Patterns of Recurrence in Patients with Non Metastatic Head and Neck Squamous Cell Cancer. Can Radiotherapy Interruptions Influence The Patients Prognosis?

Bosurgi A*; Pontoriero A; Brogna A; Siragusa C; Parisi S; Pergolizzi S

**Bosurgi A*, Pontoriero A, Brogna A, Siragusa C, Parisi S and Pergolizzi S**

Volume5-Issue8
Dates: Received: 2024-07-22 | Accepted: 2024-08-15 | Published: 2024-08-16
Pages: 989-995

Abstract

Aims: To determine the impact of interruptions/suspensions of radiotherapy in relation to the stage and histopathological features in patients with Non-Metastatic Head and Neck Squamous Cell Cancer (NMHNSCC), undergoing chemotherapy and Intensity-Modulated Radiation Therapy (IMRT).

Materials and methods: We retrospectively analyzed patients with T3-T4 N+ NMHNSCC treated with IMRT in our department from January 2014 to December 2023, matching the following inclusion criteria: age > 18 years, availability of 18F-FDG CT/PET before and after the treatment, T3-4 N+ disease, adjuvant or exclusive Concurrent Chemoradiation Therapy (cCTRT) +/- Induction Chemotherapy (ICT). The patients were divided into two groups according to the nodal disease stage: Group A with limited (N1-N2b) and group B (N2c-N3) with extensive nodal involvement. Prescribed doses and Treatment volumes extension were determined according to international guidelines. Data concerning time of treatment, interruptions, dose prescriptions, sites of progression, and histopathological features were collected.

Results: A total of 107 eligible patients were collected. Median age was 68.6 years (range 53-78 years). Median time of follow-up 36.7 months (range 12-60 months).
Group A included 79 patients; of these, 62.02% (49) achieved a complete response, 12.66% (10) showed no response to treatment; 25.32% (20) showed loco-regional progression. Median End of Treatment Delay (EoTD) for patients experiencing recurrences was 9.05 days, being > 5 days in 85% (17) of them.
Group B included 28 patients. Of these, only 14.29% (4) achieved a complete metabolic response. 21.43% (6) showed no response to treatments. 60.71% (17) showed loco-regional progression.
Median EoTD for these patients experiencing pathologic relapses was 7.4 days, being > 5 days in 71.43% (20) of them. LC for all patients was 49.53% (53). Cumulative 1 year-PFS was 71.1%. Cumulative 3 years-PFS was 55.4%.
The PFS analysis was also performed in relation to patients’ HPV status confirming worse clinical outcomes in those with HPV-unrelated tumors.

Conclusion: This study shows the role of a correctly timed radiotherapy. It was also confirmed that patients, not achieving complete remission, experience disease progression in sites located outside the areas where higher radiation doses were delivered, but still included in the treatment field. Thus, patients with tumor progression after chemoradiation should be included in clinical trials testing immunotherapy, alone or combined with chemotherapy.

FullText HTML FullText PDF DOI: 10.37871/jbres1979

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How to cite this article

Bosurgi A, Pontoriero A, Brogna A, Siragusa C, Parisi S, Pergolizzi S. Patterns of Recurrence in Patients with Non Metastatic Head and Neck Squamous Cell Cancer. Can Radiotherapy Interruptions Infl uence The Patients Prognosis? J Biomed Res Environ Sci. 2024 Aug 16; 5(8): 989-995. doi: 10.37871/jbres1979, Article ID: JBRES1979, Available at: https://www.jelsciences.com/articles/jbres1979.pdf

Subject area(s)

Oncology

Cancer

Radiation Therapy

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
Alami IE, Gihbid A, Charoute H, Khaali W, Brahim SM, Tawfiq N, Cadi R, Belghmi K, El Mzibri M, Khyatti M. Prognostic value of Epstein-Barr virus DNA load in nasopharyngeal carcinoma: a meta-analysis. Pan Afr Med J. 2022 Jan 3;41:6. doi: 10.11604/pamj.2022.41.6.28946. PMID: 35145598; PMCID: PMC8797042.
El Hussein MT, Dhaliwal S. HPV vaccination for prevention of head and neck cancer among men. Nurse Pract. 2023 Oct 1;48(10):25-32. doi: 10.1097/01.NPR.0000000000000099. PMID: 37751612.
Wippold FJ 2nd. Head and neck imaging: the role of CT and MRI. J Magn Reson Imaging. 2007 Mar;25(3):453-65. doi: 10.1002/jmri.20838. PMID: 17279529.
Sun K, Tan JY, Thomson PJ, Choi SW. Influence of time between surgery and adjuvant radiotherapy on prognosis for patients with head and neck squamous cell carcinoma: A systematic review. Head Neck. 2023 Aug;45(8):2108-2119. doi: 10.1002/hed.27401. Epub 2023 May 16. PMID: 37194205.
Haring CT, Kana LA, Dermody SM, Brummel C, McHugh JB, Casper KA, Chinn SB, Malloy KM, Mierzwa M, Prince MEP, Rosko AJ, Shah J, Stucken CL, Shuman AG, Brenner JC, Spector ME, Worden FP, Swiecicki PL. Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols. Cancer. 2023 Sep 15;129(18):2817-2827. doi: 10.1002/cncr.34823. Epub 2023 May 10. PMID: 37162461.
Wookey VB, Appiah AK, Kallam A, Ernani V, Smith LM, Ganti AK. HPV Status and Survival in Non-Oropharyngeal Squamous Cell Carcinoma of the Head and Neck. Anticancer Res. 2019 Apr;39(4):1907-1914. doi: 10.21873 / anticanres.13299. PMID: 30952732.
Rettig EM, D'Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015 Jul;24(3):379-96. doi: 10.1016/j.soc.2015.03.001. Epub 2015 Apr 9. PMID: 25979389.
Vermorken JB, Psyrri A, Mesía R, Peyrade F, Beier F, de Blas B, Celik I, Licitra L. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol. 2014 Apr;25(4):801-807. doi: 10.1093/annonc/mdt574. Epub 2014 Feb 26. PMID: 24577117; PMCID: PMC3969553.
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019 Jan 5;393(10166):40-50. doi: 10.1016/S0140-6736(18)32779-X. Epub 2018 Nov 15. Erratum in: Lancet. 2020 Mar 7;395(10226):784. doi: 10.1016/S0140-6736(20)30454-2. PMID: 30449625; PMCID: PMC6541928.
Miller JL, Evers J. Barriers to Adherence to Cancer Treatments Among Head and Neck Cancer Patients. J Adv Pract Oncol. 2022 Jul;13(5):515-523. doi: 10.6004/jadpro.2022.13.5.5. Epub 2022 Jul 27. PMID: 35910497; PMCID: PMC9328454.
Rettig EM, D’Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am. 2015;24:379-396. doi: 10.1016/j.soc.2015.03.001.
Wong WL. PET-CT for Staging and Detection of Recurrence of Head and Neck Cancer. Semin Nucl Med. 2021 Jan;51(1):13-25. doi: 10.1053/j.semnuclmed.2020.09.004. Epub 2020 Oct 22. PMID: 33246535.
Leech M, Coffey M, Mast M, Moura F, Osztavics A, Pasini D, Vaandering A. ESTRO ACROP guidelines for positioning, immobilisation and position verification of head and neck patients for radiation therapists. Tech Innov Patient Support Radiat Oncol. 2017 Jan 5;1:1-7. doi: 10.1016/j.tipsro.2016.12.001. PMID: 32095536; PMCID: PMC7033761.
Ireland RH, Dyker KE, Barber DC, Wood SM, Hanney MB, Tindale WB, Woodhouse N, Hoggard N, Conway J, Robinson MH. Nonrigid image registration for head and neck cancer radiotherapy treatment planning with PET/CT. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):952-7. doi: 10.1016/j.ijrobp.2007.02.017. Epub 2007 Apr 18. PMID: 17445999; PMCID: PMC2713594.
Den RB, Doemer A, Kubicek G, Bednarz G, Galvin JM, Keane WM, Xiao Y, Machtay M. Daily image guidance with cone-beam computed tomography for head-and-neck cancer intensity-modulated radiotherapy: a prospective study. Int J Radiat Oncol Biol Phys. 2010 Apr;76(5):1353-9. doi: 10.1016/j.ijrobp.2009.03.059. Epub 2009 Jun 18. PMID: 19540071.
Merlotti A, Alterio D, Vigna-Taglianti R, Muraglia A, Lastrucci L, Manzo R, Gambaro G, Caspiani O, Miccichè F, Deodato F, Pergolizzi S, Franco P, Corv R, Russi EG, Sanguineti G; Italian Association of Radiation Oncology. Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group. Radiat Oncol. 2014 Dec 29;9:264. doi: 10.1186/s13014-014-0264-9. PMID: 25544268; PMCID: PMC4316652.
Jensen K, Friborg J, Hansen CR, Samsøe E, Johansen J, Andersen M, Smulders B, Andersen E, Nielsen MS, Eriksen JG, Petersen JBB, Elstrøm UV, Holm AI, Farhadi M, Morthorst MH, Skyt PS, Overgaard J, Grau C. The Danish Head and Neck Cancer Group (DAHANCA) 2020 radiotherapy guidelines. Radiother Oncol. 2020 Oct;151:149-151. doi: 10.1016/j.radonc.2020.07.037. Epub 2020 Aug 8. PMID: 32781011.
Melotek JM, Cooper BT, Koshy M, Silverman JS, Spiotto MT. Weekly versus every-three-weeks platinum-based chemoradiation regimens for head and neck cancer. J Otolaryngol Head Neck Surg. 2016 Nov 24;45(1):62. doi: 10.1186/s40463-016-0175-x. PMID: 27881143; PMCID: PMC5121964.
Vermorken JB. Where and when to use induction chemotherapy in head and neck squamous cell cancer. In: Vermorken JB, Budach V, Leemans CR, Machiels JP, Nicolai P, O’Sullivan B, editors. Critical issues in head and neck oncology. Springer: Cham; 2021. doi: 10.1007/978-3-030-63234-2_11.
Jiang YT, Chen KH, Liang ZG, Yang J, Qu S, Li L, Zhu XD. A Nomogram to Identify the Optimal Candidates for Induction Chemotherapy in Advanced N-Stage Nasopharyngeal Carcinoma. Cancer Manag Res. 2022 Aug 31;14:2583-2596. doi: 10.2147/CMAR.S377731. PMID: 36068822; PMCID: PMC9441150.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7. PMID: 20530316; PMCID: PMC2943767.
Fesinmeyer MD, Mehta V, Blough D, Tock L, Ramsey SD. Effect of radiotherapy interruptions on survival in medicare enrollees with local and regional head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):675-81. doi: 10.1016/j.ijrobp.2009.08.004. Epub 2010 Feb 3. PMID: 20133084.
Thomas K, Martin T, Gao A, Ahn C, Wilhelm H, Schwartz DL. Interruptions of Head and Neck Radiotherapy Across Insured and Indigent Patient Populations. J Oncol Pract. 2017 Apr;13(4):e319-e328. doi: 10.1200/JOP.2016.017863. Epub 2017 Mar 7. Erratum in: J Oncol Pract. 2017 Jul;13(7):466. doi: 10.1200/JOP.2017.024190. PMID: 28267393.
Rao YJ, Goodman JF, Haroun F, Bauman JE. Integrating Immunotherapy into Multimodal Treatment of Head and Neck Cancer. Cancers (Basel). 2023 Jan 21;15(3):672. doi: 10.3390/cancers15030672. PMID: 36765627; PMCID: PMC9913370.