Mucosal Melanomas of the Head and Neck: The Role of Postoperative Radiation Therapy

Objectives. Mucosal melanomas are rarer than their cutaneous counterparts and are associated with a poorer prognosis. We report the clinical outcomes of patients with mucosal melanomas of the head and neck region generally treated with definitive surgery followed by postoperative radiation therapy (RT). Methods. We reviewed the records of 17 patients treated at the University of Miami in 1990–2007. Patients generally received conventionally fractionated RT regimens to the postoperative bed. Elective nodal RT was not routinely delivered. Eight patients received adjuvant chemotherapy or immunotherapy. Results. Median followup was 35.2 months (range 5–225). As the first site of failure: 3 patients recurred locally, 2 regionally and 2 distantly. All 3 patients who recurred locally had not received RT. Of the 5 locoregional recurrences, 4 were salvaged successfully with multimodality therapy with no evidence of disease at last followup. Overall survival was 64.7% at 2 years and 51.5% at 5 years. Conclusions. Patients with mucosal melanoma of the head and neck are best treated with surgery to achieve negative margins, followed by postoperative RT to optimize local control. Elective nodal irradiation may not be indicated in all cases, as regional failures were not predominant. Distant metastases were fewer when compared to historical data, potentially due to advancements in adjuvant therapies as well as aggressive multi-modality salvage at time of failure

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibition. Here we report for the first time interim results of our ongoing phase I clinical trial (NCT02544880) in patients with recurrent HNSCC to evaluate the safety of and immunological effects of combining Tadalafil with the antitumor vaccine composed of Mucin1 (MUC1) and polyICLC. The combined treatment of Tadalafil and MUC1/polyICLC vaccine was well-tolerated with no serious adverse events or treatment limiting toxicities. Immunologically, this trial also confirms the positive immunomodulation of Tadalafil in patients with recurrent HNSCC and suggests an adjuvant effect of the anti-tumor vaccine MUC1/polyICLC. Additionally, image cytometry analysis of scanned tumors indicates that the PDE5 inhibitor Tadalafil in conjunction with the MUC1/polyICLC vaccine effectively reduces the number of PDL1+macrophages present at the tumor edge, and increases the number of activated tumor infiltrating T cells, suggesting reversion of immune exclusion. However, this analysis shows also that CD163 negative cells within the tumor upregulate PDL1 after treatment, suggesting the instauration of additional mechanisms of immune evasion. In summary, our data confirm the safety and immunologic potential of PDE5 inhibition in HNSCC but also point to PDL1 as additional mechanism of tumor evasion. This supports the rationale for combining checkpoint and PDE5 inhibitors for the treatment of human malignancies

The Immune System in Head and Neck Squamous Cell Carcinoma: Interactions and Therapeutic Opportunities

Squamous cell carcinomas of the upper aerodigestive tract exhibit complex interactions with the host immune system that may simultaneously explain resistance to various therapeutic modalities and that may also provide opportunities for therapeutic intervention. The interplay between developing or established malignancy and the host immune system is best understood through a careful analysis of the key components and effector arms of the immune system. These include the complex cellular network of immune modulation as well as tumor-derived factors such as chemokines and cytokines. While the host response to the developing tumor may successfully curtail tumor growth in some cases (immunosurveillance), squamous cell carcinomas of the head and neck are characterized by their ability to create an immunosuppressive environment powerful enough to evade the immune response. It is increasingly apparent that efforts to stimulate a therapeutically effective immune response against established tumors must be coupled with strategies to abrogate this immune-suppressive environment. Preclinical studies and clinical trials have yielded promising results and provide the foundation for further refinements in a broad variety of immunotherapeutic strategies targeting all components of the immune system. Combining such approaches with the established treatment options of surgical resection, radiotherapy, and chemotherapy may ultimately yield substantive improvements in overall survival that to date have been lacking and simultaneously reduce disease-related and treatment-related morbidities for this debilitating and deadly disease

Longitudinal TEP Size Stability

Objective: Tracheoesophageal speech rehabilitation is considered the gold standard after laryngectomy. Changes in size of the prosthesis are common in the early period after initial fitting. Size may be affected by factors over time necessitating continued assessment. This study will determine size stability in laryngectomized patients over a 5-year period. Method: Individuals s/p total laryngectomy and TEP with a minimum 5-year follow-up will be accrued. Data will be derived from chart review including demographic, surgical, medical, and prosthesis factors by stability of size over time after the first three-month initial fitting phase. Results: Thirty-seven patients, 32 males and 5 females, met the criteria and were included in the study. Mean age was 63.7 years (range, 41-78 years). Medical factors leading to total laryngectomy changed over the follow-up period with more recent patients only undergoing laryngectomy for either extremely advanced disease or recurrence versus persistent disease after chemo-radiation therapy. A total of 80% of patients required a change in the length and/or diameter of their prosthesis over the 5-year follow-up period regardless of other medical and surgical factors. Conclusion: Clinicians need to continually reassess prosthesis fit for the life of the patient to prevent inadvertant closure of the posterior fistula tract from a prosthesis that is too short or pistoning resulting in aspiration from a prosthesis that is too long. This contrasts previous reports of stability after initial fitting