Gilles Poissonnet

Postoperative Radiotherapy in Head and Neck Mucosal Melanoma: A GETTEC Study

OBJECTIVE to report patterns of failure according to treatment modality, with an emphasis on the role of postoperative radiotherapy in patients with localized head and neck mucosal melanoma (HNMM) treated during a 28-year period in a multi-institutional setting. DESIGN retrospective review. SETTING french medical institutions. PATIENTS a total of 160 patients with nonmetastatic HNMM treated from 1980 through 2008. INTERVENTIONS treatment modality consisted of surgery alone (hereinafter, S group) (n = 82 patients) or with postoperative radiotherapy (hereinafter, SRT group) (n = 78). Patients and tumor characteristics were similar in the 2 groups. There was a nonsignificant trend (P = .11) for more locally advanced tumor stage (38.9%) in the SRT group compared with the S group (24.5%). RESULTS patients in the S group had an increased probability of locoregional recurrence as a first event (55.6%) compared with those in the SRT group (29.9%; P < .01). After adjusting for tumor stage (T1/T2 vs T3/T4), the subdistribution hazard ratio of locoregional relapse was 0.31, (95% confidence interval [CI], 0.15-0.61; P < .01).The rate of distant metastasis as a first event was significantly higher in the SRT group (40.6%) compared with the S group (19.9%; P = .01). Regardless of their treatment, patients who had a locoregional relapse during follow-up had an increased risk of subsequent distant metastasis (hazard ratio, 3.07; 95% CI, 1.65-5.67) and death (hazard ratio, 3.01; 95% CI, 1.91-4.78). CONCLUSIONS this large retrospective study suggests that postoperative radiotherapy improves the locoregional control of HNMM. The higher rate of distant metastasis was due to more advanced disease in the SRT group.

Free-flap head and neck reconstruction and quality of life: a 2-year prospective study.

Objectives: This prospective study was designed to evaluate quality of life (QOL) after free‐flap head and neck reconstruction.

The relationship of epidermal growth factor receptor levels to the prognosis of unresectable pharyngeal cancer patients treated by chemo-radiotherapy

The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.

T1-T2 NO oropharyngeal cancers treated with surgery alone. A GETTEC study.

The aim of this study is to show that surgical treatment of early-stage squamous cell carcinomas of the oropharynx gives identical, if not better, oncological results than the classic radiotherapy treatment in terms of locoregional control and survival. Fifty-three patients (32 T1, 21 T2, all N0) were operated on during the years 1995–2000. Surgical treatment consisted in a resection by the transoral approach in 43 patients (81.13%); ten patients (18.87%) benefited from a pharyngectomy with (seven) or without (three) mandibular resection. A level I to V selective neck dissection was performed on 35 patients, and 5 patients underwent a level II to V selective neck dissection. The 1-, 3- and 5-year overall survival rates were 100, 94.6 and 73%, respectively. There was no significant difference concerning the tumor stage (P=0.69), the initial localization (P=0.64), the macroscopic aspect (P=0.65) and the management undertaken in the different centers (P=0.19). The 5-year rate of specific survival was 100%. The 1-, 3- and 5-year locoregional control rates were 96.22, 92.45 and 88.68, respectively. The oncological occurrences observed were 2 persistent diseases, 5 local recurrences, 11 second primary cancers and 0 nodal recurrences. Seven local failures were observed, all of which were controlled after a second treatment. Eleven patients presented second primary cancers; three died, two are alive with an extension of this second localization, and six are alive and free of disease. The locoregional control provided by surgery alone on T1-T2 N0 oropharyngeal cancers is as good as radiotherapy. Moreover surgery alone makes it possible to spare patients the complications and aftereffects of radiotherapy. It also makes it possible during the recurrences to operate on patients in non-irradiated areas with lower morbidity and mortality. It is all the more beneficial since it will be possible to resort to radiotherapy after surgery if need be.

Radical ablative surgery and radial forearm free flap (RFFF) reconstruction for patients with oral or oropharyngeal cancer: postoperative outcomes and oncologic and functional results

Conclusions. Radical ablative surgery and radial forearm free flap (RFFF) reconstruction provide promising oncologic and functional results in patients with oral or oropharyngeal cancer. Objectives. To assess the postoperative outcomes and the oncologic and functional results, with their main predictive factors, after radical ablative surgery and RFFF reconstruction for patients with oral or oropharyngeal cancer. Patients and methods. Between 2000 and 2006, we prospectively analyzed the postoperative, oncologic and functional outcomes of all previously untreated patients who underwent this type of surgery. Results. A total of 132 patients were enrolled in this study. There were three RFFF failures. The rate of surgical complications was 20%. The 5-year locoregional control and overall survival rates were 68% and 52%, respectively. Advanced age, high comorbidity index, elevated overall stage and tumoral involvement of the inner part of the cheek were correlated with a lower overall survival rate. A good functional result was obtained for oral diet, speech, mouth opening and aesthetic outcome in 87%, 80%, 86% and 88% of the patients, respectively. High comorbidity index, large flap surface, radiotherapy and tumoral involvement of the mobile tongue were significant predictors of poorer functional or aesthetic outcomes.

Head and Neck Squamous Cell Carcinoma in Patients Aged ‡80 Years Patterns of Care and Survival

Scarce data exist concerning the outcome of very elderly patients with head and neck squamous cell carcinoma (HNSCC).

CONCOMITANT B.I.D. RADIOTHERAPY AND CHEMOTHERAPY WITH CISPLATIN AND 5-FLUOROURACIL IN UNRESECTABLE SQUAMOUS-CELL CARCINOMA OF THE PHARYNX: CLINICAL AND PHARMACOLOGICAL DATA OF A FRENCH MULTICENTER PHASE II STUDY

PURPOSE The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed. METHODS AND MATERIALS Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. RESULTS Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. CONCLUSION This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

Usefulness of Immunocytochemistry for the Detection of the BRAFV600E Mutation in Circulating Tumor Cells from Metastatic Melanoma Patients

Abbreviations: CMCs, circulating melanoma tumor cells; CTCs, circulating tumor cells; ICC, immunocytochemistry; IHC, immunohistochemistry; ISET, isolation by size of epithelial tumor cells

Complications of the myocutaneous platysma flap in intraoral reconstruction.

Pedicled myocutaneous flaps remain important tools in head and neck reconstruction. Evaluation of their complications are necessary to judge their merits.

Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma.

BACKGROUND It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. OBJECTIVE We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. METHODS We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. RESULTS Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity. LIMITATIONS Limitations include retrospective design and lack of multicenter interobserver reproducibility. CONCLUSION The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.