Effect of Tumor Size and p16 Status on Treatment Outcomes – Achievement of Complete Remission in Prospectively Followed Patients with Oropharyngeal Tumors
Authors:
M. Slavik 1; T. Kazda 1; I. Selingerová 2; J. Šána 3; P. Ahmad 3; D. Gurín 4; M. Hermanová 4; T. Novotný 1; R. Červená 1; R. Dymáčková 1; P. Burkoň 1; O. Slabý 3; P. Šlampa 1
Authors‘ workplace:
Klinika radiační onkologie, Masarykův onkologický ústav, Brno
1; RECAMO – Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
2; CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno
3; I. patologicko-anatomický ústav, LF MU a FN u sv. Anny v Brně
4
Published in:
Klin Onkol 2019; 32(1): 58-65
Category:
Original Articles
Overview
Background:
Oropharyngeal squamous cell tumors associated with human papillomavirus infection (p16 positive tumors) have better prognosis than p16 negative tumors regardless of the more advanced stage of the disease. Tumor volume (GTVt+n) is generally an important factor affecting treatment results of 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 tumors.
Patients and Methods:
Patients with confirmed squamous cell tumor of the oropharynx of stages III and IV, according to the 7th version of the TNM (tumor–nodes–metastases) 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 complete remission (CR) of the disease in both groups.
Results:
In total, 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 entire group, the median time to reach CR was 91 days (95% CI 86–107 days) from the end of radiotherapy. In the group of p16 negative patients, 14 achieved CR (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 GTVt+n dependence to achieve CR in p16 positive tumors in comparison with p16 negative tumors. Thus, p16 positive oropharyngeal squamous cell cancers should not be withdrawn from the curative treatment intent based on the greater GTVt+n.
Key words
oropharyngeal neoplasms – p16 status – treatment outcome – tumor burden – complete remission
This work was supported by grant of the Ministry of Health of the Czech Republic AZV 15-31627A and by grant of the Ministry of Health of the Czech Republic – Conceptual development of a research organization (MMCI 00209805).
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted: 2. 11. 2018
Accepted: 11. 11. 2018
Sources
1. Larsen CG, Gyldenløve M, Jensen DH et al. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours: a systematic review. Br J Cancer 2014; 110: 1587–1594. doi: 10.1038/ bjc.2014.42.
2. Shaw R, Beasley N. Aetiology and risk factors for head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016; 130 (Suppl 2): S9–S12. doi: 10.1017/ S0022215116000360.
3. Ang KK, Sturgis EM. Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma. Semin Radiat Oncol 2012; 22(2): 128–142. doi: 10.1016/ j.semradonc.2011.12.004.
4. Lydiatt WM, Patel SG, O’Sullivan B et al. Head and neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67(2): 122–137. doi: 10.3322/ caac.21389.
5. Gurin D, Slavik M, Hermanova M et al. Prognostic impact of combined immunoprofiles in oropharyngeal squamous cell carcinoma patients with respect to AJCC 8th edition. J Oral Pathol Med 2018; 47(9): 864–872. doi: 10.1111/ jop.12772.
6. Slavik M, Shatokhina T, Sana J et al. Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: impact on outcomes of intensitymodulated radiation therapy. Head Neck 2018; 2018: 1–10. doi: 10.1002/ hed.25533.
7. Mirghani H, Blanchard P. Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand? Clin Transl Radiat Oncol 2017; 8: 4–11. doi: 10.1016/ j.ctro.2017.10.005.
8. Knegjens JL, Hauptmann M, Pameijer FA et al. Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 2011; 33(3): 375–382. doi: 10.1002/ hed.21459.
9. Linge A, Lohaus F, Löck S et al. HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Radiother Oncol 2016; 121(3): 364–373. doi: 10.1016/ j.radonc.2016.11.008.
10. Davis KS, Lim CM, Clump DA et al. Tumor volume as a predictor of survival in human papillomavirus-positive oropharyngeal cancer. Head Neck 2016; 38 (Suppl 1): E1613–E1617. doi: 10.1002/ hed.24287.
11. Carpén T, Saarilahti K, Haglund C et al. Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy. Strahlenther Onkol 2018; 194(8): 759–770. doi: 10.1007/ s00066-018-1309-z.
12. Chao KS, Ozyigit G, Blanco AI et al. Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume. Int J Radiat Oncol Biol Phys 2004; 59(1): 43–50. doi: 10.1016/ j.ijrobp.2003.08.004.
13. Strongin A, Yovino S, Taylor R et al. Primary tumor volume is an important predictor of clinical outcomes among patients with locally advanced squamous cell cancer of the head and neck treated with definitive chemoradiotherapy. Int J Radiat Oncol Biol Phys 2012; 82(5): 1823–1830. doi: 10.1016/ j.ijrobp.2010.10.053.
14. Mendenhall WM, Mancuso AA, Strojan P et al. Impact of primary tumor volume on local control after definitive radiotherapy for head and neck cancer. Head Neck 2014; 36(9): 1363–1367. doi: 10.1002/ hed.23454.
15. Ahmad P, Slavik M, Sana J et al. MicroRNAs in prediction of response to radiotherapy in head and neck cancer patients – pilot study. Klin Onkol 2018; 31 (Suppl 1): 137–139.
16. Ahmad P, Sana J, Slavik M et al MicroRNAs involvement in radioresistance of head and neck cancer. Dis Markers 2017; 2017: 8245345. doi: 10.1155/ 2017/ 8245345.
17. Sterba KR, Garrett-Mayer E, Carpenter MJ et al. Smoking status and symptom burden in surgical head and neck cancer patients. Laryngoscope 2017; 127(1): 127–133. doi: 10.1002/ lary.26159.
18. Alberg AJ, Worley ML, Tooze JA et al. The validity of self-reported recent smoking in head and neck cancer surgical patients. Otolaryngol Head Neck Surg 2015; 153(6): 990–995. doi: 10.1177/ 0194599815594385.
19. Blanchard P, Landais C, Petit C et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 100 randomized trials and 19,248 patients, on behalf of MACH-NC group. Ann Oncol 2016; 27 (Suppl 6): 950. doi: 10.1093/ annonc/ mdw376.02.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2019 Issue 1
Most read in this issue
- Malignant Tumors of the Penis – Diagnostics and Therapy
- Stereotactic Body Radiotherapy – Current Indications
- Effect of Tumor Size and p16 Status on Treatment Outcomes – Achievement of Complete Remission in Prospectively Followed Patients with Oropharyngeal Tumors
- Is There a Benefit of HER2-Positive Breast Cancer Subtype Determination in Clinical Practice?