Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle-mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes. SIGNIFICANCE: PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.

Skull Base Reconstruction in the Pediatric Patient.

Introduction Pediatric skull base and craniofacial reconstruction presents a unique challenge since the potential benefits of therapy must be balanced against the cumulative impact of multimodality treatment on craniofacial growth, donor-site morbidity, and the potential for serious psychosocial issues. Objectives To suggest an algorithm for skull base reconstruction in children and adolescents after tumor resection. Materials and Methods Comprehensive literature review and summary of our experience. Results We advocate soft-tissue reconstruction as the primary technique, reserving bony flaps for definitive procedures in survivors who have reached skeletal maturity. Free soft-tissue transfer in microvascular technique is the mainstay for reconstruction of large, three-dimensional defects, involving more than one anatomic region of the skull base, as well as defects involving an irradiated field. However, to reduce total operative time, intraoperative blood loss, postoperative hospital stay, and donor-site morbidity, locoregional flaps are better be considered the flap of first choice for skull base reconstruction in children and adolescents, as long as the flap is large enough to cover the defect. Our "workhorse" for dural reconstruction is the double-layer fascia lata. Advances in endoscopic surgery, image guidance, alloplastic grafts, and biomaterials have increased the armamentarium for reconstruction of small and mid-sized defects. Conclusions Skull base reconstruction using locoregional flaps or free flaps may be safely performed in pediatrics. Although the general principles of skull base reconstruction are applicable to nearly all patients, the unique demands of skull base surgery in pediatrics merit special attention. Multidisciplinary care in experienced centers is of utmost importance.