Vol 18, No 5 (2022)
Review paper
Published online: 2021-07-15

open access

Page views 4228
Article views/downloads 458
Get Citation

Connect on Social Media

Connect on Social Media

Dual impact from coincide potential complications of cancer therapy and sarcopenia: a narrative review

Anmar Al-Taie1, Aygül Koseoğlu2
Oncol Clin Pract 2022;18(5):302-325.

Abstract

Sarcopenia is a disorder of progressive loss of skeletal muscle mass and strength that is linked with multiple complications, decreased physical activity, lower quality of life and accelerated mortality rate. It is more common among cancer patients and identified with reduced tolerance by the toxic effects from cancer therapy, negative outcomes, lowered response and overall survival rate. This narrative review aims to demonstrate the dual impact from the co-occurrence of cancer therapy; chemotherapy, radiotherapy, immunotherapy, and sarcopenia alongside the potential complications from their coincide effects on cancer prognosis. By searching through data sets, all articles that focused on sarcopenia and cancer therapy were collected in the indexed journals between the years 2000 and 2021 that could provide findings for the potential complications from the coinciding effects of cancer therapy and sarcopenia in cancer patients receiving chemo-radio- and immunotherapy. Outcome measures were the rate of studies showing potential complications from the co-occurrence of cancer therapies and sarcopenia. A total of hundred-two cohort studies were enrolled. The majority were about chemotherapy and sarcopenia (45%). About 56.9% of the studies designed as retrospective analysis, and a high proportion were about chemotherapy and sarcopenia (21.6%). About 63.7% of the studies reported skeletal muscle index as the primary marker. Lower than half of the reviewed studies revealed a significant increase in the rate of sarcopenia (47%). The direct toxic effects of chemotherapy on skeletal muscle were reported in 13.7% of the studies. Studies that reported the impact of sarcopenia on a reduction in chemotherapy cycles were about 10.8%. About 11.8% and 14.7% of the studies showed lowered overall survival by the coinciding impact of chemotherapy/radiotherapy and sarcopenia, respectively. In conclusion, the evaluation of sarcopenia in cancer patients should be considered a primary part of oncological care in cancer patients as there are potential complications and poor survival from the co-occurrence of sarcopenia and different cancer therapies.

Review article

Oncology in Clinical Practice

DOI: 10.5603/OCP.2022.0020

Copyright © 2022 Via Medica

ISSN 2450–1654

e-ISSN 2450–6478

Dual impact from coincide potential complications of cancer therapy and sarcopenia: a narrative review

Anmar Al-Taie1Aygül Koseoğlu2
1Pharmacy Department, Faculty of Pharmacy, Girne American University, Kyrenia, North Cyprus, Mersin, Turkey
2Clinical Pharmacy Department, Faculty of Pharmacy, Medipol University, Istanbul, Turkey

Address for correspondence:

Dr. Anmar Al-Taie

Pharmacy Department, Faculty

of Pharmacy, Girne American University,

Kyrenia, North Cyprus, Mersin 10, Turkey

e-mail: anmaraltaie@gau.edu.tr

Received: 21.04.2021 Accepted: 24.05.2021 Early publication date: 15.07.2021

ABSTRACT

Sarcopenia is a disorder of progressive loss of skeletal muscle mass and strength that is linked with multiple complications, decreased physical activity, lower quality of life and accelerated mortality rate. It is more common among cancer patients and identified with reduced tolerance by the toxic effects from cancer therapy, negative outcomes, lowered response and overall survival rate. This narrative review aims to demonstrate the dual impact from the co-occurrence of cancer therapy; chemotherapy, radiotherapy, immunotherapy, and sarcopenia alongside the potential complications from their coincide effects on cancer prognosis. By searching through data sets, all articles that focused on sarcopenia and cancer therapy were collected in the indexed journals between the years 2000 and 2021 that could provide findings for the potential complications from the coinciding effects of cancer therapy and sarcopenia in cancer patients receiving chemo-radio- and immunotherapy. Outcome measures were the rate of studies showing potential complications from the co-occurrence of cancer therapies and sarcopenia. A total of hundred-two cohort studies were enrolled. The majority were about chemotherapy and sarcopenia (45%). About 56.9% of the studies designed as retrospective analysis, and a high proportion were about chemotherapy and sarcopenia (21.6%). About 63.7% of the studies reported skeletal muscle index as the primary marker. Lower than half of the reviewed studies revealed a significant increase in the rate of sarcopenia (47%). The direct toxic effects of chemotherapy on skeletal muscle were reported in 13.7% of the studies. Studies that reported the impact of sarcopenia on a reduction in chemotherapy cycles were about 10.8%. About 11.8% and 14.7% of the studies showed lowered overall survival by the coinciding impact of chemotherapy/radiotherapy and sarcopenia, respectively. In conclusion, the evaluation of sarcopenia in cancer patients should be considered a primary part of oncological care in cancer patients as there are potential complications and poor survival from the co-occurrence of sarcopenia and different cancer therapies.

Key words: cancer, chemotherapy, immunotherapy, radiotherapy, skeletal muscle, sarcopenia

Oncol Clin Pract 2022; 18, 5: 302325

Introduction

Sarcopenia term first took its place in medical literature in the late 1980s by Rosenberg and consists of two words: “sarx (muscle)” and “penia (loss)”. It is defined as a progressive generalized loss of muscle mass and strength as a secondary complication to chronic disease conditions, sedentary lifestyle, and malnutrition [1–3]. Sarcopenia is strictly correlated with increased risk of functional impairment, disability, physical insufficiency, falls and fractures, low quality of life, poor patient outcomes, and a high rate of mortality [3]. It is categorised into three stages based on the definition of the European Working Group on Sarcopenia in Older People (EWGSOP). A pre-sarcopenia stage is characterized by a decrease in muscle mass. This stage does not affect muscle strength and physical performance and can be identified by accurate measuring of muscle mass. A sarcopenia phase is manifested by a decrease in muscle mass, strength, or physical performance. In severe sarcopenia, there is an obvious decrease in muscle mass, strength, and physical performance [4, 5].

In sarcopenia, potential components for loss of muscle quality, mass, and strength include a diminished skeletal muscle innervation and capillary density and the specific decay of type II muscle filaments; that is, a decrease in the motor units involved in the binding of neurons and muscle fibres [6]. The immediate result of sarcopenia is the loss of skeletal muscles, which are not just an essential piece of the motor system but also, modulate immune and inflammatory processes by secreting multiple cytokines, such as tissue necrosis factor-a (TNF) to promote systemic inflammation. Along these lines, sarcopenia may bring down natural killer (NK) cells in cancer patients, thereby debilitating the anti-tumour immune response and worsening patient prognosis [7–9]. Myokines, like interleukin (IL)-6, can have anti-tumorigenic impacts by interacting with NK cells and actuating the production of IL-1 receptor antagonist and IL-10 by the molecules with anti-inflammatory effects [10, 11]. On the other hand, the pro-inflammatory factors delivered by both immune cells and tumour cells advance muscle tissue disintegration and restrain skeletal muscle cell differentiation which can inhibit protein synthesis and muscle regeneration, ultimately prompting muscle atrophy [12]. Besides, TNF-a can straightforwardly instigate muscle atrophy through the ubiquitin-proteasome system (UPS) [13].

Furthermore, many risk factors are associated with the development of sarcopenia. They include age-related changes in tissue secretion or responsiveness to trophic hormonal factors, nutritional insufficiency, a diet poor in protein, muscle fibre count, genetic factors, immobility, post-traumatic, smoking, alcohol, sedentary lifestyle and acute and chronic co-morbid disease conditions such as obesity, osteoporosis and type 2 diabetes mellitus, insulin resistance and underlying malignancy [14, 15].

This narrative review aims to demonstrate the bimodal impact from the co-occurrence of cancer therapy; chemotherapy, radiotherapy, immunotherapy, and sarcopenia alongside the potential complications from their coincide effects on cancer prognosis.

Methods

Search and data extraction

By searching through data sets within PubMed, Google Scholar, ISI, Scopus, and Embase, all articles that focused on sarcopenia and cancer therapy were gathered in the indexed journals between the years 2000 and 2021 that could provide information on the correlated effects of different therapeutic agents used in cancer therapy and sarcopenia. The search strategy for this study was performed utilizing the terms of medical subject headings (MeSH) and combinations of the keywords according to the following: sarcopenia, cancer, chemotherapy, radiotherapy, chemo-radiotherapy, immunotherapy, immune checkpoint inhibitors, skeletal muscle, and body mass index. Inclusion criteria were all articles that focused on the co-existence of cancer therapy and sarcopenia regarding the potential impact of cancer therapy (chemo-radio-and immunotherapy)--induced toxicity on the incidence and prognosis of sarcopenia and vice versa. These included randomised clinical trials, case-control, and retrospective studies; while the titles, abstracts, and full texts of all imported studies were screened by the researchers. Data were extracted from included studies for the following evidence: author, country, year of publication, type of study, sample size, cancer type, cancer therapy, duration of therapy in days, body composition marker, rate of sarcopenia evaluation, and summary of main outcomes. The accuracy and quality of the included data were additionally checked and the review process excluded irrelevant studies and articles, and those not in the English language (Fig. 1).

Figure 1. Flowchart for the database searching and articles selection

Results

A review of hundred-two cohort studies conducted on the potential complications from coinciding effects of cancer therapy and sarcopenia in cancer patients receiving chemo-radio- and immunotherapy revealed varied results. Most of the reviewed studies were about the potential impact of cancer chemotherapy and sarcopenia (45%) (Tab. 1 and 2); while an equal proportion of the reviewed studies was about the impact of sarcopenia in chemo-radiotherapy and immunotherapy (27.5%), as shown in Tables 1, 3 and 4.

Table 1. Summary of findings for the reviewed cohort studies

Variable

Number of reviewed studies (n = 102)

Percentage

Studies-related cancer therapy

Chemotherapy

46

45.0

Chemo-radiotherapy

28

27.5

Immunotherapy

28

27.5

Study design

Retrospective

58

56.9

Prospective

44

43.1

Cancer diagnosis

Oesophagogastric carcinoma

14

13.7

Non-small cell lung carcinoma (NSCLC)

15

14.7

Anticancer therapy

Platinum-based compounds

14

13.7

Pembrolizumab

16

15.7

Nivolumab

16

15.7

Surrogate for skeletal muscle mass

Skeletal muscle index (total)

65

63.7

Skeletal muscle index (chemotherapy)

29

44.6

Skeletal muscle index (chemo-radiotherapy)

18

27.7

Skeletal muscle index (immunotherapy)

18

27.7

Rate of sarcopenia

48

47

Impact of chemotherapy on sarcopenia incidence

14

13.7

Impact of sarcopenia on administration of chemotherapy schedules

11

10.8

Lowered overall survival by coincide impact of chemotherapy and sarcopenia

12

11.8

Lowered overall survival by coincide impact of radiotherapy and sarcopenia

15

14.7

Impact of sarcopenia on administration of immunotherapy schedules

8

7.8

Overall outcome*

95

93.1

Table 2. Summary of clinical cohort studies regarding the potential impact of cancer chemotherapy and sarcopenia

Author/Country/ /Year

Study design

Sample size

Cancer type

Chemotherapy

Duration (pre-post therapy in days)

Body composition marker

Rate of sarcopenia evaluation

Main outcomes

Ref.

Baseline sarcopenia (%)

Post-therapy sarcopenia (%)

Gastrointestinal

Awad et al./UK/2012

Observational study

47

Oesophagogastric

Epirubicin/Cisplatin/5-fluorouracil

107

Fat mass, Fat free mass

57

79

Neoadjuvant chemotherapy was associated with an increase of sarcopenia

[32]

Yip et al./UK/2014

Prospective study

35

Oesophageal

Multiple chemotherapy regimens

60

Fat mass, Fat free mass, subcutaneous fat to muscle ratio

26

43

Sarcopenia increased following neoadjuvant chemotherapy

[33]

Reisinger et al./Netherlands/2015

Prospective study

114

Oesophageal

Multiple chemotherapy regimens

111

Skeletal muscle loss index

56

67

Measurement of muscle mass loss provide assessment to identify unfavorable postoperative outcome

[121]

Liu et al./Japan/2016

NA

84

Oesophageal

5-fluorouracil, cisplatin or nedaplatin

56

Psoas muscle index

NA

NA

Decreased psoas muscle index correlates well with a poor prognosis

[21]

Elliott et al./ /Ireland/2017

Prospective study

252

Oesophageal

(Cisplatin/5-Fluorouracil); Carboplatin/Paclitaxel); (Etoposide, Cisplatin, Fluorouracil/Capecitabine)

365

Lean body mass, skeletal muscle index, fat mass

16

31

Sarcopenia is associated with an increased risk of major postoperative complications

[122]

Paireder et al./ /Austria/2018

Retrospective study

130

Oesophageal

Taxane/platinum taxane+platinum

NA

Skeletal muscle index

42.3

57.7

Sarcopenia impacts long-term outcome

[23]

Daly et al./ /Ireland/2018

Prospective observational study

225

Foregut

Multiple chemotherapy regimens

118

Skeletal muscle index, adipose tissue area

40

NA

Patients experience significant losses of muscle during chemotherapy

[34]

Guinan et al./ /Ireland/2018

Prospective observational study

28

Oesophageal

(Etoposide, Cisplatin, Fluorouracil/Capecitabine); (Cisplatin/5-Fluorouracil, Carboplatin/Paclitaxel)

96

Lean body mass

7

22

Participants experience declines in muscle mass and strength

[35]

Järvinen et al./ /Finland/2018

Retrospective cohort study

118 (115)

Oesophageal

epirubicinoxaliplatincapecitabine

33

Skeletal muscle index

80

80

Loss of skeletal muscle tissue correlates with worse overall survival

[24]

Dijksterhuis et al./ /Netherlands/2019

NA

88

Oesophagogastric

Capecitabine/oxaliplatin

79

Skeletal muscle index, reflecting muscle mass, and skeletal muscle density

49

55

Sarcopenia was not associated with survival or treatment-related toxicity

[123]

Ma et al./South Korea/2019

Retrospective study

198

Oesophageal cancer

Chemo-radiotherapy (multiple chemotherapy regimens)

NA

Skeletal muscle index

NA

NA

Sarcopenia can be a useful predictor for long-term prognosis

[22]

Ota et al./Japan/2019

Retrospective study

31

Oesophageal cancer

Cisplatin, 5-fluorouracil/cisplatin, 5-FU, and docetaxe

NA

Skeletal muscle index

51.6

NA

Potential utility of sarcopenia assessment

[124]

Voisinet et al./ /France/2020

Retrospective study

46

Oesogastric adenocarcinoma

NA

180

Psoas, paraspinal, abdominal wall muscles

6.7

60

Feeding jejunostomy with enteral nutritional seemed to efficiently counteract sarcopenia occurrence

[125]

Palmela et al./ /Portugal/2017

Retrospective study

48

Gastric

Multiple chemotherapy regimens

86

Skeletal muscle index, visceral fat index

23

58

Sarcopenia associated with early termination of neoadjuvant chemotherapy

[55]

Dalal et al./USA/2012

Prospective cohort study

41

Pancreatic

Bevacizumab, capecitabine

104

Skeletal muscle, visceral adipose tissue, subcutaneous adipose tissue

63

90

Obese patients experience higher losses in weight

[126]

Fogelman et al./ /USA/2014

Prospective study

53

Pancreatic

Gemcitabine, erlotinib, MK-0646

60

Skeletal muscle index

NA

NA

Metastatic pancreatic cancer patients can be expected to lose muscle mass

[127]

Choi et al./South Korea/2015

Retrospective study

484

Pancreatic cancer

Multiple chemotherapy regimens (Gemcitabine, FOLFIRINOX)

NA

Skeletal muscle index

21

53

Sarcopenia was poor prognostic factors in advanced pancreatic cancer

[25]

Cooper et al./ /USA/2015

Prospective study

89

Pancreatic

Gemcitabine, cisplatin

135

Skeletal muscle, adipose tissue compartments

52

59

Further depletion of skeletal muscle occurred during neoadjuvant therapy

[36]

Benjamin et al./ /USA/2018

Retrospective study

24

Pancreatic

Multiple chemotherapy regimens

NA

Total psoas area index

38

NA

A significant decrease in total psoas area index during treatment with received neoadjuvant chemotherapy

[37]

Sandini et al./ /Italy/2018

Retrospective cohort study

193

Pancreatic

Multiple chemotherapy regimens

180

Total adipose tissue area, visceral adipose tissue area, skeletal lean mass

43

41

Patients experience a significant loss of adipose tissue during neoadjuvant chemotherapy

[38]

Prado et al./ /Canada/2007

Prospective study

62

Colon cancer

5-fluorouracil, leucovorin

168

Lean body mass

NA

NA

Lean body mass is a significant predictor of toxicity

[56]

Poterucha et al./ /USA/2012

NA

57

Colorectal cancer

Multiple chemotherapy regimens, bevacizumab

90

Skeletal muscle index

NA

NA

Prescribed bevacizumab appear to lose weight and muscle in the absence of cancer progression

[39]

Barret et al./ /France/2014

Prospective, cross-sectional, multicenter study

51

Colorectal cancer

Fluoropyrimidine ± oxaliplatin, irinotecan

60

Areas of muscle tissue, visceral adipose tissue, subcutaneous adipose tissue

NA

70.6

Sarcopenia significantly associated with severe chemotherapy toxicity

[57]

Jung et al./South Korea/2015

Prospective study

229

Colon cancer

Oxaliplatin, 5-fluorouracil, leucovorin

180

Psoas muscle index

NA

NA

Decreased muscle mass was associated with increased risk of grade 3-4 toxicity and poor prognosis

[26]

Miyamoto et al./ /Japan/2015

Retrospective study

182

Unresect-able colorectal cancer

Oxaliplatin, irinotecan

70

Skeletal muscle index

73

NA

Skeletal muscle loss was an independent, negative prognostic factor

[27]

Ali et al./France, Canada/2016

Prospective randomized clinical trials

138

Colon cancer

FOLFOX (Folinic acid, 5FU, oxaliplatin, irinotecan ± cetuximab)

180

Lean body mass

NA

NA

Low lean body mass is a significant predictor of toxicity

[54]

Blauwhoff-Buskermolen et al./Netherlands/2016

Prospective study

63

Colorectal cancer

Multiple chemotherapy regimens

NA

Skeletal muscle index

57

70

Muscle area decreased significantly during chemotherapy and was independently associated with survival

[20]

Eriksson et al./ /Sweden/2017

Retrospective study

225

Resectable colorectal liver metastases

Multiple chemotherapy regimens (majorly oxaliplatin-based)

960

Skeletal muscle index

NA

61

Skeletal muscle mass decreases during neoadjuvant chemotherapy and impairs the conditions for adjuvant chemotherapy

[40]

Antoun et al./ /France/2019

Prospective multicenter, randomized, open-labelled, non-comparative phase II trial

76

Colorectal cancer

Multiple chemotherapy regimens

120

Skeletal muscle index

NA

NA

Skeletal muscle mass depletion was not associated with survival or chemotherapy toxicity

[128]

Derksen et al./ /Netherlands/2019

Randomized controlled phase III trial

300

Colorectal cancer

Multiple chemotherapy regimens

126

Skeletal muscle index

NA

NA

Skeletal muscle index loss was associated with lifestyle-related as well as tumourand treatment-related factors

[28]

Kurk et al./ /Netherlands/2019

Observation trial study

414

Colorectal cancer

Capecitabine, bevacizumab, oxaliplatin

NA

Skeletal muscle index, body mass index

54, 46

NA

Sarcopenia and/or muscle loss was associated with an increased risk of dose-limiting toxicities

[58]

Kobayashi et al./ /Japan/2018

Retrospective study

102

Hepatocellular carcinoma

Transcatheter arterial chemoembolization and transcatheter arterial infusion multiple chemotherapy

180

Skeletal muscle index

NA

NA

Rate of change in skeletal muscle mass was an independent prognostic factor

[129]

Lung

Stene et al./ /Norway/2015

Pilot observational cohort study

35

Non-small cell lung carcinoma cancer (NSCLC)

Carboplatin Vinorelbine Gemcitabine

88

Skeletal muscle index

NA

NA

Almost half of the patients had stable or increased muscle mass during chemotherapy

[21]

Go et al./Korea/2016

Retrospective study

117

SCLC

Chemotherapy (Etoposide, platinum/Irinotecan, cisplatin) or chemo-radiotherapy

NA

Skeletal muscle index

24.8

NA

Baseline sarcopenia is associated with poor prognosis and a high incidence of dose-limiting toxicity of the standard first-line treatment

[29]

Atlan et al./ /France/2017

Retrospective study

64

NSCLC

NA

133

Skeletal muscle index, total adipose tissue

49

48.1

Skeletal muscle mass is wasting is lower when initial skeletal muscle mass and BMI values are low

[130]

Nattenmüller et al./ /Germany/2017

Retrospective single centre study

200

NSCLC

Multiple chemotherapy regimens

125

Visceral, subcutaneous-fat-area, inter-muscular-fat-area, muscle-density, muscle-area, skeletal-muscle index

NA

NA

After chemotherapy, patients exhibited sarcopenia with decreased muscle

[41]

Goncalves et al./ /USA/2018

Retrospective study

88

NSCLC

Taxane, gemcitabine, bevacizumab

120

Skeletal muscle 2-[18F]-fluoro-2-deoxy-d-glucose

NA

NA

During chemotherapy skeletal muscle volume and metabolism are altered

[42]

Kakinuma et al./ /Japan/2018

Retrospective study

44

NSCLC

Not-specified (Poly-chemotherapy)

152

Skeletal muscle index

NA

NA

Skeletal muscle loss was higher in patients receiving cytotoxic chemotherapy

[131]

Breast and ovarian

Prado et al./ /Canada/2009

Prospective Study

55

Breast cancer

Capecitabine

30

Skeletal muscle index

25

50

Sarcopenia is a significant predictor of toxicity and tumour progression

[30]

Prado et al./ /Canada/2011

Prospective study

132

Breast cancer

5FU, epirubicin, cyclophosph-amide

180

Lean body mass

NA

NA

Lean body mass was lower for patients presenting with toxicity

[59]

Mazzuca et al./ /Italy/2018

Retrospective study

21

Breast cancer

Anthracycline-based chemotherapy

NA

Skeletal muscle index

38

48

Lean body mass loss is associated with higher grade of toxicity

[60]

Rier et al./Netherlands/2018

Single-centre, retrospective study

98

Metastatic breast cancer

5-fluorouracil, doxorubicin, cyclophosphamide/Paclitaxel

118

Lumbar skeletal muscle index

NA

NA

Muscle attenuation decreased during treatment

[62]

Rutten et al./Netherlands/2016

Retrospective study

123

Ovarian cancer

Multiple chemotherapy regimens

84

Surface areas of skeletal muscle

NA

NA

Patients with ovarian cancer have a worse survival when they lose skeletal muscle

[31]

Bladder

Zargar et al./ /USA/2017

Retrospective study

60

Bladder cancer

Multiple chemotherapy regimens (majorly gemcitabine-cisplatin)

126

Bilateral total psoas muscle volume

NA

NA

A decline in psoas muscle volume during neoadjuvant chemotherapy and associated with the need for dose reduction/dose delay

[43]

Rimar et al./ /USA/2018

Retrospective study

26

Bladder carcinoma

Methotrexate, vinblastine, doxorubicin, cisplatin/gemcitabine, cisplatin/gemcitabine, carboplatin

110

Lumbar skeletal muscle index, visceral adipose index, subcutaneous, intramuscular adipose index

69

81

A significant decrease in lean muscle mass with an associated increase in the prevalence of sarcopenia

[44]

Others

Xiao et al./USA/2016

Retrospective cohort study

191

Diffuse large B-cell lymphoma

Cyclophos-phamide, doxorubicin, vincristine/prednisone, ± rituximab

90

Muscle, subcutaneous fat, visceral fat areas

NA

NA

Survivors undergo unfavorable long-term body composition changes

[132]

Table 3. Summary of clinical cohort studies regarding the potential impact of radiotherapy/chemo-radiotherapy and sarcopenia

Author/ /country/year

Study design

Sample size

Cancer type

Radiotherapy or chemo-radiotherapy

Duration (pre-post therapy in days)

Body composition marker

Rate of sarcopenia evaluation

Main outcomes

Ref.

Baseline sarcopenia (%)

Post-therapy sarcopenia (%)

Head and neck carcinoma (HNC)

Grossberg et al./ /USA/2016

Retrospective study

2840

HNC

Radiotherapy

2058

Skeletal muscle index

35.3

65.8

Diminished skeletal muscle mass

[133]

Cho et al./South Korea/2018

Retrospective study

221

HNC

Chemo-radiotherapy

NA

Skeletal muscle index

NA

48

Sarcopenia is associated with significantly inferior overall survival, progression-free survival and RT interruption more frequently

[80]

Ganju et al./ /USA/2019

Retrospective study

246

HNC

Chemo-radiotherapy (cisplatin, cetuximab),

1053

Lumbar skeletal muscle index

NA

58.1

Sarcopenic patients are more likely to require radiation treatment breaks and suffer chemotherapy toxicity

[73]

van Rijn-Dekker et al./Netherlands/2020

Prospective study

750

HNC

Chemo-radiotherapy (cisplatin, carboplatin/5-FU or cetuximab)

720

Skeletal muscle index

NA

NA

Sarcopenia is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity

[82]

Chauhan et al./India/2020

Short-term, longitudinal cohort study

19

HNC

Chemo-radiotherapy

49

Skeletal muscle index

31.5

89.4

Patients showed clinically significant increases in the incidence of sarcopenia

[134]

Thureau et al./ /France/2020

Observational prospective, unicentric study

243

HNC

Chemo-radiotherapy (Cisplatin, cetuximab)

NA

Skeletal muscle index

NA

41.7

Pretherapeutic sarcopenia remains frequent and predicts overall survival and disease-free survival

[83]

Respiratory

Op den Kamp et al./ /Netherlands/2014

Retrospective cohort study

203

Non-small cell lung carcinoma (NSCLC)

Chemo-radiotherapy

NA

Limb muscle strength

NA

NA

Weight loss starts early and requiring timely and intense nutritional rehabilitation

[135]

Sanders et al./Netherlands/2016

Retrospective study

287

Non-small cell lung carcinoma (NSCLC)

Chemo-radiotherapy (majorly platinum-based chemotherapy + etoposide)

NA

Early weight loss

NA

NA

Early weight was found to be associated with worse prognosis

[84]

Kiss et al./Australia/2019

Prospective study

41

Non-small cell lung carcinoma (NSCLC)

Multiple chemotherapy regimens

150

Muscle area, muscle density

61

85

Significant loss of muscle area and muscle density occurs early during therapy

[136]

Shen et al./ /China/2013

Retrospective cohort study

2433

Nasopharyngeal carcinoma (NPC)

Radiotherapy

60-3750

High weight loss, low weight loss

NA

NA

High weight loss was independently associated with poor survival in NPC

[85]

Li et al./China/2017

Retrospective study

322

NPC

Radiotherapy

2190

Body weight loss

NA

93.5

Acute radiation toxicities had significant and independent impact on weight loss

[75]

Gastrointestinal

Olson et al./Portland/2020

Retrospective study

245

Oropharyngeal squa mous cell carcinoma

Radiotherapy

NA

Third lumbar skeletal muscle index

NA

55.1

Sarcopenia has a negative association with survival for patients

[86]

Murimwa et al./ /USA/2017

Retrospective study

56

Oesophageal cancer

Chemo-radiotherapy

NA

First full slice of the L4 vertebra, psoas muscle

NA

NA

Sarcopenia was associated with a significant increase in acute grade ≥3 toxicity

[137]

Panje et al./Switzerland/2019

Prospective Study

61

Oesophageal cancer

Chemo-radiotherapy (multiple chemotherapy regimens)

90

Skeletal muscle index

29.5

63.9

Neoadjuvant chemoradiation increased the percentage of sarcopenia. Sarcopenic patients are at higher risk for increased toxicity during therapy

[76]

Ma et al./South Korea/2019

Retrospective study

287

Oesophageal cancer

Chemo-radiotherapy

90-180

Skeletal muscle index

NA

8.7

Sarcopenia can be a useful predictor for long-term prognosis

[87]

Yoon et al./Korea/2020

Retrospective study

248

Oesophageal cancer

Chemo-radiotherapy (5-fluorouracil, cisplatin)

35

Skeletal muscle index

62.9

83.5

Excessive muscle loss was a significant prognostic factor for overall survival and recurrence free survival

[88]

Mallet et al./ /France/2020

Retrospective study

97

Oesophageal cancer

Chemo-radiotherapy

NA

Skeletal muscle index

56

93

Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality

[81]

Liang et al./ /China/2021

Retrospective study

100

Oesophageal cancer

Radiotherapy

360

Skeletal muscle index

NA

70.1

Sarcopenia can independently predict the survival of patients

[89]

Shiba et al./ /Japan/2018

Retrospective study

68

Hepatocellular carcinoma (HCC)

Radiotherapy

1005

Skeletal muscle index

NA

32.4

Sarcopenia was not a prognostic factor for patients with HCC treated with C-ion RT

[138]

Lee et al./South Korea/2019

Retrospective study

156

Hepatocellular carcinoma (HCC)

Radiotherapy

279

Skeletal muscle index

63.5

NA

Sarcopenia, was associated with poor survival

[90]

Lin et al./China/2016

Retrospective study

364

Rectal cancer

Chemo-radiotherapy (oxaliplatin, capecitabine/oxaliplatin, leucovorin, 5-FU)

NA

Body mass index

66.2

100

Severe weight loss compromises survival outcome

[91]

Park et al./ /South/2018 Korea

Retrospective study

104

Rectal cancer

Chemo-radiotherapy (5FU, capecitabin)

NA

Skeletal muscle index

36.7

40

Sarcopenia is a poor prognostic factor in older patients

[92]

Cervical

Kiyotoki et al./ /Japan/2018

Retrospective study

60

Cervical cancer

Chemo-radiotherapy (cisplatin, nedaplatin/ifosfamide + nedaplatin)

1005

Skeletal muscle, iliopsoas muscle

NA

NA

Sarcopenia was revealed to be an important prognostic factor

[93]

Matsuoka et al./ /Japan/2019

Retrospective study

236

Cervical cancer

Chemo-radiotherapy (cisplatin, nedaplatin/ifosfamide + nedaplatin)

30-4950

Psoas muscle index, skeletal muscle index

NA

NA

Sarcopenia is not a predictive factor of outcome

[139]

Others

Couderc et al./ /France/2020

Prospective study

31

Prostate cancer

Androgen deprivation therapy+ radiotherapy

NA

Appendicular skeletal muscle mass

25.8

NA

A high prevalence of muscle disorders

[140]

Pielkenrood et al./ /Netherlands/2020

Prospective cohort study

310

Spinal metastases

Radiotherapy

202

Visceral fat area, subcutaneous fat area, total muscle area, skeletal muscle density

48

86

Sarcopenia can improve predictions of overall survival

[94]

Ferini et al./ /Italy/2021

Prospective Study

28

Bladder cancer

Radiotherapy

735

Skeletal muscle index

NA

28.6

Sarcopenia cannot be considered a negative prognostic factor for elderly patients treated with external beam radiotherapy

[141]

Zhang et al./ /China/2016

Prospective study

113

NA

Chemo-radiotherapy

NA

Total lumbar skeletal muscle cross-sectional area , total lumbar adipose tissue area

NA

84.9

Incidence of sarcopenia among patients with cancer is high, particularly for males

[142]

Table 4. Summary of clinical cohort studies regarding the potential impact of cancer immunotherapy and sarcopenia

Author/ /country/ /year

Study design

Sample size

Cancer type

Immunotherapy

Duration (pre-post therapy in days)

Body composition marker

Rate of sarcopenia evaluation

Main outcomes

Ref.

Baseline sarcopenia (%)

Post-therapy sarcopenia (%)

Non-small cell lung cancer (NSCLC)

Revel et al./ /France/2018

Prospective study

779

Lung cancer

Anti-PD-1 antibody

60

Total muscle area, skeletal muscle index

NA

70

Sarcopenia is associated with higher risk of immunotherapy interruption

[113]

Cortellini et al./ /Italy/2019

Retrospective observational study

23

NSCLC

Nivolumab

NA

Skeletal muscle index

NA

NA

Influence of nutritional status and sarcopenia on immune response, suggesting these factors could affect treatment with nivolumab

[118]

Nishioka et al./ /Japan/2019

Retrospective study

38

NSCLC

Pembrolizumab, nivolumab

NA

Psoas major muscle area

NA

NA

Patients with sarcopenia are associated with poor outcomes for immunotherapy

[110]

Shiroyama et al./Japan/2019

Retrospective study

42

NSCLC

Pembrolizumab, nivolumab

NA

Psoas muscle index

NA

52.4

Sarcopenia at baseline is a significant predictor of worse outcome

[119]

Magri et al./ /Italy/2019

Retrospective study

46

NSCLC

Nivolumab

720

Body mass index, skeletal muscle mass index, fat-free mass index, fat mass index, weight change

NA

NA

Weight loss is significant negative prognostic factors for NSCLC patients on immunotherapy

[143]

Popinat et al./ /France/2019

Retrospective study

55

NSCLC

Nivolumab

365

Lean body mass, fat body mass, muscle body mass, visceral fat mass, sub-cutaneous fat mass

NA

NA

Subcutaneous fat mass is a significant prognosis factor of stage IV NSCLC treated by nivolumab

[144]

Cortellini et al./ /Italy/2020

Retrospective study

100

NSCLC, Melanoma, Renal cell carcinoma, others

Pembrolizumab, nivolumab, atezolizumab, others

NA

Hounsfield Unit, skeletal mass index

51

NA

Low skeletal muscle index is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors

[145]

Roch et al./ /France/2020

Retrospective study

142

NSCLC

Pembrolizumab, nivolumab

165

Skeletal mass index

65.7

75.4

Cachexia sarcopenia syndrome negatively influences patients’ outcome during pembrolizumab, nivolumab therapy

[146]

Petrova et al./ /Bulgaria/2020

Retrospective study

167

NSCLC

Pembrolizumab

NA

Psoas major muscle area

30.3

NA

Presence of sarcopenia are potential risk factors for the development of disease progression

[147]

Ichihara et al./ /Japan/2020

Retrospective study

513

NSCLC

Pembrolizumab, nivolumab, atezolizumab

NA

Body mass index

NA

NA

BMI was significantly associated with the efficacy of immune checkpoint inhibitors

[148]

Minami et al. Japan/2020

Retrospective study

74

NSCLC

Pembrolizumab, nivolumab, tezolizumab

NA

Psoas muscle index, intramuscular adipose tissue content, visceral to subcutaneous ratio, visceral fat area

NA

NA

Neither sarcopenia nor visceral adiposity may be associated with the efficacy of immune checkpoint inhibitors therapy

[149]

Katayama et al./ /Japan/2020

Retrospective study

35

NSCLC

Pembrolizumab, nivolumab, atezolizumab

NA

Body mass index

NA

NA

Low BMI may be negative predictors for checkpoint inhibitors rechallenge treatment

[150]

Tsukagoshi et al./ /Japan/2020

Retrospective study

30

NSCLC

Nivolumab

NA

Skeletal mass index

NA

NA

Skeletal muscle loss may be a predictive factor of poor outcomes in NSCLS patients undergoing nivolumab therapy

[151]

Takada et al./ /Japan/2020

Retrospective study

103

NSCLC

Pembrolizumab, nivolumab

605

Skeletal mass index

NA

NA

L3 muscle index Low is an independent predictor of worse outcomes in NSCLC patients treated with anti-PD-1 inhibitors

[152]

Kichenadasse et al./Australia/2020

Pooled post hoc analysis

1434

NSCLC

Atezolizumab

210

Body mass index

NA

NA

Baseline BMI should be considered as a stratification factor in future immune checkpoint inhibitor therapy trials

[153]

Gastrointestinal

Kano et al./ /Japan/2021

Retrospective study

31

Gastric cancer

Nivolumab

NA

Psoas muscle mass index

NA

29

Psoas muscle mass index might help predict the response to nivolumab

[120]

Kim et al./ /Korea/2021

Retrospective study

149

Gastric cancer

Pembrolizumab, nivolumab

NA

Skeletal mass index

NA

53

Sarcopenia is an independent prognostic factor for progression-free survival in patients treated with PD-1 inhibitors

[154]

Qayyum et al./ /USA/2021

Retrospective study

36

Hepato- cellular carcino- ma (HCC)

Pembrolizumab or nivolumab ± ipilimumab)/ sorafenib

180

Skeletal mass index

NA

NA

Sarcopenia was associated with reduced survival and HCC necrosis

[155]

Akce et al./ /USA/2021

Retrospective study

57

Hepato- cellular carcinoma

Anti-PD-1 antibody

180

Skeletal mass index

NA

49.1

Sex-specific sarcopenia does not predict overall survival

[156]

Melanoma

Daly et al./ /Ireland/2017

Retrospective study

84

Metastatic melanoma

Ipilimumab

100

Muscle attenuation

17

32

Patients with sarcopenia and low muscle index are more likely to experience severe treatment-related toxicity. Loss of muscle during treatment was predictive of worse survival

[112]

Heidelberger et al./France/2016

Retrospective study

71

Melanoma

Pembrolizumab, nivolumab

NA

Body mass index

NA

NA

Patients with sarcopenia experienced significantly more early severe toxicities

[114]

Heidelberger et al./France/2017

Monocentric, retrospective study

68

Melanoma

Pembrolizumab, nivolumab

NA

Body mass index, skeletal muscle index

NA

19

Sarcopenic overweight is associated with more early acute limiting toxicity of anti-PD1 in melanoma patients

[111]

Hu et al./ /USA/2020

Retrospective chart review

156

Melanoma

Pembrolizumab

165

Psoas muscle index

NA

34

Sarcopenia did not appear to predict clinically relevant outcomes. Obesity, however, represents a readily available predictor of pembrolizumab toxicity

[157]

Urothelial carcinoma (UC)

Shimizu et al./ /Japan/2020

Retrospective study

27

UC

Pembrolizumab

360

Psoas major muscle area

NA

56

Evaluation of sarcopenia may help in the management of UC with pembrolizumab

[158]

Fukushima et al./Japan/2020

Retrospective study

28

UC

Pembrolizumab

NA

Skeletal muscle index

NA

68

Patients with advanced UC who received pembrolizumab had sarcopenia, which was significantly associated with poor therapeutic efficacy

[159]

Others

Massicotte et al./ /France/2013

International, double-blinded, placebo-controlled, phase III trial

23

medullary thyroid carcin-oma

Vandetanib

90

Visceral adipose tissue, skeletal muscle index

NA

NA

Patients with low muscle mass had high vandetanib serum concentration and high incidence of toxicities

[115]

Veasey-Rodrigues et al./ /USA/2013

Prospective Trial

16

Advanced solid tumors

Temsirolimus

63

Skeletal muscle index

44

56

Patients with higher grade toxicities tended to lose more body fat, suggesting a possible end-organ metabolic effect of temsirolimus

[116]

Gyawali et al./ /Japan/2016

Retrospective study

20

Breast/ Pancreatic Cancer

Everolimus/Temsirolimus

180

Body mass index, subcutaneous adipose tissue, visceral adipose tissue, skeletal muscle tissue

60

75

Long-term use of mTOR inhibitors induces a marked loss of muscle mass

[160]

The present study showed that a total of 58 studies (56.9%) were designed as retrospective analyses, and a high proportion of these retrospective studies was about cancer chemotherapy and sarcopenia (n = 22) (Tab. 1 and 2). Nearly an equal proportion of the reviewed studies were conducted among patients who suffered from oesophagogastric carcinoma received chemotherapy and non-small cell lung cancer patients received immunotherapy (NSCLC) (13.7%, 14.7%), respectively (Tab. 1, 3 and 4). Furthermore, platinum-based compounds represented the most common chemotherapeutic agents administered within the scope of chemotherapy and sarcopenia (13.7%) (Tab. 1 and 2); while both pembrolizumab and nivolumab represented the most common immune checkpoint inhibitors (15.7%) administered within the scope of immunotherapy and sarcopenia, as shown in Tables 1, 3 and 4.

Regarding the marker of body composition (a surrogate for skeletal muscle mass), skeletal muscle index was the high-ranked marker among the reviewed studies (63.7%), as following: chemotherapy (44.6%) and equal proportion for chemo-radiotherapy and immunotherapy (27.7%). The present study also showed that lower than half of the reviewed studies revealed a significant increase in the rate of sarcopenia (47%) following all cancer therapies (chemo-radio-and immunotherapy).

The direct toxic effects of chemotherapy on skeletal muscle metabolism and loss of muscle mass were reported in 13.7% of the studies, while studies that reported the impact of sarcopenia on a reduction in chemotherapy dosage or a delay in the administration of chemotherapeutic cycles was 10.8% and 7.8% for the administration of immunotherapy. A total of 11.8% of studies showed lowered overall survival by the coinciding impact of chemotherapy and sarcopenia and 14.7% by the coinciding impact of radiotherapy and sarcopenia (Tab. 1). Moreover, the outcomes of the reviewed studies derived from their findings which showed that 93.1% reported a significant negative correlation and prognosis related to the co-occurrence of sarcopenia and cancer therapy (chemo-radio-and immunotherapy) (Tab. 1).

Discussion

Cancer chemotherapy and sarcopenia

In this study, most of the reviewed studies were about the potential impact of cancer chemotherapy and sarcopenia. Chemotherapy immensely strains the body of malignancy patients, causing a more prominent consumption of energy and thus an expansion on the whole-cell catabolic cycles that, subsequently, sabotage tissue creation [16]. Malignancy is conceivably the most remarkable obsessive condition that advances muscle atrophy, especially in elderly patients. On the other hand, sarcopenia is prevalent in patients with various malignancies and the rate of its occurrence in cancer patients varies between 1174%. It has been recognized that cancer patients with sarcopenia have a poor prognosis regarding various malignancies, such as lung, stomach, pancreas, and colorectal cancers alongside different complications associated with cancer treatment [17, 18]. In addition, long-term outcomes and overall survival are significantly shorter while death rates are more frequently observed in cancer patients with sarcopenia submitted to oncological therapy [19], as reported in studies by Blauwhoff-Buskermolen et al. [20], Liu et al. [21], Ma et al. [22], Paireder et al. [23], Järvinen et al. [24], Choi et al. [25], Jung et al. [26], Miyamoto et al. [27], Derksen et al. [28], Go et al. [29], Prado et al. [30] and Rutten et al. [31].

There is also a direct toxic effect of chemotherapy on skeletal muscle metabolism and loss of muscle mass. This was reported in studies by Blauwhoff-Buskermolen et al. [20], Awad et al. [32], Yip et al. [33], Daly et al. [34], Guinan et al. [35], Cooper et al. [36], Benjamin et al. [37], Sandini et al. [38], Poterucha et al. [39], Eriksson et al. [40], Nattenmüller et al. [41], Goncalves et al. [42], Zargar et al. [43] and Rimar et al. [44].

During cancer chemotherapy, there is a progressive loss of skeletal muscle mass by 1.4 kg after 9 weeks of chemotherapy. In patients receiving systemic chemotherapy for colorectal cancer, deficiency of9 % muscle mass during 3 months was freely prescient of lower survival at 6 months. This might be related to uncontrolled muscle protein catabolism that is exaggerated as the tumour growth progresses [20, 45, 46]. As the amount of stored protein diminishes due to sarcopenia, the metabolism and immunity decline relatively to this, prompting an abatement in antitumor response and an increase in mortality [47].

Other possible contributing factors to aggressive loss of muscle mass secondary to low food intake are nausea, vomiting, diarrhoea, anorexia, and fatigue. This is induced by many chemotherapeutic agents particularly by platinum compounds, such as cisplatin, carboplatin, and oxipaltin [48], as also reported by the findings of the present study where platinum-based compounds represented the most common chemotherapeutic agents administered among the reviewed studies within the scope of chemotherapy and sarcopenia. Neuropathy and myalgia secondary to complications by taxanes chemotherapy might induce sarcopenia and skeletal muscle loss [49]. Moreover, cancer chemotherapy may also induce oxidative stress in skeletal muscle tissues through increase production of reactive oxygen species [50, 51], causing a reduction in muscle microvasculature through antiangiogenesis [52] and increase muscle catabolism secondary to the overproduction of tumour growth factors [50, 53].

Lower content of muscular fibres alongside a concomitant decrease of some metabolizing enzymes available in the skeletal muscle tissue could decrease the capability to metabolize some chemotherapeutic agents. An example of these enzymes is dihydropyrimidine dehydrogenase (DPD), which plays an important role in the catabolism of 5-Fluorouracil and capecitabine by converting fluoropyrimidines to inactive metabolites. On the other hand, patients with low lean body mass have poor tolerability and show more toxic adverse effects from anticancer drugs. This is related to a decreased volume of distribution of these agents which may lower the capacity for metabolizing anticancer [54]. Such patients are more prone to a reduction in chemotherapy dosage or a delay in the administration of chemotherapeutic cycles, as reported in studies by Ali et al. [54], Palmela et al. [55], Prado et al. [56], Barret et al. [57], Jung et al. [26], Kurk et al. [58], Go et al. [29], Prado et al. [30], Prado et al. [59], Mazzuca et al. [60], and Zargar et al. [43].

Skeletal muscle mass also decreases during neoadjuvant chemotherapy which might impair the prognosis for adjuvant therapy. Accordingly, maintaining muscle mass during chemotherapy administration is independently associated with disease stabilization and mortality reduction [21, 22, 61].

Literature reported that several molecular pathways have been recognized for muscle protein degradation and skeletal muscle depletion after cancer chemotherapy administration, such as dysregulation in energy metabolism, mitochondrion biogenesis, and dysregulation in muscle fibre metabolism following mitochondrial damage and reduced cytochrome C synthesis needed for oxidative phosphorylation and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1a) [26]. Mammalian Target Of Rapamycin (mTOR) inhibitors, such as everolimus and temsirolimus, involved insulin-like growth factor 1/ /phosphatidylinositol-3-kinase/PKBprotein kinase B)/ /mammalian target of rapamycin pathway in activating skeletal muscle synthesis [62].

Platinum compounds induced sarcopenia to include several pathways, such as ubiquitin-proteasome pathway (UPP) in the degradation of myofibrillar proteins; the autophagy-lysosome pathway (ALP) in the elimination of mitochondria, over-expression of pro-inflammatory cytokines (TNF-a) leading to the activation of the NF-kB pathway, activation of the myostatin pathway, phosphorylation of SMAD2, silences the IGF- 1/PI3K/Akt/mTOR anabolic pathway through the decreased phosphorylation of Akt and mTOR [63]. Doxorubicin and etoposide cause skeletal muscle depletion and muscle protein degradation and direct muscle loss through the activation of the NF-kB molecular pathway. This leads to up-regulation of ubiquitin and proteasomes, increasing the process of proteolysis and production of inflammatory cytokines (IL-1b, IL-6, and TNF-a) which in turn increase E3 ligases (atrogin-1), and the ubiquitin-protein binding for proteolysis [64–66].

Cancer radiotherapy and sarcopenia

Radiation restrains recovery and muscle hypertrophy by harming satellite cells. Radiation is thought to forestall satellite cell mitosis by causing breaks in strands of the cell’s DNA. If a break happens just on a single strand, the harm can be fixed by polymerases utilizing the correlative strand as a layout. If harm happens at a similar point on the two strands, the deletion may be irreparable which can prompt mitotic failure and cell death [67].

It has been reported that muscle damage and fibrosis are common and irreversible late effects of radiation on skeletal muscle tissue [68]. Radiotherapy is associated with a wide range of toxic effects that could further deteriorate the nutritional status of cancer patients, such as xerostomia, dysphagia, oral mucositis, oral pain, and sticky saliva [69–71]. Simultaneous chemotherapy and radiation are related to significant toxicities includ- ing mucositis, dysphagia, odynophagia, nausea, vomiting, anorexia, fatigue, and dysgeusia bringing about eating difficulty [72–74]. Lower content of muscular fibres, mass and strength are more likely to require radiation treatment breaks and suffer chemotherapy toxicity. These findings were reported in studies by Ganju et al. [73], Li et al. [75] and Panje et al. [76].

Moreover, numerous patients present with symptomatic tumours that lead to eating difficulty preceding the inception of treatment. Patients with HNC going through concurrent chemo-radiotherapy are regularly losing more than 5 % of their body weight in the 6 months around this therapy [77, 78]. To some extent, this has been exacerbated by a change in resting energy consumption, which assists the loss of lean body mass seen during and following treatment. Accordingly, malnutrition might be present nearly in 35-60%, weight loss in 10%, and sarcopenia in up to 70% among patients undergoing radiotherapy for HNC. Therefore, sarcopenia is associated with poor overall and disease-free survival [79], as presented in studies by Cho et al. [80], Mallet et al. [81], van Rijn-Dekker et al. [82], Thureau et al. [83], Sanders et al. [84], Shen et al. [85], Olson et al. [86], Ma et al. [87], Yoon et al. [88], Liang et al. [89], Lee et al. [90], Lin et al. [91], Park et al. [92], Kiyotoki et al. [93], and Pielkenrood et al. [94].

This expanded radiation-induced toxicity in sarcopenic patients contrarily impacts their quality of life since dysphagia altogether impacts the quality of life [95]. Furthermore, an earlier literature review showed that sarcopenia itself was related to an undeniable decrease in quality of life [96]. A recent study reported that sarcopenia is a powerful independent prognostic factor, related to an ascent of the general mortality in patients treated solely by radio-chemotherapy for locally advanced oesophageal cancer. Along these lines, the quality of life in this patient population may be influenced by both radiation-induced toxicities and sarcopenia [81].

Cancer immunotherapy and sarcopenia

The advancement of immune senescence with age is likely a result of many associating cytokine and hormonal adjustments. Increased age, muscle loss, and immune senescence are believed to be interlinked. Skeletal muscle is known to modulate the immune system by producing cytokines (myokines) such as interleukin (IL)- -15 and IL-6, and it has been proposed that sarcopenia causes a change in cytokine signalling which modifies immune cells to induce immune dysregulation and create pro-inflammatory conditions [97–99]. Changes in other immune cell populations, such as expanded myeloid-derived suppressor cells (MDSCs), that have been accounted for with increasing age may likewise be connected to skeletal muscle loss through changes production of myokines [100, 101]. Chronic inflammation within malignancy also adds to sarcopenia. For instance, a high serum level of IL-6, a pro-inflammatory cytokine adding to muscle catabolism, following PD-1 blockade was related to poor response [102, 103]. Therefore, combined blockade of IL-6 and PD-1/PD-L1 signalling exerts synergistic anti-tumour effects [104]. Furthermore, restricting T cell infiltration in the tumour due to transforming factor-b signalling, an immunosuppressive cytokine that additionally adds to sarcopenia [105, 106]. On the other hand, peroxisome proliferator-initiated receptor-gamma coactivator (PGC)-1a is a key factor created in the muscle that has fundamental negative impacts on the anti-tumour immune response. Along these lines, skeletal muscle loss may prompt expanded creation of TGF-b and IL-6, and diminished creation of PGC-1a and other myokines [107, 108], which might be related to poor response to PD-L1 blockade. Hence, sarcopenia has been related to poor outcomes or toxicity to tyrosine kinase inhibition, and to immune checkpoint inhibitors (ICIs), including programmed cells death 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab [109, 110]. This was evidenced in earlier studies by Heidelberger et al. [111], Daly et al. [112], Revel et al. [113], Heidelberger et al. [114], Massicotte et al. [115], and Veasey-Rodrigues et al. [116].

Sorafenib through multiple steps causes inhibition of PI3K, Akt, and mTOR which are directly involved in the activation of amino acid transporters and synthesis of muscle protein alongside inhibition of the physiologically activated pathways following the physical exercise involving RAF, MEK, and MAPK/ERK kinase. Moreover, it causes a reduction in muscle blood supply and substrates delivery to the muscle through antiangiogenesis properties [117]. The PD-1 inhibitors, such as nivolumab or pembrolizumab, block the PD-1/programmed death-ligand 1 (PD-L1) pathway by which malignancy cells escape immune recognition. Sarcopenic patients treated with nivolumab for non-small cell lung carcinoma (NSCLC) had more limited progression-free survival and overall survival [118]. Moreover, earlier studies found a significant relationship between sarcopenia, shorter progression-free survival, and lower response rate in NSCLC patients treated with PD-1 checkpoint inhibitors [110, 119]. A higher incidence of adverse events was also reported in sarcopenic melanoma patients treated with PD-1 inhibitors [111, 120] and ipilimumab [112].

Conclusions

Despite the high proportion of the reviewed studies that were retrospectively conducted, it was observed that the dual impact from coinciding potential complications of cancer therapy and sarcopenia are highlighted. Consequently, the evaluation of sarcopenia in cancer patients should be considered as a primary part of oncology care in cancer patients receiving diverse lines of cancer therapy.

Conflict of interest

All authors declare no conflicts of interest.

Funding

No funding was received for performing this research.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

References

  1. Santilli V. Clinical definition of sarcopenia. Clinical Cases in Mineral and Bone Metabolism. 2014, doi: 10.11138/ccmbm/2014.11.3.177.
  2. Rosenberg IH, Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997; 127(5 Suppl): 990S991S, doi: 10.1093/jn/127.5.990S, indexed in Pubmed: 9164280.
  3. Muscaritoli M, Anker SD, Argilés J, et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr. 2010; 29(2): 154159, doi: 10.1016/j.clnu.2009.12.004, indexed in Pubmed: 20060626.
  4. Kenis C, Decoster L, Van Puyvelde K, et al. Performance of two geriatric screening tools in older patients with cancer. J Clin Oncol. 2014; 32(1): 1926, doi: 10.1200/JCO.2013.51.1345, indexed in Pubmed: 24276775.
  5. 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(4): 412423, doi: 10.1093/ageing/afq034, indexed in Pubmed: 20392703.
  6. Kwan P, Kwan P. Sarcopenia, a neurogenic syndrome? J Aging Res. 2013; 2013: 791679, doi: 10.1155/2013/791679, indexed in Pubmed: 23577254.
  7. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012; 8(8): 457465, doi: 10.1038/nrendo.2012.49, indexed in Pubmed: 22473333.
  8. Quinn LS. Interleukin-15: a muscle-derived cytokine regulating fat-to-lean body composition. J Anim Sci. 2008; 86(14 Suppl): E75E83, doi: 10.2527/jas.2007-0458, indexed in Pubmed: 17709786.
  9. Lutz CT, Quinn LS. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism. Aging (Albany NY). 2012; 4(8): 535546, doi: 10.18632/aging.100482, indexed in Pubmed: 22935594.
  10. Roy P, Chowdhury S, Roy HK. Exercise-induced myokines as emerging therapeutic agents in colorectal cancer prevention and treatment. Future Oncol. 2018; 14(4): 309312, doi: 10.2217/fon-2017-0555, indexed in Pubmed: 29318900.
  11. Steensberg A, Fischer CP, Keller C, et al. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003; 285(2): E433E437, doi: 10.1152/ajpendo.00074.2003, indexed in Pubmed: 12857678.
  12. Lin JX, Lin JP, Xie JW, et al. Prognostic Value and Association of Sarcopenia and Systemic Inflammation for Patients with Gastric Cancer Following Radical Gastrectomy. Oncologist. 2019; 24(11): e1091e1101, doi: 10.1634/theoncologist.2018-0651, indexed in Pubmed: 30910865.
  13. Patel HJ, Patel BM. TNF-a and cancer cachexia: Molecular insights and clinical implications. Life Sci. 2017; 170: 5663, doi: 10.1016/j.lfs.2016.11.033, indexed in Pubmed: 27919820.
  14. Janssen I, Shepard DS, Katzmarzyk PT, et al. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 2004; 52(1): 8085, doi: 10.1111/j.1532-5415.2004.52014.x, indexed in Pubmed: 14687319.
  15. Gale CR, Martyn CN, Cooper C, et al. Grip strength, body composition, and mortality. Int J Epidemiol. 2007; 36(1): 228235, doi: 10.1093/ije/dyl224, indexed in Pubmed: 17056604.
  16. Zargar H, Almassi N, Kovac E, et al. Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Bladder Cancer. 2017; 3(1): 5763, doi: 10.3233/BLC-160080, indexed in Pubmed: 28149936.
  17. Shachar SS, Williams GR, Muss HB, et al. Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review. Eur J Cancer. 2016; 57: 5867, doi: 10.1016/j.ejca.2015.12.030, indexed in Pubmed: 26882087.
  18. Levolger S, van Vugt JLA, de Bruin RWF, et al. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg. 2015; 102(12): 14481458, doi: 10.1002/bjs.9893, indexed in Pubmed: 26375617.
  19. Kawamura T, Makuuchi R, Tokunaga M, et al. Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia. Ann Surg Oncol. 2018; 25(6): 16251632, doi: 10.1245/s10434-018-6452-3, indexed in Pubmed: 29633095.
  20. Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MAE, et al. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2016; 34(12): 13391344, doi: 10.1200/JCO.2015.63.6043, indexed in Pubmed: 26903572.
  21. Liu J, Motoyama S, Sato Y, et al. Decreased Skeletal Muscle Mass After Neoadjuvant Therapy Correlates with Poor Prognosis in Patients with Esophageal Cancer. Anticancer Res. 2016; 36(12): 66776685, doi: 10.21873/anticanres.11278, indexed in Pubmed: 27920002.
  22. Ma DW, Cho Y, Jeon MJ, et al. Relationship Between Sarcopenia and Prognosis in Patient With Concurrent Chemo-Radiation Therapy for Esophageal Cancer. Front Oncol. 2019; 9: 366, doi: 10.3389/fonc.2019.00366, indexed in Pubmed: 31139564.
  23. Paireder M, Asari R, Kristo I, et al. Impact of sarcopenia on outcome in patients with esophageal resection following neoadjuvant chemotherapy for esophageal cancer. Eur J Surg Oncol. 2017; 43(2): 478484, doi: 10.1016/j.ejso.2016.11.015, indexed in Pubmed: 28024944.
  24. Järvinen T, Ilonen I, Kauppi J, et al. Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study. World J Surg Oncol. 2018; 16(1): 27, doi: 10.1186/s12957-018-1327-4, indexed in Pubmed: 29433514.
  25. Choi Y, Oh DY, Kim TY, et al. Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index. PLoS One. 2015; 10(10): e0139749, doi: 10.1371/journal.pone.0139749, indexed in Pubmed: 26437072.
  26. Jung HW, Kim JW, Kim JY, et al. Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Support Care Cancer. 2015; 23(3): 687694, doi: 10.1007/s00520-014-2418-6, indexed in Pubmed: 25163434.
  27. Miyamoto Y, Baba Y, Sakamoto Y, et al. Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer. PLoS One. 2015; 10(6): e0129742, doi: 10.1371/journal.pone.0129742, indexed in Pubmed: 26069972.
  28. Derksen JWG, Kurk SA, Oskam MJ, et al. Factors Contributing to Cancer-Related Muscle Wasting During First-Line Systemic Treatment for Metastatic Colorectal Cancer. JNCI Cancer Spectr. 2019; 3(2): pkz014, doi: 10.1093/jncics/pkz016, indexed in Pubmed: 31360897.
  29. Go SI, Park MiJ, Song HN, et al. Sarcopenia and inflammation are independent predictors of survival in male patients newly diagnosed with small cell lung cancer. Support Care Cancer. 2016; 24(5): 20752084, doi: 10.1007/s00520-015-2997-x, indexed in Pubmed: 26546456.
  30. Prado CMM, Baracos VE, McCargar LJ, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009; 15(8): 29202926, doi: 10.1158/1078-0432.CCR-08-2242, indexed in Pubmed: 19351764.
  31. Rutten IJG, van Dijk DPJ, Kruitwagen RF, et al. Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients. J Cachexia Sarcopenia Muscle. 2016; 7(4): 458466, doi: 10.1002/jcsm.12107, indexed in Pubmed: 27030813.
  32. Awad S, Tan BH, Cui H, et al. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr. 2012; 31(1): 7477, doi: 10.1016/j.clnu.2011.08.008, indexed in Pubmed: 21875767.
  33. Yip C, Goh V, Davies A, et al. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol. 2014; 24(5): 9981005, doi: 10.1007/s00330-014-3110-4, indexed in Pubmed: 24535076.
  34. Daly LE, Ní Bhuachalla ÉB, Power DG, et al. Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer. J Cachexia Sarcopenia Muscle. 2018; 9(2): 315325, doi: 10.1002/jcsm.12267, indexed in Pubmed: 29318756.
  35. Guinan EM, Doyle SL, Bennett AE, et al. Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance. Support Care Cancer. 2018; 26(5): 15691576, doi: 10.1007/s00520-017-3993-0, indexed in Pubmed: 29197960.
  36. Cooper AB, Slack R, Fogelman D, et al. Characterization of Anthropometric Changes that Occur During Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer. Ann Surg Oncol. 2015; 22(7): 24162423, doi: 10.1245/s10434-014-4285-2, indexed in Pubmed: 25519927.
  37. Benjamin AJ, Buschmann MM, Zhang SQ, et al. The impact of changes in radiographic sarcopenia on overall survival in older adults undergoing different treatment pathways for pancreatic cancer. J Geriatr Oncol. 2018; 9(4): 367372, doi: 10.1016/j.jgo.2018.03.002, indexed in Pubmed: 29534880.
  38. Sandini M, Patino M, Ferrone CR, et al. Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer. JAMA Surg. 2018; 153(9): 809815, doi: 10.1001/jamasurg.2018.0979, indexed in Pubmed: 29801062.
  39. Poterucha T, Burnette B, Jatoi A. A decline in weight and attrition of muscle in colorectal cancer patients receiving chemotherapy with bevacizumab. Med Oncol. 2012; 29(2): 10051009, doi: 10.1007/s12032-011-9894-z, indexed in Pubmed: 21399996.
  40. Eriksson S, Nilsson JH, Strandberg Holka P, et al. The impact of neoadjuvant chemotherapy on skeletal muscle depletion and preoperative sarcopenia in patients with resectable colorectal liver metastases. HPB (Oxford). 2017; 19(4): 331337, doi: 10.1016/j.hpb.2016.11.009, indexed in Pubmed: 28089364.
  41. Nattenmüller J, Wochner R, Muley T, et al. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line- -Chemotherapy in Lung Cancer Patients. PLoS One. 2017; 12(1): e0169136, doi: 10.1371/journal.pone.0169136, indexed in Pubmed: 28107410.
  42. Goncalves MD, Taylor S, Halpenny DF, et al. Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer. Clin Radiol. 2018; 73(5): 505.e1505.e8, doi: 10.1016/j.crad.2017.12.004, indexed in Pubmed: 29317048.
  43. Zargar H, Almassi N, Kovac E, et al. Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Bladder Cancer. 2017; 3(1): 5763, doi: 10.3233/BLC-160080, indexed in Pubmed: 28149936.
  44. Rimar KJ, Glaser AP, Kundu S, et al. Changes in Lean Muscle Mass Associated with Neoadjuvant Platinum-Based Chemotherapy in Patients with Muscle Invasive Bladder Cancer. Bladder Cancer. 2018; 4(4): 411418, doi: 10.3233/BLC-180188, indexed in Pubmed: 30417052.
  45. Prado CMM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008; 9(7): 629635, doi: 10.1016/S1470-2045(08)70153-0, indexed in Pubmed: 18539529.
  46. Stene GB, Helbostad JL, Amundsen T, et al. Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer. Acta Oncol. 2015; 54(3): 340348, doi: 10.3109/0284186X.2014.953259, indexed in Pubmed: 25225010.
  47. Englesbe MJ, Patel SP, He K, et al. Sarcopenia and mortality after liver transplantation. J Am Coll Surg. 2010; 211(2): 271278, doi: 10.1016/j.jamcollsurg.2010.03.039, indexed in Pubmed: 20670867.
  48. Garcia JM, Scherer T, Chen Ja, et al. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology. 2013; 154(9): 31183129, doi: 10.1210/en.2013-1179, indexed in Pubmed: 23832960.
  49. Rier HN, Jager A, Sleijfer S, et al. Changes in body composition and muscle attenuation during taxane-based chemotherapy in patients with metastatic breast cancer. Breast Cancer Res Treat. 2018; 168(1): 95–105, doi: 10.1007/s10549-017-4574-0, indexed in Pubmed: 29147870.
  50. Chen JA, Splenser A, Guillory B, et al. Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved. J Cachexia Sarcopenia Muscle. 2015; 6(2): 132143, doi: 10.1002/jcsm.12023, indexed in Pubmed: 26136189.
  51. Gilliam LAA, St Clair DK. Chemotherapy-induced weakness and fatigue in skeletal muscle: the role of oxidative stress. Antioxid Redox Signal. 2011; 15(9): 25432563, doi: 10.1089/ars.2011.3965, indexed in Pubmed: 21457105.
  52. Barreto R, Waning DL, Gao H, et al. Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. Oncotarget. 2016; 7(28): 4344243460, doi: 10.18632/oncotarget.9779, indexed in Pubmed: 27259276.
  53. Chen JL, Colgan TD, Walton KL, et al. The TGF-b Signalling Network in Muscle Development, Adaptation and Disease. Adv Exp Med Biol. 2016; 900: 97131, doi: 10.1007/978-3-319-27511-6_5, indexed in Pubmed: 27003398.
  54. Ali R, Baracos VE, Sawyer MB, et al. Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens. Cancer Med. 2016; 5(4): 607616, doi: 10.1002/cam4.621, indexed in Pubmed: 26814378.
  55. Palmela C, Velho S, Agostinho L, et al. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer. J Gastric Cancer. 2017; 17(1): 7487, doi: 10.5230/jgc.2017.17.e8, indexed in Pubmed: 28337365.
  56. Prado CMM, Baracos VE, McCargar LJ, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007; 13(11): 32643268, doi: 10.1158/1078-0432.CCR-06-3067, indexed in Pubmed: 17545532.
  57. Barret M, Antoun S, Dalban C, et al. Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer. Nutr Cancer. 2014; 66(4): 583589, doi: 10.1080/01635581.2014.894103, indexed in Pubmed: 24707897.
  58. Kurk S, Peeters P, Stellato R, et al. Skeletal muscle mass loss and dose- -limiting toxicities in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2019; 10(4): 803813, doi: 10.1002/jcsm.12436, indexed in Pubmed: 31094083.
  59. Prado CMM, Lima ISF, Baracos VE, et al. An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity. Cancer Chemother Pharmacol. 2011; 67(1): 93101, doi: 10.1007/s00280-010-1288-y, indexed in Pubmed: 20204364.
  60. Mazzuca F, Onesti CE, Roberto M, et al. Lean body mass wasting and toxicity in early breast cancer patients receiving anthracyclines. Oncotarget. 2018; 9(39): 2571425722, doi: 10.18632/oncotarget.25394, indexed in Pubmed: 29876019.
  61. Kodera Y. More than 6 months of postoperative adjuvant chemotherapy results in loss of skeletal muscle: a challenge to the current standard of care. Gastric Cancer. 2015; 18(2): 203204, doi: 10.1007/s10120-014-0381-z, indexed in Pubmed: 24820695.
  62. Pin F, Barreto R, Couch ME, et al. Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism. J Cachexia Sarcopenia Muscle. 2019; 10(1): 140154, doi: 10.1002/jcsm.12360, indexed in Pubmed: 30680954.
  63. Moreira-Pais A, Ferreira R, Gil da Costa R. Platinum-induced muscle wasting in cancer chemotherapy: Mechanisms and potential targets for therapeutic intervention. Life Sci. 2018; 208: 19, doi: 10.1016/j.lfs.2018.07.010, indexed in Pubmed: 30146014.
  64. Nissinen TA, Degerman J, Räsänen M, et al. Systemic blockade of ACVR2B ligands prevents chemotherapy-induced muscle wasting by restoring muscle protein synthesis without affecting oxidative capacity or atrogenes. Sci Rep. 2016; 6: 32695, doi: 10.1038/srep32695, indexed in Pubmed: 27666826.
  65. Van Gammeren D, Damrauer JS, Jackman RW, et al. The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy. FASEB J. 2009; 23(2): 362370, doi: 10.1096/fj.08-114249, indexed in Pubmed: 18827022.
  66. Hiensch AE, Bolam KA, Mijwel S, et al. Doxorubicin-induced skeletal muscle atrophy: Elucidating the underlying molecular pathways. Acta Physiol (Oxf). 2020; 229(2): e13400, doi: 10.1111/apha.13400, indexed in Pubmed: 31600860.
  67. Denekamp J, Rojas A. Cell kinetics and radiation pathology. Experientia. 1989; 45(1): 3341, doi: 10.1007/BF01990450, indexed in Pubmed: 2643525.
  68. Lefaix JL, Delanian S, Leplat JJ, et al. [Radiation-induced cutaneo-muscular fibrosis (III): major therapeutic efficacy of liposomal Cu/Zn superoxide dismutase]. Bull Cancer. 1993; 80(9): 799807, indexed in Pubmed: 8204958.
  69. Al-Taie A, Al-Shohani AD, Albasry Z, et al. Current topical trends and novel therapeutic approaches and delivery systems for oral mucositis management. J Pharm Bioallied Sci. 2020; 12(2): 94101, doi: 10.4103/jpbs.JPBS_198_19, indexed in Pubmed: 32742107.
  70. Sroussi HY, Epstein JB, Bensadoun RJ, et al. Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 2017; 6(12): 29182931, doi: 10.1002/cam4.1221, indexed in Pubmed: 29071801.
  71. Arribas L, Hurtós L, Taberna M, et al. Nutritional changes in patients with locally advanced head and neck cancer during treatment. Oral Oncol. 2017; 71: 6774, doi: 10.1016/j.oraloncology.2017.06.003, indexed in Pubmed: 28688694.
  72. Alshadwi A, Nadershah M, Carlson ER, et al. Nutritional considerations for head and neck cancer patients: a review of the literature. J Oral Maxillofac Surg. 2013; 71(11): 18531860, doi: 10.1016/j.joms.2013.04.028, indexed in Pubmed: 23845698.
  73. Ganju RG, Morse R, Hoover A, et al. The impact of sarcopenia on tolerance of radiation and outcome in patients with head and neck cancer receiving chemoradiation. Radiother Oncol. 2019; 137: 117124, doi: 10.1016/j.radonc.2019.04.023, indexed in Pubmed: 31085391.
  74. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003; 349(22): 20912098, doi: 10.1056/NEJMoa031317, indexed in Pubmed: 14645636.
  75. Li G, Jiang XY, Qiu Bo, et al. Vicious circle of acute radiation toxicities and weight loss predicts poor prognosis for nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy. J Cancer. 2017; 8(5): 832838, doi: 10.7150/jca.17458, indexed in Pubmed: 28382146.
  76. Panje CM, Höng L, Hayoz S, et al. Swiss Group for Clinical Cancer Research (SAKK). Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy. Radiat Oncol. 2019; 14(1): 166, doi: 10.1186/s13014-019-1372-3, indexed in Pubmed: 31511012.
  77. Lønbro S, Petersen GB, Andersen JR, et al. Prediction of critical weight loss during radiation treatment in head and neck cancer patients is dependent on BMI. Support Care Cancer. 2016; 24(5): 21012109, doi: 10.1007/s00520-015-2999-8, indexed in Pubmed: 26553031.
  78. Ghadjar P, Hayoz S, Zimmermann F, et al. Swiss Group for Clinical Cancer Research (SAKK). Impact of weight loss on survival after chemoradiation for locally advanced head and neck cancer: secondary results of a randomized phase III trial (SAKK 10/94). Radiat Oncol. 2015; 10: 21, doi: 10.1186/s13014-014-0319-y, indexed in Pubmed: 25679310.
  79. Chargi N, Bril SI, de Jong PA, et al. Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer. Eur Arch Otorhinolaryngol. 2019; 276(5): 14751486, doi: 10.1007/s00405-019-05361-4, indexed in Pubmed: 30830300.
  80. Cho Y, Kim JW, Keum KiC, et al. Prognostic Significance of Sarcopenia With Inflammation in Patients With Head and Neck Cancer Who Underwent Definitive Chemoradiotherapy. Front Oncol. 2018; 8: 457, doi: 10.3389/fonc.2018.00457, indexed in Pubmed: 30460194.
  81. Mallet R, Modzelewski R, Lequesne J, et al. Prognostic value of sarcopenia in patients treated by Radiochemotherapy for locally advanced oesophageal cancer. Radiat Oncol. 2020; 15(1): 116, doi: 10.1186/s13014-020-01545-z, indexed in Pubmed: 32443967.
  82. 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: 103110, doi: 10.1016/j.radonc.2020.03.014, indexed in Pubmed: 32251949.
  83. Thureau S, Lebret L, Lequesne J, et al. Prospective Evaluation of Sarcopenia in Head and Neck Cancer Patients Treated with Radiotherapy or Radiochemotherapy. Cancers (Basel). 2021; 13(4), doi: 10.3390/cancers13040753, indexed in Pubmed: 33670339.
  84. Sanders KJC, Hendriks LE, Troost EGC, et al. Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC. J Thorac Oncol. 2016; 11(6): 873879, doi: 10.1016/j.jtho.2016.02.013, indexed in Pubmed: 26940529.
  85. Shen LJ, Chen C, Li BF, et al. High weight loss during radiation treatment changes the prognosis in under-/normal weight nasopharyngeal carcinoma patients for the worse: a retrospective analysis of 2433 cases. PLoS One. 2013; 8(7): e68660, doi: 10.1371/journal.pone.0068660, indexed in Pubmed: 23869226.
  86. Olson B, Edwards J, Stone L, et al. Association of Sarcopenia With Oncologic Outcomes of Primary Surgery or Definitive Radiotherapy Among Patients With Localized Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. 2020; 146(8): 714722, doi: 10.1001/jamaoto.2020.1154, indexed in Pubmed: 32525518.
  87. Ma DW, Cho Y, Jeon MJ, et al. Relationship Between Sarcopenia and Prognosis in Patient With Concurrent Chemo-Radiation Therapy for Esophageal Cancer. Front Oncol. 2019; 9: 366, doi: 10.3389/fonc.2019.00366, indexed in Pubmed: 31139564.
  88. Yoon HG, Oh D, Ahn YC, et al. Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer. Cancers (Basel). 2020; 12(4), doi: 10.3390/cancers12040925, indexed in Pubmed: 32290037.
  89. Liang H, Peng H, Chen L. Prognostic Value of Sarcopenia and Systemic Inflammation Markers in Patients Undergoing Definitive Radiotherapy for Esophageal Cancer. Cancer Manag Res. 2021; 13: 181192, doi: 10.2147/CMAR.S288522, indexed in Pubmed: 33469362.
  90. Lee J, Cho Y, Park S, et al. Skeletal Muscle Depletion Predicts the Prognosis of Patients With Hepatocellular Carcinoma Treated With Radiotherapy. Front Oncol. 2019; 9: 1075, doi: 10.3389/fonc.2019.01075, indexed in Pubmed: 31681607.
  91. Lin J, Peng J, Qdaisat A, et al. Severe weight loss during preoperative chemoradiotherapy compromises survival outcome for patients with locally advanced rectal cancer. J Cancer Res Clin Oncol. 2016; 142(12): 2551––2560, doi: 10.1007/s00432-016-2225-1, indexed in Pubmed: 27613188.
  92. Park SEe, Hwang InG, Choi CH, et al. Sarcopenia is poor prognostic factor in older patients with locally advanced rectal cancer who received preoperative or postoperative chemoradiotherapy. Medicine (Baltimore). 2018; 97(48): e13363, doi: 10.1097/MD.0000000000013363, indexed in Pubmed: 30508928.
  93. Kiyotoki T, Nakamura K, Haraga J, et al. Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy. Int J Gynecol Cancer. 2018; 28(1): 168175, doi: 10.1097/IGC.0000000000001127, indexed in Pubmed: 29040185.
  94. Pielkenrood BJ, van Urk PR, van der Velden JM, et al. Impact of body fat distribution and sarcopenia on the overall survival in patients with spinal metastases receiving radiotherapy treatment: a prospective cohort study. Acta Oncol. 2020; 59(3): 291297, doi: 10.1080/0284186X.2019.1693059, indexed in Pubmed: 31760850.
  95. Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, et al. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol. 2008; 26(22): 37703776, doi: 10.1200/JCO.2007.14.6647, indexed in Pubmed: 18669465.
  96. Tsekoura M, Kastrinis A, Katsoulaki M, et al. Sarcopenia and Its Impact on Quality of Life. Adv Exp Med Biol. 2017; 987: 213218, doi: 10.1007/978-3-319-57379-3_19, indexed in Pubmed: 28971460.
  97. Elias R, Hartshorn K, Rahma O, et al. Aging, immune senescence, and immunotherapy: A comprehensive review. Semin Oncol. 2018; 45(4): 187200, doi: 10.1053/j.seminoncol.2018.08.006, indexed in Pubmed: 30539714.
  98. Pawelec G, Derhovanessian E, Larbi A. Immunosenescence and cancer. Crit Rev Oncol/Hematol. 2010; 75(2): 165172, doi: 10.1615/critrevoncog.2013010597.
  99. Pedersen BK. Muscles and their myokines. J Exp Biol. 2011; 214(Pt 2): 337346, doi: 10.1242/jeb.048074, indexed in Pubmed: 21177953.
  100. Nagaraj S, Gabrilovich DI. Myeloid-derived suppressor cells in human cancer. Cancer J. 2010; 16(4): 348353, doi: 10.1097/PPO.0b013e3181eb3358, indexed in Pubmed: 20693846.
  101. Verschoor CP, Johnstone J, Millar J, et al. Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol. 2013; 93(4): 633637, doi: 10.1189/jlb.0912461, indexed in Pubmed: 23341539.
  102. Londhe P, Guttridge DC. Inflammation induced loss of skeletal muscle. Bone. 2015; 80: 131142, doi: 10.1016/j.bone.2015.03.015, indexed in Pubmed: 26453502.
  103. Tsukamoto H, Fujieda K, Miyashita A, et al. Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment. Cancer Res. 2018; 78(17): 50115022, doi: 10.1158/0008-5472.CAN-18-0118, indexed in Pubmed: 29967259.
  104. Kim EY, Lee HY, Kim YS, et al. Prognostic Significance of CT-Determined Sarcopenia in Patients with Small-Cell Lung Cancer. J Thorac Oncol. 2015; 10(12): 17951799, doi: 10.1097/JTO.0000000000000690, indexed in Pubmed: 26484630.
  105. Ábrigo J, Campos F, Simon F, et al. TGF-b requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy. Biol Chem. 2018; 399(3): 253264, doi: 10.1515/hsz-2017-0217, indexed in Pubmed: 29140787.
  106. Mariathasan S, Turley SJ, Nickles D, et al. TGFb attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693): 544548, doi: 10.1038/nature25501, indexed in Pubmed: 29443960.
  107. Suzuki Y, Okamoto T, Fujishita T, et al. Clinical implications of sarcopenia in patients undergoing complete resection for early non-small cell lung cancer. Lung Cancer. 2016; 101: 9297, doi: 10.1016/j.lungcan.2016.08.007, indexed in Pubmed: 27794415.
  108. Wherry EJ. T cell exhaustion. Nat Immunol. 2011; 12(6): 492499, doi: 10.1038/ni.2035, indexed in Pubmed: 21739672.
  109. Mir O, Coriat R, Blanchet B, et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One. 2012; 7(5): e37563, doi: 10.1371/journal.pone.0037563, indexed in Pubmed: 22666367.
  110. Nishioka N, Uchino J, Hirai S, et al. Association of Sarcopenia with and Efficacy of Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer. J Clin Med. 2019; 8(4), doi: 10.3390/jcm8040450, indexed in Pubmed: 30987236.
  111. Heidelberger V, Goldwasser F, Kramkimel N, et al. Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients. Invest New Drugs. 2017; 35(4): 436441, doi: 10.1007/s10637-017-0464-x, indexed in Pubmed: 28396974.
  112. Daly LE, Power DG, O’Reilly Á, et al. The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma. Br J Cancer. 2017; 116(3): 310317, doi: 10.1038/bjc.2016.431, indexed in Pubmed: 28072766.
  113. Revel MP, Raynard B, Pigneur F, et al. Sarcopenia and toxicity of the anti-PD1 inhibitors in real-life lung cancer patients: Results from the French Nationwide SCAN study. J Clin Oncol. 2018; 36(15_suppl): e21066e21066, doi: 10.1200/jco.2018.36.15_suppl.e21066.
  114. Heidelberger V, Kramkimel N, Huillard O, et al. Sarcopenia associated with a body mass index (BMI) > 25 kg/m2 predicts severe acute toxicity of nivolumab and pembrolizumab in melanoma patients. Ann Oncol. 2016; 27: vi387, doi: 10.1093/annonc/mdw379.25.
  115. Massicotte MH, Borget I, Broutin S, et al. Body composition variation and impact of low skeletal muscle mass in patients with advanced medullary thyroid carcinoma treated with vandetanib: results from a placebo-controlled study. J Clin Endocrinol Metab. 2013; 98(6): 24012408, doi: 10.1210/jc.2013-1115, indexed in Pubmed: 23543666.
  116. Veasey-Rodrigues H, Parsons HA, Janku F, et al. A pilot study of temsirolimus and body composition. J Cachexia Sarcopenia Muscle. 2013; 4(4): 259265, doi: 10.1007/s13539-013-0113-y, indexed in Pubmed: 23893509.
  117. Bozzetti F. Chemotherapy-Induced Sarcopenia. Curr Treat Options Oncol. 2020; 21(1): 7, doi: 10.1007/s11864-019-0691-9, indexed in Pubmed: 32002684.
  118. Cortellini A, Verna L, Porzio G, et al. Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non-small cell lung cancer patients: A “hypothesis-generator” preliminary report. Thorac Cancer. 2019; 10(2): 347351, doi: 10.1111/1759-7714.12965, indexed in Pubmed: 30600905.
  119. Shiroyama T, Nagatomo I, Koyama S, et al. Impact of sarcopenia in patients with advanced non-small cell lung cancer treated with PD-1 inhibitors: A preliminary retrospective study. Sci Rep. 2019; 9(1): 2447, doi: 10.1038/s41598-019-39120-6, indexed in Pubmed: 30792455.
  120. Kano M, Hihara J, Tokumoto N, et al. Association between skeletal muscle loss and the response to nivolumab immunotherapy in advanced gastric cancer patients. Int J Clin Oncol. 2021; 26(3): 523531, doi: 10.1007/s10147-020-01833-4, indexed in Pubmed: 33226523.
  121. Reisinger KW, Bosmans JW, Uittenbogaart M, et al. Loss of Skeletal Muscle Mass During Neoadjuvant Chemoradiotherapy Predicts Postoperative Mortality in Esophageal Cancer Surgery. Ann Surg Oncol. 2015; 22(13): 44454452, doi: 10.1245/s10434-015-4558-4, indexed in Pubmed: 25893413.
  122. Elliott JA, Doyle SL, Murphy CF, et al. Sarcopenia: Prevalence, and Impact on Operative and Oncologic Outcomes in the Multimodal Management of Locally Advanced Esophageal Cancer. Ann Surg. 2017; 266(5): 822830, doi: 10.1097/SLA.0000000000002398, indexed in Pubmed: 28796017.
  123. Dijksterhuis WPM, Pruijt MJ, van der Woude SO, et al. Association between body composition, survival, and toxicity in advanced esophagogastric cancer patients receiving palliative chemotherapy. J Cachexia Sarcopenia Muscle. 2019; 10(1): 199206, doi: 10.1002/jcsm.12371, indexed in Pubmed: 30666831.
  124. Ota T, Ishikawa T, Endo Y, et al. Skeletal muscle mass as a predictor of the response to neo-adjuvant chemotherapy in locally advanced esophageal cancer. Med Oncol. 2019; 36(2): 15, doi: 10.1007/s12032-018-1242-0, indexed in Pubmed: 30600347.
  125. Voisinet M, Venkatasamy A, Alratrout H, et al. How to Prevent Sarcopenia Occurrence during Neoadjuvant Chemotherapy for Oesogastric Adenocarcinoma? Nutr Cancer. 2021; 73(5): 802808, doi: 10.1080/01635581.2020.1770813, indexed in Pubmed: 32449415.
  126. Dalal S, Hui D, Bidaut L, et al. Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study. J Pain Symptom Manage. 2012; 44(2): 181191, doi: 10.1016/j.jpainsymman.2011.09.010, indexed in Pubmed: 22695045.
  127. Fogelman DR, Holmes H, Mohammed K, et al. Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer? J Cachexia Sarcopenia Muscle. 2014; 5(4): 307313, doi: 10.1007/s13539-014-0145-y, indexed in Pubmed: 24740741.
  128. Antoun S, Bayar MA, Dyevre V, et al. No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer. BMC Cancer. 2019; 19(1): 847, doi: 10.1186/s12885-019-6086-2, indexed in Pubmed: 31462288.
  129. Kobayashi T, Kawai H, Nakano O, et al. Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies. BMC Cancer. 2018; 18(1): 756, doi: 10.1186/s12885-018-4673-2, indexed in Pubmed: 30041616.
  130. Atlan P, Bayar MA, Lanoy E, et al. Factors which modulate the rates of skeletal muscle mass loss in non-small cell lung cancer patients: a pilot study. Support Care Cancer. 2017; 25(11): 33653373, doi: 10.1007/s00520-017-3755-z, indexed in Pubmed: 28593463.
  131. Kakinuma K, Tsuruoka H, Morikawa K, et al. Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. Thorac Cancer. 2018; 9(1): 99104, doi: 10.1111/1759-7714.12545, indexed in Pubmed: 29067769.
  132. Xiao DY, Luo S, O’Brian K, et al. Longitudinal Body Composition Changes in Diffuse Large B-cell Lymphoma Survivors: A Retrospective Cohort Study of United States Veterans. J Natl Cancer Inst. 2016; 108(11), doi: 10.1093/jnci/djw145, indexed in Pubmed: 27381623.
  133. Grossberg AJ, Chamchod S, Fuller CD, et al. Association of Body Composition With Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma. JAMA Oncol. 2016; 2(6): 782789, doi: 10.1001/jamaoncol.2015.6339, indexed in Pubmed: 26891703.
  134. Chauhan NS, Samuel SR, Meenar N, et al. Sarcopenia in male patients with head and neck cancer receiving chemoradiotherapy: a longitudinal pilot study. PeerJ. 2020; 8: e8617, doi: 10.7717/peerj.8617, indexed in Pubmed: 32149024.
  135. Op den Kamp CMH, De Ruysscher DKM, van den Heuvel M, et al. Early body weight loss during concurrent chemo-radiotherapy for non-small cell lung cancer. J Cachexia Sarcopenia Muscle. 2014; 5(2): 127137, doi: 10.1007/s13539-013-0127-5, indexed in Pubmed: 24452446.
  136. Kiss N, Beraldo J, Everitt S. Early Skeletal Muscle Loss in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation and Relationship to Survival. Support Care Cancer. 2019; 27(7): 26572664, doi: 10.1007/s00520-018-4563-9, indexed in Pubmed: 30478673.
  137. Murimwa GZ, Venkat PS, Jin W, et al. Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery. J Gastrointest Oncol. 2017; 8(5): 808815, doi: 10.21037/jgo.2017.06.11, indexed in Pubmed: 29184684.
  138. Shiba S, Shibuya K, Katoh H, et al. No Deterioration in Clinical Outcomes of Carbon Ion Radiotherapy for Sarcopenia Patients with Hepatocellular Carcinoma. Anticancer Res. 2018; 38(6): 35793586, doi: 10.21873/anticanres.12631, indexed in Pubmed: 29848713.
  139. Matsubara Y, Nakamura K, Matsuoka H, et al. Sarcopenia Is Not a Prognostic Factor of Outcome in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy. Anticancer Res. 2019; 39(2): 933939, doi: 10.21873/anticanres.13196, indexed in Pubmed: 30711978.
  140. Couderc AL, Muracciole X, Nouguerede E, et al. HoSAGE: Sarcopenia in Older Patients before and after Treatment with Androgen Deprivation Therapy and Radiotherapy for Prostate Cancer. J Nutr Health Aging. 2020; 24(2): 205209, doi: 10.1007/s12603-019-1294-7, indexed in Pubmed: 32003412.
  141. Ferini G, Cacciola A, Parisi S, et al. Curative Radiotherapy in Elderly Patients With Muscle Invasive Bladder Cancer: The Prognostic Role of Sarcopenia. In Vivo. 2021; 35(1): 571578, doi: 10.21873/invivo.12293, indexed in Pubmed: 33402511.
  142. Zhang G, Li X, Sui C, et al. Incidence and risk factor analysis for sarcopenia in patients with cancer. Oncol Lett. 2016; 11(2): 12301234, doi: 10.3892/ol.2015.4019, indexed in Pubmed: 26893724.
  143. Magri V, Gottfried T, Di Segni M, et al. Correlation of body composition by computerized tomography and metabolic parameters with survival of nivolumab-treated lung cancer patients. Cancer Manag Res. 2019; 11: 82018207, doi: 10.2147/CMAR.S210958, indexed in Pubmed: 31564979.
  144. Popinat G, Cousse S, Goldfarb L, et al. Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab. Oncoimmunology. 2019; 8(5): e1580128, doi: 10.1080/2162402X.2019.1580128, indexed in Pubmed: 31069139.
  145. Cortellini A, Bozzetti F, Palumbo P, et al. Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study. Sci Rep. 2020; 10(1): 1456, doi: 10.1038/s41598-020-58498-2, indexed in Pubmed: 31996766.
  146. Roch B, Coffy A, Jean-Baptiste S, et al. Cachexia - sarcopenia as a determinant of disease control rate and survival in non-small lung cancer patients receiving immune-checkpoint inhibitors. Lung Cancer. 2020; 143: 1926, doi: 10.1016/j.lungcan.2020.03.003, indexed in Pubmed: 32200137.
  147. Petrova MP, Donev IS, Radanova MA, et al. Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer. Clin Exp Immunol. 2020; 202(3): 353362, doi: 10.1111/cei.13505, indexed in Pubmed: 32757277.
  148. Ichihara E, Harada D, Inoue K, et al. The impact of body mass index on the efficacy of anti-PD-1/PD-L1 antibodies in patients with non-small cell lung cancer. Lung Cancer. 2020; 139: 140145, doi: 10.1016/j.lungcan.2019.11.011, indexed in Pubmed: 31786476.
  149. Minami S, Ihara S, Tanaka T, et al. Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer. World J Oncol. 2020; 11(1): 922, doi: 10.14740/wjon1225, indexed in Pubmed: 32095185.
  150. Katayama Y, Shimamoto T, Yamada T, et al. Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer. J Clin Med. 2019; 9(1), doi: 10.3390/jcm9010102, indexed in Pubmed: 31906082.
  151. Tsukagoshi M, Yokobori T, Yajima T, et al. Skeletal muscle mass predicts the outcome of nivolumab treatment for non-small cell lung cancer. Medicine (Baltimore). 2020; 99(7): e19059, doi: 10.1097/MD.0000000000019059, indexed in Pubmed: 32049805.
  152. Takada K, Yoneshima Y, Tanaka K, et al. Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors. J Cancer Res Clin Oncol. 2020; 146(5): 12171225, doi: 10.1007/s00432-020-03146-5, indexed in Pubmed: 32025867.
  153. Kichenadasse G, Miners JO, Mangoni AA, et al. Association Between Body Mass Index and Overall Survival With Immune Checkpoint Inhibitor Therapy for Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2020; 6(4): 512518, doi: 10.1001/jamaoncol.2019.5241, indexed in Pubmed: 31876896.
  154. Kim YY, Lee J, Jeong WK, et al. Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors. Gastric Cancer. 2021; 24(2): 457466, doi: 10.1007/s10120-020-01124-x, indexed in Pubmed: 32970267.
  155. Qayyum A, Bhosale P, Aslam R, et al. Effect of sarcopenia on systemic targeted therapy response in patients with advanced hepatocellular carcinoma. Abdom Radiol (NY). 2021; 46(3): 10081015, doi: 10.1007/s00261-020-02751-9, indexed in Pubmed: 32974761.
  156. Akce M, Liu Y, Zakka K, et al. Impact of Sarcopenia, BMI, and Inflammatory Biomarkers on Survival in Advanced Hepatocellular Carcinoma Treated With Anti-PD-1 Antibody. Am J Clin Oncol. 2021; 44(2): 7481, doi: 10.1097/COC.0000000000000787, indexed in Pubmed: 33350681.
  157. Hu JB, Ravichandran S, Rushing C, et al. Higher BMI, But Not Sarcopenia, Is Associated With Pembrolizumab-related Toxicity in Patients With Advanced Melanoma. Anticancer Res. 2020; 40(9): 52455254, doi: 10.21873/anticanres.14528, indexed in Pubmed: 32878813.
  158. Shimizu T, Miyake M, Hori S, et al. Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab. Diagnostics (Basel). 2020; 10(5), doi: 10.3390/diagnostics10050310, indexed in Pubmed: 32429323.
  159. Fukushima H, Fukuda S, Moriyama S, et al. Impact of sarcopenia on the efficacy of pembrolizumab in patients with advanced urothelial carcinoma: a preliminary report. Anticancer Drugs. 2020; 31(8): 866871, doi: 10.1097/CAD.0000000000000982, indexed in Pubmed: 32740015.
  160. Gyawali B, Shimokata T, Honda K, et al. Muscle wasting associated with the long-term use of mTOR inhibitors. Mol Clin Oncol. 2016; 5(5): 641646, doi: 10.3892/mco.2016.1015, indexed in Pubmed: 27900103.