Abstract
The recently identified bilateral macroscopic tubarial salivary glands present a potential
opportunity for further toxicity mitigation for patients receiving head and neck radiotherapy.
Here, we show superior dosimetric sparing of the tubarial salivary glands with proton
radiation therapy (PRT) compared to intensity-modulated radiotherapy (IMRT) for patients
treated postoperatively for human papillomavirus (HPV)-associated oropharyngeal squamous
cell carcinoma (OPSCC). This was a retrospective, single institutional study of all
patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each
patient had a treatment-approved, equivalent IMRT plan to serve as a reference. The
main end point was dose delivered to the tubarial salivary glands by modality, assessed
via a 2-tailed, paired t-test. We also report disease outcomes for the entire cohort,
via the Kaplan-Meier method. Sixty-four patients were identified. The mean RT dose
to the tubarial salivary glands was 23.6 Gy (95% confidence interval (CI) 21.7 to
25.5) and 30.4 Gy (28.6 to 32.2) for PRT and IMRT plans (p < 0.0001), respectively. With a median follow-up of 25.2 months, the two-year locoregional
control, progression-free survival and overall survival were 97.8% (95% CI 85.6% to
99.7%), 94.1% (82.8% to 98.1%) and 98.1% (87.4% to 99.7%), respectively. Our study
suggests that meaningful normal tissue sparing of the recently identified tubarial
salivary glands is achievable with PRT. The apparent gains with PRT did not impact
disease outcomes, with only 1 observed locoregional recurrence (0 local, 1 regional).
Further studies are warranted to explore the impact of the improved dosimetric sparing
of the tubarial salivary glands conveyed by PRT on patient toxicity and quality of
life.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Medical DosimetryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cancer statistics, 2020.CA. Cancer J. Clin. 2020; 70: 7-30https://doi.org/10.3322/caac.21590
- Human papillomavirus–attributable cancers — United States, 2012–2016.MMWR. Morb. Mortal. Wkly. Rep. 2019; 68: 724-728https://doi.org/10.15585/mmwr.mm6833a3
- Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.J. Natl. Cancer Inst. 2000; 92: 709-720https://doi.org/10.1093/jnci/92.9.709
- Human papillomavirus and survival of patients with oropharyngeal cancer.N. Engl. J. Med. 2010; 363: 24-35https://doi.org/10.1056/NEJMoa0912217
- Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): A randomised, multicentre, non-inferiority trial.Lancet. 2019; 393: 40-50https://doi.org/10.1016/S0140-6736(18)32779-X
- Enhanced radiation sensitivity in HPV-positive head and neck cancer.Cancer Res. 2013; 73: 4791-4800https://doi.org/10.1158/0008-5472.CAN-13-0587
- Head and neck cancers, version 2.2020, NCCN clinical practice guidelines in oncology.J Natl Compr Canc Netw. 2020; 18: 873-898https://doi.org/10.6004/jnccn.2020.0031
- Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): A phase 3 multicentre randomised controlled trial.Lancet Oncol. 2011; 12: 127-136https://doi.org/10.1016/S1470-2045(10)70290-4
- Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy.J. Clin. Oncol. 2008; 26: 3770-3776https://doi.org/10.1200/JCO.2007.14.6647
- Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia.Radiother. Oncol. 2015; 115: 56-62https://doi.org/10.1016/j.radonc.2015.01.019
- Potential benefits of scanned intensity-modulated proton therapy versus advanced photon therapy with regard to sparing of the salivary glands in oropharyngeal cancer.Int. J. Radiat. Oncol. Biol. Phys. 2011; 79: 1216-1224https://doi.org/10.1016/j.ijrobp.2010.05.012
- Intensity modulated proton therapy versus intensity modulated photon radiation therapy for oropharyngeal cancer: first comparative results of patient-reported outcomes.Int J Radiat Oncol Biol Phys. 2016; 95: 1107-1114https://doi.org/10.1016/j.ijrobp.2016.02.044
- Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer – A case matched analysis.Radiother. Oncol. 2016; 120: 48-55https://doi.org/10.1016/j.radonc.2016.05.022
- Dosimetric advantages of intensity-modulated proton therapy for oropharyngeal cancer compared with intensity-modulated radiation: A case-matched control analysis.Med. Dosim. 2016; 41: 189-194https://doi.org/10.1016/j.meddos.2016.01.002
- The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study.Acta Oncol. (Madr). 2013; 52: 561-569https://doi.org/10.3109/0284186X.2012.692885
- Quality of life of postoperative photon versus proton radiation therapy for oropharynx cancer.Int. J. Part. Ther. 2019; 5: 11-17https://doi.org/10.14338/IJPT-18-00032.1
- Non-neoplastic salivary gland lesions: A 15-year study.Eur. Arch. Oto-Rhino-Laryngology. 2011; 268: 1187-1190https://doi.org/10.1007/s00405-010-1460-3
- Mucous glands in the developing human rhinopharynx.Laryngoscope. 1977; 87: 987-995https://doi.org/10.1288/00005537-197706000-00016
- Anatomy, biogenesis and regeneration of salivary glands.Monogr. Oral Sci. 2014; : 1-13https://doi.org/10.1159/000358776
- Anatomy, Head and Neck, Salivary Glands. 2021 Jun 11.StatPearls. StatPearls Publishing, Treasure Island, FL2021
- The tubarial salivary glands: A potential new organ at risk for radiotherapy.Radiother. Oncol. 2020; https://doi.org/10.1016/j.radonc.2020.09.034
- Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501).Head Neck. 2005; 27: 843-850https://doi.org/10.1002/hed.20279
- CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines.Radiother. Oncol. 2015; 117: 83-90https://doi.org/10.1016/j.radonc.2015.07.041
- Target delineation for postoperative treatment of head and neck cancer.Oral Oncol. 2018; 86: 288-295https://doi.org/10.1016/j.oraloncology.2018.08.011
- NRG-HN002: A randomized phase II trial for patients with p16-positive, non-smoking-associated, locoregionally advanced oropharyngeal cancer.Int. J. Radiat. Oncol. 2019; 105: 684-685https://doi.org/10.1016/j.ijrobp.2019.08.038
- Balancing risk and reward in target delineation for highly conformal radiotherapy in head and neck cancer.Semin. Radiat. Oncol. 2009; : 43-52https://doi.org/10.1016/j.semradonc.2008.09.008
- Quantitative analyses of normal tissue effects in the clinic (QUANTEC): An introduction to the scientific issues.Int. J. Radiat. Oncol. Biol. Phys. 2010; S3: 76https://doi.org/10.1016/j.ijrobp.2009.09.040
- Radiotherapy dose-volume effects on salivary gland function.Int. J. Radiat. Oncol. Biol. Phys. 2010; 76: S58https://doi.org/10.1016/j.ijrobp.2009.06.090
Article info
Publication history
Published online: April 12, 2022
Accepted:
March 8,
2022
Received in revised form:
February 23,
2022
Received:
September 15,
2021
Identification
Copyright
© 2022 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.
