Effect of tumor size and p16 status on treatment outcomes - achievement of complete remission in prospectively followed patients with oropharyngeal tumors

Marek Slávik, Tomáš Kazda, Iveta Selingerova, Jiří Šána, Parwez Ahmad, Dominik Gurín, Markéta hermanová, Tomáš Novotný, Renata Červená, Radana Dymáčková, Petr Burkoň, Ondřej Slabý, Pavel Šlampa

Abstrakt


Background: Oropharyngeal squamous cell cancers (OPSCC) associated with HPV infection (p16 positive tumors) have better prognosis than p16 negative tumors nevertheless the more advanced stage of the disease. Tumor volume is generally an important factor affecting the results of treatment with ionizing radiation. The aim of this prospective non-randomized study is to evaluate the effect of tumor volume on the (chemo) radiation treatment results in a group of patients with p16 negative and p16 positive oropharyngeal cancers.

 

Patients and Methods: Patients with confirmed squamous cell cancer of the oropharynx  of stages III and IV, according to the 7th version of the TNM classification were eligible for this study. The main exclusion criteria were palliative treatment, neoadjuvant chemotherapy or  planned concomitant therapy with cetuximab. Patients were treated according to standardized protocols with curative intent. Primary tumor volume (GTVt) and involved nodes volume (GTVn) were obtained from radiotherapy planning system for further statistical analysis. The differences in tumor volumes between the groups according to p16 expression were assessed with subsequent  testing of probability to achieve the complete remission (CR) of the disease in both groups.

 

Results: 49 patients (84 % men, median age 60.5 years, 25 (51 %) patients p16 positive, 40 (82 %) underwent concomitant chemoradiotherapy). Median of GTVt in the whole patients group is 40.2 ccm, GTVn 11.78 ccm and median volume of the whole tumor burden (GTVt + n) 70.21 ccm (range 11.05-249). Median of GTVn was greater in the p16 positive cohort (p = 0.041). In the whole group the median time to reach complete remision was 91 days (95% CI 86-107 days) from the end of radiotherapy. In the group of p16 negative patients, CR  achieved 14 (61 %) out of 23 patients, in p16  positive group 20 (80 %) out of 25 patients (p = 0.111). P16 negative patients had a longer time to CR (p = 0.196, HR = 1.58, 95 % CI 0.79-3.18). None of the independently assessed volumetric parameters of the tumor (GTVt, GTVn, GTVt+n) affected  CR in the p16 positive patients group, while there was a significant impact of the whole tumor burden (GTVt+n) in the p16 negative cohort (median 58.1 ccm in CR patients vs. 101.9 ccm, p = 0.018).

 

Conclusion: We have showed less  tumor burden dependence to achieve CR in p16 positive tumors  in comparison with p16 negative tumors. Thus p16 positive OPSCC should not be withdrawn from the curative treatment intent based on the greater volume of the tumor mass.


Klíčová slova


Oropharyngeal Neoplasms, p16 status, Treatment Outcome, Tumor Burden, complete remission

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