA-Tyr resulted in a higher accumulation in the tumors compared with the blood. Conclusion: PEPT1 is a promising target for cancer-specific boron delivery in BNCT, using BPA-containing dipeptide-based boron agents.