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Prognosis in salivary gland cancer. Results of the dutch head and neck oncology cooperative group (NWHHT)
Friday, February 23, 2007 1THENETHERLANDSCANCERINSITUTF~ExperimentalTherapy~Headand Neck surgery,Amsterdam, TheNetherlands, ZTHENETHERLANDSCANCERINSITUTE,ExperimentalTherapy,Amsterdam, The Netherlands, 3THE NETHERLANDSCANCERINSITUTE,Pathology, Amsterdam, The Netherlands, 4THENETHERLANDSCANCERINS~TUTE,Radiotherapy,Amsterdam, The Netherlands, THE NETHERLANDSCANCERINSmTUTE,Head and Neck surgery, Amsterdam, TheNetherlands Objective: Improve prediction of local-regional control after chemoradiation in head and neck cancer using gene expression analysis. Background. Chemoradiation is the preferred treatment modality for organ-preservation in head and neck squamous cell carcinoma (HNSCC), but fails in 20-30% of cases. Surgery, chemoradiation and radiotherapy alone are employed in larger tumors, although the choice between them is often arbitrary. No reliable biological markers are yet available for aiding treatment choice. Gene expression using microarrays is expected to reveal characteristics of tumor behavior relevant to chemotherapy and radiotherapy responses and is likely to help in choosing between different treatment options. Materials/Methods: We collected 58 biopsies from previously untreated head and neck cancer patients subsequently given weekly high dose cisplatin-based chemoradiation (RADPLAT) for stage 3-4 squamous cell carcinomas. 21 patients developed a local-regional recurrence and 40 patients remained in complete remission for at least 1.5 years. This was used for training. A further 34 patients given daily low dose cisplatin concurrent with radiotherapy, of whom 7 developed a Ioco-regional recurrence, was used for validation. Extracted RNA was amplified, labeled, and hybridized to a 35K oligo array (NKI, Amsterdam). An aRNA-reference pool from 62 head and neck tumor biopsies enabled straight color and color reverse hybridizations for each patient. Results: Hierarchical clustering and class prediction analysis yielded a 7-gene profile with a sensitivity and specificity of 62% and 84% respectively for local-regional control in the training series. The predictive profile could significantly split tumors into good and poor local-regional control as assessed by Kaplan-Meier analysis (p=0.O01). This profile was also significantly predictive in the validation series (p=0.05). Other algorithms, or different training-validation splits, reduced statistical significance. Gene Set enrichment Analysis on 311 gene sets revealed 6 sets with a nominal p-value <0.05 and a false discovery rate <25%. For these sets, Kaplan-Meier analysis showed significant differences in local-regional control for high and low expressing tumors, although these were not predictive in the validation series. Conclusions: Gene sets can be found with predictive potential for local-regional control after combined radiation and chemotherapy in HNSCC, although these cannot yet be regarded as robust. Further studies are being done on radiotherapy-alone patients. 20 oral PROGNOSIS IN SALIVARY CLAN D CANCER. RESULTSOFTHE DUTCH HEAD AND NECK ONCOLOGY COOPERATIVE GROUP (NWHHT) R.J. Baatenburg de Jong% M. van der Schroeff% K. van Schie I, H. Lubsen2,CHJ. Terhaard3 IERASMUSUMC ROTFERDAM,Department of ENT,Rotterdam, The Nether-
lands, 2UMC UTRECHT,Departmentof ENT,Utrecht, TheNetherlands, 3UMC UTRECHT,Departmentof Radiotherapy, Utrecht, TheNetherlands The prognosis of patients with salivary gland cancer is usually based on the TNM and histological type. However, this classification neglects significant patient factors, such as comorbidity. For patient counselling and treatment decisions a comprehensive prognostic model would be helpful. Purpose: (1) To determine the Introduction:
Symposia/Proffered Papers effect of comorbidity on prognosis in patients with salivary gland cancer. (2) To design a comprehensive prognostic model for these patients. Materials/Methods: In 666 patients with salivary gland cancer, treatment period 1985-1994, ACE-27 grade was determined retrospectively. Parotid glands were most involved (56%) followed by minor salivary glands (32%) and submandibular glands (13%). Results: In 610 of 666 patients an ACE27 score could be retrieved retrospectively: grade 0: 392; grade 1: 120; grade 2: 69; grade 3: 29; unknown: 56. Distribution of ACE-27 grade, correlated with age and sex (male higher grade). Five and ten years overall survival were 70% and 65%, 50% and 30%, 40% and 0%, for grade 0, grade 1-2, grade 3 respectively. Multivariate analysis (Cox) for overall survival included: sex, age, site of tumor, size of the tumor, ACE27, invasion of skin, pN and WHO-72 classification. Significant predictors of overall survival were: age, ACE27, size and site, pN and invasion of skin. The RR's of ACE27 grade 1, 2 and 3 were 1.37, 1.71 and 3.10, respectively. A dynamic and comprehensive prognostic model will be presented during the lecture. Conclusions: Comorbidity is a significant predictor of overall survival.
NovelImagingTechniques 21 speaker STATE OF THE ART IN ANATOMIC IMAGING R. Hermans UNIVERSITYHOSPITALSLEUVEN,Departmentof Radiology,Leuven,Belgium The clinical evaluation allows to appreciate the mucosal layer of the head and neck region quite well. However, the deep extent of potentially infiltrating lesions can only be judged indirectly. Some regions, such as the base of the skull, pterygopalatine and infratemporal fossa, orbits and brain are beyond clinical evaluation, but critical management decisions have to be made based on the involvement of these structures; imaging findings are of the utmost importance in such cases. Perineural and/or perivascular spread, eventually leading to tumour progression or recurrences at distance from the primary tumour can often only be detected by imaging. Metastatic adenopathies can be identified by imaging studies, sometimes still in a subclinical stage or at places not accessible for clinical examination, such as the retropharyngeal or paratracheal lymph nodes. Also, information on extranodal tumor spread and the relation to critical structures such as the carotid arteries, is necessary for determining the optimal patient management. Imaging is necessary in submucosal lesions; the origin and extent of such lesions is often difficult to determine based on the clinical evaluation alone. Imaging may provide important clues to the diagnosis, as representative biopsies may be difficult to obtain in deepseated lesions. The imaging findings can profoundly influence the staging and management of the patient with head and neck cancer. Finally, imaging may be used to monitor tumour response and to try to detect recurrent or persistent disease before it becomes clinically evident, possibly with a better chance for successful salvage. The single most important factor in the optimal use of all this information is the mutual co-operation between the radiologist and the physicians in charge of patient care. 22 speaker POSITRON EMISSION TOMOGRAPHY IN HEAD AND NECK CANCER W. DyeD%D. Schinagl 2,W. Vogel ~,B. Wensing% E.Troost 2,M. Merlod, H. Marres% F.VandenHoogen%J. Kaanders2 IRADBOUDUNIVERSITYNIJMEGENMEDICALCENTRE,NuclearMedicine,Nijmeg-
en, TheNetherlands 2RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE,Radiation Oncology,
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lands, 2UMC UTRECHT,Departmentof ENT,Utrecht, TheNetherlands, 3UMC UTRECHT,Departmentof Radiotherapy, Utrecht, TheNetherlands The prognosis of patients with salivary gland cancer is usually based on the TNM and histological type. However, this classification neglects significant patient factors, such as comorbidity. For patient counselling and treatment decisions a comprehensive prognostic model would be helpful. Purpose: (1) To determine the Introduction:
Symposia/Proffered Papers effect of comorbidity on prognosis in patients with salivary gland cancer. (2) To design a comprehensive prognostic model for these patients. Materials/Methods: In 666 patients with salivary gland cancer, treatment period 1985-1994, ACE-27 grade was determined retrospectively. Parotid glands were most involved (56%) followed by minor salivary glands (32%) and submandibular glands (13%). Results: In 610 of 666 patients an ACE27 score could be retrieved retrospectively: grade 0: 392; grade 1: 120; grade 2: 69; grade 3: 29; unknown: 56. Distribution of ACE-27 grade, correlated with age and sex (male higher grade). Five and ten years overall survival were 70% and 65%, 50% and 30%, 40% and 0%, for grade 0, grade 1-2, grade 3 respectively. Multivariate analysis (Cox) for overall survival included: sex, age, site of tumor, size of the tumor, ACE27, invasion of skin, pN and WHO-72 classification. Significant predictors of overall survival were: age, ACE27, size and site, pN and invasion of skin. The RR's of ACE27 grade 1, 2 and 3 were 1.37, 1.71 and 3.10, respectively. A dynamic and comprehensive prognostic model will be presented during the lecture. Conclusions: Comorbidity is a significant predictor of overall survival.
NovelImagingTechniques 21 speaker STATE OF THE ART IN ANATOMIC IMAGING R. Hermans UNIVERSITYHOSPITALSLEUVEN,Departmentof Radiology,Leuven,Belgium The clinical evaluation allows to appreciate the mucosal layer of the head and neck region quite well. However, the deep extent of potentially infiltrating lesions can only be judged indirectly. Some regions, such as the base of the skull, pterygopalatine and infratemporal fossa, orbits and brain are beyond clinical evaluation, but critical management decisions have to be made based on the involvement of these structures; imaging findings are of the utmost importance in such cases. Perineural and/or perivascular spread, eventually leading to tumour progression or recurrences at distance from the primary tumour can often only be detected by imaging. Metastatic adenopathies can be identified by imaging studies, sometimes still in a subclinical stage or at places not accessible for clinical examination, such as the retropharyngeal or paratracheal lymph nodes. Also, information on extranodal tumor spread and the relation to critical structures such as the carotid arteries, is necessary for determining the optimal patient management. Imaging is necessary in submucosal lesions; the origin and extent of such lesions is often difficult to determine based on the clinical evaluation alone. Imaging may provide important clues to the diagnosis, as representative biopsies may be difficult to obtain in deepseated lesions. The imaging findings can profoundly influence the staging and management of the patient with head and neck cancer. Finally, imaging may be used to monitor tumour response and to try to detect recurrent or persistent disease before it becomes clinically evident, possibly with a better chance for successful salvage. The single most important factor in the optimal use of all this information is the mutual co-operation between the radiologist and the physicians in charge of patient care. 22 speaker POSITRON EMISSION TOMOGRAPHY IN HEAD AND NECK CANCER W. DyeD%D. Schinagl 2,W. Vogel ~,B. Wensing% E.Troost 2,M. Merlod, H. Marres% F.VandenHoogen%J. Kaanders2 IRADBOUDUNIVERSITYNIJMEGENMEDICALCENTRE,NuclearMedicine,Nijmeg-
en, TheNetherlands 2RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE,Radiation Oncology,
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