Prognostic impact of extranodal extension in resected head and neck squamous cell carcinomas in the era of postoperative chemoradiation: A retrospective monocentric study.

BACKGROUND: For patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC), surgery (S) followed by radiotherapy (RT) is a standard of care. Randomized controlled trials have shown that postoperative chemoradiation (CRT) increased the locoregional control (LRC) and overall survival (OS) in patient with R1-resection margin and/or extranodal extension (ENE). ENE has been introduced in the 8th TNM staging classification since its presence has been shown to have an independent adverse prognostic impact. The data supporting this finding were however mainly collected in the pre-CRT era. OBJECTIVES: The objective of this study was to challenge the adverse prognostic factor of ENE in the era of CRT. METHODS: A retrospective cohort study was performed to evaluate patients diagnosed with LAHNSCC and undergoing a treatment by S and postoperative RT or CRT in Centre Léon Bérard, Lyon, France between 2003 and 2018. Patients with oral cavity, oropharyngeal, laryngeal and hypopharyngeal SCC were included. RESULTS: 439 patients were included in the study. For patients with non-oropharyngeal p16-positive tumors without ENE, five-year OS, local control, and regional control (RC) reached 63.7%, 86.1%, and 94.9%, respectively; corresponding figures for patients with ENE reached, 42.6%, 77.5%, and 81.1%, respectively (p-value of 0.0006, 0.167, and 0.0005). In multivariable analysis, for non-oropharyngeal p16-positive tumors, ENE remained a poor prognostic factor for OS (RR = 1.74, 95%, CI = 1.16-2.61, p = 0.0069) and RC (RR 3.60, 95% CI =: 1.64-7.87, p = 0.0013). CONCLUSION: In the era or postoperative chemoradiation, pathological ENE remains an adverse prognostic factor for OS and RC.

The Slippery Role of Induction Chemotherapy in Head and Neck Cancer: Myth and Reality.

Chemoradiotherapy as an alternative to surgery can be offered to patients affected by loco-regionally advanced head and neck cancer (HNC). Induction chemotherapy is a valid option, supported by few positive trials, but its real efficacy is still a matter of debate. The standard regimen for induction chemotherapy in Europe is a combination of docetaxel (75 mg/m2) and reduced dose doses of cisplatin (75 mg/m2) and 5-fluorouracil (750 mg/m2 day, for five consecutive days) (TPF). It is less toxic and more effective than the historical therapy PF (cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/day for five consecutive days). However, in some studies treatment-related mortality has been reported to be as high as 6%. Therefore, some less toxic combinations, such as a modified TPF regimen and the combination of carboplatin plus paclitaxel have been studied. These regimens are showing promising results but deserve further validation in comparative trials. Furthermore, several trials are underway in order to enhance TPF with immune checkpoints inhibitors. Compared to chemoradiotherapy, induction chemotherapy followed by chemoradiation was shown to be non-inferior, and it could decrease the distant metastatic progression, especially in high-risk populations. For selected patients, induction chemotherapy could be a strong option. The chemoselective process that leads to immediate surgery for non-responders, the high response rate (complete responses are sometimes observed), and the survival data, are all arguments in favor of induction chemotherapy, if performed in experienced centers involving health professionals in the context of a skilled multidisciplinary team.

Induction chemotherapy in head and neck cancers: Results and controversies.

Standard treatment for locally advanced head and neck squamous cell carcinoma (LAHNSCC) consists mainly of concurrent chemoradiation (CCR) but induction chemotherapy (IC) by docetaxel-cisplatin-fluorouracil (TPF), followed by CCR, is a strong option. Comparative trials suggest that IC and CCR are equivalent, and some trials suggest superiority of IC, whereas none shows inferiority. IC might have less interest in oropharyngeal cancer (more often linked to HPV infection). When functional laryngeal preservation is the patient's priority, essays strongly suggest that IC is the best treatment. There is little data about a less toxic regimen of IC, but several schemes are promising and need to be developed. An early selection of responders to IC by metabolic imaging must be considered. Intensification attempts with cetuximab were too toxic and unsafe, but trials with immunotherapy are ongoing to enhance TPF efficacy. After IC, CCR either with cetuximab or cisplatin seems to be equally effective.

Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief.

Induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) has been used for decades. However, its role is yet to be clearly defined outside of larynx preservation. Patients with high risk of distant failure might potentially benefit from sequential treatment. It is now widely accepted that TPF (docetaxel, cisplatin, and fluorouracil) is the standard IC regimen. Essays that have compared this approach with the standard of care, concurrent chemoradiotherapy (CCRT), are mostly inconclusive. Radiotherapy (RT) can be used in the post-IC setting and be sensitized by chemotherapy or cetuximab. Again, no consensus exists but there seems to be trend in favor of potentiation by cisplatin. Less toxic schemes of IC are tested as toxicity is a major issue with TPF. IC might have an interesting role in human papilloma virus (HPV)-related LA HNSCC and lead to CCRT de-escalation.

L'immunothérapie dans les cancers ORL.

IMMUNOTHERAPY IN HEAD AND NECK CANCERS: Immunotherapy wave has also touched head and neck cancer. In recurrent or metastatic disease, checkpoint inhibitors (anti PD-1/PD-L1) are approved in 2nd line with a clear benefit on overall survival and quality of life. Multiple clinical studies are in progress in both palliative and curative intent, combined or not with other checkpoint inhibitor (anti-CTLA4) or other standard therapies (radiotherapy, chemotherapy). It is essential to define which patients will benefit from immunotherapy, according to robust biomarkers, in order to increase risk benefit balance by decreasing side effects and selecting those who respond the most. Here we present an overview of immunotherapy in 2018 in head and neck squamous cell cancer.

Nivolumab in recurrent/metastatic head and neck cancers.

Head and neck cancer is an immunosuppressive disease, with a high proportion expressing PD-L1. Until recently, options were lacking in second line. Prognosis is poor especially for patients who progress during chemotherapy with survival often inferior to 6 months. Nivolumab is the only anti-PD-1 agent to prolong survival in the second-line setting and is now the standard option since the CheckMate-141 trial. Treatment is generally well tolerated, patients seem to have a better quality of life when compared with chemotherapy. Markers of efficacy are lacking even if some data are emerging. Different combinations of immunotherapy are ongoing. Hyperprogression is a phenomenon associated with poor outcome and might be the consequence of anti-PD-1 treatment but this is yet to be proven.