Photoimmunotherapy in nasopharyngeal carcinoma recurrence.
Authors: Shinozaki Takeshi , Taruya Takayuki , Okamoto Isaku , Omura Go , Makino Takuma , Endo Kazuhira , Kushihashi Yukiomi , Ohba Shinichi , Wasano Koichiro , Saito Yuki , Mochizuki Daiki , Minagi Masahito , Kato Hisayuki , Takemoto Tsuyoshi , Sano Daisuke , Nishiya Yukio , Sakashita Shingo , Mori Taisuke 
Published: June 2024

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Background: Photoimmunotherapy is a novel anticancer treatment developed by the NCI and has been covered by insurance in Japan since January 2021 for patients with unresectable, locally advanced or locally recurrent head and neck cancers. Over 400 patients have been treated with photoimmunotherapy in Japan, including 19 cases with recurrent nasopharyngeal carcinoma. Photoimmunotherapy uses an antibody-drug conjugate, cetuximab sarotalocan sodium, comprising cetuximab, a chimeric monoclonal antibody (IgG1) that targets human EGFR, and a light-sensitive dye, IRDye 700DX (IR700). The conjugate exhibits a strong affinity for cells expressing EGFR, which is enhanced in HNSCC. When exposed to a 690 nm (red) laser beam from the BioBlade laser system, the dye is activated, resulting in selective and rapid death of cells to which the conjugate is bound. The mechanism involves: (i) activation of the antibody conjugate by laser illumination, (ii) damage to the cell membrane, (iii) increased transmembrane water flux, and (iv) cell rupture and necrosis. The entire process occurs rapidly following laser illumination. Nasopharyngeal carcinoma is primarily treated with radiation therapy; however, if it persists, therapy becomes challenging. Surgical intervention for local recurrence or residual disease can be difficult due to the anatomical characteristics of the disease. Drugs and re-irradiation have limited effectiveness and significant adverse events have been reported. Photoimmunotherapy is considered more effective for nasopharyngeal carcinoma than other treatment sites. Methods: Nineteen patients with recurrent residual nasopharyngeal carcinoma following irradiation, who were treated with photoimmunotherapy at 15 centers across Japan, were reviewed. The study analyzed patients’ previous treatment regimens, laser irradiation methods employed in photoimmunotherapy, and pathological characteristics before and after treatment. Results: The mean observation duration was 368 days (median 302 days). A total of 10 patients received photoimmunotherapy once, 5 received it twice, 2 received it three times, and 2 received it four times. Final local control was achieved in 14 patients with CR, 3 with PR and 1 with SD. Regrettably, 3 patients developed distant metastases after the start of photoimmunotherapy. At the end of the observation period, 11 patients were disease-free, 6 were alive with cancer, and 2 died of carotid artery rupture despite achieving local tumor control. The overall survival rate at 1 year was 88.2 %. Conclusions: The outcomes of the photoimmunotherapy demonstrated successful local control of recurrent nasopharyngeal carcinoma. This innovative therapeutic approach holds significant potential for addressing nasopharyngeal cancer recurrence. However, it is crucial to carefully evaluate patients who can safely be treated using this method.