Introduction

Head and Neck Cancers (HNC) are malignant tumors located in the lip, oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, and salivary glands. It is estimated that HNCs are responsible for more than 450,000 deaths annually [57].

Radiotherapy is one of the main treatments for these tumors and is sometimes combined with surgery and/or chemotherapy [37]. The most frequent side effects are mucositis and dysphagia, leading to malnutrition and cachexia [29], with consequent loss of physical function, strength, and quality of life, and increased fatigue [28].

Multicomponent exercise programs (a combination of strength and aerobic exercises) aim to improve the adverse effects of treatment, increase lean mass, and regulate anabolic hormones [8, 34, 35, 52, 63]. Additionally, improved adherence, treatment adherence, and quality of life have been documented in patients with advanced cancer [2, 19, 60].

However, the success of different interventions is conditioned by factors such as frequency, intensity, duration, and type of exercise, that is, the Frequency, Intensity, Time and Type (FITT) principle [7, 16]. For positive adaptations caused by physical training, it is necessary to comply with the principle of training progression, according to which the load (volume × intensity) of exercise is increased in a controlled manner as the intervention program progresses (Gil-Rey et al. [7, 18].

Although, the ideal exercise program for these patients (aerobic vs. strength, duration, and intensity) and the optimal timing (during or after cancer treatment) are unknown. Evidence of the benefit of physical exercise programs is more limited in patients with head and neck cancer than in those with other cancers, such as breast cancer [25].

Thus, the present systematic review aimed to collect randomized clinical trials (RCTs) in which physical exercise is used as supportive therapy in patients with HNC, and to analyze compliance with the FITT principle and the principle of training progression in different interventions.

Methods

Search Strategy and Selection Criteria

The PRISMA methodology was used in this review [43]. The PubMed/MEDLINE, CINAHL, and Embase databases were searched for articles published up to February 2, 2022. The search strategy was adapted to the characteristics of each of the databases as follows within PubMed: “Head and Neck Neoplasms” [Mesh] AND (“exercise” [Mesh] OR “resistance training” [Mesh]) (Supplementary Table 1).

Inclusion criteria were determined using the PICO tool [43] and included publications that included at least 10 participants diagnosed with head and neck cancer (P), (I) the intervention protocol included programmed strength training, but may additionally include aerobic exercise or other types of exercise performed before, during, or after cancer treatment; (C) patients were distributed in different intervention and/or control groups; and (O) they reported at least results concerning the impact of physical exercise on body composition, physical function, and/or quality of life of patients. The following exclusion criteria were applied: study protocols, systematic reviews and meta-analyses, case reports, interventions without physical exercise, and interventions focused on the improvement of a single organ (e.g., dysphagia). Only original articles written in English were selected. In addition, two researchers (E.M. and G.A.) independently reviewed the list of articles found in order to select eligible articles at each stage of the search. If any doubts were found regarding a particular study, they were evaluated and resolved in consensus with all researchers.

The information was extracted (with the help of a professional librarian) by two researchers and the resulting disparities were determined by consensus of the whole team. The final results of the search and selection of articles are presented in the PRISMA diagram (Fig. 1) and Table 2.

Fig. 1
figure 1

Study selection based on inclusion and exclusion criteria

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Data Extraction

The following demographic data and characteristics of the participants and the intervention were extracted from each study: study title, lead author, year of publication, study design, total sample, intervention and control group samples, disease stage, treatment, timing of treatment, and nutritional support. On the other hand, the following variables concerning the training programme were analyzed: duration of the intervention (weeks), frequency (weekly sessions), number of supervised sessions per week, volume (strength training: sets and repetitions; aerobic training: time) and intensity of strength and aerobic exercise, specifications of the training performed (aerobic, strength: elastic bands, free weights, guided machines), and results obtained (see Table 3).

Assessment of Risk of Bias

The risk of bias was determined using the PEDro scale, which scores studies on a scale from 0 to 10 [36]. The score was determined using the PEDro database (https://www.pedro.org.au). If any of the studies were not scored within the database, they were scored according to the PEDro criteria of the researchers (see Table 1).

Table 1 Risk of bias assessment
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Assessment of the Quality of the Exercise Programs

The training programs were analyzed according to the FITT parameters that they met [16]. Additionally, the progression of the loads used in the different programs was analyzed to determine whether they complied with the aforementioned principle of load progression [1] (see Table 3).

Results

A total of 1318 results were obtained by searching the indicated databases, one article was manually included and 386 duplicates were eliminated. Subsequently, 924 articles were reviewed following the PRISMA methodology. The abstracts and full texts of 98 articles were analyzed, and 15 studies met the PICO inclusion and exclusion criteria determined in the previous section (see Fig. 1).

The basic characteristics of the included studies are presented in Table 2. In total, within the 15 studies, data were collected from 910 participants diagnosed with HNC from 7 countries, with stages I to IVb. Participants received radiotherapeutic treatment (RTx), except in two studies, where they only received chemotherapy (CTx), and some received CTx and surgery (S) as adjuvant treatment.

Table 2 Characteristics of the included studies (alphabetically organized)
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The risk of bias of the studies, as determined using the PEDro scale, is listed in Table 1.

In reference to the timing of the physical exercise intervention, 10 programs were performed during RTx, CTx, or RTx + CTx treatment [9, 21, 32,33,34,35, 49, 50, 62, 63], 2 programs were performed after the end of antineoplastic treatment [40, 56],and finally, 3 interventions were performed during and after treatment [20, 51, 52] (see Table 3).

Table 3 Characteristics of the intervention programs with FITT criteria applied (alphabetically organized)
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Regarding physical exercise programs, eight programs performed only strength exercise [9, 20, 21, 32, 34, 35, 49, 52], five combined strength training and aerobic training [50, 51, 56, 62, 63], one added flexibility training [33], and one study performed strength and range of motion (ROM) training [40] (see Table 2).

The duration of the interventions ranged from 6 [21, 50] to 12 weeks [9, 32, 34, 35, 40, 49, 56], with exercises ranging from 1 [49] to 5 days a week [50, 51, 56]. The supervision of physical exercise varied from no supervised sessions [50] to interventions in which 100% of the sessions were carried out together with a professional [20, 21, 32, 33, 52].

The results of the analysis of the FITT principle and progression of the exercise load of the program are shown in Table 3. Out of the 15 physical exercise programs studied, only five (33.3%) detailed all the parameters mentioned [9, 20, 21, 33, 56], while six (40.0%) did not include one of the five parameters measured [32, 40, 49, 50, 62, 63], and four (26.7%) studies did not detail more than one of the parameters studied [34, 35, 51, 52].

On the other hand, four trials provided nutritional support for the participants [8, 21, 34, 52], while two had follow-up and nutritional advice [49, 63]. The remaining 10 studies did not indicate whether nutritional support or advice was provided during the process [20, 32, 33, 35, 40, 50, 51, 56, 62].

Regarding outcome measures, 10 trials measured changes in body composition, measured by bioimpedance, DEXA, or cross-sectional area tomography (CSAT) [9, 20, 32,33,34,35, 49, 52, 62, 63],participants’ general and/or specific quality of life was recorded in 10 of the 15 studies using self-reported questionnaires [21, 32, 33, 35, 40, 49,50,51, 56, 63], and functional capacity was determined by the 6MWT in 7 studies [9, 20, 50, 51, 56, 62, 63], while 10 trials measured changes in participants’ strength, with different combinations of tests [9, 20, 21, 32,33,34,35, 40, 49, 63].

Discussion

Multi-component physical exercise programs, combining strength and aerobic exercises, have been shown to be effective in improving physical function and body composition in patients with head and neck cancer, as well as quality of life and tolerance to treatment. However, it is recommended that interventions comply with and detail some key aspects of the world of physical exercise, as detailed below:

This review collected 15 RCTs in which physical exercise was used as a supportive intervention in patients with head and neck cancer. Analysis of the FITT principle and progression of loads showed that only 33.3% of the studies met all the parameters. This is a remarkable detail in exercise programming because, as indicated by the ACSM, they are essential for the adaptations sought in the different types of variables to be produced [1, 16].

The frequency of training varied among the trials analyzed, from 1 day a week to 5. Thus, the current literature for cancer survivors recommends cardiovascular exercise three times a week, to which a minimum of two days of strength training is added [42]. Therefore, participation in a single weekly training session may be insufficient to acquire the beneficial adaptations caused by physical exercise.

On the other hand, in addition to the frequency of training, the intensity of training must also be taken into account. In the present review, five studies were found in which the intensity at which both strength and cardiovascular training exercises should be performed was not detailed [32, 34, 35, 49, 52]. This made it difficult to interpret the results. The recommendations for cancer patients state that the intensity of strength training should be at least 60% of 1RM, while cardiovascular exercises should be moderate. According to various exercise prescription guidelines, moderate intensity is defined as a score of 12–13 on the RPE scale, 64%–76% of maximum heart rate or 40%–59% of heart rate reserve [1, 17, 26, 42]. Therefore, detailing the intensity characteristics is considered an added value that brings quality and reproducibility to interventions.

However, with regard to the time or volume of the programs (represented in sets of each exercise), similarities were observed between all the interventions studied, generally between two and three sets. However, to determine the total training volume, it would be convenient to know the repetitions performed in each series (strength training) and the aerobic training time, as detailed in all interventions. Recommendations for cancer patients indicate that the optimal training program for general improvement is 2 to 3 sets with 8–15 repetitions, and for cardiovascular exercise, a minimum volume of 30 min per workout is recommended [5, 26, 42]. In the case of strength training, in two of the fifteen studies retrieved, the recommendations were not respected, performing fewer sets [9, 21],on the other hand, four of the six programs that included aerobic exercise complied with the minimum recommendation of 30 min [33, 56, 62, 63], while two did not exceed 20 min [50, 51] (see Table 3).

The main type of exercise is strength training in the programs studied, and six programs combine strength training with aerobic exercise [33, 50, 51, 56, 62, 63]. Physical exercise programs that only prescribe strength training have been shown to be beneficial in improving the strength levels and body composition of participants, however, they appear to be insufficient [5, 18, 26, 42]. Aerobic exercise in cancer patients has a positive association with reducing disease-related fatigue as well as increasing cardiorespiratory fitness [13, 53]. Therefore, there is a need to combine strength training with aerobic training, following the volume and intensity recommendations mentioned above [47].

Training programs produce adaptations to body systems; therefore, for the physical exercise stimulus to be optimal throughout the intervention, training loads must increase as the adaptations increase [7, 42, 47]. However, only nine programs reported this feature [9, 20, 21, 32, 33, 40, 49, 50, 56], just as intensity is vital when replicating or implementing the exercise program elsewhere.

In addition, exercise supervision is another important aspect to highlight to ensure adherence to the program and quality of exercise execution. It should be noted that oncology patients may have no previous experience in performing physical exercise and that they are generally a group of patients with a history of toxic habits and comorbidities. However, of the 15 physical exercise programs, only five were 100% supervised by professionals [20, 21, 32, 33, 52], and the level of supervision in the rest of the studies ranged between 26.6% and 66.6% (see Table 3). We consider that this fact may hinder the interpretation of the results in relation to the knowledge of the real adherence that patients had to the exercise program, as well as the quality of the execution (presumably better in the case of studies with a supervised program).

Supervised programs are more effective than unsupervised or self-conducted programs at home. This seems to be for two reasons: either because of the higher intensity of physical exercise when supervised, or because of other attributes such as motivation, attentiveness that are developed when training under professional guidance [3, 7].

Supervision may be even more relevant in certain patients who have difficulty performing certain exercises as a consequence of cancer treatment. In the case of patients with head and neck cancer, those undergoing up-front surgery before radiation therapy may have shoulder mobility dysfunction associated with neck lymph node dissection. This should be considered in the design of an exercise program to obtain the maximum possible benefit, considering individual limitations. Ideally, patients should be stratified according to previous yes/no surgery [3, 7]. However, having undergone surgery prior to the start of the physical exercise programme was not identified as a limiting factor in the investigations analysed.

Regarding the timing of interventions with respect to cancer treatment, interventions are found during and/or after treatment. Physical exercise interventions produce general improvements in patients with cancer, regardless of the time of application [54, 55]. However, there is no evidence of exercise programs initiated prior to the start of radiotherapy in patients with HNC.

Moreover, nutritional support is an aspect to be highlighted in patients diagnosed with head and neck cancer because weight loss is a frequently observed problem in this type of patient [14, 23]. In fact, up to 63% of the patients had a high state of malnutrition before starting treatment [10, 11, 23, 30]. In addition, weight loss as a consequence of (chemo-)radiotherapy is a common problem in patients with head and neck cancer [31]. During treatment, patients may develop side effects, among which dysphagia associated with mucositis is the most frequently observed. Acute toxicity causes pain and discomfort, leading to difficulties in eating. Therefore, during radiotherapy, the prevalence of malnutrition can be as high as 41%–88% of patients according to different authors [30, 46, 58].

Pretreatment weight loss has been shown to be a prognostic factor for overall survival (van den [59]. Furthermore, according to Langius et al. [31] critical weight loss during radiotherapy, defined as a body weight loss > 5% from the start of radiotherapy to week 8 or > 7.5% to week 12 according to the international consensus [61], is independently associated with a 1.7-fold risk of head and neck cancer-specific mortality. Although weight stabilization during radiotherapy may be difficult despite nutritional support, critical weight loss can be avoided [6]. Several studies in patients with HNC have shown that early and proactive nutritional intervention can be effective in stabilizing body weight during radiotherapy treatment and improving tolerance to cancer treatment [22, 48].

In this sense, both the European (ESPEN) [44] and American (ASPEN) [39] international guidelines recommend individualized early nutritional support during and after the end of (chemo-)radiotherapy treatment in patients with head and neck cancer. This nutritional approach involves dietary advice, oral supplementation, or feeding tubes depending on the patient’s nutritional status.

The importance of nutritional support may be even more relevant in patients with head and neck cancer who participate in physical exercise programs because proper nutrition is essential for the effectiveness of the exercise program (maintaining the necessary caloric and protein intake to control weight and eventually facilitate muscle mass gain) [38]. In addition to enabling the beneficial effects of the exercise intervention, proper nutrition is also necessary to prevent catabolism, which could be brought on by exercise without adequate nourishment [12]. However, only 4 of the 15 studies in this review specified a nutritional approach for patients [9, 21, 34, 52]. This may have influenced the results of the exercise program in terms of functional improvement and body composition.

However, it is estimated that up to 70% of weight loss can be attributed to loss of muscle mass, leading to a state of sarcopenia associated with decreased strength, functional capacity, and quality of life [24]. Additionally, sarcopenia has recently been associated with increased acute toxicity (dysphagia grade ≥ 3) during radiotherapy [27] and is an independent poor prognostic factor associated with decreased survival in patients undergoing radiotherapy with curative intent [4, 15, 45].

This clinical context supports the need to combine a supportive nutritional approach with physical exercise programs for such patients. Therefore, the need for body composition measurements as part of the diagnosis and follow-up of patients during cancer treatment is emphasised, especially if physical exercise programmes are established in order to be able to objectify the real impact (muscle mass gain) of exercise on patients’ body composition. In the present review, only 10 out of 15 studies included measurements of body composition (mostly by bioimpedance or DEXA) [9, 20, 32,33,34,35, 49, 52, 62, 63]. Overall, patients stabilized or improved their body composition and, to a lesser extent, lean body mass [20, 32,33,34,35, 49, 62, 63]. Additionally, gains in strength and functional capacity were observed in 13 out of the 15 programs studied [20, 21, 32,33,34,35, 40, 49,50,51, 56, 62, 63].

Sequelae secondary to cancer treatment as well as loss of body weight may continue for several weeks after the end of radiotherapy treatment [30, 41]. This fact should be considered when establishing the timing of a physical exercise program. While an exercise program established during treatment may help mitigate the loss of muscle mass during cancer treatment, programme-initiated post-treatment may be critical in the recovery of sequelae. The optimal time to initiate a program is currently unknown, and in general, mid-term measurements during the follow-up of patients have shown similar results in body composition [9].

The availability of high-quality primary studies may have limited the present review as well as the search terms used, which could affect the analysis made. In addition, heterogeneity in study design and reported outcomes may make data synthesis difficult. Furthermore, the lack of uniform standars in the definition of exercise programs and outcomes of interest may complicate the comparision between studies. Finally, publication bias and the possibility that studies with negative results may not be published may have influenced the results.

Further research is needed on the timing of the physical exercise program during comprehensive treatment of patients. So far, the impact of exercise during and after treatment has been evaluated. Therefore, as a future line of research, it is proposed to test the efficacy of a multicomponent physical exercise program (strength training and aerobic training), initiated before starting radiotherapy treatment as a prehabilitating exercise and to continue during cancer treatment. Thus, it would be possible to determine the best time to administer physical exercise and increase the level of evidence in this field of study.

Additionally, we consider necessary the association of nutritional support (to decrease sarcopenia and maximize muscle gain) of the patient and the association of measuring the impact on muscle composition and quality of life of the patients. Another endpoint to be considered in future studies is to evaluate the impact of exercise on progression-free survival or overall survival, as there is currently no evidence in this regard.

Likewise, it is appropriate to apply the FITT and progressive overload principle in future physical exercise programs to ensure an effective and reliable intervention that can be replicated by other professionals. We also enhance to further explore the role of the exercise program supervision (by a professional in the field) to optimize the results.

Currently, several trials are underway (NCT05432297, NCT04658706, NCT05594069, NCT04598087, and NCT05418842) that aim to study the application of the physical exercise program prior to starting cancer treatment, thus addressing the lack of information on this aspect in patients with head and neck cancer.

Conclusion

In conclusion, some evidence suggests that physical exercise programs may have positive impact on body composition, strength, and quality of life in patients with head and neck cancer. However, it is crucial to exercise caution in drawing definitive conclusions because of the need for mor precise information regarding FITT principles and load progression within these interventions. This additional detail is essential to conduct a more precise analysis of the dose–response effects of physical exercise in this population. By doing so, we can gain a clearer understanding of which type of exercise program (aerobic, strength, or combination) as well as the appropriate intensity, frequency and volume (number of sets and repetitions or times) would be the most beneficial for patients with head and neck cancer.