- Email: [email protected]
PD6. Pre-treatment assessment in oral cancer
Pan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings Poster Abstracts Oral AbstractsPoster List
12
Panel discussions and symposia abstracts / Oral Oncology Supplement 3 (2009) 11–23
efficient anti-tumor immune responses. Very little is known about the expression of markers and the function of the innate immune system in HNSCC. We analyzed the expression, subcellular localization and function of different receptor proteins such as the Toll like receptors (TLR) TLR3, TLR4, TLR7, the Rig Helicases RIG I, MDA5, and the NOD like receptor system NOD1/2 in malignant tumor cells as well as in immune cell subsets of HNSCC patients. TLR but also the RIG helicase and NOD pathways directly regulate cytokine release especially of proinflammatory cytokines, such as IL1b, IL6, IL8 and other immune response regulating cytokines such as IL10 or TNF alpha. HNSCC have adopted markers of the innate immune system to drive tumor progression and due to many receptors feeding the same signal transduction pathway, different stimuli will add to keep up a dysregulated inflammatory-type cytokine micromilieu. This leads to dysregulation of the TLR and RIG Helicase system on immune effector cells in the surrounding environment, blinding the cells to adequately detect the stimuli and function or react in tumor response. TLR-, RIG Helicase-, MDA5- and NOD-like receptor profiles can serve as prognostic parameters of HNSCC patients as well as targets in novel immunotherapeutic approaches against HNSCC.
doi:10.1016/j.oos.2009.06.016
PD4. Proteomics based diagnostic and prognostic biomarkers for head-and-neck precancer and cancer R. Ralhan University of Toronto, Canada Proteomics combined with mass spectrometry (MS) is a powerful paradigm for unprecedented large-scale sequencing of tryptic peptides and identification of proteins in clinical samples for biomarker discovery. Multidimensional liquid chromatography (LC) -MS was used for the analysis of isobaric mass tags (iTRAQ) labeled biological samples to identify and quantify differentially expressed proteins in Head and neck/oral squamous-cell carcinomas (HNOSCCs) and Oral premalignant lesions (OPLs) in relation to non-cancerous head-and-neck tissues (control) and tumor surrounding mucosa (field cancerization). A panel of identified potential cancer markers (PCMs) was verified using independent set of clinical samples by immunohistochemistry (IHC) and correlated with clinical follow up of 51 patients to develop molecular predictors of clinical outcome. A panel of three PCMs showed 92% sensitivity and 91% specificity in discriminating HNOSCC from non-malignant head and neck tissue in iTRAQ analysis and 92% sensitivity and 87% specificity in IHC analysis. Interestingly, PCM 69 and PCM 70, were also differentially expressed in OPLs, albeit at a lower level than in HNOSCCs. Kaplan Meier survival analysis revealed that HNOSCC patients showing overexpression of both PCMs had significantly decreased median disease free survival (DFS) of 13 months relative to patients showing no over-expression of these two proteins (median = 38 months, p = 0.02). Increased heterogeneous ribonucleoprotein K (hnRNP K) expression was an early event in head and neck tumorigenesis, suggesting its utility in identifying oral leukoplakic lesions in early stages, prior to the onset of dysplasia The most important finding of our follow-up study was that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, while its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis,
suggesting its putative utility in clinical management of HNOSCC. Pathway analysis using literature mining algorithms unraveled the perturbed signaling pathways and biological networks in different stages of head and neck tumorigenesis and identified molecular targets for designing new therapeutic strategies. doi:10.1016/j.oos.2009.06.017
Panel discussion 2: Pre-treatment assessment in oral cancer PD5. The role of FDG PET/CT in clinical decision making for the management of oral cavity cancer J. Waldron University of Toronto, Canada FDG PET/CT can provide both functional and anatomic information regarding the location and distribution of squamous cell carcinomas of the head and neck. The roles for this technology in terms of clinical decision making for oral cavity cancer relate to its potential to discriminate tumour at the primary site, regional lymph nodes, synchronous sites and at distant metastatic sites for the purposes of prognostication, treatment planning and subsequent follow-up. The ultimate utility and cost effectiveness of this technology depends on its ability to achieve these endpoints significantly more often and accurately than existing practices. It is vital that clinicians have a sound appreciation of the strengths and limitations of this technology before relying on it to guide management decisions. This presentation will review the current literature with respect to each of these endpoints and identify the strengths and limitations of FDG PET/CT as a tool for the guidance of management and follow-up of patients with oral cavity cancer. doi:10.1016/j.oos.2009.06.018
PD6. Pre-treatment assessment in oral cancer R.J. Baatenburg de Jong Erasmus Medical Centre, The Netherlands Optimal assessment of oral cancer requires not only a thorough diagnostic work-up in order to establish a proper TNM stage. In order to predict the impact and outcome of treatment we should also evaluate the oral functions, such as speech, articulation, chewing, deglutition, taste and sensation. In addition, pain, social background and quality of life should be appraised since optimal treatment includes care for these aspects as well. The aforementioned factors are well recognised. In this presentation we will focus on comorbidity and performance status. These factors determine whether a patient can cope with the burdens of treatment, especially chemoradiation and surgery. In addition, the impact of comorbidity on shortterm and overall survival will also be addressed. In a recent study of 1376 patients, comorbidity was measured with the ACE-27. Comorbidity was present in 36.4% of patients. Mild decompensation was seen in 17.4%, moderate decompensation in 13.5% and severe decompensation in 5.5%. Most frequently observed ailments were cardiovascular, respiratory and gastro-intestinal. In univariate analyses, all prognostic variables (age, gender, site, T-, N-, M-stage, prior malignancies, comorbidity), contributed significantly to overall survival. Their contribution (except gender) remained significant in the multivariate Cox model.
doi:10.1016/j.oos.2009.06.019
PD7. Delineation of ‘‘at-risk” oral mucosal fields via fluorescence visualization: First steps M. Rosin British Columbia Cancer Research Centre, Canada The management of oral cancers is hampered by our current inability to detect and delineate the spread of the disease across the oral mucosa. In recognition of this difficulty, clinicians set surgical margins beyond the clinically apparent lesions. However, this strategy is not always effective; recurrence is frequent and associated with residual disease. Direct fluorescence visualization (FV) is a novel solution to this problem, permitting the resolution of disease not visible to the naked eye. This presentation will discuss our use of direct fluorescence visualization (FV) to track high-risk spread of invasive/preinvasive disease in patients enrolled in an ongoing longitudinal study, looking at associations between FV change and tissue pathology, the presence of high-risk molecular clones and disease outcome after FV-guided surgery. This is a promising new procedure that could have significant impact on detection of disease spread, potentially improving the identification of tumour margins at treatment and allowing for early identification of re-emergence of disease at treated sites. doi:10.1016/j.oos.2009.06.020
PD8. Role of CT and MRI in treatment planning of oral cavity cancer H. Stambuk Memorial Sloan-Kettering Cancer Center, USA [Abstract not available at time of print.] doi:10.1016/j.oos.2009.06.021
Panel discussion 3: Minimally invasive surgery in head and neck cancer PD9. Minimally invasive surgery in head and neck cancer P. Ambrosch Universitätsklinikum Schleswig-Holstein, Germany Minimally invasive surgery in head and neck cancer means the replacement of open ablative and reconstructive surgical techniques by endoscopic procedures using the CO2 laser. Transoral laser microsurgery (TLM) of upper aerodigestive tract carcinomas has developed to a method unifying the endoscopic approach with the advantages of the laser like surgical precision and optimal laser tissue interactions. The primary concern is complete tumor removal with sufficient resection margins and precise histopathologic examination of the resected specimens. The tumor site needs to be adequately exposed with complete visualization of the cancer. Decision-making in TLM is based on local tumor spread. Larger tumors are transected and the tumor is removed blockwise. The advantages of TLM in the treatment of early glottic carcinomas are widely recognized. The results in the treatment of glottic carcinomas with impaired vocal cord mobility or fixation are not yet to be evaluated finally. Present data show, that with the laser resection local control can be achieved in about 70% of cases. In early and moderately advanced supraglottic carcinomas the results of TLM are comparable with open supraglottic resections concerning local control and survival. Concerning organ preservation TLM is superior to primary radiotherapy. In the treatment of hypopharyngeal carcinomas TLM is a therapeutic alternative to surgical standard procedures and novel organ preservation protocols (neoadjuvant chemotherapy and radiotherapy, simultaneous chemoradiation). The en- or transoral approach in the treatment of carcinomas of the oral cavity and the oropharynx means much less morbidity by avoiding pharyngotomy, splitting or partial resection of the mandible and tracheostomy. The resulting defects after TLM are not covered and no reconstructive surgery is needed, which means not necessarily a disadvantage for postoperative swallowing and speech rehabilitation. doi:10.1016/j.oos.2009.06.022
PD10. Minimally invasive surgery in head and neck cancer J.G. Newman University of Pennsylvania, USA Robotic surgery has, in many ways, improved upon the minimally invasive approaches popularized by laparoscopy and endoscopy. By bringing instrument control into the field, adding three-dimensional vision, and allowing for wristed movement, robotics surgery has already taken hold as the dominant force in many surgical specialties. The head and neck regions provide unique challenges for robotic surgery, many of which are still being explored. In this session we will discuss the changing role of robotics in head and neck surgery, from the already-established role in trans-oral robotic surgery (TORS) to some of the new areas of exploration, including thyroid and skull base surgery. doi:10.1016/j.oos.2009.06.023
Pan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Short-term mortality was seen in 5.7% of our patients. Cardiovascular comorbidity, respiratory comorbidity, gastrointestinal comorbidity and diabetes showed a significant relationship with short-term mortality. Severity and treatment options for comorbid disease, e.g. cardiac or respiratory decompensation, have an important influence on the choices for tumor treatment. Severe decompensation may exclude options such as chemoradiation and major surgery, thereby changing curative intentions into a palliative approach. In other patients, optimalization of comorbid disease may permit optimal treatment in formerly unfit patients. The impact on prognosis may be illustrated by comparing the impact of comorbidity to the impact of T- and N-stage. The impact of an ACE-27 grade 3 appears to be comparable to the impact of a T4 tumor or a N2 neck. In conclusion: pretreatment assessment of oral cancer requires a ‘‘holistic” approach. In addition to the well-established diagnostic armamentarium, we value instruments that measure comorbidity, QoL and oral function as well. When these data are combined with the patients’ preferences and a reliable prognosis, an individual and tailored approach seems feasible.
13
Poster Abstracts Oral AbstractsPoster List
Panel discussions and symposia abstracts / Oral Oncology Supplement 3 (2009) 11–23
12
Panel discussions and symposia abstracts / Oral Oncology Supplement 3 (2009) 11–23
efficient anti-tumor immune responses. Very little is known about the expression of markers and the function of the innate immune system in HNSCC. We analyzed the expression, subcellular localization and function of different receptor proteins such as the Toll like receptors (TLR) TLR3, TLR4, TLR7, the Rig Helicases RIG I, MDA5, and the NOD like receptor system NOD1/2 in malignant tumor cells as well as in immune cell subsets of HNSCC patients. TLR but also the RIG helicase and NOD pathways directly regulate cytokine release especially of proinflammatory cytokines, such as IL1b, IL6, IL8 and other immune response regulating cytokines such as IL10 or TNF alpha. HNSCC have adopted markers of the innate immune system to drive tumor progression and due to many receptors feeding the same signal transduction pathway, different stimuli will add to keep up a dysregulated inflammatory-type cytokine micromilieu. This leads to dysregulation of the TLR and RIG Helicase system on immune effector cells in the surrounding environment, blinding the cells to adequately detect the stimuli and function or react in tumor response. TLR-, RIG Helicase-, MDA5- and NOD-like receptor profiles can serve as prognostic parameters of HNSCC patients as well as targets in novel immunotherapeutic approaches against HNSCC.
doi:10.1016/j.oos.2009.06.016
PD4. Proteomics based diagnostic and prognostic biomarkers for head-and-neck precancer and cancer R. Ralhan University of Toronto, Canada Proteomics combined with mass spectrometry (MS) is a powerful paradigm for unprecedented large-scale sequencing of tryptic peptides and identification of proteins in clinical samples for biomarker discovery. Multidimensional liquid chromatography (LC) -MS was used for the analysis of isobaric mass tags (iTRAQ) labeled biological samples to identify and quantify differentially expressed proteins in Head and neck/oral squamous-cell carcinomas (HNOSCCs) and Oral premalignant lesions (OPLs) in relation to non-cancerous head-and-neck tissues (control) and tumor surrounding mucosa (field cancerization). A panel of identified potential cancer markers (PCMs) was verified using independent set of clinical samples by immunohistochemistry (IHC) and correlated with clinical follow up of 51 patients to develop molecular predictors of clinical outcome. A panel of three PCMs showed 92% sensitivity and 91% specificity in discriminating HNOSCC from non-malignant head and neck tissue in iTRAQ analysis and 92% sensitivity and 87% specificity in IHC analysis. Interestingly, PCM 69 and PCM 70, were also differentially expressed in OPLs, albeit at a lower level than in HNOSCCs. Kaplan Meier survival analysis revealed that HNOSCC patients showing overexpression of both PCMs had significantly decreased median disease free survival (DFS) of 13 months relative to patients showing no over-expression of these two proteins (median = 38 months, p = 0.02). Increased heterogeneous ribonucleoprotein K (hnRNP K) expression was an early event in head and neck tumorigenesis, suggesting its utility in identifying oral leukoplakic lesions in early stages, prior to the onset of dysplasia The most important finding of our follow-up study was that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, while its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis,
suggesting its putative utility in clinical management of HNOSCC. Pathway analysis using literature mining algorithms unraveled the perturbed signaling pathways and biological networks in different stages of head and neck tumorigenesis and identified molecular targets for designing new therapeutic strategies. doi:10.1016/j.oos.2009.06.017
Panel discussion 2: Pre-treatment assessment in oral cancer PD5. The role of FDG PET/CT in clinical decision making for the management of oral cavity cancer J. Waldron University of Toronto, Canada FDG PET/CT can provide both functional and anatomic information regarding the location and distribution of squamous cell carcinomas of the head and neck. The roles for this technology in terms of clinical decision making for oral cavity cancer relate to its potential to discriminate tumour at the primary site, regional lymph nodes, synchronous sites and at distant metastatic sites for the purposes of prognostication, treatment planning and subsequent follow-up. The ultimate utility and cost effectiveness of this technology depends on its ability to achieve these endpoints significantly more often and accurately than existing practices. It is vital that clinicians have a sound appreciation of the strengths and limitations of this technology before relying on it to guide management decisions. This presentation will review the current literature with respect to each of these endpoints and identify the strengths and limitations of FDG PET/CT as a tool for the guidance of management and follow-up of patients with oral cavity cancer. doi:10.1016/j.oos.2009.06.018
PD6. Pre-treatment assessment in oral cancer R.J. Baatenburg de Jong Erasmus Medical Centre, The Netherlands Optimal assessment of oral cancer requires not only a thorough diagnostic work-up in order to establish a proper TNM stage. In order to predict the impact and outcome of treatment we should also evaluate the oral functions, such as speech, articulation, chewing, deglutition, taste and sensation. In addition, pain, social background and quality of life should be appraised since optimal treatment includes care for these aspects as well. The aforementioned factors are well recognised. In this presentation we will focus on comorbidity and performance status. These factors determine whether a patient can cope with the burdens of treatment, especially chemoradiation and surgery. In addition, the impact of comorbidity on shortterm and overall survival will also be addressed. In a recent study of 1376 patients, comorbidity was measured with the ACE-27. Comorbidity was present in 36.4% of patients. Mild decompensation was seen in 17.4%, moderate decompensation in 13.5% and severe decompensation in 5.5%. Most frequently observed ailments were cardiovascular, respiratory and gastro-intestinal. In univariate analyses, all prognostic variables (age, gender, site, T-, N-, M-stage, prior malignancies, comorbidity), contributed significantly to overall survival. Their contribution (except gender) remained significant in the multivariate Cox model.
doi:10.1016/j.oos.2009.06.019
PD7. Delineation of ‘‘at-risk” oral mucosal fields via fluorescence visualization: First steps M. Rosin British Columbia Cancer Research Centre, Canada The management of oral cancers is hampered by our current inability to detect and delineate the spread of the disease across the oral mucosa. In recognition of this difficulty, clinicians set surgical margins beyond the clinically apparent lesions. However, this strategy is not always effective; recurrence is frequent and associated with residual disease. Direct fluorescence visualization (FV) is a novel solution to this problem, permitting the resolution of disease not visible to the naked eye. This presentation will discuss our use of direct fluorescence visualization (FV) to track high-risk spread of invasive/preinvasive disease in patients enrolled in an ongoing longitudinal study, looking at associations between FV change and tissue pathology, the presence of high-risk molecular clones and disease outcome after FV-guided surgery. This is a promising new procedure that could have significant impact on detection of disease spread, potentially improving the identification of tumour margins at treatment and allowing for early identification of re-emergence of disease at treated sites. doi:10.1016/j.oos.2009.06.020
PD8. Role of CT and MRI in treatment planning of oral cavity cancer H. Stambuk Memorial Sloan-Kettering Cancer Center, USA [Abstract not available at time of print.] doi:10.1016/j.oos.2009.06.021
Panel discussion 3: Minimally invasive surgery in head and neck cancer PD9. Minimally invasive surgery in head and neck cancer P. Ambrosch Universitätsklinikum Schleswig-Holstein, Germany Minimally invasive surgery in head and neck cancer means the replacement of open ablative and reconstructive surgical techniques by endoscopic procedures using the CO2 laser. Transoral laser microsurgery (TLM) of upper aerodigestive tract carcinomas has developed to a method unifying the endoscopic approach with the advantages of the laser like surgical precision and optimal laser tissue interactions. The primary concern is complete tumor removal with sufficient resection margins and precise histopathologic examination of the resected specimens. The tumor site needs to be adequately exposed with complete visualization of the cancer. Decision-making in TLM is based on local tumor spread. Larger tumors are transected and the tumor is removed blockwise. The advantages of TLM in the treatment of early glottic carcinomas are widely recognized. The results in the treatment of glottic carcinomas with impaired vocal cord mobility or fixation are not yet to be evaluated finally. Present data show, that with the laser resection local control can be achieved in about 70% of cases. In early and moderately advanced supraglottic carcinomas the results of TLM are comparable with open supraglottic resections concerning local control and survival. Concerning organ preservation TLM is superior to primary radiotherapy. In the treatment of hypopharyngeal carcinomas TLM is a therapeutic alternative to surgical standard procedures and novel organ preservation protocols (neoadjuvant chemotherapy and radiotherapy, simultaneous chemoradiation). The en- or transoral approach in the treatment of carcinomas of the oral cavity and the oropharynx means much less morbidity by avoiding pharyngotomy, splitting or partial resection of the mandible and tracheostomy. The resulting defects after TLM are not covered and no reconstructive surgery is needed, which means not necessarily a disadvantage for postoperative swallowing and speech rehabilitation. doi:10.1016/j.oos.2009.06.022
PD10. Minimally invasive surgery in head and neck cancer J.G. Newman University of Pennsylvania, USA Robotic surgery has, in many ways, improved upon the minimally invasive approaches popularized by laparoscopy and endoscopy. By bringing instrument control into the field, adding three-dimensional vision, and allowing for wristed movement, robotics surgery has already taken hold as the dominant force in many surgical specialties. The head and neck regions provide unique challenges for robotic surgery, many of which are still being explored. In this session we will discuss the changing role of robotics in head and neck surgery, from the already-established role in trans-oral robotic surgery (TORS) to some of the new areas of exploration, including thyroid and skull base surgery. doi:10.1016/j.oos.2009.06.023
Pan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Short-term mortality was seen in 5.7% of our patients. Cardiovascular comorbidity, respiratory comorbidity, gastrointestinal comorbidity and diabetes showed a significant relationship with short-term mortality. Severity and treatment options for comorbid disease, e.g. cardiac or respiratory decompensation, have an important influence on the choices for tumor treatment. Severe decompensation may exclude options such as chemoradiation and major surgery, thereby changing curative intentions into a palliative approach. In other patients, optimalization of comorbid disease may permit optimal treatment in formerly unfit patients. The impact on prognosis may be illustrated by comparing the impact of comorbidity to the impact of T- and N-stage. The impact of an ACE-27 grade 3 appears to be comparable to the impact of a T4 tumor or a N2 neck. In conclusion: pretreatment assessment of oral cancer requires a ‘‘holistic” approach. In addition to the well-established diagnostic armamentarium, we value instruments that measure comorbidity, QoL and oral function as well. When these data are combined with the patients’ preferences and a reliable prognosis, an individual and tailored approach seems feasible.
13
Poster Abstracts Oral AbstractsPoster List
Panel discussions and symposia abstracts / Oral Oncology Supplement 3 (2009) 11–23