The Effectiveness of Physical Therapy Following Neck Dissection: A Meta-Analysis

Purpose: Head and neck cancers (HNC) have high predilection of cervical lymph node metastases resulting in patients undergoing neck dissection (ND). Due to post-operative shoulder morbidity risks from ND, physical therapy (PT) has been used to address those complications, though studies are limited in demonstrating its efficacy. This study aims to evaluate the effects of PT on measures of shoulder pain and disability, quality of life, and shoulder mobility of patients that underwent ND as part of treatment for HNC. Methods: Literature search was performed by two authors independently. Studies assessing effects of PT for HNC patients treated with ND were evaluated. Primary outcomes and measurements were Shoulder Pain and Disability Index (SPADI), Neck Dissection Impairment Index (NDII), and active shoulder abduction (ASA) in degrees. Results: 108 patients from 3 studies. Effectiveness of PT on shoulder pain and disability, quality of life, and shoulder mobility were evaluated by SPADI, NDII, and ASA respectively. Pooled analyses of intervention (structured PT) versus control (standard, self-directed PT) mean differences (MD) for SPADI (MD=-8.13, 95% CI [-14.06, -2.12], p=0.007) and ASA (MD=24.74, 95% CI [6.71,42.76], p=0.007) favoured intervention, while NDII (MD=6.74, 95% CI [-2.55,16.03], p=0.16) favoured neither. Conclusions: Rigorous therapy appears to provide greater benefits for shoulder pain, disability, and mobility. Further studies are warranted to characterize programs offering maximal support for this cohort of patients. Implications for Cancer Survivors: Suggests that cancer survivors should be more aggressive towards physical therapy to improve shoulder function and pain after undergoing ND.


Introduction
Head and neck cancer (HNC) represents an increasingly common disease that is responsible for about 3% of all malignancies, corresponding to a total of nearly 62,000 patients affected annually and 13,000 annual deaths in the United States [1]. These cancers often originate in the upper aerodigestive tract and metastasize to the neck requiring treatment with radiation, chemoradiation, and/ be addressed given its identified impact on patients' quality of life [2,3]. Although there has been a recent shift from radical ND to modified radical and selective ND to spare the spinal accessory nerve, shoulder complaints are still prevalent in 18-77% of modified radical and 29-39% of selective ND patients, and shoulder dysfunction in around 22% of spinal accessory nerve sparing ND patients [4][5][6]. Due to the spinal accessory nerve being responsible for innervation of the trapezius muscle, damage to the structure may result in shoulder dysfunction manifesting as decrease or loss of abduction, pain, girdle depression, trapezius atrophy, and scapular dyskinesia. If left untreated, it could ultimately lead to adhesive capsulitis and shoulder contractures [6,7].
The role of physical therapy (PT) has become pertinent in the post-operatively treatment of HNC patients following ND, with or without spinal accessory nerve preservation, due to its potential in decreasing shoulder pain, maintaining and improving range of motion, and preventing secondary disorders, such as adhesive capsulitis [6,8]. Although the benefits of PT are recognized, its current utilization is not standard. For example, the modalities of postoperative PT employed to prevent shoulder dysfunction can range from self-directed exercises to structured sessions or programs. Furthermore, among these programs, specifications regarding type of exercise, load, frequency, number of repetitions, duration, and goals vary widely. New efforts to synthesize literature since the Cochrane review by Carvalho et al. in 2012 is needed to further expand upon the effects and benefits of PT, and therefore, the focus of this review is to evaluate functional and quality of life outcomes of HNC patients who underwent ND and subsequent post-operative PT as a part of their treatment regimen [9].

Study Selection
Inclusion criteria were as follows: studies pertaining to adults (≥ 18 years of age), who underwent ND, as either a single or as part of multimodal treatment for HNC, and post-operative PT as treatment for ND side effects and/or complications, with pre-and post-PT measurements of Shoulder Pain and Disability Index (SPADI), Neck Dissection Impairment Index (NDII), and/or active shoulder abduction (ASA) in degrees. These outcome measures were selected for relevance, validity, and consistency in the current literature.
SPADI and NDII are validated tools in assessing shoulder pain, disability, and quality of life. The former index is utilized internationally for a variety of clinical conditions and contexts outside of HNC patients to quantify shoulder pain and functionality [10,11]. NDII on the other hand is an index specifically developed and aimed to assess the effect of ND on the quality of life of patients [12]. These validated indices combined provide a more comprehensive, general, and specific, analysis to quantify the functional status of the current patient cohort. Furthermore, shoulder syndrome, which is characterized by shoulder pain, winged scapula, and impaired shoulder abduction is one of the most significant functional complications of NDs. Although shoulder pain and having a winged scapula are points of great concern, limited shoulder abduction will inevitably affect patient capacities to fulfill activities of daily living (ADLs) such as washing hair and changing light bulbs [13]. Lastly, these measurements have been used frequently in the current literatures, particularly when studying the HNC patient cohorts, and therefore selected for the purposes of the current review.

Data Extraction and Quality Assessment
Data from included studies were independently extracted by 2 authors and then compared to confirm for accuracy. Additionally, the Sterne and Egger tests were performed for further assessment of risk of publication bias [14,15]. The outcomes of interest were pre-to post-PT changes in SPADI score, NDII score, and ASA degree for the control and intervention group. The mean and standard deviation for each outcome were obtained and a weighted average from each article was determined, which were utilized for further analysis.

Data Synthesis and Analysis
The meta-analysis used pre-PT ( Under the fixed effects model, it is assumed that all studies come from a common population, and that the effect size (standardized mean difference [SMD]) is not significantly different among the different trials. This assumption is tested by the heterogeneity test or I2. If this test yields a low probability value (P < .05), then the fixed effects model may be invalid. In this case, the random effects model may be more appropriate, in which both the random variation within the studies and the variation between the different studies are incorporated. Under the random effects model, the true effects in the studies are assumed to vary between studies, and the summary effect is the weighted average of the effects reported in the different studies [16]. The random effects model provides a more conservative estimate (i.e., with a wider confidence interval [CI]), but the results from the 2 models usually agree when there is no heterogeneity. When heterogeneity was present, the random effects model was the preferred model. For this study, the null hypothesis was that there was no difference between baseline and post-PT. Data are presented as mean ± standard deviation (95% CI) in this text and as mean difference (MD) in the figures. The total MD with 95% CI is given for both the fixed effects model and the random effects model.
If the value 0 is not within the 95% CI, then the SMD is statistically significant at the 5% level (P < .05).  c Supervised active and passive range of motion (ROM)/stretching exercises, postural exercises, and basic strengthening exercises with light weights (1-5 kilograms) and elastic resistance bands. Focus on rhomboids/middle trapezius, levator scapula/upper trapezius, biceps, triceps, deltoid, and pectoralis major.
d Same active and passive ROM/stretching exercises and postural exercises as standardized therapeutic exercise protocol (c), but progressive resistance exercise training (PRET) program replaced basic strengthening exercises and was tailored to each patient based on baseline testing results and was prescribed with intent to provide progressive overload to the specific muscle groups.
e Consisted of active and passive ROM exercises and stretching exercises.

Results
Following inclusion and exclusion criteria, 3 articles were included in the analysis [17][18][19] [17]. These studies were found to present a low risk of bias (Figure 2), and moreover, the I2 statistic of 0% suggested non-significant study heterogeneity.
Thus, a meta-analysis of these studies was performed utilizing the fixed-effect models.  [17][18][19]. Therefore, data analysis between the studies was only considered at the 3-month follow-up for consistency.

Active Shoulder Abduction (ASA)
2 studies, totaling 56 patients, measured pre-and post-PT ASA degree measurements. Difference of means between the intervention and control groups revealed a statistically significant, higher mean of ASA degree in the intervention group by 24.74 degrees (95% CI [6.71,42.76], p=0.007) ( Figure 3C) [17,18].

Discussion
The progressive utilization and involvement of post-operative PT in HNC patients treated with ND is often discussed among HNC surgeons for improving the likelihood of patient recovery, regaining functionality, and preserving quality of life. However, there is limited evidence and studies in the medical literature on its effectiveness. The present study is currently the largest and most recent meta-analysis addressing this topic. Although a similar analysis was conducted by Carvalho et al. in 2012, the study was limited to two studies, while this analysis contributes an additional study with a large cohort of 39 patients [9,17]. Not only does this add greater power to this analysis, but it also expands to include a different PT regimen to allow for more generalized application of results.
The first measured outcome is the SPADI score. The 100-point SPADI scoring system is a valid and reliable questionnaire that is responsive to change in clinical status and is used to assess for shoulder pain and disability [22,23]. The higher the SPADI score, the greater the degree of shoulder impairment. This meta-analysis that a change in as little as 8 points on the scoring system was associated with clinical significance perceived by patients [23]. This indicates that PT in general is beneficial, however, a more structured PT program may provide greater and perceivable benefit in alleviating shoulder pain and disability.
The second measured outcome, NDII, is an instrument utilized to assess quality of life. The NDII is a reliable 10-question tool, scored from 1 ("a lot") to 5 ("not at all"), that is scaled to a 100-point cumulative score that has been validated for assessing impairment following ND [12]. The higher the score, the lesser the impairment to quality of life. The analysis showed an increase in the mean NDII scores in both groups at 3 months, and although the results favored the intervention group, it was not statistically significant (MD of  [18,19]. Furthermore, the intervention programs in all the studies involved progressive strengthening exercises, and two of the three programs involved individualizing the program to better accommodate each participant [17][18][19].
Despite these limitations, the short follow-up period may imply that improvements can be achieved earlier with more structured PT programs. Moreover, this study groups specific PT modalities or regimens to the category of structured PT programs and may provide a more generalizable portrayal of structured PT benefits. It is noted with certainty that more studies are necessary to further characterize the varying PT modalities as well as regimens according to their differential impact on functional outcomes and quality of life in HNC patients treated with ND.

Conclusion
Shoulder pain, dysfunction, and impairment are pervasive in HNC patients who have undergone ND. Post-operative PT modalities have promising benefits with the present study showing that more rigorous and structured PT programs lead to greater improvement in shoulder pain, disability, and mobility when compared to selfdirected exercises. This was identified by observing greater improvements in SPADI scores and ASA degrees. Given the small number of studies included in this analysis, in addition to limited sample size, differing PT regimens, and heterogeneity in PT outcome measurements, it is recommended that additional studies are conducted to further characterize PT regimens to expand upon their potential impact on the recovery of this patient cohort.