Three-year results after radiotherapy for locally advanced sinonasal adenoid cystic carcinoma, using highly conformational radiotherapy techniques proton therapy and/or Tomotherapy.

PURPOSE: We report the patient outcomes of a treatment combining proton therapy and Tomotherapy in sinonasal adenoid cystic carcinoma involving skull base. MATERIALS AND METHODS: We included patients treated at Curie Institute, Paris, France, between March 2010 and February 2014 for an advanced adenoid cystic carcinoma involving skull base. Patients received Tomotherapy, proton therapy or both. We evaluated treatment toxicity (according to CTCAE V4), local control, distant metastasis-free survival and overall survival. RESULTS: Thirteen patients were included, with a median follow-up of 34 months. Radiation therapy followed surgery for 77% of the patients and margins were positive in all those cases. Median dose was 73.8Gy. Local control, distant metastasis-free survival and overall survival at 3 years were respectively 60%, 48% and 60%. One-sided grade 3 hearing impairment occurred in 46% of the patients. CONCLUSION: Combining high-dose proton therapy and Tomotherapy is effective and has moderate toxicity in the treatment of T4 sinonasal adenoid cystic carcinoma involving skull base.

Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals FGFR1 amplifications and tumour genomic alterations burden as prognostic biomarkers of survival.

BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.

Protontherapy of head and neck paragangliomas: A monocentric study.

PURPOSE: The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues. PATIENTS AND METHODS: Ten patients with a paraganglioma of the head and neck were treated from 2001 to 2014 with image-guided proton therapy. Neurological and ear nose throat symptoms were collected in addition to audiometric testing, before and after the treatment. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4. RESULTS: Median age at diagnosis was 52.6years (range: 18.2-65.8years). Proton therapy was the exclusive treatment in six patients and four patients had a postoperative radiotherapy. Median dose was 50.4Gy relative biological effectiveness (RBE; range: 45.0-67.0Gy). With a median follow-up of 24.6months (range: 6.7-46.2 months), local tumour control rate was 100% (stable, n=10). No upper grade 2 acute toxicity was reported. To the latest news, seven patients had controlled symptoms (improved, n=1, stabilized, n=6). One patient out of seven with initial tinnitus had a decrease in his symptoms, while the six other patients had a sustained stabilization. CONCLUSION: Proton beam therapy is an effective and well-tolerated treatment modality of skull base paragangliomas, with documented functional benefit. A longer follow-up is planned in order to assess local control and long-term toxicities.

Combined laser and robotic approach for the management of a mixed laryngomucocele.

Treatment of laryngoceles is surgical resection, through an external approach for external laryngoceles and through an endoscopic approach for internal laryngoceles. We report the first case of a mixed laryngomucocele treated with transoral robotic surgery. A patient presented with a history of chronic cough. Nasolaryngoscopy showed a sub-mucosal swelling into the larynx. Computed tomography confirmed the diagnosis of a right mixed laryngomucocele. A transoral robotic- and laser-assisted surgery was performed. Oral feeding was started on the first post-operative day. No post-operative complication was observed. There has been no evidence of recurrence during the following months. The generally used external and endoscopic approaches each have their limits in the treatment of laryngoceles. Transoral robotic surgery allows a minimally invasive approach with a wide exposure, making possible an absence of scar and a good functional recovery after the operation. Transoral robotic approach seems to allow an endoscopic approach for mixed and external lesions. Transoral robotic surgery combined with laser is an efficient minimally invasive technique and is the best option for the treatment of mixed laryngoceles and laryngomucoceles.

[Impact of nutrition management in patients with head and neck cancers treated with irradiation: is the nutritional intervention useful?]. / Intérêt de la prise en charge nutritionnelle des patients traités par irradiation des voies aérodigestives supérieures: la consultation diététique est-elle utile?

AIMS: The head and neck tumors are most often associated with a precarious nutritional status. Radiotherapy increases the risk of denutrition because of its secondary effects on the secretory and sensorial mucous membranes. The purpose of our retrospectively study was to evaluate the interest of a precocious and regular nutritional therapy on the ability to maintain the nutritional status of the patient during the radiotherapy. PATIENTS AND METHODS: The fifty-two patients included in the survey have been classified retrospectively in two different groups based on their observance to the nutritional therapy: group 1 "good observance", group 2 "bad observance". RESULTS: The 31 patients of group 1 have lost an average of 1.9 kg by the end of the irradiation, whereas the 21 patients of group 2 have lost an average of 6.1 kg (p<0.001). The almost stability in weight of patients in group 1 was linked to a lower frequency of breaks in the radiotherapy (6 vs 33% p=0.03) and in a decrease in grade of inflammatory mucous membranes (10% of grade 3 in group 1 vs 52% in group 2, p=0.006). The quantity of calories ingested in form of nutritional supplements was greater in group 1 and consequently enabled patients to stabilized their weight (1200 calories in group 1 versus 850 calories in group 2, p<0.005). CONCLUSIONS: The given nutritional advice and the prescription of adapted nutritional supplements consequently allowed limiting efficiently the weight lost during the irradiation and the grade of mucositis. The systematization of a precocious nutritional therapy for patients irradiated for head and neck tumors seems absolutely essential.

Serum soluble interleukin-2 receptor concentrations as an independent prognostic marker in head and neck cancer.

Currently head and neck squamous cell-carcinomas are staged clinically, though this is not ideal. We did a multivariate prospective study of 234 patients with head and neck squamous-cell carcinoma and showed that high serum concentrations of sIL-2Ralpha at diagnosis were highly correlated with a shorter survival (p<0.0001). In addition, patients who had low serum sIL-2Ralpha concentrations at diagnosis were less likely to develop distant metastasis during the 36 months follow up compared with the group with high serum sIL-2Ralpha concentrations (p<0.001). These findings suggest that serum sIL-2Ralpha could be considered as an independent serum biomarker in head and neck cancer patients.

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis.

PURPOSE: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patients treated by conventional radiotherapy. MATERIALS AND METHODS: Data from 11 different centers were pooled. Inclusion criteria were such that the patients received radiotherapy alone, and that the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) intravenously prior to treatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were subsequently calculated from flow cytometry data, obtained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own flow cytometry analysis. RESULTS: From the 11 centers, a total of 476 patients conforming to the inclusion criteria were analyzed. Median values for overall time and total dose were 49 days and 69 Gy, respectively. Fifty one percent of patients had local recurrences and 53% patients had died, the majority from their disease. Median follow-up was 20 months; being 30 months for surviving patients. Multivariate analysis revealed that T-stage, maximum tumor diameter, differentiation grade, N-stage, tumor localization and overall time correlated with locoregional control, in decreasing order of significance. For the cell kinetic parameters, univariate analysis showed that only LI was significantly associated with local control (P=0.02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer values did worse, but this was not significant (P=0.06). Tpot showed no trend (P=0.8). When assessing survival in a univariate analysis, neither LI nor Tpot associated with outcome (P=0.4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P=0.02). In the multivariate analysis of local control, LI lost its significance (P=0.16). CONCLUSIONS: The only pretreatment kinetic parameter for which some evidence was found for an association with local control (the best end-point for testing the present hypothesis) was LI, not Tpot, and this evidence disappeared in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using flow cytometry, only provide a relatively weak predictor of outcome after radiotherapy in head and neck cancer.