Table 4.
The US skin changes and the association with clinical assessments.
| Author(s), Year | US Changes in Parameter | Association with Clinical Assessment | Notes | |
|---|---|---|---|---|
| Early (≤3 Months) | Late (˃3 Months) | |||
| (Borm et al. 2021) [39] | ↑ skin thickness compared to the HB | At the end of RT: no significant difference in skin thickness but significant difference (p = 0.03) in the CTCAE score 6 weeks post RT: no significant difference in skin thickness or CTCAE score (p = 0.39) |
HF is associated with a lower degree of acute RD compared to CF at the end of treatment CTCAE scores and US measurements do not reliably reflect the patient’s perception |
|
| (Garnier et al. 2017) [41] | ↑ dermal thickness compared to the HB | The mean relative ↑ in dermal thickness in irradiated skin (RIDTIS) was greater for grades 2 and 3 than 1: 0.53 vs. 0.29 mm (p = 0.023) | US of dermal thickness may be a reliable tool to quantify acute RD | |
| (Wang et al. 2020) [33] | Increased STRA compared to baseline | Increased STRA compared to baseline | A significant association between STRA and breast asymmetry (p = 0.02, 0.04, <0.01 at baseline, 12 weeks, and 1 year post RT, respectively) | HF is associated with better long-term cosmetic outcomes Supraclavicular nodal irradiation and CF are associated with worse cosmetic outcomes 1 year post RT |
| (Torres et al. 2016) [32] | Significant difference compared to baseline (p < 0.001) and the end of RT (p = 0.03) | Correlated with RTOG Mean STRA is ↑ in patients with grade 2 than grade 0 at the end of RT (p = 0.001) and 6 weeks post RT (p < 0.03) |
RT had a synergistic effect with lymph node surgery on breast skin thickening | |
| (Lin et al. 2019) [9] | Significant changes compared to baseline (p < 0.001) | Significant changes compared to baseline (p < 0.001) | NR | ALND has a long-term impact on breast skin thickening |
| (Yoshida et al. 2011) [35] | Significant difference of skin thickness (p < 0.001) and PCC (p < 0.001). | PCC correlated with RTOG late toxicity, but skin thickness did not (↑38.4% for RTOG grade 0, 23.8% for grade 1, and 31.1% for grade 2 toxicity); p-value NR | Quantitative US is an objective tool that assesses RT-induced tissue injury, which may improve patients’ quality of life | |
| (Yoshida et al. 2012) [34] | Significant dermal (p < 0.0001) and hypodermal toxicity (p = 0.0027) | -Significant dermal toxicity (p < 0.05) -Not significant hypodermal toxicity (p = 0.22) |
Late toxicity assessments correlated with RTOG (Patients with RTOG grade 1 or 2 have greater US toxicity changes than patients with RTOG grade 0, p = 0.04 for dermal toxicity and p = 0.22 for hypodermis toxicity) |
Early and late radiation-induced effects on normal tissue can be reliably assessed using the quantitative US |
| (Keskikuru et al. 2004) [43] | Significant changes in skin thickness (p < 0.05, p < 0.01 at different timepoints) | Significant changes (p < 0.05, p < 0.01 at different timepoints) until one year then declined | No significant correlations between the skin thickness and the score of erythema or subcutaneous induration | Increased collagen synthesis is associated with oedema resulting from radiation-induced damage to skin microvasculature |
| (Wratten et al. 2000) [38] | Significant changes (p < 0.001) | There was a persistent ↑ in cutaneous thickness in the treated breast | The most prominent visual breast oedema exhibited the greatest total cutaneous thickness (p-value NR) | HFUS can quantify cutaneous breast oedema accurately |
| (Wratten et al. 2002) [37] | No obvious skin thickness changes during RT (p-value NR). | The most marked cutaneous thickness was in patients with obvious visible breast oedema before RT (p-value NR) | HFUS is not an ideal, sensitive, and quantitative measure of acute RD in this group of patients | |
| (Wratten et al. 2007) [36] | A minor ↑ in epidermal thickness (p-value NR) | Significant changes (p = 0.000 with or without level 2 nodal dissection) |
NR | The utility of HFUS is in a research setting when assessing interventions that aim to reduce breast oedema |
| (Warszawski et al. 1998) [44] | Significant changes in the dermis thickness and echogenicity (p < 0.001) Nonsignificant changes in the structure of the dermis-subcutis border (p = 0.07) |
Significant changes in the dermis thickness (p = 0.0018) and echogenicity (p < 0.001 for lower dermis, p = 0.0027 for upper dermis) Nonsignificant changes in the structure of the dermis-subcutis border (p = 0.08) |
There were discrepancies between the clinical and US assessments, mainly in the late reactions (K = −0.13, Pearson’s correlation) Early skin reactions: structural changes could be recorded by US evaluation much earlier than visible reactions by the naked eye |
High resolution 20 MHz US is noninvasive, quantitative, and reproducible for assessing early and late skin reactions US skin changes depend on the time interval between completion of RT and US evaluations |
| (Landoni et al. 2013) [40] | Statistically significant difference (p < 0.001) |
US assessments were in agreement with clinical assessments A significant direct correlation was found between the increment in skin thickness with fibrosis (grade ≥ 1) in the irradiated breast (p-value = 0.0236) and the boost region (p-value = 0.0164) |
Late cutaneous reactions can be reliably assessed by US | |
| (Liu et al. 2008) [42] | Significant skin thickness (p = 0.005) and Pearson coefficient (p = 0.02) changes | NR | US technique is noninvasive and feasible to detect and quantify radiation-induced skin changes | |
| (Liu et al. 2010) [31] | Significant skin thickness and Pearson coefficient changes (p < 0.001) | US evaluations were consistent with RTOG scores Skin thickness correlated with RTOG late subcutaneous toxicity, and PCC correlated with late skin toxicity (p-value NR) |
The quantitative US is noninvasive and objective for assessing radiation-induced changes to the skin | |
| (Schack et al. 2016) [45] | Significant differences (p = 0.0003) | The highest mean difference in dermis thickness (1.61 mm (95% CI 0.41–2.82) was in patients with clinical oedema and grade 2 induration (p = 0.02) | HFUS evaluation of the skin is not part of large-scale follow-up routines in assessing radiation-induced morbidity | |
| (Wong et al. 2011) [46] | Significant skin thickness changes of the Rt chest (p = 0.007) and Lt chest (p = 0.025) | US measurements correlated with RTOG Patients with grade 2 acute skin toxicity presented with thinner skin (mean skin thickness 0.1720 mm) compared to patients with grade 1 (0.1879 mm) (p = 0.006) |
HFUS can be utilised to document quantitative skin changes following postmastectomy RT | |
Abbreviations: NR = not reported, RT = radiotherapy, US = ultrasound, HB = healthy breast, HFUS = high-frequency ultrasound, RD = radiation dermatitis, RTOG = Radiation Therapy Oncology Group, CTCAE = Common Terminology Criteria for Adverse Events, CF = conventional fractionation, HF = hypofractionation, ALND = axillary lymph node dissection, PCC = Pearson correlation coefficient, STRA = skin thickness ratio.