Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting. Clinical Trial Registration: NCT03700905 (ClinicalTrials.gov).

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Molecular targeting in combination with platinum-based chemoradiotherapy in head and neck cancer treatment.

BACKGROUND: Significant evidence exists supporting the use of platinum-based chemoradiotherapy (CRT) as a primary curative approach in locoregionally advanced head and neck cancer (HNSCC). Despite these aggressive protocols, 70% of patients die within 5 years because of locoregional recurrence or distant metastasis. To increase the response and survival of patients with HNSCC, CRT has been combined with molecular agents targeting distinct kinases. METHODS: This study was performed using a systematic literature review. RESULTS: The effect of targeted therapy on patient survival in the context of CRT remains controversial, with toxicities tending to be more severe but still acceptable. CONCLUSION: Supplementing CRT with target therapeutics might only improve survival in some patients with locally advanced HNSCC. Therefore, future studies must address the underlying biological mechanisms that can have an impact on treatment response. Such knowledge is essential in order to facilitate the effective and personalized treatment of patients with locally advanced HNSCC by combining CRT and targeted therapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2173-E2181, 2016.

A comparison of hearing results following stapedotomy under local versus general anesthesia.

Advances in operative technique, instrumentation, and prosthesis design in otosclerosis surgery continue since Shea performed the first successful surgery. This is the first analysis to specifically compare post-operative hearing outcomes following stapedotomy surgery performed under local versus general anesthesia. Hearing outcomes were further stratified by comparing conventional perforator and Er:YAG laser ablation perforation techniques. Pre- and post-operative audiograms were retrospectively analyzed together with the method of anesthesia and the perforation technique for all patients with otosclerosis who underwent stapedotomy between 1998 and 2007. Pre-operative individual standard audiometry frequency thresholds (IFTs), air (AC) and bone conduction pure tone averages (PTA), and air bone gaps (ABG) were compared against post-operative results. Differences between pre- and post-operative PTAs and ABGs were compared between patients who received stapedotomy under local versus general anesthesia, as well as for patients who underwent conventional versus Er:YAG laser ablation perforations. Eighty-six patients were identified of which 24 % (n = 21) received local and 76 % (n = 65) received general anesthesia. Post-operative audiograms were available for 84 and 48 patients, respectively. Significant improvements were seen across all groups for standard 4-frequency AC-PTA and ABG and for IFTs up to 3 kHz. No significant difference was seen for IFTs between 4 and 6 kHz. A significant decline in post-operative hearing thresholds was seen at 8 kHz. Significant improvements in PTA and ABG were seen for all groups. There was a trend toward general compared to local anesthesia post-operative hearing results furthermore in combination with conventional perforation technique then with laser technique.