Preoperative Immunotherapy in the Multidisciplinary Management of Oral Cavity Cancer

Abstract

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor and the associated native immune infiltration, supercharging the adaptive anti-tumor immune response. It also provides the basis for scientific discovery where the molecular profile of responders can be interrogated to elucidate prognostic markers to aid in future patient selection. Preoperative immunotherapy is not without limitations. The risk of surgical delay due to immune adverse events must be carefully discussed by members of a multidisciplinary treatment team and patient selection will be critical. One day, the discovery of predictive biomarkers may allow for algorithms where pre-surgical immunotherapy decreases the size of surgical defect and impacts the intensity of adjuvant therapy leading to improved patient survival and decreased morbidity. With further study, immunotherapy could become a key component of future treatment algorithm.

Tumor microenvironment and immunotherapy of oral cancer

“…Although the above-mentioned traditional tumor treatment methods can temporarily curb the development of tumor, they cannot fundamentally solve the problems of tumor recurrence and metastasis. Moreover, oral cancer shows a high mutation rate associated with DNA damage caused by smoking and alcohol [ 127 ]. Therefore, it is urgent to develop new cancer treatment strategies to achieve efficient tumor treatment while reducing toxicity and improving the quality of life of patients.…”

Effect of preoperative programmed death‐1 or programmed death ligand‐1 immune check point inhibition on complications after surgery for primary head and neck cancer

“…1,2,[4][5][6] Recently, trials have introduced ICI in the neoadjuvant setting for HNSCC. 3,[9][10][11][12][13] Neoadjuvant ICI (nICI) was initially added to the treatment algorithm in melanoma, and subsequently in various other cancers. [14][15][16] nICI in melanoma has shown promising pathologic response rates and survival outcomes.…”

“…Although aPD1 ICI has proven therapeutic benefit and a more tolerable side effect profile than chemotherapy for patients with HNSCC, it is not without limitations. 9,24 Adverse events (AEs) are primarily related to autoimmune mechanisms with a grade 3/4 AE rate of approximately 8%-17% in HNSCC. 9,[25][26][27] High-grade AEs can result in treatment delays and persistent morbidity.…”

“…9,24 Adverse events (AEs) are primarily related to autoimmune mechanisms with a grade 3/4 AE rate of approximately 8%-17% in HNSCC. 9,[25][26][27] High-grade AEs can result in treatment delays and persistent morbidity. 10,28 Although rates of AEs are well studied, research on the effects of nICI on postoperative complications are lacking.…”

“…Several practice‐changing clinical trials have demonstrated outcomes of aPD1 ICI in recurrent and metastatic (RM) HNSCC with clinical response rates of approximately 10%–20% 1,2,4–6 . Recently, trials have introduced ICI in the neoadjuvant setting for HNSCC 3,9–13 . Neoadjuvant ICI (nICI) was initially added to the treatment algorithm in melanoma, and subsequently in various other cancers 14–16 .…”