Radiomic Biomarkers to Refine Risk Models for Distant Metastasis in HPV-related Oropharyngeal Carcinoma.

PURPOSE Distant metastasis (DM) is the main cause of death for patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs); yet, there are few reliable predictors of DM in this disease. The role of quantitative imaging (ie, radiomic) analysis was examined to determine whether there are primary tumor features discernible on imaging studies that are associated with a higher risk of DM developing. METHODS AND MATERIALS Radiation therapy planning computed tomography scans were retrieved for all nonmetastatic p16-positive OPC patients treated with radiation therapy or chemoradiation therapy at a single institution between 2005 and 2010. Radiomic biomarkers were derived from each gross tumor volume. The biomarkers included 4 representative radiomic features from tumor first-order statistics, shape, texture, and wavelet groups, as well as a combined 4-feature signature. Univariable Cox proportional hazards models for DM risk were identified. The discriminative performance of prognostic univariable and multivariable models was compared using the concordance index (C-index). Subgroup analyses were performed. RESULTS There were 300 HPV-related OPC patients who were eligible for the analysis. A total of 36 DM events occurred within a median follow-up period of 5 years. On univariable analysis, top results included the 4 representative radiomic features (C-index, 0.670-0.686; P < .001), the radiomic signature (C-index, 0.670; P < .001), tumor stage (C-index, 0.633; P < .001), tumor diameter (C-index, 0.653; P < .001), and tumor volume (C-index, 0.674; P < .001), which demonstrated moderate discrimination of DM risk. Combined clinical-radiomic models yielded significantly improved performance (C-index, 0.701-0.714; P < .05). In subgroup analyses, the radiomic biomarkers consistently stratified patients for DM risk, particularly for those cohorts with greater risks (C-index, 0.663-0.796), such as patients with stage III disease. CONCLUSIONS Radiomic biomarkers appear to classify DM risk for patients with nonmetastatic HPV-related OPC. Radiomic biomarkers could be used either alone or with other clinical characteristics in the assignment of DM risk in future HPV-related OPC clinical trials.

[1]  B. O'Sullivan,et al.  Exploring the Impact of Human Papillomavirus Status, Comorbidity, Polypharmacy, and Treatment Intensity on Outcome of Elderly Oropharyngeal Cancer Patients Treated With Radiation Therapy With or Without Chemotherapy. , 2017, International journal of radiation oncology, biology, physics.

[2]  J. Waldron,et al.  The Challenges of Treatment Adaptation and De-intensification in Human Papillomavirus-Positive Oropharyngeal Cancer: The Difficult Journey Back. , 2016, International journal of radiation oncology, biology, physics.

[3]  Patrick Granton,et al.  Radiomics: extracting more information from medical images using advanced feature analysis. , 2012, European journal of cancer.

[4]  Shao Hui Huang,et al.  Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. , 2016, The Lancet. Oncology.

[5]  N. Aaronson,et al.  Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  Peter A Balter,et al.  Impact of image preprocessing on the volume dependence and prognostic potential of radiomics features in non-small cell lung cancer , 2016 .

[7]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[8]  J. Tepper,et al.  Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. , 2015, International journal of radiation oncology, biology, physics.

[9]  S. Lippman,et al.  Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC) , 2010, Head & neck oncology.

[10]  Wei Xu,et al.  Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. , 2013, Oral oncology.

[11]  Eckehard Olbrich,et al.  Shared Information -- New Insights and Problems in Decomposing Information in Complex Systems , 2012, ArXiv.

[12]  E. Sturgis,et al.  Epidemiology of HPV-associated oropharyngeal cancer. , 2014, Oral oncology.

[13]  C. Chung,et al.  Emerging biomarkers in head and neck cancer in the era of genomics , 2015, Nature Reviews Clinical Oncology.

[14]  John Cho,et al.  Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Eckehard Olbrich,et al.  Information Decomposition and Synergy , 2015, Entropy.

[16]  K. Ang,et al.  Human papillomavirus and survival of patients with oropharyngeal cancer. , 2010, The New England journal of medicine.

[17]  A. Garden,et al.  Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  Balaji Ganeshan,et al.  Quantifying tumour heterogeneity with CT , 2013, Cancer imaging : the official publication of the International Cancer Imaging Society.

[19]  A. Garden,et al.  TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. , 2007, The Lancet. Oncology.

[20]  H. Frieboes,et al.  An integrated computational/experimental model of tumor invasion. , 2006, Cancer research.

[21]  Wei Xu,et al.  Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  P. Lambin,et al.  Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach , 2014, Nature Communications.

[23]  Esther Kim,et al.  Human papillomavirus and rising oropharyngeal cancer incidence in the United States. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  E. Taioli,et al.  Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta‐analysis , 2007, International journal of cancer.

[25]  B. Burtness,et al.  Treatment de-intensification strategies for head and neck cancer. , 2016, European journal of cancer.

[26]  H. Ford,et al.  Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis , 2015, Cell adhesion & migration.

[27]  L. Specht,et al.  The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: evaluation of the randomised DAHANCA 6&7 trial. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  C. Chung,et al.  E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC). , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  A. Olshan,et al.  Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell carcinoma. , 2016, Oral oncology.

[30]  P. Blanchard,et al.  Treatment de‐escalation in HPV‐positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives , 2015, International journal of cancer.

[31]  A. Eisbruch,et al.  Matted nodes: High distant‐metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus–related oropharyngeal cancer , 2016, Head & neck.

[32]  Andriy Fedorov,et al.  Computational Radiomics System to Decode the Radiographic Phenotype. , 2017, Cancer research.

[33]  Iain J Hyndman.  Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours , 2016, Cancer Microenvironment.

[34]  P. Lambin,et al.  CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma. , 2015, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[35]  L. Murray,et al.  Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. , 2012, Oral oncology.

[36]  L. Dawson,et al.  Lack of influence of intravenous contrast on head and neck IMRT dose distributions , 2008, Acta oncologica.

[37]  Jens Overgaard,et al.  Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  P. Lambin,et al.  Radiomic Machine-Learning Classifiers for Prognostic Biomarkers of Head and Neck Cancer , 2015, Front. Oncol..

[39]  N J Sarlis,et al.  Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[40]  Wei Xu,et al.  Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  Chia-Chun Kuo,et al.  Tumor compactness improves the preoperative volumetry-based prediction of the pathological complete response of rectal cancer after preoperative concurrent chemoradiotherapy , 2016, Oncotarget.

[42]  Shao Hui Huang,et al.  External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma , 2015, Acta oncologica.

[43]  I. El Naqa,et al.  A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities , 2015, Physics in medicine and biology.

[44]  Shao Hui Huang,et al.  Point-of-care outcome assessment in the cancer clinic: audit of data quality. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[45]  A. Hui,et al.  Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  Paul Kinahan,et al.  Radiomics: Images Are More than Pictures, They Are Data , 2015, Radiology.

[47]  Brian O'Sullivan,et al.  Human Papillomavirus Genotype Association With Survival in Head and Neck Squamous Cell Carcinoma. , 2016, JAMA oncology.

[48]  R. Fisher,et al.  Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  H. Quon,et al.  Controversies in treatment deintensification of human papillomavirus-associated oropharyngeal carcinomas: should we, how should we, and for whom? , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  Philippe Lambin,et al.  Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells. , 2015, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[51]  A. Cmelak,et al.  Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. , 2008, Journal of the National Cancer Institute.