O. Malard

Induction Chemotherapy Followed by Either Chemoradiotherapy or Bioradiotherapy for Larynx Preservation: The TREMPLIN Randomized Phase II Study

PURPOSE To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP). PATIENTS AND METHODS Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months. RESULTS Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only. CONCLUSION There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.

Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

SIGNIFICANCE Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for restoring functionality to the irradiated tissue bed. RECENT ADVANCES Preclinical studies presented in this review provide encouraging proof of concept regarding the therapeutic potential of stem cells for treating the adverse side effects associated with radiotherapy in different organs. Early-stage clinical data for radiation-induced lung, bone, and skin complications are promising and highlight the importance of selecting the appropriate stem cell type to stimulate tissue regeneration. CRITICAL ISSUES While therapeutic efficacy has been demonstrated in a variety of animal models and human trials, a range of additional concerns regarding stem cell transplantation for ameliorating radiation-induced normal tissue sequelae remain. Safety issues regarding teratoma formation, disease progression, and genomic stability along with technical issues impacting disease targeting, immunorejection, and clinical scale-up are factors bearing on the eventual translation of stem cell therapies into routine clinical practice. FUTURE DIRECTIONS Follow-up studies will need to identify the best possible stem cell types for the treatment of early and late radiation-induced normal tissue injury. Additional work should seek to optimize cellular dosing regimes, identify the best routes of administration, elucidate optimal transplantation windows for introducing cells into more receptive host tissues, and improve immune tolerance for longer-term engrafted cell survival into the irradiated microenvironment.

Adénocarcinomes de l’ethmoïde : expérience nantaise (80 cas): Place de la résection de la base du crâne par voie trans-faciale

OBJECTIVE To present results of a retrospective analysis of eighty cases of ethmoid adenocarcinoma. Carcinologic and surgical results of anterior skull base resection via the transfacial approach are presented. METHODS Tumors were classified as 5% T1, 23% T2, 31% T3, 21% T4a and 20% T4b. Thirty-four patients were treated via a paralateronasal approach without skull base resection. Anterior skull bas resections were performed via the transfacial approach for 26 patients and by combined neurosurgical approach for 21. RESULTS Mean follow-up was 4.8 years. Survival rate was 63.4% at 5 years and 57.9% at 8 years. Forty-two patients were alive and disease-free at last follow-up. Three patients were alive with recurrence. The rate of local recurrence was 38.8%. Complications occurred in 20% of the patients who had a transfacial approach. Complications appeared to be less frequent than with the combined approach. CONCLUSION Prognosis is related to local control and could be improved by using skull base resection more systematically. In our experience this can be managed by a transfacial approach with similar carcinological results and less complications than the combined approach.Objectifs Les auteurs presentent les resultats de l’analyse retrospective de 80 adenocarcinomes de l’ethmoide. Les resultats chirurgicaux et carcinologiques des resections de la base du crâne par voie trans-faciale sont egalement evalues. Methode Les tumeurs ont ete classees en 5 % de T1, 23 % de T2, 31 % de T3, 21 % de T4a et 20 % de T4b. Trente quatre patients ont ete traites par voie para-lateronasale avec conservation de la base du crâne. Vingt six resections de la base du crâne ont ete realisees par voie transfaciale et 21 par voie mixte. Resultats Le recul a ete de 4,8 ans. La survie a ete de 63,4 % a 5 ans et de 57,9 % a 8 ans. 45 patients sont en vie dont 3 en recidive. Le taux de recidive locale a ete de 38,8 %. Les complications ont concerne 20 % des voies trans-faciales. Ces complications ont ete moins frequentes et moins graves que par voie mixte. Conclusion Le pronostic est lie au controle local. Celui-ci peut etre ameliore par une resection plus systematique de la base du crâne. Dans notre experience, celle-ci peut etre realisee par voie trans-faciale avec des resultats carcinologiques similaires aux voies mixtes et avec une meilleure securite chirurgicale.

Gene expression profiling in sinonasal adenocarcinoma

BackgroundSinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.MethodsTo identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.ResultsAmong the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.ConclusionWithin our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.

Prognostic factors for T1–T2 squamous cell carcinomas of the mobile tongue: A retrospective cohort study

The aim of this study was to identify factors predicting poor prognosis at the time of early oral tongue carcinoma diagnosis.

Reconstruction of circumferential pharyngolaryngectomy using a 'horseshoe-shaped' pectoralis major myocutaneous flap.

Eighteen patients underwent a circumferential pharyngolaryngectomy reconstruction post pharyngolaryngectomy. All tumours showed pharyngo-oesophageal junction invasion or circular involvement of the hypopharynx, requiring total, circumferential pharyngolaryngectomy. A pectoralis major myocutaneous flap was directly sutured to the pre-vertebral fascia. A Montgomery salivary bypass tube was introduced into the oesophagus, and a nasogastric tube was placed within it. No post-operative complications occurred for 14 patients and only minor ones for the other four. Average post-operative stay was 12 days. For 15 patients, feeding returned to normal throughout the follow-up period. No fistulae were noted and neopharyngeal stenosis occurred in three patients (16 per cent). Thirteen had complete resection with normal margins. Thirteen were still alive after one to three years of follow up. The local recurrence rate was 16 per cent. The use of a pectoralis major myocutaneous flap with Sprianos technique provides a simple, reliable method for circumferential hypopharyngeal resection. It has been applied to a wide range of patients, especially elderly ones and those with poor general status, as well as to cases in which widespread involvement was detected during surgery.

Management of the Neck in the Setting of Definitive Chemoradiation: Is There a Consensus? A GETTEC Study

BackgroundThe management of the neck remains controversial in the definitive chemoradiation setting of advanced N2–3 head and neck squamous cell carcinoma. Most published data favor omission of neck dissection (ND) after complete response for N2–3 or selective ND for residual diseaseMethodsWe studied the patterns of care in the French-Belgian Groupe d’Etude des Tumeurs de la Tête Et du Cou (GETTEC) through a questionnaire-based survey.ResultsEighteen percent of institutions never performed up-front ND, 20% rarely, 40% sometimes, 14% often, and 8% systematically. Induction chemotherapy was indicated in 30% of the cases, and most ND were performed either between induction and radiation or after chemoradiation for residual disease. Response to chemoradiation was assessed by computed tomographic scan and positron emission tomography in 72% of cases. Selective ND was more common than radical ND.ConclusionsOmission of ND based on computed tomographic scan and positron emission tomography–based complete response to chemoradiation is the most common strategy for advanced nodal disease among centers. However, neck management strategies vary among institutions, and some institutions continue advocating systematic ND before irradiation. The new treatment options and the changing epidemiology, namely docetaxel-based induction chemotherapy and human papilloma virus–related head and neck squamous cell carcinoma having better response profiles and prognosis, are adding to the nonconsensual approach. The best therapeutic index in terms of neck management remains to be defined in this evolving context.

Prognostic factors for secondary recurrence of pleomorphic adenoma: a 20-year, retrospective study.

PURPOSE To evaluate the results of treatment of parotid pleomorphic adenoma, and the risk factors for secondary recurrence. MATERIALS AND METHODS Single-centre, retrospective study of 32 patients with pleomorphic adenoma recurrence managed between 1988 and 2008. RESULTS The mean age at diagnosis of primary pleomorphic adenoma recurrence was 43.4 years. Twenty-eight per cent of patients had secondary recurrence; 32 per cent had undergone two or more surgical resections and external adjuvant radiotherapy. An age of less than 25 years was significantly associated with an earlier primary recurrence (p = 0.008). The most significant histopathological risk factor for secondary recurrence was the presence of a multifocal tumour (p = 0.019). Other histopathological criteria (i.e. cellularity and capsule rupture) were not significant. Radiotherapy was not associated with a decrease in recurrence. Nine per cent of patients progressed to malignancy. The main surgical complication was definitive facial palsy (14 per cent). CONCLUSION Pleomorphic adenoma recurrence requires surgery, with greatly increased risk to the facial nerve. Resection with clear surgical margins is required, especially in young patients with multifocal tumours. Radiotherapy may delay second recurrence in cases of multifocal tumour.

Computed tomography in TN stage evaluation of oral cavity and oropharyngeal cancers

Oral and oropharyngeal carcinomas are characterized by a high incidence of node metastatic involvement and local extension. The study compared the TN stage of patients by clinical and computed tomography (CT) examination to postoperative histopathology. Sensitivity of CT for tumor extension was 82%, predictive value for bone involvement 67%. Clinical examination was poor in predicting the presence (54%) or absence (56%) of node involvement. Sensitivity of CT for assessment of node involvement was 80%, specificity 71%, positive predictive value 67%, and negative 83%. Node involvement was high (30%) in clinically NO necks versus only 9% for negative CT.

Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study

AIMS To evaluate the impact of human papillomavirus (HPV) status, tobacco smoking and initial treatment approach on progression-free survival (PFS) and overall survival (OS) for oropharyngeal cancer (OPC) in France, a country where smoking declines started late (1990s). METHODS 340 OPC patients (median age: 60years) from 14 French hospitals were followed up (median 26.7months). PCR-based positivity for both HPV DNA and E6/E7 mRNA was used to distinguish HPV-positive OPC (27.1%). Hospital-stratified hazard ratios (HR) and corresponding 95% confidence intervals (CI) were used to compare PFS and OS according to HPV and other prognostic factors in hospital-stratified unadjusted and multivariate models. The combined effect of HPV status with either smoking, stage, or initial treatment on PFS was also evaluated. RESULTS PFS in multivariate analysis was better in HPV-positive patients (HR=0.42; 95% CI: 0.24-0.73) and worse in older patients (HR for 5-year age increase=1.12) and those having had firstly radiotherapy (HR=1.86; 95% CI: 1.19-2.92) or induction chemotherapy (HR=1.73; 95% CI: 1.08-2.79) instead of upfront surgery. Findings for OS were similar. Loco-regional recurrences were less frequent in HPV-positive (10.5%) than HPV-negative patients (26.0%) but distant recurrences were similarly frequent. HPV status did not modify the influence of smoking or stage on PFS but the impossibility to perform upfront surgery may be more relevant for HPV-negative patients. CONCLUSIONS HPV-positive OPC patients fare better than HPV-negative OPC and may benefit from toxicity-sparing. Whether HPV-negative patients responded less well to radiation and chemotherapy because of more severe genomic damage or bulkier tumours is unclear.