1. www.OncologyEducation.ca Results of an Ontario Clinical Oncology Group (OCOG) prospective cohort study on the use of FDG PET/CT to predict the need for neck dissection following radiation therapy of head and neck cancer (HNC) Authors: Waldron JN, Gilbert RW, Eapen L, Hammond A, Hodson DI, Hendler A, Perez-Ordonez B, Gu C, Julian JA, Julian DH and MN Levine Reviewed by Dr. Stephanie Snow ASCO 2011 abstract 5504 Oral Session June 6, 2011 Date posted: June 2011

2. www.OncologyEducation.ca Thank you for downloading this update. Please feel free to use it for educational purposes. Please acknowledge OncologyEducation.ca and Dr. Stephanie Snow when using these slides.

3. www.OncologyEducation.ca Background Upwards of 50% of node-positive head and neck cancer (HNC) patients will have residual nodes visible on CT following curative intent radiation +/- chemotherapy ~1/3 of these will harbour residual cancer and can be cured by surgical neck dissection CT, MRI and US guided FNA have limited sensitivity and/or specificity in detecting residual nodal disease The question has been raised whether FDG-avidity on the post-therapy PET/CT can be used to better predict which patients are likely to need surgery: –2 prospective case series reached differing conclusions

4. www.OncologyEducation.ca Study Design Prospective multi-centre study performed at four regional cancer centres in Ontario, Canada with n=398 Subjects: –Squamous cell HNC with N2 or N3 neck disease –Post-curative intent treatment with radiation +/- chemotherapy with full dose radiation delivered to all suspected nodal disease –All subjects had CT and PET/CT performed before treatment and 8-10 weeks post therapy Intervention: –All subjects with residual nodes >1cm axial dimension on post- treatment CT or positive PET-CT underwent neck dissection within four weeks of imaging –Pathologic results of neck dissection were correlated with post treatment imaging –Patients were then followed for two years

5. www.OncologyEducation.ca Subject Characteristics CharacteristicFrequency Sex Male Female 84% 16% Age (range) 27-84 (mean 57) Primary Site Oropharynx Hypopharynx Larynx Oral cavity Unknown primary site 73% 5% 4% 2% 15% Tumour Stage T0 T1-2 T3-4 15% 48% 37% Nodal Stage N2a N2b N2c N3 15% 43% 33% 10%

6. www.OncologyEducation.ca RESULTS: PET/CT Residual Disease Present No Residual Disease Present PET +ve 2734 PET -ve 2367 353 subjects had post therapy PET/CT scan at a mean of 9.2 weeks (range 4- 19) 151 underwent a neck dissection

7. www.OncologyEducation.ca RESULTS: PET/CT Utility of PET/CT for Residual Nodal Disease Sensitivity 54% (95% CI 40-67) Specificity 66% (95% CI 57-75) Positive Predictive Value 44% (95% CI 33-57) Negative Predictive Value 74% (95% CI 65-82)

8. www.OncologyEducation.ca RESULTS: CT Residual Disease Present No Residual Disease Present CT +ve 4790 CT -ve 314 154 patients who had a post- treatment CT underwent a neck dissection

9. www.OncologyEducation.ca RESULTS: CT Utility of PET/CT for Residual Nodal Disease Sensitivity 94% (95% CI 84-98) Specificity 13% (95% CI 8-21) Positive Predictive Value 34% (95% CI 27-43) Negative Predictive Value 82% (95% CI 59-94)

10. www.OncologyEducation.ca STUDY COMMENTARY Largest prospective trial to address this question to date Canadian data There is significant potential for functional impairment and compromise in quality of life after a neck dissection A test with high sensitivity and negative predictive value could help predict who does NOT have residual disease In this trial, enhanced CT scan was superior to PET/CT in sensitivity and negative predictive value, and the authors concluded that PET/CT should NOT be used to determine need for neck dissection

11. www.OncologyEducation.ca BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS This trial does not provide evidence for a clear role of PET/CT to assess for nodal disease post HNC therapy, however, the conclusion that PET/CT should not be used in neck dissection decisions may be pre-mature This is a question that is still important to explore as there were a number of potentially confounding issues: –Impact of HPV status on radiographic nodal response rates is unknown and could have been important in this study with 73% oropharyngeal primaries –Optimal timing for post-treatment PET/CT – the positive prospective trial did PET/CT at 12 weeks