The optimal treatment for regional lymphatic recurrences from head and neck cancer has not been fully established. In order to explore the therapeutic benefit of surgical resection and adjuvant brachytherapy, the authors reviewed their experience utilizing interstitial brachytherapy (IBT) at the M. D. Anderson Cancer Center.A retrospective chart review of the 51 patients who received salvage surgical resection of lymphatic recurrences and adjuvant IBT between 1993 and 2012 at the M. D. Anderson Cancer Center was undertaken. All patients underwent neck dissection with complete resection and intraoperative placement of afterloading brachytherapy catheters. Soft tissue reconstruction was performed as necessary. The technical aspects of IBT were reviewed, and the overall and disease free survival rates and the recurrence rates were determined.All patients had received external beam radiation (EBRT) as part of their initial treatment to a median dose of 66 Gy; 40 and 68% of the patients also had a neck dissection or chemotherapy, respectively. The cumulative regional recurrence probability is 28 and 38% at 5 years and 10 years. All of the patients underwent salvage neck dissection and IBT, with 81% also undergoing soft tissue reconstruction. The median dose delivered to the tumor bed was 60 Gy over a median duration of 4.5 days. There were 21 early adverse events, 8 of which were severe, and 19 late adverse events, 6 of which were severe. The most common early and late adverse events due to surgery and brachytherapy were dysphagia (7.1%) and true vocal cord paralysis (17.9%), respectively. There were no perioperative deaths or carotid hemorrhages. Nineteen patients developed recurrence including regional recurrence and distinct metastasis. The median time to recurrence is 130 months using Kaplan-Meier product limit method. The 2-year disease-free survival rate was 58%. The 2-year, 5-year, and 10-year overall survival rates were 69, 56, and 46%, respectively.Regional recurrences in previously irradiated tissues after the definitive treatment of primary head and neck cancers represent a challenging problem. We demonstrated that salvage neck dissection with IBT provided encouraging regional control and survival rates, while maintaining relatively low acute and long-term toxicity rates.
Sinonasal malignancies are a rare subset of head and neck tumors, and surveillance strategies after definitive tumor treatment are often generalized from those for overall head and neck cancer outcomes data. However, recent literature suggests that the posttreatment period in sinonasal cancer is fundamentally different and a more tailored surveillance approach may be beneficial. Although rates of symptomatology are high in head and neck cancer recurrence and patient-driven follow-up is common, rates of symptomatology are unknown in sinonasal cancer specifically.Patients with recurrence of sinonasal malignancy were identified at 3 academic rhinology and skull base surgery centers. Demographic, tumor, and treatment data were collected. Rates of symptomatology at presentation were tabulated and examined in the context of several other variables.Fifty-five patients had recurrence of sinonasal malignancy after definitive treatment. Fifty-one percent of patients had no suspicious symptoms at the time of tumor recurrence, with an average time to recurrence of 33 months. Male patients and patients with stage IVA or lower disease were significantly more likely to be asymptomatic at the time of recurrence (p < 0.05).Patients with sinonasal malignancy have a much lower rate of symptomatology during tumor recurrence than that observed in head and neck cancer overall. Furthermore, time to recurrence is substantially longer, as a majority of head and neck cancer recurrences occur in the first 12 months after treatment. These differences highlight the need for more tailored surveillance paradigms in asymptomatic patients with a history of a definitively treated sinonasal neoplasm.
BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), continues to be a major concern for the postoperative hospitalized patient, especially after long and complex procedures. Cancer itself also contributes to the hypercoagulable state, further complicating the management of patients. Despite prophylaxis, breakthrough events occur. We aimed to assess our institutional VTE and bleeding rates following free flap reconstruction of the head and neck region and the factors associated with these events. METHODS: A retrospective review of the patients who underwent head and neck free flap reconstruction at a tertiary center from 2012 to 2021 was performed from a prospectively maintained database. Data regarding patient demographics, past medical history, surgical details, and overall outcomes were collected. Outcomes studied included postoperative 30-day VTE rates and bleeding events. VTE was defined as documented PE or DVT events. Bleeding events included major events that required an intervention or return to the OR. Patients that had a VTE event were compared with the rest of the cohort to identify factors associated with VTE. Statistical analysis was performed using chi-square and T-tests, and P-value ≤ 0.05 was considered statistically significant. RESULTS: Free flap reconstruction of the head and neck region was performed in 928 patients. Reconstruction after cancer extirpation was the most common etiology (89%). The most preferred donor site was thigh (50%), followed by fibula (29%). All patients received postoperative VTE chemoprophylaxis, and the most common regimen was enoxaparin 30 mg BID (83%). The VTE and bleeding rates over the 10-year period were 4% (n=35) and 9% (n=82), respectively. Although not statistically significant, there was an improvement in the overall VTE (4% vs 3%, p=0.365) and bleeding (10% vs 8%, p=0.492) rates in the last five years, compared with the first. This trend was consistent with the institutional changes to control both rates, such as implementation of a TXA protocol. Gender, age, BMI, Caprini score, and tobacco use were not significantly different between the patients that had a VTE event versus those that did not. Pulmonary comorbidities were found to be significantly higher in patients that had a VTE event (57% vs 26%, p<0.001). The ischemia duration of the flaps in patients with a VTE event was longer (149±57 vs 126±44, p=0.005), despite having similar overall operative duration (712±153 vs 695±152, p=0.517). Patients with a VTE event also had higher rates of bleeding events (29% vs 8%, p<0.001) and had a prolonged hospital stay of 11 more days (22±19 vs 11±7, p=0.001). CONCLUSION: Postoperative VTE is a significant complication, associated with increased length of hospitalization in patients undergoing free flap reconstruction of the head and neck region. There is also a relation of VTE with major bleeding events, likely due to the VTE treatment. Institutional measures should be implemented on an individualized basis based on patient comorbidities to improve the postoperative VTE rates, while balancing the bleeding events.
Abstract TMEM16A, a Ca 2+ ‐activated Cl − channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family‐targeting biological therapies. Inhibition of TMEM16A Cl − channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl − channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride‐deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.
Abstract Head and neck squamous cell carcinoma (HNSCC) constitutes one of the most common types of human cancers and often metastasizes to lymph nodes. Platinum-based chemotherapeutic drugs are commonly used for treatment of a wide range of cancers, including HNSCC. Its mode of action relies on its ability to impede DNA repair mechanisms, inducing apoptosis in cancer cells. However, due to acquired resistance and toxic side-effects, researchers have been focusing on developing novel combinational therapeutic strategies to overcome cisplatin resistance. In the current study, we identified p90RSK, an ERK1/2 downstream target, as a key mediator and a targetable signaling node against cisplatin resistance. Our results strongly support the role of p90RSK in cisplatin resistance and identify the combination of p90RSK inhibitor, BI-D1870, with cisplatin as a novel therapeutic strategy to overcome cisplatin resistance. In addition, we have identified TMEM16A expression as a potential upstream regulator of p90RSK through the ERK pathway and a biomarker of response to p90RSK targeted therapy in the context of cisplatin resistance.
<p>Supplemental packet contains supplemental figures for "TMEM16A/ANO1 overexpression inhibits apoptosis via down-regulation of Bim expression." It also contains uncropped blots corresponding to blots in the main and supplemental figures. Uncropped blots are labeled & grouped by figure and panel in which the cropped version of the blots are used.</p>
