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Impact of Sarcopenia on Head and Neck Cancer Treatment: A Review of Literature

CC BY 4.0 · Indian J Med Paediatr Oncol 2023; 44(04): 391-397

DOI: OI: 10.1055/s-0043-1768690

Author : Balateja Kantamani, Manasi Bavaskar, Rathan Shetty, Hitesh R. Singhavi

Abstract

The overall outcome of head and neck cancer (HNC) patients undergoing any treatment modality may significantly depend upon their general nutritional condition. Poor nutritional status leading to sarcopenia may be a negative prognostic factor in determining the outcome of HNC patients. PubMed database was searched to identify studies published between 2015 and 2022. All studies reporting the index for sarcopenia as well as its effect on HNC were included. This narrative review was conducted to specifically evaluate the impact of sarcopenia on HNC patients undergoing surgery/ free flap reconstruction/ adjuvant treatment. In oncology, computed tomography assessment of skeletal mass at C3 and L3 is the most suitable index to detect sarcopenia. From the articles yielded, the prevalence rate of sarcopenia ranges from 6 to 70%-worldwide. Indian population presents with a significantly higher rate of 31.5%-sarcopenia HNC patients. Sarcopenic patients have an increased propensity for surgical site infections, as high as 24.6%-owing to the reduced skeletal muscle mass. These patients are also prone to have frequent breaks during radiation treatment of more than 1 week and increased chemotherapy-related toxicities. Further, sarcopenic individuals tend to have higher Ryle's tube dependency of more than 90 days. Sarcopenic patients undergoing surgery have a poor overall survival (OS) and disease-free survival (DFS). In terms of hazards ratio, sarcopenic patients have 1.96 times poor OS and 2.00 times poor DFS when compared to normal individuals who undergo HNC surgery. Sarcopenia is an indispensable part of cancer ailment and it is an independent factor negatively influencing DFS and OS. Thus, nutritional strategy needs to be developed to mitigate sarcopenic effects, especially in the Indian population in preoperative setting.

Keywords

sarcopenia - head and neck cancer - chemotherapy - radiation - overall survival - sarcopenic index

Publication History

Article published online:
08 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Abstract

The overall outcome of head and neck cancer (HNC) patients undergoing any treatment modality may significantly depend upon their general nutritional condition. Poor nutritional status leading to sarcopenia may be a negative prognostic factor in determining the outcome of HNC patients. PubMed database was searched to identify studies published between 2015 and 2022. All studies reporting the index for sarcopenia as well as its effect on HNC were included. This narrative review was conducted to specifically evaluate the impact of sarcopenia on HNC patients undergoing surgery/ free flap reconstruction/ adjuvant treatment. In oncology, computed tomography assessment of skeletal mass at C3 and L3 is the most suitable index to detect sarcopenia. From the articles yielded, the prevalence rate of sarcopenia ranges from 6 to 70%-worldwide. Indian population presents with a significantly higher rate of 31.5%-sarcopenia HNC patients. Sarcopenic patients have an increased propensity for surgical site infections, as high as 24.6%-owing to the reduced skeletal muscle mass. These patients are also prone to have frequent breaks during radiation treatment of more than 1 week and increased chemotherapy-related toxicities. Further, sarcopenic individuals tend to have higher Ryle's tube dependency of more than 90 days. Sarcopenic patients undergoing surgery have a poor overall survival (OS) and disease-free survival (DFS). In terms of hazards ratio, sarcopenic patients have 1.96 times poor OS and 2.00 times poor DFS when compared to normal individuals who undergo HNC surgery. Sarcopenia is an indispensable part of cancer ailment and it is an independent factor negatively influencing DFS and OS. Thus, nutritional strategy needs to be developed to mitigate sarcopenic effects, especially in the Indian population in preoperative setting.

Keywords

sarcopenia - head and neck cancer - chemotherapy - radiation - overall survival - sarcopenic index

Introduction

Head and neck cancer (HNC) is one of the most common malignancies in India, predominantly affecting the males.[1] [2] In 2020, India estimated nearly 1, 35,929 (10.3%) new oral cavity cancer cases as per the Globocan data.[3] Surgery has been the mainstay treatment modality and well-established standard of care for HNC.[4] [5] However, surgical procedures are lengthy and result in deformities, often followed by reduced food intake leading to nutritional deficiencies and weight loss. Additionally, a shift in paradigm has been observed for the treatment of locally advanced HNC cases utilizing radiotherapy (RT) and concurrent chemotherapy in adjuvant settting.[6] [7] Nonetheless, adjuvant treatment leads to remarkable toxicities such as nausea, vomiting, mucositis, dysphagia, and dermatitis, making maintenance of adequate nutrition a challenge.[8] Thus, knowing nutritional status is highly essential prior to such intense treatment regime during the management of HNC. Given the emerging impact of sarcopenia in the overall survival (OS) of HNC patients, this review was aimed to analyze the mechanism of action and assess the effect of low skeletal muscle mass (SMM) on surgical and postoperative complications in head and neck oncosurgery patients. In this study, we intended to review the literature for incidence of sarcopenia in HNC, mechanism of action, prognostic impact of sarcopenia on various treatment procedures including surgery, radiation, and chemotherapy.

Materials and Methods

PubMed database was searched to identify studies reporting the outcome of sarcopenia in HNC patients. All articles published from January 2015 to March 2022 were searched for this narrative review. The subsequent search terms were used: “Sarcopenia,” and “HNC” in conjunction with “surgery,” “free flap reconstruction,” “postoperative complications,” “overall survival,” “disease free survival,” or “adjuvant treatment,” “chemotherapy,” “sarcopenia index.” Boolean operators (NOT, AND, OR) were also used in succession to modify the search. Additionally, the references of all studies were also searched individually for any additional publications. Only studies in English language, full text publications, and those establishing the impact of sarcopenia in HNC in terms of surgery, OS, disease-free survival (DFS), adjuvant radiation, and chemotherapy were deemed eligible to be included in this review. Case reports, pediatric studies, and any cancer apart from HNC were excluded. The literature search was screened by two authors (HS and KBT) and any differences were sorted in consultation with third author (MB). Each study was assessed for afore mentioned inclusion criteria. The data was extracted by two different authors (HS and KBT) independently. The extracted data included first author, study designs, index to measure sarcopenia, and the criteria assessed.

What Is Sarcopenia?

Sarcopenia is defined as advanced and generalized loss of skeletal muscle with compromise in muscle strength as well as physical function.[9] [10] Nutritional status, including muscle mass, may play a crucial role in determining the overall response of the patient to the subjected treatment. Current literature in general has demonstrated sarcopenia to be a positive predictor of increased postsurgical complication.[9] Sarcopenia, also referred as loss of SMM, has been defined as an independent risk factor of both surgical and adjuvant treatment outcomes of cancer patients.[10] The definition proposed by European Working Group on Sarcopenia in Older People is most popular and stresses on physical strength, mass, and strength of the muscle.[11] The frequency of sarcopenia in patients with HNC reported in literature is as high as 71%, which may vary depending on geographic region and index used to calibrate sarcopenia.[12] Indian population itself presents with a sarcopenic prevalence of alarmingly high as 31.5%.[13] [14]

Reports of sarcopenia causing higher incidence of postoperative complications is well documented, and attributes significantly to chemotherapy related toxicity, longer hospital stays and lower survival outcomes.[10] However, data on sarcopenic patients undergoing HNC management is lacking.[9] [10] [15] In the few studies that highlighted the relationship of sarcopenia on survival of HNC patients was only guided radiologically assessed low SMM was used to define sarcopenia.[15]

Mechanism of Action

Tumor microenvironment, a recent concept consists of inflammatory markers involving inflammatory cells, cytokines and chemokines which induces carcinogenesis.[16] The exact pathogenesis of sarcopenia and its influence on the survival outcomes of HNC patients remains to be elucidated. Cancer progression is characterized by systemic inflammatory response (SIR), which tremendously exerts catabolic effects on the host metabolism to cause muscle breakdown leading to SIR cascade is characterized by cachexia and local inflammation.[17] This SIR in turn leads to further muscle breakdown and increased release of pro-inflammatory cytokines such as interleulin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor beta receptor.[18] Hence, we focused to provide with a simple flowchart ([Fig. 1]) to understand the factors conducive to cancer progression as well as those associated with sarcopenia, thereby suggesting the interlinking negative synergetic prognosis factor in the survival outcomes of HNC patients.


| Fig 1 : Inter-relation of sarcopenia on treatment of head and neck cancers (HNC).


How to Measure Sarcopenia

Till date, there is no consensus on a specific sarcopenic assessment method that can be incorporated in routine clinical practice. Therefore, we extrapolated the most common indices used from the literature for determining the SMM. Various tools for sarcopenia case finding and for measurement of muscle strength, muscle mass, and physical performance in clinical practice and in research are described in [Table 1], while various studies stating the cutoff values of the indices used in the literature are described in [Table 2].[19] [20] [21] [22] [23] [24] [25] [26] [27] [28]

Table 1

Various indices to measure sarcopenia

Abbreviations: ASMM, appendicular skeletal muscle mass; BIA, bioelectrical impedance analysis; CT, computed tomography; DXA, dual-energy X-ray absorptiometry; MRI, magnetic resonance imaging; SARC-F, strength, assistance walking, rise from a chair, climb stairs, and falls; SarQoL, sarcopenia quality of life; SPPB, short physical performance battery; TUG, timed-up and go test.

Index criteria

Types of index

Questionnaire

SARC-F, SarQoL

Muscle strength

Grip strength, Chair stand test

Muscle quantity

ASMM by DXA, SMM with BIA, ultrasound assessment of muscle

Physical performance

Gait speed, SPPB, TUG

Specific biomarkers

Creatine dilution test

Radiographic measurement

Lumbar muscle cross-sectional area by CT or MRI, C3 vertebra SMI

Mid-thigh muscle measurement, psoas muscle measurement
Table 2

Indices to measure sarcopenia with their cutoff values

Abbreviations: ASMM, appendicular skeletal muscle mass; BIA, bioelectrical impedance analysis; DXA, dual-energy X-ray absorptiometry; PMI, psoas muscle index; SARC-F, strength, assistance walking, rise from a chair, climb stairs, and falls; SMI, skeletal muscle index; SPPB, short physical performance battery; TUG, timed-up and go test.

a Muscle mass from D3-Crn enrichment with spillage correction by 24 h D3-Cr subtraction.

Analyzing the study characteristics, we observed that third cervical vertebra C3, followed by third lumbar vertebra L3, were the two frequent sites for assessing computed tomography (CT)-defined sarcopenia; and this goes in consistency with the findings of Takenaka et al in 2021.[29] The most accurate explanation for utilizing these two indices would be that, CT scan usually forms the investigation of choice for assessing primary and neck node metastasis thus it can further be used to asses sarcopenia. However, CT image is sensitive enough to assess muscle quantity and muscle density identifying sarcopenia.[29] Collectively with the stated facts, we recommend skeletal muscle index at 3rd lumbar vertebra (SMI-L3) and skeletal muscle index at 3rd cervical vertebra (SMI-C3) methods ideal for the assessment of sarcopenia in patients with H

Preoperative Effect of Sarcopenia in HNC Patients

The nutritional support of HNC patients represents a uniquely challenging cohort. Various factors such as the inherent biology of oral cancers, the tumor size, hindrance in proper swallowing, poor socioeconomic status, and the lack of social support all contribute the malnourished status of the patients.[30] Body mass index (BMI) less than 20 kg/m2 and recently laboratory measurements such as total serum protein, hemoglobin, transferrin, prealbumin, retinol-binding protein, neutrophil–lymphocyte ratio, and other inflammatory markers have been routinely used to analyze the preoperative status of HNC patients.[31]

It is imperative to optimize the preoperative nutritional balance in such patients before ablative surgery. Dietary counseling must be mandatory to maintain appropriate nutritional intake, thereby preventing progression of the patient to loss of lean muscle mass.[30] Further, surgery alters the anatomy of enteral route and compromises the swallowing efficiency. RT and chemotherapy also produce adverse effects such as mucositis, xerostomia, odynophagia, altered taste sensations, and nausea-vomiting, which exaggerate the poor nutritional intake of patients.[30] Hence, establishment of enteral route for access of adequate nutrition without reliance on oral intake is crucial. Preoperative placement of nasogastric tube or percutaneous endoscopic gastrostomy can significantly mitigate the problem of nutritional rehabilitation.

Preoperative Recommendation for Mitigation of Effects of Sarcopenia

Preoperative carbohydrate loading with ingestion of an 800 mL of 12.5%-carbohydrate drink on the night before surgery followed by 400 mL on the morning of the procedure, consistent with Enhanced Recovery After Surgery Group, has been recommended.[30] [31] Also, HNC patients tend to have immunosuppression that in turn increases the rate of postsurgical complications. Arginine is known to be an essential amino acid when body undergoes metabolic stress.[30] Therefore, provision of arginine-supplemented immunonutrition and additional supplementation with omega-3 fatty acids has gained acceptance and should be encouraged.

ffect of Sarcopenia in Surgical Outcomes Intraoperatively

Surgical site infection (SSI) can be defined as an infection in a surgical wound within 30 days postoperatively. It can lead to increased hospital stay, higher cost, and delayed adjuvant therapy after surgical management of HNC patients. The reported frequency of SSI after head and neck oncology surgery in healthy patients varies between 3 and 41%-in numerous published studies.[32]

Literature suggests a significant relation between SMM and the prognosis of HNC patients undergoing free flap reconstruction. Makiguchi et al in a retrospective analysis in 2019 investigated the SSI rate in 122 patients with sarcopenia.[33] Makiguchi et al reported 30 patients (24.6%) suffered with recipient site SSI and the authors concluded that lower SMM was an independent significant risk factor in such patients.

Further, Alwani et al stated that the definition of sarcopenia should be constantly evolving.[9] However, the measurement of SMM remains the integral part. Additionally, he also noted that sarcopenic patients had higher frequency of blood transfusion; and they were more susceptible to prolonged ventilation.

Effect of Sarcopenia Postoperatively on Free Flap Reconstruction

Ansari et al in 2019 aimed to identify role of SMM on intraoperative and postoperative complications, as well as on survival rates in 78 patients who underwent mandibular reconstruction with free fibula flaps (FFF) in oral cancer resection.[10] They suggested that sarcopenia tends to increase the complication rates in patients with FFF and subjects them to severe postoperative complications (Clavien Dindo grade III-IV). The frequently encountered complications are flap congestion (38.5%), partial skin paddle necrosis (23.1%), dehiscence (15.4%), and complete flap failure rate of 7.7%. After introspecting the study, we can understand that among these four major complications, dehiscence may be the sole complication that could be directly related to sarcopenia; rest all are outcomes of vascular compromise. Furthermore, comparing the rate of wound dehiscence in using FFF in healthy patients would have given more insight on independent impact of sarcopenia on HNC. Lodders et al reported a 10.5%-rate that is evidently lower in contrast to dehiscence rate noted in sarcopenic patients.[34] Another study with level IV evidence by Alwani et al, retrospectively determined the clinical impact of sarcopenia on postoperative outcomes in 168 patients receiving autologous free tissue reconstruction for HNC.[9] Fistula formation, wound disruption, and longer intensive care unit stays signify that sarcopenia has a negative prognostic factor in surgical outcomes with HNC patients. The authors put forward a possible hypothesis for this correlation, suggesting that skeletal muscles produce myokines that exert antineoplastic effect. Myocyte apoptosis in sarcopenic patients cause depletion of SMM, which in turn causes a reduction in myokine-mediated antineoplastic activity that makes them vulnerable to adverse postoperative events

Effects of Sarcopenia on Adjuvant Therapy

Surgery has been the established treatment modality and best standard of care for early HNC.

However, concurrent chemoradiotherapy (CRT) have now led to a shift in the paradigm for the treatment of locally advanced HNC. The addition of chemotherapy improves the survival rate, but it is not without added toxicities.[8] With the impact of existing sarcopenia in such patients, the OS outcomes become questionable. The exact relation between effect of sarcopenia and occurrence of adverse effects of adjuvant therapy has yet not been elucidated distinctly. It can be understood that radiation induced fatigue is responsible for the increased toxicity of radiation therapy in sarcopenic patients. This is known to be associated with increased levels of proinflammatory cytokines, including TNF-α and IL-6, which leads to increased adverse effects. Ganju et al in 2019 reviewed the effect of sarcopenia on 246 HNC patients receiving concurrent chemo radiation.[8]

Sarcopenia was associated with worse OS and progression-free survival as 37%-patients experienced chemotherapy delays of more than 1 week and 14%-had radiation treatment breaks more than 1 week. They estimated that patients with age more than 65 years, BMI less than 30, and sarcopenia predicted for prolonged break from radiation and concluded that sarcopenic patients receiving concurrent chemoradiation are more likely to require frequent breaks during radiation treatment. Furthermore, these patients also suffer from increased chemotherapy-related toxicity such as mucositis, dysphagia, and nausea/vomiting than their nonsarcopenic counterparts. On multivariate analysis, these patients were 2.15 times more prone for above-mentioned toxicities than the normal patients. So, it can be noted that larger breaks in such patients could further lead to slower tumor depletion and increased chances of recurrence.

Additionally, tackling sarcopenia can lead to optimization of the condition of patients with HNC before adjuvant therapy to prevent long-term functional swallowing impairment, such as feeding tube dependency. Karsten et al in 2019 analyzed that sarcopenia led to prolonged (>90 days) feeding tube dependency in 61 HNC patients.[35] The extent of tumor and treatment disrupts normal swallowing physiology, followed by loss of muscle mass and function due to poor nutritional intake. Due to reduction in swallowing muscle activity, nonuse of atrophy of these muscles is inevitable, which is associated with further development of dysphagia and gets exaggerated by loss of muscle mass in sarcopenia. Thus, it can be safely concluded that sarcopenia may lead to Ryle's tube dependency patients with HNC treated with primary CRT.

Effect of Sarcopenia during Follow-Up of Head and Neck Cancer Patients—(Overall Survival and Disease-Free Survival)

Takenaka et al in a meta-analysis in 2021 studied the prognosis of sarcopenia in patients with HNC treated with surgery versus radiation.[12] In total 18 studies enrolling 3,233 patients were included which yielded that sarcopenia was associated with poor OS, DFS and disease-specific survival (DSS) in both surgery and RT groups with sarcopenia affecting more in surgery group. The hazards ratios for OS, DFS, and DSS were 2.50, 2.59, and 2.96, respectively, for surgery group and 1.63, 1.56, and 2.67, respectively, in the RT group. Another meta-analysis by Surov and Wienke in 2021 analyzed the influence of sarcopenia on clinical outcomes in 7,704 patients with head and neck squamous cell carcinoma (HNSCC) from 27 clinical studies, most frequently affecting nasopharynx (47.1%).[36] The study showed that the cumulative prevalence of sarcopenia is 42.0%; and it is an independent risk factor of OS and DFS attributing to hazard ratio of 1.96 and 2.00, respectively, in patients with HNSCC who underwent curative therapy. Sarcopenic patients predicted lower OS undergoing definitive chemotherapy and/or radiation, and primary surgery with hazard ratio of 1.95 and 2.21, respectively.

A retrospective analysis by Lee et al in 2020 investigated the impact of sarcopenia and systemic inflammation on survival in 174 oral squamous cell carcinoma (OSCC) patients.[18] The skeletal muscle index was assessed at the C3 vertebra and the modified Glasgow scale was used to evaluate the systemic inflammation. The authors concluded that sarcopenia and systemic inflammation may significantly exert a negative synergistic prognostic impact in advanced-stage OSCC patients.

Another retrospective study by Stone et al in 2019 aimed at studying the mortality rate associated with sarcopenia in 260 HNC patients.[37] They suggested that sarcopenia can be considered as an apt marker for malnutrition than other conventional assessments, such as BMI, albumin level, or prealbumin level. The authors defined sarcopenia using previously determined thresholds of less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women. They analyzed that at 5 years, the OS was 36.5%-in patients with sarcopenia and 60.5%-in patients without sarcopenia, implying sarcopenia to be a significant negative predictor of long-term OS in HNC patients. Sarcopenia has more deteriorating impact on geriatric HNC patients (≥70 years old). Chargi et al in 2019 conducted a retrospective study on 85 elderly HNSCC patients and investigated SMM and muscle function as a combination contributing to sarcopenia.[15] The study concluded that sarcopenia is associated with impaired OS in such patients with median OS of 12.07 months, compared to 13.60 months in nonsarcopenic individuals. Similarly, in a prospective setting by Jung et al in 2020 evaluated the impact of sarcopenia on postsurgical and oncological outcomes in 190 older adult patients with HNC.[26] They concluded that on multivariate analysis in elderly patient who underwent curative treatment for HNC had 3.2 times higher early complication especially those who were sarcopenic and 4.5-fold increase in mortality over a period of 5 years.

Sarcopenia in Indian Population with Head and Neck Cancer

HNC is the sixth most common cancers worldwide, while in India it is the most common cancer in males.[38] A study involving 18,363 older adults (aged 65 years and older) from three European, three Asian, two African, and one South American country demonstrated higher sarcopenia prevalence rates in older Indians (17.5%) as compared to the other eight countries assessed (12.6–16.7%).[39] After India, Mexico reported with 16.7%, China with 15%, Russia with 14%, and Spain with 13.8%. The probable reason can be attributed to the fact that Indians have a reduced BMI, higher percentage body fat and reduced SMM and strength in comparison to the western population.[13] Additionally, according to the 2021 Global Hunger Index, India ranks 101 out of the 116 countries, with a score of 27.5, which is a serious level of hunger. This data enables to understand the impending hunger levels in India, which disposes the majority of HNC patients to develop sarcopenia.

With the prevalent data of foreign literature suggesting higher incidence of sarcopenia in Indian HNSCC patients, it becomes prudent to tackle this setback and develop potentially feasible approaches to reduce the burden. India's greater population warrants universal health screening programs and relevant questionnaire or index to identify sarcopenia and lastly develops stringent measures to address these patients for better outcomes especially those with HNC.

Conclusion

Sarcopenia is characterized by depletion of SMM, strength, and function and is associated with an adverse effect on the prognosis of patients with cancer.

Sarcopenia is an indispensable part of cancer cachexia and is a predictor of poorer outcomes in HNC. It can be established that patients with sarcopenia have worse OS and DFS. Additionally, it has a negative prognostic effect on free flap-related complications, followed by the increased incidence of postoperative SSIs. When analyzing the effect on concurrent CRT in patients with locally advanced HNSCC, sarcopenia proves to cause greater toxicity and increased treatment breaks. Further, studies assessing SMM and providing information for its nutritional strategy are the need of the hour. Universal index to measure this deleterious prognostic factor and eventually to establish if sarcopenia must be part of a selection plan for surgical treatment of HNC patients warrants larger studies. Furthermore, recommendations for monitoring and surveillance strategies in managing outcomes of sarcopenia in HNSCC patients are yet to be established.

Recommendation

From this review, we would like to highlight few important factors associated with sarcopenia that affect the overall outcome of a HNC patient.

We suggest the CT assessment of skeletal mass at C3 and L3 as the most suitable index for diagnosis of sarcopenia in HNC. Maintaining the preoperative nutrition is equally crucial after analyzing the SMM of these patients. BMI and presurgical albumin levels indicate the nutritional status of the patient. Proper diet with nutritional supplements needs to be incorporated as strategy in wholesome management of HNC patients.

Essentially, a number of complications arise intraoperatively in sarcopenic patients. Such comorbidities warrant higher care level in terms of blood transfusion, prevention of SSI, and prolonged intensive care unit support. Sarcopenia also increased the postoperative complications in patients who have undergone free flap reconstruction, thereby severely exerting a negative effect on the survival outcomes of the patient. Further, the exaggerated side effects of adjuvant therapy and the need for longer radiation breaks predispose the sarcopenic patients to a higher risk of tumor relapse.

With the above-mentioned statements, it can be established that sarcopenia has an impaired overall effect on HNC patients, subjecting them to suboptimal healing and increased mortality.

Conflict of Interest

None declared.

Sr. no.

Author

Year

Variable

Index

Cutoff Value

1

Malmstrom et al[19]

2016

Questionnaire

SARC-F

Score ≥ 4–better outcome

2

Dodds et al[20]

2014

Muscle strength

Grip strength

<27>

<16>

3

Studenski et al [21]

2014

Muscle quantity

ASMM by DXA

<20>

<15>

4

Yamada et al[22]

2017

Muscle quantity

SMM with BIA

6.8 kg/m2 for men

5.7 kg/m2 for women

5

Cruz-Jentoft et al[11]

2010

Physical performance

Gait speed

≤0.8 m/s

6

Pavasini et al[23]

2016

Physical performance

SPPB

≤8 point score

7

Bischoff et al[24]

2003

Physical performance

TUG

≥20 s

8

Shanakaran et al[25]

2018

Specific biomarkers

Creatine dilution test[a]

37 ± 10 kg for men

23 ± 4 kg for women

9

Jung et al[26]

2020

Radiographic measurement

SMI at L3

52.4 for male

38.5 for female

10

van Rijn-Dekker et al[27]

2020

Radiographic measurement

SMI at C3

42.4 for male

30.6 for female

11

Yoshimura et al[28]

2020

Radiographic measurement

PMI

6.05 for male

5.097 for female

References

  1. Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am 2014; 26 (02) 123-141
    Crossref PubMed Google Scholar
  2. Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013; 4 (01) 29-35
    Google Scholar
  3. The Global Cancer Observatory - March, 2021. Accessed April 18, 2023 at:  https://gco.iarc.fr
    Google Scholar
  4. Lo Nigro C, Denaro N, Merlotti A, Merlano M. Head and neck cancer: improving outcomes with a multidisciplinary approach. Cancer Manag Res 2017; 9: 363-371
    Crossref PubMed Google Scholar
  5. Anand AK, Agarwal JP, D'Cruz A. et al. Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India ✰ . Cancer Treat Res Commun 2021; 26: 100269
    Crossref PubMed Google Scholar
  6. Bonner JA, Harari PM, Giralt J. et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354 (06) 567-578
    Crossref PubMed Google Scholar
  7. Pignon JP, le Maître A, Maillard E, Bourhis J. MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009; 92 (01) 4-14
    Crossref PubMed Google Scholar
  8. Ganju RG, Morse R, Hoover A, TenNapel M, Lominska CE. The impact of sarcopenia on tolerance of radiation and outcome in patients with head and neck cancer receiving chemoradiation. Radiother Oncol 2019; 137: 117-124
    Crossref PubMed Google Scholar
  9. Alwani MM, Jones AJ, Novinger LJ. et al. Impact of sarcopenia on outcomes of autologous head and neck free tissue reconstruction. J Reconstr Microsurg 2020; 36 (05) 369-378
    Article in Thieme Connect PubMed Google Scholar
  10. Ansari E, Chargi N, van Gemert JTM. et al. Low skeletal muscle mass is a strong predictive factor for surgical complications and a prognostic factor in oral cancer patients undergoing mandibular reconstruction with a free fibula flap. Oral Oncol 2020; 101: 104530
    Crossref PubMed Google Scholar
  11. Cruz-Jentoft AJ, Baeyens JP, Bauer JM. et al; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on Sarcopenia in older people. Age Ageing 2010; 39 (04) 412-423
    Crossref PubMed Google Scholar
  12. Takenaka Y, Takemoto N, Oya R, Inohara H. Prognostic impact of sarcopenia in patients with head and neck cancer treated with surgery or radiation: a meta-analysis. PLoS One 2021; 16 (10) e0259288
    Crossref PubMed Google Scholar
  13. Chauhan NS, Samuel SR, Meenar N, Saxena PP, Keogh JWL. Sarcopenia in male patients with head and neck cancer receiving chemoradiotherapy: a longitudinal pilot study. PeerJ 2020; 8: e8617
    Crossref PubMed Google Scholar
  14. Mohanty L, Sahoo D. Prevalence and risk factors of sarcopenia: a study in a tertiary care centre. International Journal of Advances in Medicine 2016; 3: 364-36
    Google Scholar
  15. Chargi N, Bril SI, Emmelot-Vonk MH, de Bree R. Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer. Eur Arch Otorhinolaryngol 2019; 276 (05) 1475-1486
    Crossref PubMed Google Scholar
  16. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454 (7203): 436-444
    Crossref PubMed Google Scholar
  17. Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 2017; 35: 200-221
    Crossref PubMed Google Scholar
  18. Lee J, Liu SH, Dai KY. et al. Sarcopenia and systemic inflammation synergistically impact survival in oral cavity cancer. Laryngoscope 2021; 131 (05) E1530-E1538
    PubMed Google Scholar
  19. Malmstrom TK, Miller DK, Simonsick EM, Ferrucci L, Morley JE. SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes. J Cachexia Sarcopenia Muscle 2016; 7 (01) 28-36
    Crossref PubMed Google Scholar
  20. Dodds RM, Syddall HE, Cooper R. et al. Grip strength across the life course: normative data from twelve British studies. PLoS One 2014; 9 (12) e113637
    Crossref PubMed Google Scholar
  21. Studenski SA, Peters KW, Alley DE. et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 2014; 69 (05) 547-558
    Crossref PubMed Google Scholar
  22. Yamada Y, Nishizawa M, Uchiyama T. et al. Developing and validating an age-independent equation using multi-frequency bioelectrical impedance analysis for estimation of appendicular skeletal muscle mass and establishing a cutoff for sarcopenia. Int J Environ Res Public Health 2017; 14 (07) 809 DOI:  10.3390/ijerph14070809.
    Crossref PubMed Google Scholar
  23. Pavasini R, Guralnik J, Brown JC. et al. Short physical performance battery and all-cause mortality: systematic review and meta-analysis. BMC Med 2016; 14 (01) 215
    Crossref PubMed Google Scholar
  24. Bischoff HA, Stähelin HB, Monsch AU. et al. Identifying a cut-off point for normal mobility: a comparison of the timed ‘up and go’ test in community-dwelling and institutionalised elderly women. Age Ageing 2003; 32 (03) 315-320
    Crossref PubMed Google Scholar
  25. Shankaran M, Czerwieniec G, Fessler C. et al. Dilution of oral D 3 -Creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm. J Cachexia Sarcopenia Muscle 2018; 9 (03) 540-546
    Crossref PubMed Google Scholar
  26. Jung AR, Roh JL, Kim JS, Choi SH, Nam SY, Kim SY. The impact of skeletal muscle depletion on older adult patients with head and neck cancer undergoing primary surgery. J Geriatr Oncol 2021; 12 (01) 128-133
    Crossref PubMed Google Scholar
  27. van Rijn-Dekker MI, van den Bosch L, van den Hoek JGM. et al. Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy. Radiother Oncol 2020; 147: 103-110
    Crossref PubMed Google Scholar
  28. Yoshimura T, Suzuki H, Takayama H. et al. Impact of preoperative low prognostic nutritional index and high intramuscular adipose tissue content on outcomes of patients with oral squamous cell carcinoma. Cancers (Basel) 2020; 12 (11) 385
    Crossref PubMed Google Scholar
  29. Takenaka Y, Oya R, Takemoto N, Inohara H. Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta-analysis. J Cachexia Sarcopenia Muscle 2021; 12 (05) 1122-1135
    Crossref PubMed Google Scholar
  30. Nesemeier R, Dunlap N, McClave SA, Tennant P. Evidence-based support for nutrition therapy in head and neck cancer. Curr Surg Rep 2017; 5 (08) 18
    Crossref PubMed Google Scholar
  31. van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van Binsbergen JJ, Merkx MA. A prospective study on malnutrition and quality of life in patients with head and neck cancer. Oral Oncol 2008; 44 (09) 830-837
    Crossref PubMed Google Scholar
  32. Cannon RB, Houlton JJ, Mendez E, Futran ND. Methods to reduce postoperative surgical site infections after head and neck oncology surgery. Lancet Oncol 2017; 18 (07) e405-e413
    Crossref PubMed Google Scholar
  33. Makiguchi T, Yamaguchi T, Nakamura H. et al. Impact of skeletal muscle mass volume on surgical site infection in free flap reconstruction for oral cancer. Microsurgery 2019; 39 (07) 598-604
    Crossref PubMed Google Scholar
  34. Lodders JN, Schulten EA, de Visscher JG, Forouzanfar T, Karagozoglu KH. Complications and risk after mandibular reconstruction with fibular free flaps in patients with oral squamous cell carcinoma: a retrospective cohort study. J Reconstr Microsurg 2016; 32 (06) 455-463
    Article in Thieme Connect PubMed Google Scholar
  35. Karsten RT, Al-Mamgani A, Bril SI. et al. Sarcopenia, a strong determinant for prolonged feeding tube dependency after chemoradiotherapy for head and neck cancer. Head Neck 2019; 41 (11) 4000-4008
    Crossref PubMed Google Scholar
  36. Surov A, Wienke A. Low skeletal muscle mass predicts relevant clinical outcomes in head and neck squamous cell carcinoma. A meta-analysis. Ther Adv Med Oncol 2021;13:17588359211008844
    Google Scholar
  37. Stone L, Olson B, Mowery A. et al. Association between sarcopenia and mortality in patients undergoing surgical excision of head and neck cancer. JAMA Otolaryngol Head Neck Surg 2019; 145 (07) 647-654
    Crossref PubMed Google Scholar
  38. Dandekar M, Tuljapurkar V, Dhar H, Panwar A, DCruz AK. Head and neck cancers in India. J Surg Oncol 2017; 115 (05) 555-563
    Crossref PubMed Google Scholar
  39. Tyrovolas S, Koyanagi A, Olaya B. et al. Factors associated with skeletal muscle mass, sarcopenia, and sarcopenic obesity in older adults: a multi-continent study. J Cachexia Sarcopenia Muscle 2016; 7 (03) 312-321



  43. Address for correspondence

    Hitesh R. Singhavi, MDS
    1131, OPD B, Department of Surgical Oncology, Fortis Hospital
    Mulund, Mumbai 400078, Maharashtra
    India   

    Publication History

    Article published online:
    08 May 2023

    © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

    Thieme Medical and Scientific Publishers Pvt. Ltd.
    A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

| Fig 1 : Inter-relation of sarcopenia on treatment of head and neck cancers (HNC).

References

  1. Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am 2014; 26 (02) 123-141
    Crossref PubMed Google Scholar
  2. Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013; 4 (01) 29-35
    Google Scholar
  3. The Global Cancer Observatory - March, 2021. Accessed April 18, 2023 at:  https://gco.iarc.fr
    Google Scholar
  4. Lo Nigro C, Denaro N, Merlotti A, Merlano M. Head and neck cancer: improving outcomes with a multidisciplinary approach. Cancer Manag Res 2017; 9: 363-371
    Crossref PubMed Google Scholar
  5. Anand AK, Agarwal JP, D'Cruz A. et al. Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India ✰ . Cancer Treat Res Commun 2021; 26: 100269
    Crossref PubMed Google Scholar
  6. Bonner JA, Harari PM, Giralt J. et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354 (06) 567-578
    Crossref PubMed Google Scholar
  7. Pignon JP, le Maître A, Maillard E, Bourhis J. MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009; 92 (01) 4-14
    Crossref PubMed Google Scholar
  8. Ganju RG, Morse R, Hoover A, TenNapel M, Lominska CE. The impact of sarcopenia on tolerance of radiation and outcome in patients with head and neck cancer receiving chemoradiation. Radiother Oncol 2019; 137: 117-124
    Crossref PubMed Google Scholar
  9. Alwani MM, Jones AJ, Novinger LJ. et al. Impact of sarcopenia on outcomes of autologous head and neck free tissue reconstruction. J Reconstr Microsurg 2020; 36 (05) 369-378
    Article in Thieme Connect PubMed Google Scholar
  10. Ansari E, Chargi N, van Gemert JTM. et al. Low skeletal muscle mass is a strong predictive factor for surgical complications and a prognostic factor in oral cancer patients undergoing mandibular reconstruction with a free fibula flap. Oral Oncol 2020; 101: 104530
    Crossref PubMed Google Scholar
  11. Cruz-Jentoft AJ, Baeyens JP, Bauer JM. et al; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on Sarcopenia in older people. Age Ageing 2010; 39 (04) 412-423
    Crossref PubMed Google Scholar
  12. Takenaka Y, Takemoto N, Oya R, Inohara H. Prognostic impact of sarcopenia in patients with head and neck cancer treated with surgery or radiation: a meta-analysis. PLoS One 2021; 16 (10) e0259288
    Crossref PubMed Google Scholar
  13. Chauhan NS, Samuel SR, Meenar N, Saxena PP, Keogh JWL. Sarcopenia in male patients with head and neck cancer receiving chemoradiotherapy: a longitudinal pilot study. PeerJ 2020; 8: e8617
    Crossref PubMed Google Scholar
  14. Mohanty L, Sahoo D. Prevalence and risk factors of sarcopenia: a study in a tertiary care centre. International Journal of Advances in Medicine 2016; 3: 364-36
    Google Scholar
  15. Chargi N, Bril SI, Emmelot-Vonk MH, de Bree R. Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer. Eur Arch Otorhinolaryngol 2019; 276 (05) 1475-1486
    Crossref PubMed Google Scholar
  16. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454 (7203): 436-444
    Crossref PubMed Google Scholar
  17. Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 2017; 35: 200-221
    Crossref PubMed Google Scholar
  18. Lee J, Liu SH, Dai KY. et al. Sarcopenia and systemic inflammation synergistically impact survival in oral cavity cancer. Laryngoscope 2021; 131 (05) E1530-E1538
    PubMed Google Scholar
  19. Malmstrom TK, Miller DK, Simonsick EM, Ferrucci L, Morley JE. SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes. J Cachexia Sarcopenia Muscle 2016; 7 (01) 28-36
    Crossref PubMed Google Scholar
  20. Dodds RM, Syddall HE, Cooper R. et al. Grip strength across the life course: normative data from twelve British studies. PLoS One 2014; 9 (12) e113637
    Crossref PubMed Google Scholar
  21. Studenski SA, Peters KW, Alley DE. et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 2014; 69 (05) 547-558
    Crossref PubMed Google Scholar
  22. Yamada Y, Nishizawa M, Uchiyama T. et al. Developing and validating an age-independent equation using multi-frequency bioelectrical impedance analysis for estimation of appendicular skeletal muscle mass and establishing a cutoff for sarcopenia. Int J Environ Res Public Health 2017; 14 (07) 809 DOI:  10.3390/ijerph14070809.
    Crossref PubMed Google Scholar
  23. Pavasini R, Guralnik J, Brown JC. et al. Short physical performance battery and all-cause mortality: systematic review and meta-analysis. BMC Med 2016; 14 (01) 215
    Crossref PubMed Google Scholar
  24. Bischoff HA, Stähelin HB, Monsch AU. et al. Identifying a cut-off point for normal mobility: a comparison of the timed ‘up and go’ test in community-dwelling and institutionalised elderly women. Age Ageing 2003; 32 (03) 315-320
    Crossref PubMed Google Scholar
  25. Shankaran M, Czerwieniec G, Fessler C. et al. Dilution of oral D 3 -Creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm. J Cachexia Sarcopenia Muscle 2018; 9 (03) 540-546
    Crossref PubMed Google Scholar
  26. Jung AR, Roh JL, Kim JS, Choi SH, Nam SY, Kim SY. The impact of skeletal muscle depletion on older adult patients with head and neck cancer undergoing primary surgery. J Geriatr Oncol 2021; 12 (01) 128-133
    Crossref PubMed Google Scholar
  27. van Rijn-Dekker MI, van den Bosch L, van den Hoek JGM. et al. Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy. Radiother Oncol 2020; 147: 103-110
    Crossref PubMed Google Scholar
  28. Yoshimura T, Suzuki H, Takayama H. et al. Impact of preoperative low prognostic nutritional index and high intramuscular adipose tissue content on outcomes of patients with oral squamous cell carcinoma. Cancers (Basel) 2020; 12 (11) 385
    Crossref PubMed Google Scholar
  29. Takenaka Y, Oya R, Takemoto N, Inohara H. Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta-analysis. J Cachexia Sarcopenia Muscle 2021; 12 (05) 1122-1135
    Crossref PubMed Google Scholar
  30. Nesemeier R, Dunlap N, McClave SA, Tennant P. Evidence-based support for nutrition therapy in head and neck cancer. Curr Surg Rep 2017; 5 (08) 18
    Crossref PubMed Google Scholar
  31. van den Berg MG, Rasmussen-Conrad EL, van Nispen L, van Binsbergen JJ, Merkx MA. A prospective study on malnutrition and quality of life in patients with head and neck cancer. Oral Oncol 2008; 44 (09) 830-837
    Crossref PubMed Google Scholar
  32. Cannon RB, Houlton JJ, Mendez E, Futran ND. Methods to reduce postoperative surgical site infections after head and neck oncology surgery. Lancet Oncol 2017; 18 (07) e405-e413
    Crossref PubMed Google Scholar
  33. Makiguchi T, Yamaguchi T, Nakamura H. et al. Impact of skeletal muscle mass volume on surgical site infection in free flap reconstruction for oral cancer. Microsurgery 2019; 39 (07) 598-604
    Crossref PubMed Google Scholar
  34. Lodders JN, Schulten EA, de Visscher JG, Forouzanfar T, Karagozoglu KH. Complications and risk after mandibular reconstruction with fibular free flaps in patients with oral squamous cell carcinoma: a retrospective cohort study. J Reconstr Microsurg 2016; 32 (06) 455-463
    Article in Thieme Connect PubMed Google Scholar
  35. Karsten RT, Al-Mamgani A, Bril SI. et al. Sarcopenia, a strong determinant for prolonged feeding tube dependency after chemoradiotherapy for head and neck cancer. Head Neck 2019; 41 (11) 4000-4008
    Crossref PubMed Google Scholar
  36. Surov A, Wienke A. Low skeletal muscle mass predicts relevant clinical outcomes in head and neck squamous cell carcinoma. A meta-analysis. Ther Adv Med Oncol 2021;13:17588359211008844
    Google Scholar
  37. Stone L, Olson B, Mowery A. et al. Association between sarcopenia and mortality in patients undergoing surgical excision of head and neck cancer. JAMA Otolaryngol Head Neck Surg 2019; 145 (07) 647-654
    Crossref PubMed Google Scholar
  38. Dandekar M, Tuljapurkar V, Dhar H, Panwar A, DCruz AK. Head and neck cancers in India. J Surg Oncol 2017; 115 (05) 555-563
    Crossref PubMed Google Scholar
  39. Tyrovolas S, Koyanagi A, Olaya B. et al. Factors associated with skeletal muscle mass, sarcopenia, and sarcopenic obesity in older adults: a multi-continent study. J Cachexia Sarcopenia Muscle 2016; 7 (03) 312-321

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