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PO-130: The Role of Irradiation in Differentiated Thyroid Carcinomas
4th ICHNO Purpose/Objective: HPV16 infection has been proven to be associated with oropharyngeal squamous cell carcinomas (SCCs) and is probably the main reason of the reported increase in the incidence. The role of high risk (HR) HPV for carcinogenesis of other sites in the head and neck awaits confirmation. The primary aim of the present study is the evaluation of the incidence of HPV infection and of the reliability of different diagnostic tools in SCCs of different sites. Materials and Methods: 109 consecutive untreated head and neck SCCs were enrolled, and fresh tumor samples collected. HPV DNA was detected by DigeneHybrid Capture 2 (HC2). HPV E6 and E7 mRNA were detected by NucliSENS®EasyQ®HPVv1. p16 expression was evaluated by immunohistochemistry Results: 12.84% of cases were infected by HR and 1.84% by low risk genotypes. HPV16 accounted for 87% of high risk infections. The overall agreement between DNA and RNA detection is 99.1%. Although p16 expression clearly correlates with HPV infection (p=0.0051), the inter-rater agreement is poor (k=0.27). The oropharynx showed the highest HR HPV infection rate (47.6%) and was also the only site in which p16 IHC revealed to be a fair, but not excellent, diagnostic assay (kappa=0.61). Conclusions: The prognostic role of HR HPV infection in oropharyngeal oncology, with its potential clinical applications, underscores the need for a consensus on the most appropriate detection methods. The present results suggest that viral mRNA detection could be the standard for fresh samples, while DNA detection could be routinely employed in FFPE samples.
POSTER: THYROID CANCER PO-129 OPTIMIZING RADIOSENSITIZATION WITH METABOLIC IMAGING IN ANAPLASTIC THYROID CANCER V.C. Sandulache1, Y. Chen1, J. Lee2, C.M. Walker2, J.A. Bankson2, S.Y. Lai1 1 University of Texas MD Anderson Cancer Center, Head and Neck Surgery, Houston TX, USA 2 University of Texas MD Anderson Cancer Center, Imaging Physics, Houston TX, USA Purpose/Objective: Anaplastic thyroid carcinoma (ATC) is an aggressive disease that accounts for over 50% of thyroid cancer mortality and is refractory to conventional treatment with ionizing radiation (IR) and/or chemotherapy. To maintain high energy levels required for tumorigenesis and progression, ATC exhibits increased dependence upon glucose uptake and utilization. Our previous work has demonstrated that inhibition of cellular metabolic pathways can inhibit production of reducing equivalents and increase basal levels of reactive oxygen species (ROS) to mediate IR cytotoxicity through DNA damage and cell death. We evaluated targeting metabolism as a means to optimize radiosensitization of ATC. Materials and Methods: Sensitivity to specific metabolic inhibitors and IR was assayed using flow cytometry to assess ROS levels and clonogenic assays to assess cell survival. Using a murine orthotopic xenograft model of ATC, we examined changes in tumor metabolism following targeted pharmacologic inhibition or exposure to IR using [1-13C] pyruvate in hyperpolarized magnetic resonance imaging (HPMRI). Results: Glycolytic inhibition using 2-deoxyglucose (2-DG) increased ROS levels and sensitized ATC cells to IR and conventional chemotherapy agents. 2-DG induced a decrease in conversion of pyruvate into lactate in ATC tumors (p=0.054). A more complete assessment of the degree of metabolic inhibition was achieved using kinetic models that account for the exchange between physical and chemical
S55 pools to more closely mimic in vivo biochemical dynamics (p) Conclusion: HP MRI can be used to detect perturbations in tumor metabolism following metabolic inhibition or exposure to IR. In combination with IR, metabolic inhibition could be an effective means of increasing ROS levels sufficiently to induce tumor cell death even in radioresistant tumor cells. Real-time measurement of changes in tumor reducing potential may facilitate optimization of radiosensitization strategies in ATC. PO-130 THE ROLE OF IRRADIATION IN DIFFERENTIATED THYROID CARCINOMAS X.S. Sun1, N. Guevara2, N. Fakhry3, S.R. Sun4, P.Y. Marcy5, J. Santini6, J.F. Bosset7, J. Thariat8 1 Hôpital Univ. Jean Minjoz, Radiotherapy, Besançon, France 2 Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Head and Neck Surgery and Otology, Nice, France 3 Aix-Marseille Univ – Centre Hospitalier Universitaire La Timone, Department of Head and Neck Surgery, Marseille, France 4 Centre Hospitalier Belfort-Montbéliard, Department of Anothomopatology, Montbéliard, France 5 Centre Antoine Lacassagne - Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Radiology, Nice, France 6 Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Head and Neck Surgery, Nice, France 7 Hôpital Univ., Radiotherapy, Besançon, France 8 Centre Antoine Lacassagne - Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis. 33 av Valombrose, Department of Radiation Oncology, Nice, France Purpose/Objective: The mainstay of treatment for differentiated thyroid carcinomas (DTC) is surgery. There is hardly any room for external beam radiation therapy in differentiated thyroid carcinomas. We aimed to update recommendations for RT in the context of histological variants, increased use of radioiodine and new irradiations techniques. Materials and Methods: A search of the French and English literature was performed with terms: thyroid carcinoma, radiation therapy, surgery, prognostic factors. Results: Papillary, follicular and Hürthle carcinomas represent about 80%, 11% and 3% of all thyroid carcinomas, respectively. Their 10-year survival rates are 93%, 85%, and 76%, respectively.The occurrence of criteria such as older age (45 or 60 year-old) and massive primary disease and extensive extracapsular spread and macroscopic iodinenegative components indicate external beam irradiation (EBRT). The impact of EBRT for poorer-prognosis histological variants such as tall- cell, hûrtle-cell, columnar cell; male gender and recurrent disease are increasingly reported in retrospective studies as additional minor criteria suggesting EBRT. Noteworthy, morbidity has been an important limitation of 2D EBRT. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumor coverage and organ sparing such as the larynx, reducing late toxicities to less than 5%. Conclusions: The mainstay of treatment of differentiated carcinomas is surgery (+/- radioiodine). Radiation therapy has a role in selected patients who are at high-risk for local recurrence with DTC. There remains uncertainty in how to select high-risk patients for radiotherapy. A scoring system including classical prognostic factors and histologies is proposed, and warrants validation.
POSTER: THYROID CANCER PO-129 OPTIMIZING RADIOSENSITIZATION WITH METABOLIC IMAGING IN ANAPLASTIC THYROID CANCER V.C. Sandulache1, Y. Chen1, J. Lee2, C.M. Walker2, J.A. Bankson2, S.Y. Lai1 1 University of Texas MD Anderson Cancer Center, Head and Neck Surgery, Houston TX, USA 2 University of Texas MD Anderson Cancer Center, Imaging Physics, Houston TX, USA Purpose/Objective: Anaplastic thyroid carcinoma (ATC) is an aggressive disease that accounts for over 50% of thyroid cancer mortality and is refractory to conventional treatment with ionizing radiation (IR) and/or chemotherapy. To maintain high energy levels required for tumorigenesis and progression, ATC exhibits increased dependence upon glucose uptake and utilization. Our previous work has demonstrated that inhibition of cellular metabolic pathways can inhibit production of reducing equivalents and increase basal levels of reactive oxygen species (ROS) to mediate IR cytotoxicity through DNA damage and cell death. We evaluated targeting metabolism as a means to optimize radiosensitization of ATC. Materials and Methods: Sensitivity to specific metabolic inhibitors and IR was assayed using flow cytometry to assess ROS levels and clonogenic assays to assess cell survival. Using a murine orthotopic xenograft model of ATC, we examined changes in tumor metabolism following targeted pharmacologic inhibition or exposure to IR using [1-13C] pyruvate in hyperpolarized magnetic resonance imaging (HPMRI). Results: Glycolytic inhibition using 2-deoxyglucose (2-DG) increased ROS levels and sensitized ATC cells to IR and conventional chemotherapy agents. 2-DG induced a decrease in conversion of pyruvate into lactate in ATC tumors (p=0.054). A more complete assessment of the degree of metabolic inhibition was achieved using kinetic models that account for the exchange between physical and chemical
S55 pools to more closely mimic in vivo biochemical dynamics (p) Conclusion: HP MRI can be used to detect perturbations in tumor metabolism following metabolic inhibition or exposure to IR. In combination with IR, metabolic inhibition could be an effective means of increasing ROS levels sufficiently to induce tumor cell death even in radioresistant tumor cells. Real-time measurement of changes in tumor reducing potential may facilitate optimization of radiosensitization strategies in ATC. PO-130 THE ROLE OF IRRADIATION IN DIFFERENTIATED THYROID CARCINOMAS X.S. Sun1, N. Guevara2, N. Fakhry3, S.R. Sun4, P.Y. Marcy5, J. Santini6, J.F. Bosset7, J. Thariat8 1 Hôpital Univ. Jean Minjoz, Radiotherapy, Besançon, France 2 Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Head and Neck Surgery and Otology, Nice, France 3 Aix-Marseille Univ – Centre Hospitalier Universitaire La Timone, Department of Head and Neck Surgery, Marseille, France 4 Centre Hospitalier Belfort-Montbéliard, Department of Anothomopatology, Montbéliard, France 5 Centre Antoine Lacassagne - Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Radiology, Nice, France 6 Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis, Department of Head and Neck Surgery, Nice, France 7 Hôpital Univ., Radiotherapy, Besançon, France 8 Centre Antoine Lacassagne - Institut Universitaire de la Face et du Cou – Université Nice Sophia Antipolis. 33 av Valombrose, Department of Radiation Oncology, Nice, France Purpose/Objective: The mainstay of treatment for differentiated thyroid carcinomas (DTC) is surgery. There is hardly any room for external beam radiation therapy in differentiated thyroid carcinomas. We aimed to update recommendations for RT in the context of histological variants, increased use of radioiodine and new irradiations techniques. Materials and Methods: A search of the French and English literature was performed with terms: thyroid carcinoma, radiation therapy, surgery, prognostic factors. Results: Papillary, follicular and Hürthle carcinomas represent about 80%, 11% and 3% of all thyroid carcinomas, respectively. Their 10-year survival rates are 93%, 85%, and 76%, respectively.The occurrence of criteria such as older age (45 or 60 year-old) and massive primary disease and extensive extracapsular spread and macroscopic iodinenegative components indicate external beam irradiation (EBRT). The impact of EBRT for poorer-prognosis histological variants such as tall- cell, hûrtle-cell, columnar cell; male gender and recurrent disease are increasingly reported in retrospective studies as additional minor criteria suggesting EBRT. Noteworthy, morbidity has been an important limitation of 2D EBRT. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumor coverage and organ sparing such as the larynx, reducing late toxicities to less than 5%. Conclusions: The mainstay of treatment of differentiated carcinomas is surgery (+/- radioiodine). Radiation therapy has a role in selected patients who are at high-risk for local recurrence with DTC. There remains uncertainty in how to select high-risk patients for radiotherapy. A scoring system including classical prognostic factors and histologies is proposed, and warrants validation.