Does radiotherapy treatment alter the pulp condition in patients with head and neck cancer? A systematic review

RIBEIRO, Thalles Eduardo; NOVAIS, Veridiana Resende; ESTRELA, Carlos; SANTANA, Maria Luiza Lima; ROSSI-FEDELE, Giampiero; DECURCIO, Daniel de Almeida

doi:10.1590/1807-3107bor-2023.vol37.0079

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Systematic Review, Endodontic Therapy • Braz. oral. res. 37 • 2023 • https://doi.org/10.1590/1807-3107bor-2023.vol37.0079 copy

Does radiotherapy treatment alter the pulp condition in patients with head and neck cancer? A systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The main purpose of this study was to answer the question: “Can radiotherapy cause changes in the dental pulp condition of patients treated with irradiation in the head and neck region?” Clinical observational studies in adults with head and neck cancer undergoing treatment with ionizing radiation, longitudinal or cross-sectional follow-up to measure oxygen saturation (SpO₂), and/or pulp sensitivity test to cold stimulation, were considered eligible. A systematic literature search was performed in six different databases, including the gray literature, and in article references. Two independent evaluators selected the studies, extracted the data, recorded the data on electronic spreadsheets, and then evaluated the methodological quality using the Checklist for Quasi-Experimental Studies tool devised by JBI. The data were assessed qualitatively using the Synthesis Without Metanalysis (SWiM) guidelines. After removing the duplicate articles, carefully analyzing the titles and abstracts, and reading the papers in full, seven studies were included. Four of the studies evaluated applied the cold sensitivity test, two associated pulse oximetry and cold sensitivity, and only one used just pulse oximetry. Evaluation using the cold sensitivity test and pulse oximetry in the initial periods before radiotherapy showed a decrease in the sensitive response and in SpO₂ levels during a maximum period of 1 year. However, analyses thereafter indicated a normal response in both tests from 5 to 6 years after the end of radiotherapy treatment. Radiotherapy causes changes in pulp behavior patterns in the short term; however, recovery and return to average values occurs after long periods.

Dental Pulp; Dental Pulp Test; Oximetry; Radiotherapy; Systematic Review

Database	Search strategy (August/2021 and December/2022)	Results
PubMed (https://www.ncbi.nlm.nih.gov/pubmed/)	((((((Cancer of the Head and Neck) AND (Radiation Treatment)) OR (Radiation, Ionizing)) AND (Time)) AND (Dental Pulp Test)) OR (Tooth Sensitivity)) OR (Dental Pulp Devitalization)	7730
Scopus (http://www.scopus.com/)	(ALL(“Cancer of the Head and Neck”) AND ALL(“Radiation, Ionizing”) OR ALL (Radiation Therapy) AND ALL(Time) AND ALL(Dental Pulp Test) OR ALL(Tooth Sensitivity) OR ALL(Dental Pulp Devitalization))	568
Embase (http://www.embase.com)	(‘cancer of the head and neck’ AND ‘radiation treatment’ OR ‘ionizing radiation’) AND ‘time’ AND ‘dental pulp test’ OR ‘tooth sensitivity’ OR ‘dental pulp devitalization’	632
Web of Science (http://apps.webofknowledge.com/)	((((((TS=(cancer of the head and neck)) AND TS=(radiation treatment )) OR TS=(radiation, ionizing)) AND TS=(time)) AND TS=(dental pulp test)) OR TS=(tooth sensitivity)) OR TS=(dental pulp devitalization)	254
LILACS (lilacs.bvsalud.org/)	“Neoplasias de Cabeça e Pescoço” AND “Radioterapia” AND “Polpa Dentária”	11
Google Scholar (https://scholar.google.com.br/?hl =pt)	Cancer of the Head and Neck AND Radiation Ionizing AND Dental Pulp Sensitivity Treatment OR Dental Pulp Test	100
Open Grey (http://www.opengrey.eu/)		0

Author	Title	Reason for exclusion
Antic et al. ³⁴34. Antic S, Markovic-Vasiljkovic B, Dzeletovic B, Jelovac DB, Kuzmanovic-Pficer J. Assesment of radiotherapy effects on the blood flow in gingiva and dental pulp - a laser Doppler flowmetry study. J Appl Oral Sci. 2022 Dec;30:e20220329. https://doi.org/10.1590/1678-7757-2022-0329 https://doi.org/10.1590/1678-7757-2022-0...	Assesment of radiotherapy effects on the blood flow in gingiva and dental pulp - a laser Doppler flowmetry study	The study was carried using Laser Doppler Flowmetry study and the patients received varying doses of ionizing radiation
Cooperstein et al. ³⁵35. Cooperstein E, Gilbert J, Epstein JB, Dietrich MS, Bond SM, Ridner SH, et al. Vanderbilt head and neck symptom survey version 2.0: report of the development and initial testing of a subscale for assessment of oral health. Head Neck. 2012 Jun;34(6):797-804. https://doi.org/10.1002/hed.21816 https://doi.org/10.1002/hed.21816...	Vanderbilt head and neck symptom survey version 2.0: Report of the development and initial testing of a subscale for assessment of oral health.	It did not assess pulp outcomes.
Faria et al. ³⁰30. Faria KM, Brandão TB, Ribeiro AC, Vasconcellos AF, Carvalho IT, Arruda FF, et al. Micromorphology of the dental pulp is highly preserved in cancer patients who underwent head and neck radiotherapy. J Endod. 2014 Oct;40(10):1553-9. https://doi.org/10.1016/j.joen.2014.07.006 https://doi.org/10.1016/j.joen.2014.07.0...	Micromorphology of the dental pulp is highly preserved in cancer patients who underwent head and neck radiotherapy.	The study was in vitro, and the analysis was performed in the form of histological slides.
Fônseca et al. ³⁶36. Fonsêca JM, Palmier NR, Silva WG, Faria KM, Vargas PA, Lopes MA, et al. Dentin-pulp complex reactions in conventional and radiation-related caries: A comparative study. J Clin Exp Dent. 2019 Mar;11(3):e236-43. https://doi.org/10.4317/jced.55370 https://doi.org/10.4317/jced.55370...	Dentin-pulp complex reactions in conventional and radiation-related caries: A comparative study.	The study was in vitro and evaluated the dentinal changes.
Lopes et al. ²¹21. Lopes RP, Akisue E, Nakamura VC, Caldeira CL, Lemos EM, Carrillo CM, et al. Evaluation of pulp vitality using a pulse oximeter in patients undergoing radiotherapy for rhabdomyosarcoma or rhinopharynxcarcinoma. RSD. 2021	Evaluation of pulp vitality using a pulse oximeter in patients undergoing radiotherapy for rhabdomyosarcoma or rhinopharynxcarcinoma.	The study was carried out in a pediatric population.
Weissheimer et al. ²⁶26. Weissheimer T, Só BB, Pradebon MC, Figueiredo JA, Martins MD, Só MV. Head and neck radiotherapy effects on the dental pulp vitality and response to sensitivity tests: a systematic review with meta-analysis. Int Endod J. 2022 Jun;55(6):563-78. https://doi.org/10.1111/iej.13726 https://doi.org/10.1111/iej.13726...	Head and neck radiotherapy effects on the dental pulp vitality and response to sensitivity tests: A systematic review with meta-analysis.	The study was a systematic review

Author	Country	Study	Population	Groups	Rt type	Dose	Tumor	Tooth	Total teeth	Period	Tests	Outcome

												Primary	Secondary
Rodrigues et al. ⁸8. Rodrigues HM, Franzi SA. [Evaluation of pulp response in patients undergone radiation therapy for treatment of head and neck câncer]. Rev Bras Cir Cabeça Pescoço. 2007 Mar;36(1):23-6. Portuguese.	Brazil	Cross-sectional Retrospective Observational	HNC patients submitted to RT. The mean age of patients was 54.4 years, ranging 40 to 74 years.	RT Group (n = 12)	-	Fractional Dose totaling at least 45 Gy and max 71.2 Gy.	Tumors are located in Tonsils, Tongue Edge, Soft Palate, Tongue Base, Tongue Belly, Anterior Pillar, Thyroid, Zygomatic Region, and Neck.	Lower, Superior Incisors and Canines	Control Group: 103 teeth	The analysis was performed at the end of the RT, with an average time of 4.3 months.	Cold Sensitivity Test	In the RT Group, 28.6% of the teeth did not respond to the Thermal Test, while 71.4% showed a positive response. In the Control Group, the rate was 11% for negative responses and 89% for positive responses, with a statistically significant difference.	-
	Brazil	Cross-sectional Retrospective Observational		Control Group (n = 12)	-	Fractional Dose totaling at least 45 Gy and max 71.2 Gy.		Lower, Superior Incisors and Canines	RT Group: 91 teeth		Cold Sensitivity Test		-
Kataoka et al. ¹¹11. Kataoka SH, Setzer FC, Gondim-Junior E, Pessoa OF, Gavini G, Caldeira CL. Pulp vitality in patients with intraoral and oropharyngeal malignant tumors undergoing radiation therapy assessed by pulse oximetry. J Endod. 2011 Sep;37(9):1197-200. https://doi.org/10.1016/j.joen.2011.05.038 https://doi.org/10.1016/j.joen.2011.05.0...	Brazil	Cohort	Patients with cancer in the oronasopharyngeal region. The mean age was 47.2 years, ranging 35 to 55 years.	RT Group	-	Fractional Doses totaling 60 to 70 Gy	Intraoral Malignant Neoplasms in the oronasopharynx	Incisors Lower, Superior	22 upper and 18 lower	Before the beginning of RT (TP1), during RT (between doses of 30 and 35 Gy) (TP2), at the end of RT (total doses between 60 and 70 Gy) (TP3), and 4 to 5 months after completing treatment (TP4).	Pulse Oximetry and Pulpal Cold Sensitivity Test	SpO₂ values in the study were 93% (TP1), 83% (TP2), 77% (TP3) and 85% (TP4). There were responses from TP1 to the Thermal Test (100%); however, only 9 continued to respond positively in TP2 (23%). No response was recorded in TP3 (0%) and TP4 (0%).	There was a recovery of SpO2 from oxygen in TP4, 4 to 5 months after the end of RT.
	Brazil	Prospective		(n = 20)	-	Fractional Doses totaling 60 to 70 Gy	Intraoral Malignant Neoplasms in the oronasopharynx	Incisors Lower, Superior	22 upper and 18 lower		Pulse Oximetry and Pulpal Cold Sensitivity Test
Kataoka et al. ²⁴24. Kataoka SH, Setzer FC, Fregnani ER, Pessoa OF, Gondim E Jr, Caldeira CL. Effects of 3-dimensional conformal or intensity-modulated radiotherapy on dental pulp sensitivity during and after the treatment of oral or oropharyngeal malignancies. J Endod. 2012 Feb;38(2):148-52. https://doi.org/10.1016/j.joen.2011.09.022 https://doi.org/10.1016/j.joen.2011.09.0...	Brazil	Cohort	Patients with oral and oropharynx cancer. The average age was 47.2 years, ranging 35 to 55 years.	IMRT Group (n = 12)	IMRT	Fractionated doses totaling 60 to 70 Gy	Oropharyngeal Cancer, Mouth Cancer.	Incisors Lower, Superior	22 upper and 18 lower	Before the beginning of RT (TP1), during RT (between doses of 30 and 35 Gy) (TP2), at the end of RT (total doses between 60 and 70 Gy) (TP3), and after 4 to 5 months of completion of treatment (TP4).	Cold Sensitivity Test	All 40 teeth showed positive responses to the TP1 Sensitivity Test (40/40, 100%). Nine teeth continued to respond positively in TP2 (9/40, 22.5%): 3 of 16 (18.8%) in the 3D-RT and 6 of 24 (25.0%) in the IMRT group.	During the RT, there was a decrease in the number of teeth that responded to the Sensitivity Test after doses greater than 30 to 35 Gy of radiation. There was no difference among the RT techniques
	Brazil	Prospective		3D RT Group (n = 8)	3D RT	Fractionated doses totaling 60 to 70 Gy	Oropharyngeal Cancer, Mouth Cancer.	Incisors Lower, Superior	22 upper and 18 lower		Cold Sensitivity Test
Garg et al. ²⁰20. Garg H, Grewal MS, Rawat S, Suhag A, Sood PB, Grewal S, et al. Dental pulp status of posterior teeth in patients with oral and oropharyngeal cancer treated with concurrent chemoradiotherapy. J Endod. 2015 Nov;41(11):1830-3. https://doi.org/10.1016/j.joen.2015.08.006 https://doi.org/10.1016/j.joen.2015.08.0...	India	Cohort	Patients with HNC treated with chemoradiotherapy. The mean age was 52.5.	Group Chemotherapy (n = 20).	IMRT	Fractionated doses totaling 60 to 70 Gy	Oral or Oropharyngeal Cancer	Posterior	42 upper and 42 lower	Before the beginning of RT (TP1), during RT (between doses of 30 and 35 Gy) (TP2), at the end of RT (total doses between 60 and 70 Gy) (TP3), and after 4 to 5 months of completion of treatment (TP4).	Cold Sensitivity Test	All teeth showed positive responses to the thermal sensitivity test in PT1 (100%) and 25 (29%) in PT2. No teeth responded to the PT3 and PT4 sensitivity test (0%).	During the RT, there was a decrease in the number of teeth that responded to the sensitivity test after doses greater than 30 to 35 Gy of radiation. There was no difference among the RT techniques.
	India	Prospective		Group Chemotherapy (n = 20).	IMRT	Fractionated doses totaling 60 to 70 Gy	Oral or Oropharyngeal Cancer	Posterior	42 upper and 42 lower		Cold Sensitivity Test
Kataoka et al. ¹⁹19. Kataoka SH, Setzer FC, Gondim-Junior E, Fregnani ER, Moraes CJ, Pessoa OF, et al. Late effects of head and neck radiotherapy on pulp vitality assessed by pulse oximetry. J Endod. 2016 Jun;42(6):886-9. https://doi.org/10.1016/j.joen.2016.02.016 https://doi.org/10.1016/j.joen.2016.02.0...	Brazil	Cross-sectional Retrospective Observational	Patients with HNC submitted to RT. The average age of the patients was in 49.4 years for the RT Group, and 49.6 years for the control group was	RT Group (n = 90)	IMRT	Fractional doses of 2 Gy daily, totaling 66 to 70 Gy	Cancer in Oropharynx, Oral Cavity, Nasopharynx, and Hypopharynx.	Upper Incisors, Upper Canines, Lower Incisors, Lower Canines.	Total of 1386 teeth, being 693 teeth in the RT Group (240 maxillary incisors, 104 maxillary canines, 240 mandibular incisors, and 109 mandibular canines), and there were 693 (235 maxillary incisors in the control group, 115 maxillary canines, 225 mandibular incisors, and 118 lower canines).	The patients were rated from 4 to 6 years after the end of RT.	Pulse Oximetry and Cold Sensitivity Test	The mean SpO2% recorded in the RT group was 92.7%, and 92.6% in the Control Group. All the teeth showed positive responses to the Sensitivity Test.	There was a recovery of SpO2 levels 4 to 6 years after radiotherapy treatment.
	Brazil	Cross-sectional Retrospective Observational		Control Group (n = 90)	IMRT	Fractional doses of 2 Gy daily, totaling 66 to 70 Gy					Pulse Oximetry and Cold Sensitivity Test
Gupta et al. ²²22. Gupta N, Grewal MS, Gairola M, Grewal S, Ahlawat P. Dental Pulp Status of Posterior Teeth in Patients with Oral and Oropharyngeal Cancer Treated with Radiotherapy: 1-year Follow-up. J Endod. 2018 Apr;44(4):549-54. https://doi.org/10.1016/j.joen.2017.12.017 https://doi.org/10.1016/j.joen.2017.12.0...	India	Cohort	Patients with oral or oropharyngeal cancer. The mean age was 58.5 years.	RT Group (n = 79).	IMRT	Fractionated doses totaling 60 to 70 Gy.	Oral or pharyngeal cancer	Posterior	288	Patients were evaluated before RT (TP1), at the end of radiotherapy treatment (TP2), 4 months after the end of RT (TP3), 6 months after RT (TP4), and finally 1 year after the end of RT (TP5).	Cold Sensitivity Test	All teeth (100%) responded to cold tests at TP1. In TP2 and TP3, only 23 (7.98%) and 6 (2.08%) teeth gave a positive response to the cold test. In TP4 and TP5, none of the teeth responded to the cold test.	There was no recovery of response levels, as sensitivity progressively decreased.
	India	Prospective		RT Group (n = 79).	IMRT	Fractionated doses totaling 60 to 70 Gy.	Oral or pharyngeal cancer	Posterior	288		Cold Sensitivity Test
Daveshwar et al. ²⁵25. Daveshwar SR, Kapoor SV, Daveshwar MR. A clinical study determining pulp vitality in oropharyngeal cancer patients undergoing radiotherapy using diagnostic tool-pulse oximetry. Curr Health Sci J. 2021;47(1):5-9. https://doi.org/10.12865/CHSJ.47.01.01 https://doi.org/10.12865/CHSJ.47.01.01...	India	Cohort	Patients with oropharyngeal cancer. The mean age was 46.04.	RT Group (n = 25)	-	Fractionated doses totaling 60 to 70 Gy	Oropharyngeal Cancer	1st Lower Premolar	25 tooth	Before initiation of RT (TP 1), immediately after RT (TP 2), and six months after RT (TP 3)	Pulse Oximetry	The mean SpO2 before RT (TP1) was 93.60, 75.12 after RT (TP2), and 81.04 six months later (TP3).	There was partial recovery at the end of the 6 months after completing RT (TP3); however, the values are still lower than those in TP1.
	India	Prospective	Patients with oropharyngeal cancer. The mean age was 46.04.	RT Group (n = 25)	-	Fractionated doses totaling 60 to 70 Gy	Oropharyngeal Cancer	1st Lower Premolar	25 tooth		Pulse Oximetry

Variable	Rodrigues et al. ⁸8. Rodrigues HM, Franzi SA. [Evaluation of pulp response in patients undergone radiation therapy for treatment of head and neck câncer]. Rev Bras Cir Cabeça Pescoço. 2007 Mar;36(1):23-6. Portuguese.	Kataoka et al. ¹¹11. Kataoka SH, Setzer FC, Gondim-Junior E, Pessoa OF, Gavini G, Caldeira CL. Pulp vitality in patients with intraoral and oropharyngeal malignant tumors undergoing radiation therapy assessed by pulse oximetry. J Endod. 2011 Sep;37(9):1197-200. https://doi.org/10.1016/j.joen.2011.05.038 https://doi.org/10.1016/j.joen.2011.05.0...	Kataoka et al. ²⁴24. Kataoka SH, Setzer FC, Fregnani ER, Pessoa OF, Gondim E Jr, Caldeira CL. Effects of 3-dimensional conformal or intensity-modulated radiotherapy on dental pulp sensitivity during and after the treatment of oral or oropharyngeal malignancies. J Endod. 2012 Feb;38(2):148-52. https://doi.org/10.1016/j.joen.2011.09.022 https://doi.org/10.1016/j.joen.2011.09.0...	Garg et al. ²⁰20. Garg H, Grewal MS, Rawat S, Suhag A, Sood PB, Grewal S, et al. Dental pulp status of posterior teeth in patients with oral and oropharyngeal cancer treated with concurrent chemoradiotherapy. J Endod. 2015 Nov;41(11):1830-3. https://doi.org/10.1016/j.joen.2015.08.006 https://doi.org/10.1016/j.joen.2015.08.0...	Kataoka et al. ¹⁹19. Kataoka SH, Setzer FC, Gondim-Junior E, Fregnani ER, Moraes CJ, Pessoa OF, et al. Late effects of head and neck radiotherapy on pulp vitality assessed by pulse oximetry. J Endod. 2016 Jun;42(6):886-9. https://doi.org/10.1016/j.joen.2016.02.016 https://doi.org/10.1016/j.joen.2016.02.0...	Gupta et al. ²²22. Gupta N, Grewal MS, Gairola M, Grewal S, Ahlawat P. Dental Pulp Status of Posterior Teeth in Patients with Oral and Oropharyngeal Cancer Treated with Radiotherapy: 1-year Follow-up. J Endod. 2018 Apr;44(4):549-54. https://doi.org/10.1016/j.joen.2017.12.017 https://doi.org/10.1016/j.joen.2017.12.0...	Daveshwar et al.25
Does the study leave clear what the cause and what the effect are (i.e., no confusion about which variable comes first)?	1	1	1	1	1	1	1
Were the participants included in any similar comparisons?	0	1	1	1	1	1	1
Were the participants included in any comparisons receiving similar treatment/care, other than the exposure or intervention of interest?	0	1	1	1	1	1	0
Was there a control group?	1	1	1	1	1	1	1
Were there multiple measurements of the outcome, both pre and post intervention/exposure?	0	1	1	1	0	1	1
Was follow-up complete; if not, were differences among the groups in terms of follow-up adequately described and analyzed?	N/A	1	1	1	N/A	1	1
Were the outcomes of participants included in any comparisons measured in the same way?	1	1	1	1	1	1	1
Were outcomes measured in a reliable way?	1	1	1	1	1	1	1
Was appropriate statistical analysis used?	1	1	1	1	1	1	1
Methodological quality	Moderate	High	High	High	High	High	High

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[1] Corresponding Author: Daniel de Almeida Decurcio E-mail: danieldecurcio@gmail.com