Benjamin S Rosen1, Joel R Wilkie2, Yilun Sun3, Mohannad Ibrahim4, Keith A Casper5, Jessa E Miller6, Thong Chotchutipan7, Chaz L Stucken5, Carol Bradford5, Mark E P Prince5, Andrew J Rosko5, Kelly M Malloy5, Scott A McLean5, Steven B Chinn5, Andrew G Shuman5, Matthew E Spector5, Paul L Swiecicki8, Francis P Worden9, Jennifer L Shah2, Caitlin A Schonewolf2, Christina H Chapman10, Avraham Eisbruch2, Michelle L Mierzwa2. 1. Department of Radiation Oncology, Michigan Medicine, Ann Arbor, United States. Electronic address: rosenbs@med.umich.edu. 2. Department of Radiation Oncology, Michigan Medicine, Ann Arbor, United States. 3. Department of Radiation Oncology, Michigan Medicine, Ann Arbor, United States; Department of Biostatistics, University of Michigan, Ann Arbor, MI, Uninet States. 4. Department of Radiology, Division of Neuroradiology, Michigan Medicine, Ann Arbor, United States. 5. Department of Otolaryngology-Head and Neck Surgery, Michigan Medicine, Ann Arbor, United States. 6. Department of Head and Neck Surgery, UCLA, Los Angeles, United States. 7. Department of Radiation Oncology, Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand. 8. Department of Internal Medicine, Michigan Medicine, Ann Arbor, United States; U.S. Department of Veterans Affairs, VA Center for Clinical Management Research, Ann Arbor, United States. 9. Department of Internal Medicine, Michigan Medicine, Ann Arbor, United States. 10. Department of Radiation Oncology, Michigan Medicine, Ann Arbor, United States; U.S. Department of Veterans Affairs, VA Center for Clinical Management Research, Ann Arbor, United States.
Abstract
PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.
PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.
Authors: Yue Cao; Catherine T Haring; Michelle Mierzwa; J Chad Brenner; Collin Brummel; Chandan Bhambhani; Madhava Aryal; Choonik Lee; Molly Heft Neal; Apurva Bhangale; Wenjin Gu; Keith Casper; Kelly Malloy; Yilun Sun; Andrew Shuman; Mark E Prince; Matthew E Spector; Steven Chinn; Jennifer Shah; Caitlin Schonewolf; Jonathan B McHugh; Ryan E Mills; Muneesh Tewari; Francis P Worden; Paul L Swiecicki Journal: Clin Cancer Res Date: 2021-10-26 Impact factor: 13.801
Authors: Gabriel Adrian; Henrik Carlsson; Elisabeth Kjellén; Johanna Sjövall; Björn Zackrisson; Per Nilsson; Maria Gebre-Medhin Journal: Radiat Oncol Date: 2022-06-14 Impact factor: 4.309