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Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

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SummaryThe five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1 nu and NOD/SCID mice and treated with intratumoral injection of 30 μg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1 nu mice compared to NOD/SCID mice.Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

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IntroductionThe incidence of nonmelanoma cutaneous head and neck malignancies is increasing worldwide.1 In a small percentage of cases, associated perineural spread (PNS) of cranial nerves occurs, resulting in poor prognosis, with a recorded 5-year survival rate of 50% to 64.3%. 2,3 Patients with clinical PNS from cutaneous head and neck malignancies are treated with surgical resection and postoperative radiotherapy. Recent literature provides few reports of PNS that extends across the facial midline to affect the contralateral cranial nerves. 4 This report describes patients with ipsilateral cranial nerve PNS that has subsequently progressed to contralateral cranial nerves, to both highlight and address the potential implications for the postoperative radiotherapy volume. Case ReportsWithin a cohort of 55 patients who were treated from 1996 to 2011 with confirmed PNS from a cutaneous malignancy, six patients with ipsilateral cranial nerve PNS and subsequent contralateral PNS were identified. Patient demographic and clinical characteristics were reviewed and are summarized in Table 1. Ethics approval was obtained from our institution's Human Research Ethics Committee.Case Example. A 49-year-old woman (Table 1, patient 4) presented with a 3-month history of increasing swelling and pain in the left cheek. Twelve years before, the patient had sustained a blast/burn injury to the left hemiface, and 18 months before presentation, had a squamous cell carcinoma (SCC) on the left side of the nose excised with adjuvant radiotherapy. A computed tomography scan indicated recurrence of the lesion, with bony erosion of the inferior orbit and anterior maxillary wall and extension into the antrum. A magnetic resonance imaging (MRI) scan showed involvement of V2 at the foramen rotundum to the anterior aspect of Meckel's cave. Surgery involved en bloc removal of the left cheek skin, lateral nose wall, orbit floor, periorbita, and the infraorbital nerve to the gasserian ganglion. Reconstruction was performed with radial artery forearm flap and split skin graft. Histopathology confirmed SCC with PNS of left V2 to the anterior aspect of Meckel's cave. The patient received postoperative radiotherapy to the operative bed, as previously described, back to the gasserian ganglion, using a total dose of 60 Gy in 30 fractions. The cutaneous branches of V2 (with some extension into V3 cutaneous distribution) were treated, but only the proximal part of V3. This was delivered by a mix of electrons and three-dimensional conformal photon radiotherapy. Five years after surgery, the patient developed paresthesia, formication, and pain in the right cheek. An MRI scan showed abnormal thickening and enhancement that were consistent with PNS along the intra-and extracranial segments of right V2 and V3. The patient refused additional treatment and died as a result of her contralateral disease 13 months after detection. DiscussionThe trigeminal (V) and facial (VII) nerves are the most common cranial nerves to be affected by PNS, 5 and disease may prog...

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