Efficacy and safety of an artificial dermal graft for the reconstruction of exenterated sockets: a preliminary report.

PURPOSE: The purpose of this study is to report our experience with the use of artificial dermis grafts for orbital socket reconstruction following orbital exenteration (OE). METHOD: A retrospective study was conducted in our ocular oncology centre from May 2018 to June 2020 in patients undergoing OE for orbital malignancies in whom an artificial dermis device (Integra® template, 2 layers) was used for reconstruction. Data recorded included demographics, previous and adjuvant treatments, aetiologies, surgical procedure, surgical reconstruction, complications and follow-up. The main outcome measure was the time between OE and the full granulation of the cavity. RESULTS: Ten patients (mean age, 71.3 years [43-92]) were included. Tumours originated from the conjunctiva (n = 5, 50%), eyelid (n = 3, 30%) and orbit (n = 2, 20%). Nine patients underwent total OE, and one required enlarged OE. Orbital reconstruction was performed using an artificial dermis alone (n = 9, 90%) or combined with regional flaps (n = 1, 10%). The mean granulation time was 3.3 weeks (2-4). Three (30%) patients received adjuvant radiotherapy 1 month post-surgery. The mean time to spontaneous epithelialization was 9.4 weeks (6-12). Preoperative and postoperative radiotherapy was not associated with a delayed epithelialization of the socket (p = 0.463 and p = 0.236, respectively). One (10%) and 2 (20%) patients experienced postoperative socket infection and an ethmoidal fistula, respectively. The mean follow-up was 11.6 months (6-16). CONCLUSION: Using artificial dermis grafts alone or with regional flaps appears to be a viable surgical procedure for orbital socket reconstruction. They reduce surgical morbidity and hospital stay. Preoperative and postoperative radiotherapy does not seem to delay socket healing.

Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).

BACKGROUND: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. OBJECTIVES: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. METHODS: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. RESULTS: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. CONCLUSIONS: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.

[Ectopic thyroid basi-lingual: A case report].

Introduction: The thyroid ectopic gland is a rare anomaly, especially when it's a lingual thyroid. It is characterized by aspecific clinical presentation, causing a diagnostic problem. The diagnosis is based on a combination of imaging techniques as well as histological examination. Case presentation: We are presenting a case of a patient with thyroid basi-lingual treated surgically. Discussion: The low incidence of ectopic lingual thyroid , and their clinical variability requires radiological and isotopic investigations. Conclusion: The diagnosis of this disease is primarily histological. The management of these ectopic thyroid is surgical.

[Free-flap head and neck reconstruction failures: predictive factors and management]. / Les échecs de la chirurgie reconstructrice cervicofaciale par lambeaux libres : facteurs favorisants et prise en charge.

BACKGROUND: Failure after head and neck reconstruction using free flap are rare but their management remains a challenging problem. The purpose of this study was to analyze the causes and the subsequent treatment of free-flap failure in head and neck reconstruction. PATIENTS AND METHODS: A retrospective review of patients who had undergone free flap transfer between 2000 and 2007 was performed in our center. Data were collected from computerized medical record to determine patient and tumor characteristics, as well as their treatment. Moreover, a univariate analysis was performed to determine factors associated with free flap failure. RESULTS: Three hundred and twelve patients had a free flap transfer after head and neck cancer resection. A total of 22 failures (7%) were encountered. Previous surgery for head and neck cancer (p=0.02), surgery after cancer recurrence (p=0.02) and reconstructions after circular pharyngolaryngectomy (p=0.008) were significantly associated with free-flap failure. A second free-flap was performed in 12 patients and the overall success rate of the repeated free flap was 92 percent (11 of 12 patients). CONCLUSION: After a free flap failure, surgeons should determine subsequent treatments after a reconsideration of the need of a second free flap, an analysis of the cause of the first flap failure and an evaluation of local and general conditions. In selected patients, second free flap has a high success rate.

[Total pharyngolaryngectomy in the 21st century: indications, oncologic and functional outcomes]. / Les pharyngo-laryngectomies totales au 21ème siècle : indications, résultats carcinologiques et fonctionnels.

INTRODUCTION: The development of laryngeal preservation protocols has considerably modified the indications for total (pharyngo-)laryngectomy (TPL). The objectives of our study are to analyze the current indications for TPL and to evaluate the oncologic and functional outcomes after TPL and their predictive factors. METHODS: All patients who underwent TPL for squamous cell carcinoma of the larynx or hypopharynx, at our institution, between 2000 and 2009, were included in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analyzes. RESULTS: A total of 130 patients were enrolled in our study including 119 men and 11 women, with a mean age of 65.9 years. TPL was realized for salvage in 65 patients. Extra-laryngeal tumor extension (n = 42) was the main indication for TPL in the 65 remaining patients. Overall survival was 49 and 41% at 3 and 5 years respectively. In multivariate analysis, primary tumor site (hypopharynx in comparison to larynx; p = 0.04) has a significant pejorative impact on overall survival. Oral alimentation (no enteral nutrition) was recovered successfully by 94% of the patients. In multivariate analysis, primary tumor site (hypopharynx) has a significant pejorative impact on functional results (deglutition: p < 0.0001; phonation: p = 0.03). CONCLUSION: Primary tumor site is one of the main predictive factor of oncologic and functional outcomes after TPL.

[Does orbital exenteration still has a place in 2019?] / L'exentération orbitaire a-t-elle encore sa place en 2019 ?

INTRODUCTION: Orbital exenteration is a radical anatomically and psychologically disfiguring procedure. It is mostly performed for management of orbital cancers or cancers with orbital involvement. The lack of benefit in terms of overall survival and the development of new molecular therapies (targeted therapies, immunotherapy) in recent years leads us to question its use. The goal of our review is to answer to the following question: is orbital exenteration a viable procedure in 2019? MATERIALS AND METHODS: A literature review was performed using the PUBMED and MEDLINE databases. The following terms were used then crossed with each other: "orbital exenteration", "exenterated socket", "overall survival", "life expectancy", "orbital reconstruction", "socket reconstruction". Oncology articles from the past 15 years were included and separated into those in the oculoplastic literature and those in the ENT literature. RESULTS: Nineteen articles were included in this review. Eyelid tumours represent the main etiology of orbital exenteration. Basal cell carcinoma is the most frequently incriminated tumor, while sebaceous carcinoma and conjunctival squamous cell carcinoma are the most frequently encountered in Asian series. Non-conservative orbital exenteration is the most prevalent surgery performed. Orbital reconstruction depends on the surgeon's speciality: healing by secondary intention and split thickness skin grafts are mostly performed by oculoplastic surgeons, whereas regional or free flaps are mostly performed by ENT surgeons. Cerebrospinal fluid leakage is the most common intraoperative complication, encountered in 0 to 13 % of cases. The most common postoperative complications are ethmoid fistula and infection of the operative site, encountered in 0 to 50 % and 0 to 43 % of cases respectively. Orbital exenteration allows surgical resection of R0 tumors in 42.5 % to 97 % of cases. Overall survival following orbital exenteration is 83 % (50.5-97) and 65 % (37-92) at 1 and 5 years respectively. Identified risk factors for poor overall survival are: age, tumor histology (worse prognosis with choroidal melanoma, better prognosis with basal cell carcinoma), non-R0 surgical resection, locally advanced tumors (size>20mm, BCVA<20/400 and the presence of metastases at diagnosis). Recent studies have demonstrated favorable outcomes when managing locally advanced basal cell carcinoma, lacrimal gland cancer and conjunctival melanoma with targeted therapies or immunotherapies without performing orbital exenteration. CONCLUSION: Orbital exenteration remains a major part of our therapeutic arsenal. Although orbital exenteration has failed to demonstrate any overall survival benefit, it allows satisfactory local control of the disease with an increasingly less invasive procedure. The development of targeted therapies and immunotherapies may change our therapeutic decisions in the future.

[T1-T2 NO hypopharyngeal cancers treated with surgery alone. A GETTEC study (French Neck Study Group)]. / Cancers de l'hypopharynx T1-T2 "N0" traités par chirurgie exclusive. Etude GETTEC.

OBJECTIVE: Consider whether surgery alone in the treatment of early cancers of the hypopharynx can give identical or better results in terms of survival and local control than radiotherapy. METHODS: Forty-five patients were operated on during the years 1991-2004. Surgical treatment consisted in a resection by the transoral approach in four patients and 41 patients had a partial pharyngolaryngectomy. An elective neck dissection was performed on 43 patients. RESULTS: The 1-, 3-, and 5-year overall survival rates were 100, 95, and 75%. The 1-, 3-, and 5-year locoregional control rates were 93, 88, and 82% and were influenced by the presence of dysplasia on surgical margins (p=0.027). The oncological occurrences observed were five local recurrences, two nodal recurrences, ten second primary cancers, and two metastases. Five locoregional failures out of seven were controlled after a second treatment. CONCLUSION: Surgery alone gives completely satisfactory results in terms of survival and locoregional control. In case of recurrence, this makes it possible to operate on patients in nonirradiated areas with lower morbidity and mortality and better results. These results must be confirmed by a randomized trial.

[Transoral and cervical approach without mandibulotomy for oropharynx cancer with fasciocutaneous radial forearm free flap reconstruction]. / Voie d'abord transorale et cervicale sans mandibulotomie dans les cancers de l'oropharynx avec réparation par lambeau libre fasciocutané antébrachial.

OBJECTIVE: To evaluate the role of a combined transoral and cervical approach without mandibulotomy for surgery of oropharyngeal cancer with fasciocutaneous radial forearm free flap reconstruction. MATERIAL AND METHODS: All patients who underwent this type of surgery between 2003 and 2007 were included in this retrospective study. We analyzed postoperative outcomes, surgical margins (histological study) and the oncological and functional results. RESULTS: A total of 24 patients were included in this study. There was no free flap failure. Surgical margins were negative for 23 of the 24 patients. At 3 years, overall, cause-specific, and disease-free survival rates were 73, 76 and 68%, respectively. A good functional result (normal or slightly impaired function) was obtained for oral diet, speech, mouth opening and esthetic outcome in 78, 82, 92 and 86% of the patients, respectively. CONCLUSION: This double surgical approach without mandibulotomy in selective cases can replace the transmandibular approach in locally advanced oropharyngeal cancer surgery.

[Planned reconstruction after broad carcinological demolition of the face: case report]. / Reconstruction planifiée après large démolition carcinologique de la face: à propos d'un cas.

UNLABELLED: The authors present their approach in face reconstruction after carcinological demolition. CASE REPORT: A 40-years-old patient presented an epidermoid carcinoma starting at the level of the right jawbone, few differentiated, massively destroying the roof of the maxillary sinus with subcutaneous and cutaneous infiltration in front and extension to the orbit. A broad right hemifacial right amputation was decided with ocular exenteration, cutaneo-palpebral sacrifice, parotidectomy with conservation of the facial nerve and standard cervical neck. After study and 3D simulation the reconstruction was carried out by an osteocutaneous parascapular flap using the external columna of the scapula for the repair of the lower orbital edge in order to accomodate an epithesis. CONCLUSION: We think that the planning step and preoperative three-dimensional measurement is of primary importance. It defines the size and type of flap to be taken in order to rebuild as well as possible the face while respecting the aesthetic units.

[Papillary thyroid microcarcinomas: review of 230 cases]. / Les microcarcinomes papillaires de la glande tyroïde: à propos de 230 cas.

OBJECTIVES: Papillary microcarcinoma (PMC) is one of the most frequent pathological forms of thyroid cancer Here, we describe the circumstances of diagnosis and the clinical and pathological characteristics of this tumour We also analyze the therapeutic management and compare it with the recent published guidelines. METHODS: Between 2000 and 2006, a total of 230 patients with a PMC of the thyroid gland were included in this retrospective study. We have investigated the correlations between some pathological parameters (plurifocality, lymph node invasion...) and several factors (age, gender, tumour size...). RESULTS: The diagnosis of PMC was suspected in the preoperative period in 15% of the patients, and was confirmed intraoperatively by the pathologist in 42% of the cases. Plurifocal or bilateral PMC were discovered in respectively 30 and 17% of the patients. The rate of lymph node invasion in the central neck (level VI) was 26%. An elevated tumor size was correlated with a higher rate of plurifocal or bilateral PMC and of lymph node metastasis (p < 0.05). The indications for postoperative radioiodine therapy were reduced by approxiately 50% in the second part of our study. There were no case of thyroid PMC-related death. CONCLUSIONS: Even for these small tumours, tumour size remains correlated with the tumour aggressiveness. The place of radioiodine therapy in the management of thyroid PMC was progressively reduced because of the good prognosis of this tumour.

Role of supracricoid partial laryngectomy with cricohyoidoepiglottopexy in glottic carcinoma with anterior commissure involvement.

OBJECTIVES: To analyze oncologic and functional outcomes after supracricoid laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP) in glottic carcinoma with anterior commissure (AC) involvement, to determine predictive factors, and to compare results with those reported for other therapeutic strategies. MATERIAL AND METHODS: A retrospective analysis included all patients who underwent SCL-CHEP for glottic squamous cell carcinoma with anterior commissure involvement in our institution, between 2000 and 2014. Swallowing function was evaluated on the DOSS (Dysphagia Outcomes and Severity Scale). RESULTS: Fifty-three patients were included. Three-year overall, cause-specific and recurrence-free survival rates were 86, 95 and 80%, respectively. There were 5 cases of local recurrence (9%), all treated by total laryngectomy. Smoking was the only predictive factor of recurrence-free survival (P=0.02). Mean DOSS score was 5.5±0.9. DOSS scores≥6 (normal oral feeding) were recovered by 59% of patients. T-stage≥2 was the only predictive factor for DOSS score (P=0.04). CONCLUSION: In glottic carcinoma with anterior commissure involvement, SCL with CHEP provided a local control rate of more than 90%, which is higher than reported with endoscopic surgery or external radiotherapy. However, contrary to LSC, salvage of local recurrence can often be obtained by conservative treatments after endoscopic surgery. Therefore, total-laryngectomy-free survival rates after SCL-CHEP and endoscopic surgery are finally comparable.

[Ameloblastomas]. / Les améloblastomes.

OBJECTIVES: The aim of this work was to report on the clinical, radiological and histological characteristics of ameloblastomas concerning bone structures of the face, rare but not exceptional tumours, and to communicate our experience of their treatment. MATERIAL AND METHODS: The authors reexamined six recent cases of patients presenting with ameloblastoma at the centre Antoine Lacassagne in Nice. The diagnostic context, the treatment and the development of the disease are given in detail, emphasizing the frequency of local relapse of this histologically benign condition. RESULTS: The study of these cases confirmed the benefit of surgical treatment of ameloblastoma. The frequency of local relapse in the cases of close resection, leaving in place micro-foci, justifies enlarged intervention, which is often bone destructive. CONCLUSION: When the continuity of the bone is interrupted, in particular at the level of the mandible, and if the general condition of the patient permits, repair is preferable. In this situation, the procedure of choice is micro-anastomosis of the fibula.

[Mandibular reconstruction with osseous free flaps: functional results]. / La reconstruction mandibulaire par lambeaux libres osseux: résultats fonctionnels.

OBJECTIVES: The aim of this retrospective study is to evaluate functional results of oromandibular reconstruction with osseous free flaps. MATERIAL AND METHODS: A total of 67 patients who underwent oromandibular reconstruction with fibula (n=60) or scapular (n=7) free flap between 2000 and 2004 were included in this study. We analysed functional results (alimentation, elocution, mouth opening and cosmetic appearance) and researched the potentially predictive factors of these results (age, comorbidity, preoperative irradiation, type of defect...; Chi(2) test). RESULTS: The rate of free flap success was 89.6%. A functional result considered as normal or subnormal was obtained by more than 50% of patients. Oral alimentation (without tube feeding) and intelligible speech were recovered by 92.5% of patients. Through and through defects and free flap failures were determinant predictive factors of worse functional outcomes. CONCLUSION: Fibula free flap is considered as the flap of choice for oromandibular reconstruction and allows excellent functional results.

[Head and neck reconstructive surgery with free flaps and quality of life: a prospective study]. / Chirurgie reconstructive cervico-faciale par lambeaux libres et qualité de vie: étude prospective sur 1 an.

OBJECTIVE: The aim of this prospective study is to evaluate functional results and quality of life after head and neck reconstructive surgery with free flaps. MATERIAL AND METHODS: All patients who have beneficed of head and neck reconstructive procedures with free flaps during the year 2004 were included in this study. EORTC quality of life questionnaire (QLQ-C30/H&N35) was used before and 6 months after surgery. A head and neck functional evaluation was realized 6 months after surgery. RESULTS: Thirty four patients were examinate 6 months after surgery. Global quality of life remained at its preoperative level (61.3% VS 62.8%). Physical, role and social functioning decreased significantly (p = 0.05), but emotional and cognitive functioning remained stable. Pain decreased considerably after treatment in the head and neck area (p = 0.001). Oral (eating: p = 0.05, speaking: p = 0.008) and sensorial functions (p = 0.001) decreased after treatment. All patients except one have recovered sufficient oral intakes, an intelligible speech and a good cosmetic result. CONCLUSION: Functional and cosmetic results after head and neck reconstructive surgery are the key factors of quality of life. Free flaps are considered actually as an indispensable technique to achieve an optimal reconstruction.

[Oropharyngeal reconstruction with radial forearm free flap: functional results]. / Les reconstructions buccopharyngées par lambeau libre antebrachial: résultats fonctionnels.

OBJECTIVE: The aim of this retrospective study is to evaluate functional results of oral and oropharyngeal reconstructions with radial forearm free flap. MATERIAL AND METHODS: We present our experience with radial forearm free flap for reconstructing oral and oropharyngeal defect between 2000 and 2004. A total of 96 patients were included in this study. We analysed functional results (alimentation, elocution, mouth opening and cosmetic appearance) and researched the potentialy predictive factors of these results (age, comorbidity, preoperative irradiation...; Chi 2 test). RESULTS: The rate of free flap success was 97.9%. Good functional results (normal or quasi normal function) were obtained for alimentation, elocution, mouth opening and cosmetic appearance in respectively 92.6%, 64.9%, 81.9% and 84.1% of cases. Age (p = 0.05), preoperative irradiation (p = 0.005) and T stage (p = 0,02) had a negative effect on elocution, free flap failure on mouth opening (p = 0.03), preoperative irradiation (p = 0.05) and free flap failure (p = 0,02) on cosmetic appearance. CONCLUSION: Radial forearm free flap is considered as the flap of choice for oral and oropharyngeal reconstructions and allows excellent functional results.

Primary total laryngectomy and pharyngolaryngectomy in T4 pharyngolaryngeal cancers: Oncologic and functional results and prognostic factors.

OBJECTIVES: The aims of this study were to assess oncologic and functional outcome in primary total laryngectomy or pharyngolaryngectomy (TL/TL/TPL) for laryngeal or hypopharyngeal cancer with extra-laryngeal extension (T4) and to determine the predictive factors of these results. MATERIAL AND METHODS: A retrospective analysis was performed on the computerized medical records of all patients undergoing primary TL/TPL for T4 larynx or hypopharynx squamous cell carcinoma between 2000 and 2014 at our institution. Predictive factors of oncologic and functional outcome were investigated on univariate and multivariate analysis. RESULTS: Sixty-three patients (58 men, 5 women; mean age, 68.8±9.7 years) were included. Overall and disease-specific survivals were 69% and 80% at 3 years, and 56% and 69% at 5 years, respectively. On multivariate analysis, gender (female, P<0.001), ASA score (ASA≥3; P=0.006) and vascular embolism (P=0.006) had significant pejorative impact on overall survival. Six months after end of treatment, 90% of patients had recovered independent oral feeding and 83% of those with tracheoesophageal voice prostheses had recovered an intelligible voice. CONCLUSION: Primary TL/TPL remains the gold standard treatment for T4 larynx or hypopharynx cancer. It provides satisfactory oncologic and functional outcomes.

Transoral-transcervical oropharyngectomy without mandibulotomy, associated to fasciocutaneous radial forearm free-flap reconstruction, for oropharyngeal cancer: Postoperative course, oncologic and functional results, and prognostic factors.

OBJECTIVE: To analyze postoperative course, oncologic and functional results and prognostic factors of transoral-transcervical oropharyngeal cancer surgery without mandibulotomy, associated to radial forearm free-flap reconstruction. MATERIAL AND METHODS: Retrospective analysis of computerized medical records of all patients who underwent this type of surgery in our institution between 2004 and 2014. Predictive factors of oncologic and functional results were investigated on univariate and multivariate analyses. RESULTS: Forty-four patients (37 male, 7 female; mean age, 62.3±9.3years) were included. Three-year overall, disease-specific and recurrence-free survival was 90%, 92% and 79%, respectively. Functional scores were satisfactory (normal or slight impairment) for feeding, speech and oral opening functions in 86%, 93% and 100% of cases, respectively. ASA score≥III had significantly negative impact on overall survival (P=0.005) and on feeding (P=0.01) and speech (P=0.01). CONCLUSION: Transoral-transcervical oropharyngeal cancer surgery without mandibulotomy provided excellent oncologic and functional outcomes; it is an advantageous alternative to the conventional conservative transmandibular oropharyngectomy.

Review of sentinel node procedure in cN0 head and neck squamous cell carcinomas. Guidelines from the French evaluation cooperative subgroup of GETTEC.

The reliability of the sentinel lymph node (SN) technique has been established for more than ten years in T1-T2 oral cavity and oropharynx squamous cell carcinoma. Although most authors stress the necessity of rigorous implementation, there are no agreed guidelines. Moreover, other indications have been described, in other anatomical areas of the upper aerodigestive tract and in case of previous surgery or radiotherapy. SN expert teams, under the GETTEC head and neck tumor study group, conducted a review of the key points for implementation in head and neck cancers through guidelines and a review of classical and extended indications. Reliability depends on respecting key points of preoperative landmarking by lymphoscintigraphy, and intraoperative SN sampling and histological analysis. The SN technique is the best means of diagnosing occult lymph node involvement, whatever the primary tumor location, T stage or patient history.

[Reirradiation of head and neck cancers]. / Réirradiation des cancers des voies aérodigestives supérieures.

Locoregional relapse in previously irradiated region for head and neck tumours is associated with a bad locoregional and distant prognosis. Reirradiation might be exclusive, or feasible in addition with surgery and/or chemotherapy, according to histopronostic factors. Data show that reirradiation is feasible with some severe toxicity due to the bad prognosis of this situation. Hyperfractionnated regimen with split course or normofractionnated regimen without split course are possible with similar efficacy. If tumour size is small, stereotactic ablative radiotherapy may be considered, and if the treatment centre has proton therapy, it could be proposed because of better organs at risk sparing. There is no standard regarding reirradiation schedules and several trials have to be done in order to determine the best technique. Nevertheless, it is agreed that a total dose of 60Gy (2Gy per fraction) is needed. Other trials testing the association with new systemic agents have to be performed, among them agents targeting the PD1/PD-L1 axis.

Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer.

INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity. RESULTS: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis. CONCLUSION: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases.