Head and neck reconstructive surgery with free flaps and quality of life: A prospective study

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Symposia/Proffered Papers after IMRT (p=O.O08). Finally, the significant reduction of radiationinduced xerostomia translated in a significant benefit regarding a number of other head and neck and general symptoms, including fatigue, pain, appetite loss, teeth problems and trismus. Conclusions: This is the first clinical study that shows better outcome with IMRT compared to CBI with regard to acute xerostomia according to the RTOG and patient-rated xerostomia upto 6 weeks after completion of radiation. In addition, the lower incidence in radiation-induced xerostomia also translates into better outcome regarding other QoL dimensions.

Saturday, February 24, 2007 survivors demonstrated a benefit of IMRT, particularly in the fields of salivary dysfunction and oral discomfort.

EORTC QLQ-H&N35 symptom scale scores significantly different between the 2 matched populations Populations Mean Scores CRT IMRT

44 oral THE IMPACT OF INTENSITY-MODULATED RADIOTHERAPY ON HEALTH-RELATED QUALITY OF LIFE FOR HEAD AND NECK CANCERS PATIENTS.MATCHED-PAIR COMPARISON WITH CONVENTIONAL RADIOTHERAPY. R Graftn, M. Lapeyre 2, E. Desandes 3,C. Ortholan 4, RJ. Bensadoun4, M. AlfonsP, R Maingon 6, R Giraud 7,J. Bourhis8,V. MarchesP, A. MLage~,D. Peiffert ~ 7CENTREALEXISVAUTRIN~Radiation Ontology, Vandoeuvre-L~s-Nancy,

21.5 23.0 26.9 19.5 28.8

p

Pain Swallowing Social eating Teeth Open mouth

33.5 35.1 3B.2 34.9 48.3

0.01 0.01 0.03 0.02 0.001

Dry mouth Sticky saliva

83.1 5 7 . 2 <0.0001 7 6 , 6 47.1 <0,0001

CRT=Conventional Radiotherapy IMRT=I ntensity-Modulated Radiotherapy

France, 2CENTREJEANPERRIN,Radiation Oncology, Clermont-Ferrand, France, 3CENTREALEXISVAUTRIN,Clinical Research, Vandoeuvre-L~s-Nancy, France, 4CENTREANTOINELACASSAGNE,Radiation Oncology, Nice, France, SCUN~QUESAINTECATHERINE,Radiation Ontology, Avignon, France, 6CENTREGEORGEs-FRANCOISLECLERC,Radiation Oncology, Dijon, France, 71NST~TUTCURIE,Radiation Oncology, Paris, France, 81NSTITUTGUSTAVEROUSSY,Radiation Oncology, Villejuif, France, 9CENTRE ALEXIS VAUTRIN, Radiation Physics, Vandoeuvre-L~s-Nancy,

France Purpose/Objective: To assess the benefit of Intensity-Modulated Radiotherapy (IMRT), versus Conventional Radiotherapy (CRT), in terms of quality of life (QOL) of head and neck cancers survivors. Materials/Methods: This was a cross-sectional QOL assessment conducted in a multicentric French cohort (6 participating cancer centers). Eligibility criteria included head and neck cancers patients treated with a curative intent (follow-up >1 year), without clinical evidence of disease recurrence or a second primary at the time of the QOL evaluation. All patients received bilateral neck irradiation () 45 Gy) as part of their initial treatment. QOL data were collected using the EORTCQLQ-C30 (version 3.0) questionnaire and the EORTCQLQH&N35 module. Questionnaires were mailed after phone patient's agreement and self-assessed. For QOL scores comparison, patients were divided into 2 matched groups (1/1) according to RT modalities (CRT versus IMRT). Matching criteria were the delay between end of RT and time of QOL evaluation and the T stage. In accordance with EORTCQLQ-C30 scoring manual recommendations, individual QOL items of particular interest were divided into 2 relevant levels of severity. The association between the type of RT and prevalence of sever symptoms (responses 'Quite a bit' and 'Very much') was approximated, through multivariate analysis (conditional logistic regression), by the prevalence odds-ratio (POR). Results: The two matched groups (67 pairs) were comparable for most of the study variables including patients, diseases and treatments characteristics. The EORTC QLQ-C30 mean scores were not greatly different between the 2 groups. Inversely, seven QLQ-H&N35 mean scores were markedly better for IMRT patients. The most important differences concerned dry mouth (25.9 points; p(O.O001) and sticky saliva (29.5 points; p(O.O001). Prevalent cases of sever symptoms were higher among CRT patients concerning saliva modifications, oral discomfort and eating difficulties. The adjusted PORs were 3.17 (p=O.04) for dry mouth, 3.16 (p=O.02) for sticky saliva, 3.58 (p=O.02) for pain in mouth, 3.35 (p=O.04) for pain in jaw, 2.60 (p=O.02) for difficulties in opening mouth, 2.76 (p=O.02) for difficulties in swallowing and 2.68 (p=O.03) for troubles with eating. Conclusions: Assessment of QOL among head-and-neck cancers

45 oral RESULTS OF PROSPECTIVESTUDY OF SENTINEL NODE BIOPSY IN ORAL CAVITYTUMOURS G. Mamelle1,S.Temam 1, O. Casiraghi 2,M. Julieron ~, A.M. Le Ridant1 IINSTITUTGUSTAVEROUSSY,Head an Neck Departement, Villejuif, France, 21NSTITUTGUSTAVEROUSSY,Departement of Pathology, Villejuif, France

Purpose/Objective: Evaluate the accuracy of sentinel node biopsy for assessing the neck status for those patients with squamous cell carcinoma T1T2 NO of oral cavity. Materials/Methods: Fifty five patients were included in a prospective study between 2000 and 2003. Fifty three underwent a sentinel node biopsy (SNB) followed by an elective neck dissection (END) during the same surgical procedure. Pathological examination with stepped serial sectionings and immunohistochemistry of sentinel node (SN) has been compared with routine pathology examination of remaining END nodes. Results: Twelve patients had a positive SN. No false negative was found. Patient follow up on, at less of 3 years, did not show any node recurrence for those patients with negative SN. After that study, 48 patients had a SNB without END. SN was not found in 4 procedures. Eleven patients (25%) had a positive SN on 44 remaining patients. Follow up showed a node recurrence for 2 patients with negative SN. In one of these, pathological reexamination showed a micrometastase in SN. SN failure rate is less than 2% for those 103 patients. Conclusions: SNB is a liable procedure. Failure rate is less than in traditional END. 46 oral HEAD AND NECK RECONSTRUCTIVESURGERY WITH FREE FLAPS AND QUALITY OF LIFE : A PROSPECTIVESTUDY. G. Poissonnet.A. Bozec, J. Vallicioni, F. Demard, O. Dassonville CENTREANTOINELACASSAGNE,Surgery, Nice, France

Purpose/Objective: The aim of this prospective study is to evaluate quality of life after head and neck reconstructive surgery with free flaps. Materials/Methods: Free flap head and neck reconstructions were performed in 95 consecutive patients between 2004 and 2005. EORTC quality of life questionnaire (QLQ-C30/H&N35) was used before, 6 and 12 months after surgery. Predictive factors of poor quality of life were examined among the following: age, comorbidity, preoperative radiotherapy, tumor stage, type of surgery, type of

Saturday, February 24, 2007 defect. Results: Global quality of life decreased slightly at 6 months after surgery but remained approximately constant between 6 et 12 months (68.6%, 63.9% and 62.6 %0). Physical, role and social functioning decreased significantly at 1 year (p ~0.05), but emotional and cognitive functioning remained stable. Pain decreased considerably after treatment in the head and neck area (p (0.OS). Oral (eating and speaking) and sensorial problems increased significantly after treatment, with a slight functional deterioration between 6 and 12 months. Conclusions: Free flap reconstruction of head and neck defects allows good functional results and acceptable quality of life. 47 oral INTENSITY-MODULATED RADIOTHERAPY REDUCES LONG-TERM PAROTID GLAND FUNCTION COMPLICATIONS COMPARED WITH CONVENTIONAL RADIOTHERAPY R Braam, C.PJ. Raaijmakers,J.M. Roesink, Ch. Terhaard UNIVERSITYMEDICALCENTERUTRECHT,Radiotherapy, Utrecht, The Nether-

lands Purpose/Objective: In a phase II study we investigated the value of intensity-modulated radiotherapy (IMRT) for long-term objective and subjective preservation of the parotid gland function compared with conventional radiotherapy (CRT). Materials/Methods: A total of 56 patients with oropharyngeal cancer were enrolled in a prospective salivary function study. Inverseplanned step-and-shoot IMRT with integrated boost was used to treat 30 patients and CRT in 26 patients. Before, and 6 weeks, 6 months and 12 months after treatment, objective stimulated parotid salivary flow rates and subjective xerostomia (LENT-SOMA scale) were measured. Objective measurements were converted into the percentage of baseline flow rates (flow ratio). A complication was defined as the stimulated parotid flow ratio <25%. Results:A significant difference in dose to the parotid gland was observed between the two groups; the mean parotid gland dose was 33.7 Gy (SD 10 Gy) for IMRT and 48.1 Gy (SD 14 Gy) for CRT (p ~0.005). The mean parotid flow ratio 6 weeks, 6 months and 12 months after treatment was 41%, 64%, and 73% for IMRT and 11%, 18%, and 23% for CRT, respectively. The number of complications at 12 months after treatment was 41% for IMRT and 83% for CRT (p = 0.002). In subjective outcome, at all time points no significant differences between the two groups were found. At 12 months still 72% (13 out of 18) patients treated with IMRT and 80% (4 out of 5) patients treated with CRT complained of partial or complete persistent dryness. Conclusions: Using IMRT compared with CRT resulted in a significant long-term objective preservation of parotid gland function, but no subjective improvement was found using the LENT-SOMA scale.

MolecularTargetedTherapiesfor Headand NeckSCC 48 speaker CLINICAL APPLICATIONS WITH EGFR AND BEYOND

J. Baselga HOSPITALUNIVERSITARIOVALLo'HEBRON,Barcelona, Spain Abstract not received. 49 speaker PROMISING NEW TARGETS IN COMBINATION WITH RADIOTHERAPY G. Lammering UNIVERSITYHOSPITALMAASTRICHTANDUNIVERSITYMAASTRICNT,Radiation Ontol-

ogy (Maastro Clinic), Maastricht, Netherlands

Symposia/Proffered Papers Clinical optimization of combination regimens in the treatment of H&N cancer is ongoing but with challenges related to the development of new compounds, like the molecular targeted agents. These novel drugs are the result of the increased knowledge of the molecular and genetic events leading to cancer development and treatment resistance, like the cellular resistance in response to ionizing radiation, in our efforts to improve the clinical outcome of radiotherapy for solid tumors like H&N cancer, three major factors contributing to the failure of radiotherapy are the focus of these new molecular- targeted drugs: Tumor cell hypoxia/angiogenesis, intrinsic cellular radiosensitivity and tumor cell proliferation. Pre-clinical experiments in a variety of tumor models indicate that inhibition of angiogenic growth factors or growth factor receptors in combination with irradiation is a promising concept. Both, radiosensitization of endothelial cells by e.g. vascular endothelial growth factor (VEGF) inhibition as well as sensitization of endothelial cells against anti-angiogenic agents by ionizing radiation appear to play an important role. Whether simultaneous radiochemotherapy and anti-VEGF combinations improve the therapeutic window remains to be determined.. Both the antibody and the small molecule approach to target epidermal growth factor receptor (EGFR) have shown to confer a significant improvement in the radiosensitivity of human tumor cells, although the antibody approach seems to provide a more profound enhancement. There remains, however, a varying efficiacy, which might in part be related to mutations either at the level of EGFR or at the level of downstream effectors. Nevertheless, emerging new opportunities for pharmacological manipulation of other attractive molecular targets, such as the PI3K pathway in the radiation treatment of cancer are pending and may also ultimately prove efficacious.Within the PI3K pathway, mTor represents a central molecule for hypoxic responses and proliferation signaling. Thus Rapamycin and its analogs, which are known mTor inhibitor drugs, are also promising targeted drugs under current intensive investigation in combination with radiotherapy. Interestingly, Rapamycin also seems to function as an anti-angiogenic agent. The challenge in future research development will be to identify the appropriate inhibitor for the specific individual tumor. This will need further studies at all levels of translational research. S0 speaker CLINICAL APPLICATIONS OF PHARMACOGENOMICS iN HEAD AND NECK CANCER G. Milano CENTREANTOINELACASSAGNE,Oncopharmacology, Nice, France Pharmacogenomics will be considered according to two approaches: the analysis of gene expression profiles derived from clinical samples with DNA-array and proteomic tools and the germinal polymorphisms in genes important for response and toxicity to treatment (pharmacogenetics). Tumor analyzes with gene expression patterns may be useful for the discovery of tumor factors able to characterise progression of premalignant lesions, to predict for clinical outcome and to identify new targets for therapy. Germinal gene polymorphisms in epidermal growth factor receptor (EGFR) have been reported and may influence EGFR expression levels in tissues and the pharmacodynamics of EGFR targeting. Recent clinical data suggest that the presence of polymorphic variants in DNA-repair genes may be linked to response to radiotherapy and to cisplatinbased chemotherapy.

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