The influence of tumor volume on the risk of distant metastases in head and neck cancer
OC-0108
Abstract
The influence of tumor volume on the risk of distant metastases in head and neck cancer
Authors: Julie Kjems1, Katrin Elisabet Håkansson2, Claus Andrup Kristensen2, Jesper Grau Eriksen3, Morten Horsholt Kristensen3, Anne Ivalu Sander Holm4, Jens Overgaard3, Christian Rønn Hansen5, Ruta Zukauskaite5, Jørgen Johansen5, Ivan Richter Vogelius2, Jeppe Friborg2
1Copenhagen University Hospital, Rigshospitalet , Department of Oncology, Copenhagen, Denmark; 2Copenhagen University Hospital, Rigshospitalet, Department of Oncology, Copenhagen, Denmark; 3Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark; 4Aarhus University Hospital, Department of Oncology, Aarhus, Denmark; 5Odense University Hospital, Department of Oncology, Odense, Denmark
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Purpose or Objective
Metastatic disease is the most significant factor for survival in cancer. In most circumstances, distant metastasis (DM) in head and neck cancer is non-curable. The current TNM staging system is insufficient to predict the risk of DM and identifying high-risk patients may facilitate interventions to reduce this risk. We hypothesize that the risk of DM in head and neck cancer can be determined using a multivariate model including pre-treatment total tumor volume.
Material and Methods
The study includes patients from three large head and neck cancer centers with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database, which has a coverage of close to 100%. Patient-specific, tumor-specific and treatment-specific data were extracted and verified from patient file review. Tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems (TPS) and represented the total volume of the primary tumor and nodal metastases at time of primary treatment planning.
Results
We included 2,865 patients, of which 305 (11%) developed DM. The risk of DM was assessed in a multivariate model (Cox proportional hazard regression) based on 2,708 patients controlled for pre-selected clinical values: age, gender, center, subsite incl. p16-status for oropharyngeal carcinoma, stage (UICC/AJCC-8), differentiation grade, smoking and GTV. The GTV was binned into four groups by volume (cm3): small [0-10), medium [10-25), large [25-50), and very large [50+). The analyses were performed on p16-positive oropharyngeal squamous cell carcinoma (OPSCC, N = 1,006) and all other sites separately (N = 1,702). Very large tumor volume was significantly associated with the risk of DM in both patient populations (Figure 1 and 2), hazard ratio (HR) 10.0 (p<0.001) for patients with p16-positive OPSCC and HR 4.2 (p<0.001) in other pharynx and larynx carcinomas (excl. p16-positive OPSCC). Analyzing all patients together in a combined model (N = 2,708), stage, tumor differentiation, and GTV were significantly associated with the risk of DM. In the combined model HRs for tumor volume were 2.0 (medium GTV, p = 0.01), 2.1 (large GTV, p<0.01) and 5.3 (very large GTV, p<0.001).
Conclusion
Tumor volume is an independent factor strongly associated with the risk of DM. Adding total tumor volume from TPS to a predictive model is important in identifying subgroups of head and neck cancer patients at high risk of DM.