Measurement of psoas major muscle area
The psoas major muscle area was calculated at the L3 position on
computed tomography. The PMMA was calculated before chemotherapy and
before pembrolizumab infusion. We were able to measure ∆PMMA in only 112
patients of the whole cohort, since the rest were staged only with a CT
scan of the thorax and upper abdomen and the area of the patient’s psoas
major muscle at the L3 position was not available. The PPMA was measured
in the region of interest by tracing an outline using the image viewer
software “DICOM”. The following formula was used: % change of PMMA=
([1-PMMA before P/PMMA before CT]*100. Patients with a change in
PMMA≥10% were considered to have sarcopenia [16].
Endpoints
The tumor response was assessed according to the Response Evaluation
Criteria in Solid Tumors (ver. 1.1) (RECIST 1.1), and clinical tumor
response was assessed every 3 months or at clinical deterioration.
Hyperprogression was defined if at least three of the following existed:
1. time to treatment failure<3 months; 2. increase ≥50% in
the sum of target lesion major diameters between baseline and first
radiological evaluation; 3. appearance of at least two new lesions in an
organ already involved between baseline and first radiological
evaluation; 4. spread of the disease to a new organ between baseline and
first radiological evaluation; and 5. clinical deterioration with a
decrease in ECOG PS ≥2 during the first three months of treatment.
Pseudoprogression was defined as initial progression followed either by
partial response or stable disease lasting at least 6 months. OS was
defined as the interval between diagnosis of the disease and death or
the date of the last follow-up evaluation.
Statistical design and
analysis
Data were managed and analyzed using SPSS software ver. 23. The
demographic characteristics were expressed as frequencies and
percentages for categorical variables and as medians and means with
standard deviations for quantitative variables. The Mann–Whitney U
test, Spearman correlation and χ2 test were used to
compare and evaluate the correlations between the biomarkers and the
clinicopathological characteristics of the patients, such as age, sex,
the NLR, and the PLR. To assess the correlations between test results,
rho values were interpreted as follows: <0.39, weak
correlation; 0.40-0.59, moderate correlation; 0.60-0.79, strong
correlation; and ≥0.80, very strong correlation. The Kruskal-Wallis
one-way analysis of variance with was used to compare the levels of
hematological biomarkers, ΔPMMA and response to pembrolizumab at the
first CT scan. The Wilcoxon and McNemar tests were used to compare
quantitative and categorical biomarker values and their derivations. The
diagnostic accuracy of biomarkers was determined by obtaining the
largest possible area under the curve (AUC) in receiver operating
characteristic curve (ROC) analysis. AUC values ≥0.9 were considered
“excellent”, ≥0.80 were considered “good”, ≥0.7 were considered
“fair” and <0.70 were considered “poor”. Survival curves
according to the response on the first CT scan were estimated using the
Kaplan-Meier method, and differences were assessed using the log-rank
test. We also performed multinomial logistic regression to estimate the
effects of hematological biomarkers and ∆PMMA on the response to
treatment. Two-tailed p-values <0.05 were considered
significant.