Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

Abstract

BackgroundThe treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient’s prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy.Case PresentationWe describe the case of a woman in her late 30’s who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence.ConclusionsThe case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.

Case report: Patient specific combination of surgery and immunotherapy in advanced squamous cell carcinoma of the head and neck – a case series and review of literature

“…Cases A and B, as well as our previously published case report on neoadjuvant immunotherapy (39), show that neoadjuvant ICI can be performed successfully and should be evaluated in selected cases. Nevertheless, the optimal timing for neoadjuvant ICI remains unclear.…”

“…Although timing of neoadjuvant ICI differed significantly from the optimal administration schedule proposed by Liu et al. ( 16 ), all cases presented, as well as the previously published case, can be classified as pTR-2 9 [ Cases B and ( 39 )] or pTR-1 ( Case A ) according to the histologic response classification proposed by Uppaluri et al. ( 11 ).…”

“…In the ongoing and highly anticipated Keynote-689 trial, Pembrolizumab 200 mg is administered on day 1 of a 21-day cycle for 2 cycles (NCT03765918). Regarding our cases, Pembrolizumab 200 mg was given 15 ( Case A ), 17 ( Case B ) and 19 days ( 39 ) before surgery. – Reason was not to delay the planned surgery and to stick to the seemingly biologically reasonable time frame given in the literature available at the time ( 11 ).…”

“…Subsequently, immunohistochemical assessment of the tumor mass was performed. Methods were identical to our previously published case report on neoadjuvant IT ( 39 ). A significant factor increase was observed in TPS, IC-Score, CPS and immune cell infiltration (CD8/mm2), comparing initial biopsy and final tumor resection ( Figures 2A–D ).…”

Clinical Response to Neoadjuvant Immunotherapy Combined with Targeted Therapy and Chemotherapy in Oral Squamous Cell Carcinoma: Experience in Three Patients

“… 4 A recently published case report showed considerable clinical benefit of neoadjuvant use of single-agent pembrolizumab prior to surgical resection in an OSCC patient. 5 To date, the benefits of immunotherapy and targeted therapy plus chemotherapy in HNSCC, especially in giant or unresectable HNSCC remain to be determined.…”