Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

Consensus on resectability in N3 head and neck squamous cell carcinomas: GETTEC recommendations.

BACKGROUND: Among patients with T0-2 N3 head and neck squamous cell carcinomas (HNSCC), those undergoing upfront neck dissection have better oncological outcomes. However, there is no consensual definition of disease resectability of N3 nodes, leading to major treatment attrition and interpretation biases between studies. We established a Delphi method-based consensus to define resectability and impact on decision-making for upfront neck dissection in N3 patients. METHODS: The Delphi method was designed as recommended by the French Haute Autorite de Sante among head and neck surgeons from university hospitals and cancer centers, using a 24-item questionnaire. Strong and relative agreements were subsequently established, and recommendations were written. The resulting recommendations were assessed by 30 independent surgeons. RESULTS: N3 nodes with intraparenchymal brain invasion, foramen invasion, skull base erosion, nodes requiring bilateral XIIth cranial nerve sacrifice, retropharyngeal N3 node or a node above the plan of soft palate are major contraindications to neck dissection. When neck dissection requires unilateral sacrifice of the IXth or Xth or XIIth cranial nerves or cervical nerve roots, upfront neck dissection may be performed, based on a case-by-case assessment of other patient and tumor estimates. CONCLUSION: Consensual contraindications to neck dissection in patients with T0-2 N3 HNSCC were defined among French head and neck surgeons as concerns skull base invasion, retropharyngeal nodes and bilateral XIIth cranial nerve sacrifice. This consensus should allow more reliable comparisons between surgical and non-surgical strategies in N3 patients.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Stereoscopic Surgical Video of Combined Petrosectomy With Virtual Reality Headset: 3-Dimensional Operative Video.

The use of 3-dimensional (3D) videos allows students to visualize surgical procedures from the perspective of the surgeon without missing the essential parts.1 This 3D commented video demonstrates the operative technique and surgical nuances of the combined petrosectomy, visualize using virtual reality headsets. Historically, traditional intradural cisternal routes using suboccipital and pterional approaches have been proposed to remove petroclival tumors.2-5 It allows rapid identification of neurovascular structures and a short exposure time. However, access to the petroclival region is far, not direct, and requires intradural cerebral retraction.6 In order to improve the access for tumoral dissection, lateral transpetrosal approaches have been proposed.7-12 The extradural route shortened the distance to the petroclival region, allows to better preserve the veins, to decrease the cerebral retraction, to interrupt early the tumor vascular supply, and a larger extent of resection.6 Transpetrosal approaches includes middle fossa approach8,10 (removing the petrous apex), posterior petrosal approach9,13,14 (removing of presigmoid retrolabyrinthine bone), and translabyrinthine petrosectomy.12 A combined petrosectomy may be used to approach larger tumor extending across the clival midline, upward to the tentorium or downward to the lower cranial nerves.6,10,15,16 Alternatively, according to Nanda, a retro-sigmoid approach may need to be performed to avoid critical draining veins injury.10,17 Good resection and outcomes are obtained when experienced surgeons use familiar approaches and microsurgical techniques.10.

Exclusive concurrent radiochemotherapy for advanced head and neck cancers with 'fractionated' 5-fluorouracil and cisplatin.

Concurrent radiochemotherapy (CRC) is a standard treatment in patients with inoperable locoregionally advanced ear-nose-throat (ENT) cancer. We report the safety and efficacy of CRC with daily fractionated 5-fluorouracil and cisplatin ('F' 5FU-CDDP) in a monocentric retrospective cohort. From January 2006 to August 2012, all patients with unresectable (or inoperable) nonmetastatic locoregionally advanced ENT cancer treated curatively by means of radiotherapy (normal fractionated 70 Gy to the macroscopic tumor and prophylactic 50 Gy) with three courses (week 1-week 4-week 7) of 'F' 5FU-CDDP regimen (800 mg/m/day of 5-fluorouracil and 20 mg/m/day of CDDP from day 1 to day 4) were included. Seventy patients underwent CRC (86% men, median age 58 years old, 100% squamous cell carcinoma, 97% stage III/IV). Fifty-six patients received the three complete courses of chemotherapy with cumulative doses of CDDP of 217 mg/m/patient (dose intensity ratio of 90.5%). After a median follow-up period of 30.7 months, median overall and disease-free survivals were 34.1 [95% confidence interval (CI) (21.6-56.8)] and 50.2 months [95% CI (17.4-NA)] with 71% [95% CI (57.5-81)] and 67% [95% CI (51.8-78.5)] for locoregional control at 2 and 5 years, respectively. In all, 58.5% of grade 3 or higher mucositis and 24% of radioepithelitis were observed, but only 11.5, 3, and 1.5% of grade 3 or higher neutropenia, nephrotoxicity, and neurotoxicity were observed, respectively. No deaths from toxicity occurred. CRC with three courses of 'F' 5FU-CDDP appears effective and could be an alternative to standard CRC treatment. Randomized studies are required to be able to use this treatment regimen routinely.

Feasibility and safety of dose-dense modified docetaxel-cisplatin or carboplatin and 5-fluorouracil regimen (mTPF) in locally advanced or metastatic head and neck cancers: a retrospective monocentric study.

BACKGROUND: Docetaxel-cisplatin and 5-fluorouracil (TPF) chemotherapy (days 1-21) represents a standard but toxic regimen for advanced head and neck cancer (HNC). We report a retrospective monocentric study evaluating the safety and the efficacy of a dose-dense modified TPF (mTPF) regimen (days 1-14) in patients with stage III-IV HNC. METHODS: Thirty-seven patients retrospectively included from May 2011 to May 2014 were treated with a bimonthly dose-dense mTPF regimen (40 mg/m(2) docetaxel, 40 mg/m(2) cisplatin or AUC2 carboplatin, folinic acid 400 mg/m(2) for 2 h, bolus 5-FU 400 mg/m(2) for 10 min and 5-FU 1,000 mg/m(2)/day) by continuous infusion over 46 h). RESULTS: Chemotherapy was used as induction or palliative treatment in 12 and 25 patients, respectively, with a median age of 60 years (range 46-83). Median follow-up time was 7.4 months (2.53-16.7 months). There was no intestinal toxicity in 25 patients (68 %). Grade 3-4 hematological toxicity was noticed for 5 (13.5 %) patients. Granulocyte-colony stimulating factor was used as primary prophylaxis in 30 patients (81 %). After at least 4 delivered cycles, complete responses, partial responses and stable diseases were reported in 5 (15 %), 13 (39 %) and 5 (15 %) of the 33 evaluable patients, respectively, yielding an objective response rate of 54.5 % (39 % for palliative chemotherapy and 90 % for induction chemotherapy). CONCLUSION: Dose-dense mTPF (days 1-14) is safe and seems to be as effective as TPF (days 1-21). Future prospective trials are required to confirm our results.

Cancer cachexia: measured and predicted resting energy expenditures for nutritional needs evaluation.

OBJECTIVE: Cancer cachexia is associated with weight loss, poor nutritional status, and systemic inflammation. Accurate nutritional support for patients is calculated on resting energy expenditure (REE) measurement or prediction. The present study evaluated the agreement between measured and predicted REE (mREE and pREE, respectively) and the influence of acute phase response (APR) on REE. METHODS: Thirty-six patients with cancer were divided into weight-stable (WS; weight loss <2%) and weight-losing (WL; weight loss >5%) patients. Measured REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM). The Bland-Altman approach was used to assess the agreement between mREE and pREE from the Harris-Benedict equations (HBE). Blood levels of C-reactive protein were assessed. RESULTS: There was no difference in mREE between groups (WS 1677 +/- 273, WL 1521 +/- 305) even when mREE was adjusted for FFM (WS 1609 +/- 53, WL 1589 +/- 53). In WL patients, FFM-adjusted REE correlated with blood C-reactive protein levels (r = 0.471, P = 0.048). HBEs tend to underestimate REE in both groups. CONCLUSION: WL and WS patients with cancer had similar REEs but were different in terms of APR. APR could contribute to weight loss through enhancing REE. In a clinical context, HBE was in poor agreement with mREE in both groups.

Horizontal supraglottic partial laryngectomy for selected squamous carcinoma of the vallecula.

BACKGROUND: Our aim was to determine the incidence of local control in patients with selected squamous carcinoma of the vallecula treated with horizontal supraglottic laryngectomy; to analyze the consequences of local recurrence in terms of nodal recurrence, distant metastasis, survival, causes of death, overall local control, and laryngeal preservation; and to identify any clinical factors predictive of these outcomes. METHODS: This was a retrospective nonrandomized case series in a university teaching hospital. An inception cohort of 95 previously untreated patients were followed until death or for a minimum of 5 years. According to the 2002 Union Internationale Contre le Cancer (UICC) staging classification system, the tumor was classified as T1, T2, and T3 in 13, 60, and 22 patients, respectively, while disease in 67 patients was considered to be in stages III to IV. All patients underwent a horizontal partial supraglottic partial laryngectomy. Ninety-four patients had an associated neck dissection. An induction chemotherapy regimen was used in 91 patients; postoperative radiation therapy was given for 49 patients. The main outcome measures were local recurrence, nodal recurrence, distant metastasis, and survival. RESULTS: The 1-, 3-, and the 5-year actuarial survival estimates were 86.3%, 64.2%, and 47.4%, respectively. Overall, the main causes of death were as follows: metachronous second primary tumor (47.2% of patients), intercurrent disease (16.7%), distant metastasis (15.3%), local recurrence (6.3%), and nodal recurrence, (4.2%). The 1-, 3-, and 5-year actuarial local recurrence rates were 4.5%, 11%, and 11%, respectively. Nine patients developed a local recurrence; 3 were successfully salvaged. Using multivariate analysis, no single variable was found to increase the risk for local recurrence. The overall laryngeal preservation rate and local control rate were 89.5% (85/95) and 93.4% (89/95), respectively. Local recurrence was associated with a significant increase in nodal recurrence (p <.04) and distant metastasis (p = .03). CONCLUSIONS: Based on this experience, horizontal partial supraglottic laryngectomy appears to be a valid approach for functional organ-preservation in patients with selected T1-T3 SCC of the vallecula.