Pain management for persistent pain post radiotherapy in head and neck cancers: systematic review

Jamie Young; Divya Rattan; Ada Cheung; Smaro Lazarakis; Sophie McGilvray

doi:10.1515/sjpain-2023-0069

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Pain management for persistent pain post radiotherapy in head and neck cancers: systematic review

Jamie Young , Divya Rattan , Ada Cheung , Smaro Lazarakis und Sophie McGilvray

Veröffentlicht/Copyright: 15. November 2023

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Aus der Zeitschrift Scandinavian Journal of Pain Band 24 Heft 1

Abstract

Objectives

To systematically review the existing literature for evidence of efficacy around interventions in the management of persistent pain post radiotherapy for head and neck cancers.

Methods

A systematic review of the literature was conducted to assess the effectiveness and safety of interventions for the management of persistent post-radiotherapy pain in head and neck cancers. The primary outcome evaluated whether an intervention resulted in a reduction in pain which was determined using validated pain tools.

Results

Two randomised controlled trials involving 196 participants fulfilled the inclusion criteria, one evaluating the effect of hypnotherapy and the other evaluating the effect of pregabalin on radiotherapy related pain in head and neck cancer patients. In one study by Thuma et al. (2016) there was a decrease in pain scores in the hypnotherapy group (p<0.001). In the other study, by Jiang et al. (2018) patients treated with pregabalin had a greater reduction in pain intensity, pain severity and a reduction in pain functional interference (p<0.001).

Conclusions

The findings of our review suggest that in chronic post-radiotherapy pain for head and neck cancers there is very-low level evidence for the use of hypnotherapy in reducing pain scores and for the use of pregabalin in reducing pain intensity, severity, functional interference and psychological distress with significant improvement in quality of life.

Keywords: cancer pain; radiotherapy orofacial pain; chronic mucositis; head and neck cancer

Introduction

Oral mucositis is a major cause for acute pain in head and neck cancer patients, and this can be attributed to anti-cancer therapy which includes radiotherapy [1, 2]. Acute pain post radiotherapy usually lasts for 2–4 weeks however it is known that some patients develop a persistent pain syndrome which continues beyond 6 months [3]. There is limited data on the prevalence of persistent pain post radiotherapy but a retrospective study by Kallurkar et al., investigated the prevalence and causes of persistent pain in head and neck patients who were in remission [4]. This study found that persistent pain post radiotherapy affected 60.38 % of the cohort with the most common pain descriptors suggesting neuropathic pain as the underlying mechanism [4] (Tables 1 and 2).

There is a paucity of literature on persistent pain post radiotherapy, its pathophysiology, and its management [5, 6]. The current evidence base proposes chronic mucositis as a contributing factor in the development of this pain syndrome [3] and manifestations of chronic mucositis include mucosal swelling, erythema, and atrophy. The ‘mucositis pathogenesis model’ describes chronic mucositis as either a ‘persistent’ or ‘recurrent’ phenomenon [3]. A diagnosis of persistent pain post radiotherapy should be considered when symptoms persist for longer than 3 months post radiotherapy and cannot be attributed to another aetiology [3, 6]. Central sensitisation is another proposed phenomenon for persistent pain post radiotherapy due to its inflammatory and nociceptive mechanisms causing peripheral sensitisation and in-turn central changes. Central sensitisation is well established as a perpetuating pain mechanism in other chronic pain syndromes due to upregulation of the peripheral and central nervous system [7].

Persistent pain post radiotherapy results in pain related distress and disability with potential consequences impacting completion of anti-cancer therapy [8]. In addition to this, chronic pain impacts quality of life including activities of daily living, relationships, and social roles. It is associated with an increased risk of psychological and pain related disability [8, 9]. Traditionally, persistent pain has been treated with a multimodal approach, largely involving opioids, mouthwashes, anti-neuropathic agents, and non-pharmacological strategies but the level of evidence supporting these is largely unknown [3].

To our knowledge there are no systematic reviews evaluating pain management strategies for persistent pain post radiotherapy. A systematic evaluation of existing evidence was therefore considered necessary to determine the effectiveness of non-pharmacological and pharmacological interventions, providing clinicians with clear guidance for clinical decision‐making and appropriate pain management.

Objectives

To assess the effectiveness and safety of interventions for the management of persistent post radiotherapy pain in head and neck cancers. Specific questions addressed by this review included the following:

Are interventions (non-pharmacological and pharmacological), effective in reducing persistent post radiotherapy pain for head and neck cancers?
What type of interventions (non-pharmacological and pharmacological) are effective in reducing persistent post radiotherapy pain for head and neck cancers?

Methods

Criteria for considering studies for this review:

Types of studies

All published randomised controlled trials (RCTs), cross‐over studies and clinical controlled trials (CCTs) comparing interventions with a control for managing chronic pain in participants with persistent post radiotherapy pain for head and neck cancers were included. We included trials with full journal publication and a minimum treatment period of two weeks or more. We excluded studies that were non‐randomised, studies of experimental pain, case reports, and clinical observations.

Types of participants

Inclusion criteria comprised study populations with a confirmed diagnosis of head and neck cancer who were aged over 18 years, had completed radiotherapy, and experienced persistent pain beyond 3 months, irrespective of varying definitions for the chronicity of pain. The definition of head and neck cancers included the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. We also included studies that recruited participants with a minimum of 3/10 on the numerical rating scale. Studies including participants with other cancer diagnoses and had a diagnosis of acute mucositis were excluded.

Types of interventions

All nonpharmacological and pharmacological therapies were included to manage persistent post radiotherapy pain for head and neck cancers delivered in any settings (inpatient, outpatient, community, or home‐based).

Primary outcomes

The primary outcome evaluated whether an intervention resulted in a reduction in pain. This was determined using validated pain tools such as, the visual analogue scale (VAS), numerical rating scale (NRS), McGill Pain Questionnaire (MPQ), Short Form McGill Pain Questionnaire (SFMPQ), or Brief Pain Inventory (BPI). Psychometric Likert scales were also used including the Patient’s Global Impression of Change (PGIC) or Clinical Global Impression of Change (CGIC).

We used the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), defined as:

at least 30 % pain relief over baseline (moderate);
at least 50 % pain relief over baseline (substantial);
much improved-on Patient Global Impression of Change Scale (PGIC; moderate);
very much improved on PGIC (substantial).

Secondary outcomes

Secondary outcomes aimed to reflect whether an improvement in pain (due to the proposed intervention) had implications for other symptoms or impairments, functional activity, psychosocial outcomes, vocational outcomes, quality of life, healthcare utilisation, experience of adverse effects, withdrawals due to lack of efficacy and impact on carers.

Search methods for identification of studies

We considered articles in all languages with a view to translation, if necessary.

Electronic searches

Cochrane Central Register of Controlled Trials (CENTRAL)	2016 to present
MEDLINE (PubMed)	1966 to present
Embase (Embase.com)	1974 to present
Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost)	1981 to present
Latin American and Caribbean Health Science Information Database (LILACS) (Bireme)	1982 to present
ClinicalTrials.gov (https://clinicaltrials.gov/)	1980 to present
World Health Organization (WHO) International Clinical Trials Registry Platform	1980 to present
PsycINFO	1980 to present
Allied and Complementary Medicine Database (AMED)	1985 to present
MANTIS/Ovid	Up to 2022
ProQuest Dissertations and Theses	Up to 2022
Web of Science for citation of key authors	Up to 2022
SIGLE (System for Information on Grey Literature in Europe)	Up to 2022

See Appendix A.

Data collection and analysis

Selection of studies

Two review authors independently screened all abstracts and titles of studies identified by the search strategy for appropriateness based on the selection criteria. The full text article was obtained to determine if the study met the inclusion/exclusion criteria. Papers assessed that did not meet the inclusion criteria were listed in the ‘Characteristics of excluded studies’ table with the reasons for exclusion. If no consensus was met about the possible inclusion/exclusion of any individual study, a final consensus decision was made by discussion with a third author.

Review authors were not masked to the name(s) of the author(s), institution(s) or publication source at any level of the review. Further information was sought about the method of randomisation and other methodological issues, if required.

Studies with fatal flaws (for instance, withdrawals by more than 40 % of the participants or near total non‐adherence to the protocol, very poor or non‐adjusted comparability in the baseline criteria) were excluded.

Data extraction and management

Two review authors independently extracted the data from the included trials which included: year of publication, year the study was undertaken, and geographical location of the study; number of study participants, age and gender; the type of pain (neuropathic/nociceptive) targeted by the study intervention; the type of study intervention and treatment duration; the control intervention(s); duration of the study recruitment and follow‐up time; adverse events recorded; study participant withdrawals; whether the study was specifically designed to measure pain in head and neck cancer; information about study quality; and measures of treatment effect (outcome measures).

A final check was made by a third review author. The benchmarks of the IMMPACT recommendations for the evaluation of reduction in pain were used to summarize all data.

We summarised all studies that met the inclusion criteria in the ‘Characteristics of included studies’ table.

Assessment of risk of bias in included studies

Two review authors independently assessed the methodological quality of the included studies using the ‘Risk of bias’ tool outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the following for each study:

Random sequence generation (checking for possible selection bias). We assessed the method used to generate the allocation sequence as: low risk of bias (any truly random process, random number table, computer random generator) and unclear risk of bias (when the method is not clearly stated). We excluded studies with a non‐random process.
Allocation concealment (checking for possible selection bias). The method used to conceal the allocation to interventions prior to assignment determined whether the intervention allocation could have been foreseen in advance, during recruitment, or changed after assignment. We assessed methods as low risk of bias (telephone or central randomisation; consecutively numbered, sealed, opaque envelopes) or unclear risk of bias (when method is not clearly stated). We excluded studies that did not conceal allocation.
Blinding of participants, personnel, and outcome assessment (checking for possible performance bias and detection bias). We assessed the methods used to blind study participants, personnel, and outcome assessors from knowledge of which intervention a participant received. We assessed methods as low risk of bias (study states it was blinded and described the method used to achieve the blinding) or unclear risk of bias (study stated it was blinded but did not provide an adequate description of how this was achieved). We excluded studies that were not double blinded.
Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data). We assessed the methods used to deal with incomplete data as low risk of bias (fewer than 10 % of participants did not complete the study or used ‘baseline observation carried forward’ analysis or both), unclear risk of bias (used ‘last observation carried forward’ analysis) or high risk of bias (used ‘completer’ analysis).
Size of study (checking for possible studies confounded by small size). We assessed methods as being at low risk of bias (200 participants or more per treatment arm), unclear risk of bias (50–199 participants per treatment arm) or high risk of bias (fewer than 50 participants per treatment arm).

Any disagreements or lack of consensus were resolved by a third review author.

Assessment of the quality of evidence

We assessed the quality of the body of evidence using the GRADE approach as outlined in the GRADE handbook (GRADE Working Group 2004), relating to the following outcomes for the main comparisons:

pain (severity, grade);
quality of life;
functional activity; and
psychosocial outcomes.

We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group approach n order to create ‘Summary of findings’ tables. We included key information concerning the quality of evidence, the magnitude of effect of the interventions examined, and the sum of available data on the main outcomes.

The GRADE system uses the following criteria for assigning grades of evidence:

High=further research is very unlikely to change our confidence in the estimate of effect.
Moderate=further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low=further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low=any estimate of effect is very uncertain.

Assessment of reporting biases

Publication bias was minimized by performing comprehensive searches of multiple databases. Where data was not reported in full for certain outcomes, authors were contacted for the full data set or the reason for not publishing specific data. If we identified sufficient studies (at least 10), potential biases of reporting were assessed using funnel plots and visual inspection for asymmetry according to the approach outlined in the Cochrane Handbook for Systematic Reviews of Interventions [10].

Results

See Prisma Flowchart – Supplementary Material.

Included studies

Overall, two randomised controlled trials (RCTs) involving 196 participants fulfilled the inclusion criteria for this review. One study was conducted in Thailand [11] and one was conducted in China [5]. The included studies were a study by Thuma et al., which evaluated the effect of hypnotherapy in head and neck cancer patients after radiotherapy and Jiang et al., which evaluated the effect of pregabalin on radiotherapy related neuropathic pain in head and neck cancer patients.

Excluded studies

Please see ‘characteristics of excluded studies’. Overall 869 studies were excluded.

Risk of bias

For a summary, please see Risk of bias in Figure 1.

Figure 1:

Risk of bias.

Random sequence generation

Both studies were considered to have a low risk bias for this domain [5, 11].

Allocation concealment

The study by Thuma et al., was considered to have high risk of bias for allocation concealment due to block randomisation whereas the study by Jiang et al. was considered to have low risk of bias for allocation concealment with double blinded randomisation.

Blinding of participants and personnel

The study by Thuma et al., was considered to have high risk of performance and detection bias as the participants and personnel were not blinded. The study by Jiang et al. was considered to have low risk of performance and detection bias as it was a double-blinded study.

Incomplete outcome data

Both studies provided information on participant withdrawals and loss to follow up. The effect on risk of bias is unclear.

Selective reporting

All included studies assessed pre-specified primary and secondary outcomes and were assessed as ‘low’ risk.

Effect of interventions

Hypnotherapy

The study by Thuma et al., evaluated the effect of hypnotherapy in head and neck cancer patients after radiotherapy. This included participants aged between 40 and 70 years with a visual analogue scale (VAS) pain score of at least 4/10 on the first visit.

In this study 68 participants were randomly assigned equally into two groups (N=34). One group underwent conventional treatment and the other underwent 20 min of hypnotherapy in addition to conventional treatment.

There was a decrease in pain scores in the hypnotherapy group in the visual analogue scores (p<0.001).

Pregabalin

The study by Jiang et al. evaluated the effect of pregabalin on radiotherapy related neuropathic pain in head and neck cancer patients. This study was a randomised, double-blind, placebo-controlled trial. The participants (N=128) were randomly assigned treatment with a flexible dose of pregabalin or placebo for 16 weeks.

Patients treated with pregabalin had a greater reduction in pain intensity (NRS). They also had a significant reduction (p=0.047) in pain severity (BPI-SF) and reduction in pain functional interference (p<0.001). Additionally, this study showed significant reduction (p<0.001) in psychological distress (POMS-SF), significant improvement (p=0.004) in quality of life (WHOQOL-BREF) and improvement in satisfaction (PGIC).

Summary of findings for the main comparison:

Table 1: Hypnosis as an adjunct for managing pain in head and neck cancer patients post radiotherapy.
Table 2: Effect of pregabalin on radiotherapy-related neuropathic pain in patients with head and neck cancer: a RCT.

Table 1:

Hypnosis as an adjunct for managing pain in head and neck cancer patients post radiotherapy.

Patient or population	Head and neck cancer patients between the ages of 40–70. Visual analogue scale (VAS) score of at least 4 on the first visit
Setting	Head and neck cancer patients after radiotherapy between August 2015-March 2016 Srinagarind Hospital, Thailand
Intervention	Hypnotherapy
Comparison	Control

Outcomes	Impact	Number of participants (studies)	Certainty of the evidence (GRADE)

Reduction in pain Severity	Hypnosis reduced pain in patients with head and neck cancer after radiation therapy when compared to no hypnosis therapy	68 (1 RCT)	⨁◯◯◯
Assessed with: VAS	Intervention group: coefficient −1.966 (95 % CI −2.26 to −1.67) p=0.00		VERY LOW ^a,b
	The patient’s demographic characteristics were comparable in the two groups. This included age, gender, religion, occupation, level of education, cancer diagnosis, current treatment, level of pain at admission and location of pain

VAS, Visual Analogue Scale. GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. ^aDowngraded 1 or 2 levels due to small sample size. ^bDown graded 1 or 2 levels due to study limitations (risk of bias): lack of allocation concealment and lack of blinding.

Table 2:

Effect of pregabalin on radiotherapy-related neuropathic pain in patients with head and neck cancer: a RCT.

Patient or population	Radiotherapy related neuropathic pain in head and neck cancer
Setting	Treatment of radiotherapy-related neuropathic pain in head and neck cancer patients
Intervention	Pregabalin
Comparison	Placebo

Outcomes	Impact	Number of participants (studies)	Certainty of the evidence (GRADE)

Reduction in pain intensity (NRS)	Pain intensity score decreased in both treatment and placebo groups at week 16. With overall change in baseline score of −2.44 in pregabalin group and −1.58 in placebo group. Adjusted difference between groups reached statistical significance	128 (1 RCT)	⨁◯◯◯
	Patients who achieved pain relief of 50 % or greater was 29.7 % for pregabalin vs. 7.8 % in placebo group		VERY LOW ^a
Reduction in pain Severity (BPI-SF)	Pain severity significantly reduced in the pregabalin group at week 16 compared to placebo group with clinical significant reached in BPI score. (Adjusted difference, 0.7; 95 % CI, 0.01 to 1.3; p=0.047)	128 (1 RCT)	⨁◯◯◯
			VERY LOW ^a
Reduction in pain functional interference (BPI-SF)	The mean BPI interference total score reduction at week 16 was significantly greater in the pregabalin group than placebo group. (13.4 vs. 8.6; adjusted difference, 4.8; 95 % CI, 2.9 to 6.8; p<0.001)	128 (1 RCT)	⨁◯◯◯
			VERY LOW ^a
Reduction in psychological distress (POMS-SF)	There were significant improvements in all subscales of POMS-SF except in the Vigor-activity and Confusion-Bewilderment subscales for pregabalin vs. placebo. (14.0 vs. 8.0; adjusted difference, 5.9; 95 % CI, 3.2 to 8.6; p<0.001)	128 (1 RCT)	⨁◯◯◯
			VERY LOW ^a
Improvement in quality of life (WHOQOL-BREF)	The physiology and psychology domains of WHOQOL-BREF score improved with pregabalin vs. placebo with clinical significance reached. (p=0.004 and 0.01 respectively)	128 (1 RCT)	⨁◯◯◯
			VERY LOW ^a
Improvement in satisfaction (PGIC)	Significant difference reported in treatment success with 47.6 % in the pregabalin group vs. 12.9 % placebo group according to PGIC scale	128 (1 RCT)	⨁◯◯◯
(CGIC)	Similarly, 57.1 % in the pregabalin group reported treatment success by the CGIG scale vs. 16.1 % in the placebo group with absolute rate difference reached statistical significance		VERY LOW ^a

BPI-SF, Brief Pain Inventory-Short Form; NRS, numeric rating scale; POMS-SF, Profile of Mood States-Short Form; WHOQOL-BREF, World Health Organization Quality of Life-BREF; PGIC, Patient Global Impression of Change; CGIC, Clinical Global Impression of Change. GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. ^aDowngraded two levels due to high risk of bias for imprecision (singular study of small sample size).

Discussion

Summary of main results

Overall, two randomised control studies with a total of 196 participants fulfilled the inclusion criteria of this review, which sought to assess the effectiveness and safety of interventions for the management of persistent post radiotherapy pain in head and neck cancers.

In these two studies this involved evaluating the effect of hypnotherapy vs. conventional treatment and the effect of pregabalin vs. placebo. The included trials were heterogeneous in terms of type of intervention and outcome measures used. The study quality varied and formulating pooled evidence was limited due to the high risk of bias in one study, the underpowered nature of both due to small sample size, and the limited number of studies meeting eligibility criteria for our review.

The findings of Thuma, suggest there is very-low level evidence for the use of hypnotherapy (as an adjunct) in reducing pain scores [11]. The results of Jiang also suggest very-low level evidence supporting the use of pregabalin (flexible dosing) for reduction in pain intensity and severity, functional interference, and psychological distress with significant improvement in quality of life and improvement in satisfaction [5].

Overall completeness and applicability of the evidence

Despite a comprehensive search of the literature, only two trials fulfilled the inclusion and exclusion criteria.

Quality of the evidence

Both studies included limitations that affected the quality of evidence.

The hypnotherapy study was rated as very-low quality for methodological evidence due to high risk of bias and flaws in its methodological design including: allocation concealment; blinding of participants; and blinding of outcome assessment [11].

The pregabalin study had a low risk of bias in its methodological design and both studies had an unclear risk of attrition bias [5, 11].

Potential biases in the review process

The review authors followed a number of processes to facilitate a reduction in bias within the review process. In the first instance, the review authors independently screened, short listed and then assessed all articles. Secondly, they adhered to the inclusion and exclusion criteria for the studies and followed the GRADE handbook.

However, limitations in the completeness of the retrieved literature could not be ruled out primarily due to risk of selection bias in the literature search. Possibility of publication bias existed as we did not include studies that are yet been published in academic literature.

Agreements and disagreements with other reviews or studies

There is a paucity of randomised control trials, case control trials and cross-over studies in the area of interventions for persistent pain post radiotherapy in head and neck cancers. This review illustrates existing evidence and the significant gaps in the literature.

Authors conclusions

Implications for practice

Despite the two randomised control trials reviewed in this study reaching statistical significance for their interventions, there is only very-low evidence for the use of such interventions. In light of this, it is difficult to recommend routine use of these interventions alone for the treatment of persistent post radiotherapy pain in head and neck cancers.

The findings illustrate a significant gap in the literature and the need for robust evidence to generate and support best practice in this cohort of patients. The prevalence of persistent post radiotherapy pain in head and neck cancers ranges (in the literature) from 20–77 % [6]. Like all chronic pain syndromes this is a complex condition and requires a multimodal and multidisciplinary approach to care. The pain experience and its impacts are significant with implications for eating, drinking, swallowing, talking and the fear of cancer recurrence. The literature suggests that pain and its associated distress is challenging to treat in this cohort which mirrors our anecdotal experience [2].

Medication management is challenging as there are many guidelines which primarily rely on the use of opioids for this condition. However, in this time where we are increasingly aware of the need for opioid stewardship and the long-term potential for negative outcomes of opioid use there is an increasing need to improve the breadth of current pain management strategies. There is space for considering the benefit of chronic pain programs in this cohort, operating with our understanding of the sociopsychobiomedical framework within which pain exists.

The clinical applicability of findings in this review needs to be replicated in further studies with robust design, larger sample sizes and long-term follow up.

Implications for research

This review demonstrates the considerable gaps in the literature on pharmacological and non-pharmacological interventions (their efficacy and safety) in the management persistent post radiotherapy pain in head and neck cancers.

Future research implications include studies with reduced risk of bias with adequate allocation and randomisation methods; larger sample sizes with appropriate selection of study cohort; tolerability of interventions and perceived benefits; adverse or side-effects of any interventions; long-term impact of interventions using validated pain measures as well as validated quality of life assessments; impact on carers and family members as well as costs associated with interventions.

Whilst most research focuses on treatment of acute mucositis, it would be beneficial to direct attention to the development of persistent pain syndromes and prevention strategies for these. There also needs to be consensus on an approach to the language and definitions around head and neck cancer pain to derive greater understanding of the mechanisms driving associated pain syndromes.

Corresponding author: Jamie Young, MBBS, FAFRM, FFPMANZCA, Clin Dip Pal Care, AFRACMA, PhD, Peter Mac: Peter MacCallum Cancer Centre, Melbourne, Australia; and Department of Critical Care, University of Melbourne, Melbourne, Victoria, E-mail: jamie.young@petermac.org

Acknowledgments

There are no acknowledgements for this publication.

Research ethics: Not applicable.
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

Appendix A: search strategy

Database: Ovid MEDLINE(R) ALL <1946 to November 25, 2020>

Search strategy:

exp Pain Management/(35026)
(pain adj3 (manag* or treat* or therap* or relief or reliev* or reduc* or minimi* or control* or approach* or intervention* or thermotherapy or phototherapy)).mp. (174900)
1 or 2 (174900)
exp “head and neck neoplasms”/rt (34583)
(((head adj2 neck) or pharyng* or pharynx* or larynx* or laryng* or oropharyn* or hypopharyn* or nasopharyn* or throat or mouth or tongue or lip or lips or palatal or gingival or transoral or oral or nasal or nose or paranasal or sinus* or salivary or ear or thyroid or parathyroid or tracheal or facial or eyelid or otorhinolaryngologic) adj3 (neoplasm* or cancer* or tumo?r* or carcinoma* or malignan* or oncolog*)).mp. (310980)
(radiotherap* or radiation or irradiation or brachytherap* or sabr or sbrt or chemoradi* or chemo-radi*).mp. or radiotherapy.fs. (888,705)
5 and 6 (64632)
4 or 7 (69098)
3 and 8 (405)
(exp child/or exp pediatrics/or exp infant/or exp adolescent/) not exp adult/(1916715)
((child* or infant* or newborn* or p?ediatric* or juvenile* or adolescen* or teen* or youth) not adult*).ti. (1302276)
exp animals/not exp humans/(4760027)
((animal* or rat or rats or swine or mouse or mice) not human*).ti. (1428987)
10 or 11 or 12 or 13 (7228976)
exp Randomized Controlled Trials as Topic/(141609)
randomized controlled trial.pt. (517933)
(random* or rct or trial* or placebo* or sham).ti,ab. (1887016)
15 or 16 or 17 (2010664)
9 not 14 (397)
18 and 19 (104)
limit 20 to english language (96)

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/sjpain-2023-0069).

Received: 2023-05-30

Accepted: 2023-10-26

Published Online: 2023-11-15

This work is licensed under the Creative Commons Attribution 4.0 International License.

Supplementary Material

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cancer pain; radiotherapy orofacial pain; chronic mucositis; head and neck cancer

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Pain management for persistent pain post radiotherapy in head and neck cancers: systematic review

Artikel

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Objectives

Methods

Types of studies

Types of participants

Types of interventions

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Assessment of the quality of evidence

Assessment of reporting biases

Results

Included studies

Excluded studies

Risk of bias

Random sequence generation

Allocation concealment

Blinding of participants and personnel

Incomplete outcome data

Selective reporting

Effect of interventions

Hypnotherapy

Pregabalin

Discussion

Summary of main results

Overall completeness and applicability of the evidence

Quality of the evidence

Potential biases in the review process

Agreements and disagreements with other reviews or studies

Authors conclusions

Implications for practice

Implications for research

Acknowledgments

Appendix A: search strategy

References

Supplementary Material

Zusatzmaterial

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