Elsevier

Oral Oncology

Volume 61, October 2016, Pages 166-176
Oral Oncology

Cytoreductive surgery for head and neck squamous cell carcinoma in the new age of immunotherapy

https://doi.org/10.1016/j.oraloncology.2016.08.020Get rights and content

Highlights

Abstract

Cytoreductive surgery is an approach to cancer treatment that aims to reduce the number of cancer cells via resection of primary tumor or metastatic deposits, in an effort to minimize a potentially immunosuppressive tumor burden, palliate symptoms, and prevent complications. Furthermore, it provides a platform for investigation of biomarkers with the goal of optimizing immunotherapy to reverse the immunosuppressive tumor microenvironment and enhance adaptive immune responses. Ultimately, our group aims to exploit the concept that successful cancer therapy is dependent upon an effective immune response. Surgery will remain an integral part of head and neck squamous cell carcinoma (HNSCC) treatment in the future, even as checkpoint inhibitors, co-stimulatory molecules, vaccines, adoptive T cell therapy and other novel agents enter clinical routine. Cytoreductive resection may provide an effective platform for immunotherapy and biomarker directed interventions to improve outcomes for patients with HNSCC.

Introduction

Patients with head and neck squamous cell carcinomas (HNSCC) have a relatively poor prognosis, which despite 5 decades of advancements in surgery, radiation therapy and chemotherapy, has not significantly improved. Recurrent/metastatic (R/M) HNSCC is especially challenging, regardless of HPV-status, and has few effective treatment options. HPV-negative HNSCC is associated with a local-regional relapse rate of between 19% and 35% and a distant metastatic rate of 14–22% following standard of care, compared to rates of 9–18% and 5–12% respectively for HPV-positive HNSCC [1], [2], [3]. The median overall survival for patients with R/M disease is 10–13 months in the setting of first line chemotherapy and 6 months in the second line setting. The current standard of care is platinum-based doublet chemotherapy with or without cetuximab. Second-line standard of care options include cetuximab, methotrexate, and taxanes. All of these chemotherapeutic agents are associated with significant side effects and only 10–13% of patients respond to treatment. HNSCC regressions from existing systemic therapies are transient, do not add significantly increased longevity, and virtually all patients succumb to their malignancy. Clinical trials should be a priority for these high-risk patients.

Complicating this situation in the head and neck region is that many patients with metastatic HNSCC suffer significant morbidity following treatment failure. Patients who develop local-regional disease progression in conjunction with distant metastasis have usually already received full course radiation therapy and therefore have few good palliative options available to achieve local tumor control and/or relieve symptoms other than surgery or re-irradiation. Surgical resection for previously untreated locally advanced disease offers benefit in terms of overall and disease free survival [4], [5], but is palliative in the setting of carotid artery involvement [5], [6], [7] or distant metastasis [8], [9], [10], with median survival of 3.6–13.5 months. Because of these discouraging statistics, surgeons have been reluctant to offer even palliative resections in the context of distant metastasis due to the ineffectiveness of systemic therapies. Therefore, patients with local recurrence often experience severe pain, bleeding, airway compromise, speech/swallowing dysfunction and death within one year of diagnosis, even though they may have low volume disease distantly.

Recent advances in immunotherapy are poised to transform the practice of oncology. In particular, adoptive cell transfer with tumor infiltrating lymphocytes [11], [12] or receptor-engineered T cells [13], [14], [15], [16], [17], [18], as well as checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein-4 (anti CTLA-4) anti-programmed death-1 (anti PD-1), are resulting in durable responses in patients with numerous types of cancer [19], [20], [21], [22], [23], [24], [25], [26]. Two anti-PD-1 antibodies, nivolumab and pembrolizumab, have shown efficacy in clinical trials for R/M HNSCC and are poised for approval by the Federal Drug Administration (FDA) [27], [28]. These findings have ushered in a new era in the treatment of HNSCC and give cause to re-assess therapeutic approaches, as anti-PD-1 and other immunotherapies are integrated into standard of care (Table 1).

Section snippets

Cytoreductive surgery

Surgery remains the primary mode of treatment for most patients with HNSCC. In many oncologic settings, surgery is not attempted unless there is potential for complete removal of all cancer cells (an “R-0” resection). Nevertheless, many surgical approaches are accompanied by radiation therapy with or without chemotherapy to minimize the chance of local or distant recurrence from microscopic disease. By contrast, the goal of cytoreductive surgery is to minimize tumor-induced immune suppression

Summary

Cytoreductive surgery is an approach to cancer treatment that aims to reduce the number of cancer cells via resection of primary tumor or metastatic deposits, in an effort to minimize a potentially immunosuppressive tumor burden, palliate symptoms, and prevent complications. Furthermore, it provides a platform for investigation of biomarkers with the goal of optimizing immunotherapy to reverse the immunosuppressive tumor microenvironment and enhance adaptive immune responses. The utility of

Conflict of interest statement

The authors declare the following potential conflicts of interest:

Dr. Bell: Advisory Board: Janssen Research and Development, LLC; Consultant: Stryker CMF

Dr. Leidner: none

Dr. Crittenden: Consultant: Regeneron

Dr. Curti: Consultant: Prometheus

Dr. Jutric: none

Dr. Gough: none

Dr. Seung: none

Dr. Fox: Consultant/Advisory boards: MicroMet, MannKind, BioSante, Immunophotonics, Ventana/Roche, Dendreon, Perkin-Elmer, Definiens, Janssen Research and Development, LLC; Research support: Perkin-Elmer,

Acknowledgements

Funding sources: Oral and Maxillofacial Surgery Foundation Research Support Grant, Robert W. and Elsie Franz, Wes and Nancy Lematta, Lynn and Jack Loacker, and The Chiles foundation.

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