Sex-Specific Cut-Off Values for Low Skeletal Muscle Mass to Identify Patients at Risk for Treatment-Related Adverse Events in Head and Neck Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Ethical Approval
2.2. Patient Population
2.3. Baseline Characteristics
2.4. Skeletal Muscle Mass Analysis
2.5. Endpoints for Adverse Events
2.6. Statistical Analysis
3. Results
3.1. Patients’ and Baseline Characteristics
3.2. Occurrence of Adverse Events
3.3. Observer Analysis, Skeletal Muscle Quantification and SMI Cut-Off Values
3.4. Relationship between Low Skeletal Muscle Mass and Adverse Events
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Total | (Chemo-) Radiotherapy | Surgery | p-Value |
---|---|---|---|---|
n = 196 | n = 135 | n = 61 | ||
Sex | ||||
Male | 128 (65.3%) | 99 (73.3%) | 29 (47.5%) | <0.001 * |
Female | 68 (34.7%) | 36 (26.7%) | 32 (52.5%) | |
Age (years) | 64.2 (±11.2) | 63.5 (±10.5) | 65.8 (±12.5) | 0.176 ** |
BMI (kg2/m2) | 25.8 (±5.3) | 25.4 (±5.4) | 26.5 (±5.0) | 0.184 ** |
Tumour site | ||||
Oropharynx | 69 (35.2%) | 67 (49.6%) | 2 (3.3%) | <0.001 *** |
Oral cavity | 60 (30.6%) | 5 (3.7%) | 55 (90.2%) | |
Larynx | 56 (28.6%) | 52 (38.5%) | 4 (6.6%) | |
Hypopharynx | 10 (5.1%) | 10 (7.4%) | 0 (0%) | |
Nasopharynx | 1 (0.5%) | 1 (0.7%) | 0 (0%) | |
Stage | ||||
I | 23 (11.7%) | 3 (2.2%) | 20 (32.8%) | <0.001 * |
II | 24 (12.2%) | 17 (12.6%) | 7 (11.5%) | |
III | 37 (18.0%) | 31 (23.0%) | 6 (9.8%) | |
IV | 112 (57.1%) | 84(62.2%) | 28 (45.9%) | |
HPV (Oropharynx) | ||||
+ | 22 (40.7%) | 21 (39.6%) | 1 (100%) | 0.223 * |
− | 32 (59.3%) | 32 (60.4%) | 0 (0%) | |
Missing | 15 | 14 | 1 | |
ACE-27 | ||||
None | 32 (28.3%) | 24 (28.6%) | 8 (37.6%) | 0.113 * |
Mild | 37 (32.7%) | 32 (38.1%) | 5 (17.2%) | |
Moderate | 30 (26.5%) | 20 (23.8%) | 10 (34.5%) | |
Severe | 14 (12.4%) | 8 (9.5%) | 6 (20.7%) | |
Missing | 83 | 51 | 32 | |
Smoking | ||||
Never | 9 (8.8%) | 3 (4.0%) | 6 (22.2%) | 0.004 * |
Active/quit | 93 (91.2%) | 72 (96.0%) | 21 (77.8%) | |
Missing | 94 | 60 | 34 | |
Alcohol | ||||
No abuse | 72 (77.4%) | 51 (73.9%) | 21 (87.5%) | 0.170 * |
Abuse | 21 (22.6%) | 18 (26.1%) | 3 (12.5%) | |
Missing | 103 | 66 | 37 | |
GFI | ||||
Non-frail | 67 (69.1%) | 50 (71.4%) | 18 (64.3%) | 0.419 * |
Frail | 30 (30.9%) | 20 (28.6%) | 10 (35.7%) | |
Missing | 99 | 65 | 34 | |
G8 | ||||
Non-frail | 41 (42.7%) | 32 (46.4%) | 9 (33.3%) | 0.245 * |
Frail | 55 (57.3%) | 37 (53.6%) | 18 (66.7%) | |
Missing | 100 | 66 | 34 |
Characteristics | (Chemo-)Radiotherapy Toxicities | |
---|---|---|
All-cause (n = 135) | Dysphagia (n = 135) | |
CTCAE | ||
None | 8 (5.9%) | 40 (29.6%) |
Grade I | 45 (33.3%) | 36 (26.7%) |
Grade II | 49 (36.3%) | 30 (22.2%) |
≥Grade III | 33 (24.4%) | 29 (21.5%) |
Characteristics | Postoperative complications | |
All-cause (n = 61) | Wound infection (n = 61) | |
Clavien–Dindo | ||
None | 32 (52.5%) | 51 (78.5%) |
Grade I | 8 (13.1%) | 3 (4.6%) |
Grade II | 12 (19.7%) | 7 (10.8%) |
Grade III | 9 (14.8%) | 4 (6.2%) |
≥Grade II | 21 (34.4.0%) | 11 (16.9%) |
SMI Cut-Off | Sensitivity | Specificity | AUC | 95%CI | p-Value | |
---|---|---|---|---|---|---|
Toxicities | ||||||
All-cause | ||||||
Male | 46.49 | 0.67 | 0.63 | 0.632 | 0.47–0.78 | 0.082 |
Female | 37.90 | 0.93 | 0.43 | 0.648 | 0.47–0.83 | 0.136 |
Dysphagia | ||||||
Male | 46.49 | 0.65 | 0.62 | 0.610 | 0.45–0.77 | 0.156 |
Female | 34.91 | 0.75 | 0.58 | 0.642 | 0.46–0.83 | 0.169 |
Postoperative complications | ||||||
All-cause | ||||||
Male | 41.97 | 0.33 | 0.94 | 0.549 | 0.32–0.78 | 0.658 |
Female | 39.09 | 0.89 | 0.65 | 0.512 | 0.31–0.71 | 0.917 |
Wound infection | ||||||
Male | 40.79 | 0.14 | 0.96 | 0.409 | 0.15–0.67 | 0.476 |
Female | 35.64 | 1.00 | 0.54 | 0.607 | 0.42–0.79 | 0.494 |
Characteristics | (Chemo-)Radiotherapy Toxicities | |||||
---|---|---|---|---|---|---|
All-Cause | Dysphagia | |||||
OR | 95% CI | p-Value | OR | 95% CI | p-Value | |
Sex | ||||||
Male | Ref | Ref | ||||
Female | 0.31 | 0.14–0.72 | 0.006 | 0.42 | 0.17–0.99 | 0.047 |
Age (years) | 0.97 | 0.93–1.00 | 0.076 | 0.97 | 0.93–1.01 | 0.126 |
BMI (kg/m2) | 0.84 | 0.75–0.93 | 0.001 | 0.85 | 0.77–0.95 | 0.003 |
Tumour site | ||||||
Oral cavity | Ref | 0.007 | Ref | 0.011 | ||
Nasopharynx/Oropharynx | 0.83 | 0.13–5.24 | 1.91 | 0.20–18.14 | ||
Hypopharynx/Larynx | 0.19 | 0.03–1.35 | 0.43 | 0.04–4.48 | ||
Stage | ||||||
I–III | Ref | 0.010 | Ref | 0.014 | ||
IV | 3.55 | 1.35–9.34 | 3.68 | 1.30–10.38 | ||
HPV (oropharynx) | ||||||
+ | Ref | Ref | ||||
− | 0.73 | 0.23–2.31 | 0.593 | 0.76 | 0.26–2.65 | 0.833 |
ACE-27 | ||||||
None | Ref | 0.704 | Ref | 0.837 | ||
Mild | 1.24 | 0.20–7.67 | 1.00 | 0.16–6.35 | ||
Moderate | 1.17 | 0.20–6.94 | 1.00 | 0.14–5.99 | ||
Severe | 0.53 | 0.07–3.98 | 0.54 | 0.07–3.98 | ||
GFI | ||||||
Non-frail | Ref | 0.265 | Ref | 0.482 | ||
Frail | 1.91 | 0.61–5.95 | 1.52 | 0.47–4.88 | ||
G8 | ||||||
Non-frail | Ref | 0.621 | Ref | 0.810 | ||
Frail | 1.32 | 0.44–4.01 | 1.15 | 0.37–3.54 | ||
Smoking | ||||||
Never | Ref | Ref | ||||
Active/quit | 0.67 | 0.06–7.80 | 0.747 | 0.62 | 0.05–7.25 | 0.702 |
Alcohol | ||||||
No abuse | Ref | Ref | ||||
Abuse | 0.53 | 0.13–2.11 | 0.336 | 0.59 | 0.15–2.35 | 0.449 |
SMI (cm2/m2) | 0.91 | 0.86–0.96 | <0.001 | 0.92 | 0.87–0.97 | 0.002 |
Low SMI | ||||||
No | Ref | Ref | ||||
Yes | 3.86 | 1.69–8.86 | 0.001 | 2.70 | 1.12–6.47 | 0.026 |
Characteristics | Postoperative Complications | |||||
---|---|---|---|---|---|---|
All-Cause | Wound Infection | |||||
OR | 95%CI | p-Value | OR | 95%CI | p-Value | |
Sex | ||||||
Male | Ref | Ref | ||||
Female | 1.80 | 0.62–5.25 | 0.279 | 2.23 | 0.58–8.59 | 0.245 |
Age (years) | 0.97 | 0.93–1.02 | 0.188 | 0.99 | 0.94–1.04 | 0.616 |
BMI (kg/m2) | 0.96 | 0.86–1.07 | 0.479 | 1.01 | 0.89–1.15 | 0.830 |
Tumour site | ||||||
Oral cavity | Ref | 0.827 | Ref | 0.026 | ||
Nasopharynx/Oropharynx | 2.44 | 0.14–41.40 | 6.86 | 0.38–122.52 | ||
Hypopharynx/Larynx | * | * | 20.57 | 1.87–226.32 | ||
Stage | ||||||
I–III | Ref | 0.463 | Ref | 0.060 | ||
IV | 1.49 | 0.52–4.30 | 4.00 | 0.95–16.93 | ||
HPV (oropharynx) | ||||||
+ | * | * | ||||
− | ||||||
ACE-27 | ||||||
None | Ref | 0.303 | Ref | 0740 | ||
Moderate | 0.67 | 0.07–6.87 | 1.67 | 0.12–24.26 | ||
Severe | 5.33 | 0.50–127.90 | 1.25 | 0.06–26.87 | ||
Missing | 1.33 | 0.24–16.36 | 3.33 | 0.28–40.29 | ||
GFI | ||||||
Non-frail | Ref | 0.517 | Ref | 0.974 | ||
Frail | 1.69 | 0.35–8.22 | 0.97 | 0.18–537 | ||
G8 | ||||||
Non-frail | Ref | 0.069 | Ref | 0.454 | ||
Frail | 5.50 | 0.88–34.46 | 1.75 | 0.28–11.15 | ||
Smoking | ||||||
Never | * | * | * | * | ||
Active/quit | ||||||
Alcohol | ||||||
No abuse | * | * | * | * | ||
Abuse | ||||||
SMI (cm2/m2) | 1.02 | 0.96–1.08 | 0.529 | 1.04 | 0.96–1.11 | 0.344 |
Low SMI (sex-specific) | ||||||
No | Ref | 0.377 | Ref | |||
Yes | 0.62 | 0.21–1.81 | 0.67 | 0.17–2.58 | 0.562 | |
Surgical intensity | ||||||
Minor | Ref | 0.287 | Ref | 0.148 | ||
Major | 1.80 | 0.61–5.28 | 2.89 | 0.69–12.17 |
Characteristics | (Chemo-)Radiotherapy Toxicities | |||||
---|---|---|---|---|---|---|
All-Cause | Dysphagia | |||||
OR | 95%CI | p-Value | OR | 95%CI | p-Value | |
Low SMI | ||||||
No | Ref | 0.006 | Ref | 0.046 | ||
Yes | 3.33 | 1.41–7.82 | 2.50 | 1.02–6.14 | ||
Stage | ||||||
I–III | Ref | 0.014 | Ref | 0.020 | ||
IV | 3.45 | 1.28–9.29 | 3.47 | 1.21–9.92 |
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Zwart, A.T.; Pörtzgen, W.; van Rijn-Dekker, I.; Sidorenkov, G.A.; Dierckx, R.A.J.O.; Steenbakkers, R.J.H.M.; Wegner, I.; van der Hoorn, A.; de Bock, G.H.; Halmos, G.B. Sex-Specific Cut-Off Values for Low Skeletal Muscle Mass to Identify Patients at Risk for Treatment-Related Adverse Events in Head and Neck Cancer. J. Clin. Med. 2022, 11, 4650. https://doi.org/10.3390/jcm11164650
Zwart AT, Pörtzgen W, van Rijn-Dekker I, Sidorenkov GA, Dierckx RAJO, Steenbakkers RJHM, Wegner I, van der Hoorn A, de Bock GH, Halmos GB. Sex-Specific Cut-Off Values for Low Skeletal Muscle Mass to Identify Patients at Risk for Treatment-Related Adverse Events in Head and Neck Cancer. Journal of Clinical Medicine. 2022; 11(16):4650. https://doi.org/10.3390/jcm11164650
Chicago/Turabian StyleZwart, Aniek T., Wolf Pörtzgen, Irene van Rijn-Dekker, Grigory A. Sidorenkov, Rudi A. J. O. Dierckx, Roel J. H. M. Steenbakkers, Inge Wegner, Anouk van der Hoorn, Geertruida H. de Bock, and Gyorgy B. Halmos. 2022. "Sex-Specific Cut-Off Values for Low Skeletal Muscle Mass to Identify Patients at Risk for Treatment-Related Adverse Events in Head and Neck Cancer" Journal of Clinical Medicine 11, no. 16: 4650. https://doi.org/10.3390/jcm11164650