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The role of haematological parameters in predicting the response to radical chemoradiotherapy in patients with anal squamous cell cancer

Suzana Stojanovic-Rundic
Suzana Stojanovic-Rundic
, 
Mladen Marinkovic
Mladen Marinkovic
, 
Milena Cavic
Milena Cavic
, 
Vesna Plesinac Karapandzic
Vesna Plesinac Karapandzic
, 
Dusica Gavrilovic
Dusica Gavrilovic
, 
Radmila Jankovic
Radmila Jankovic
, 
Richarda M. de Voer
Richarda M. de Voer
, 
Sergi Castellvi-Bel
Sergi Castellvi-Bel
 y 
Zoran Krivokapic
Zoran Krivokapic
   | 08 oct 2021
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Article Category: Research Article
Publicado en línea: 08 oct 2021
Páginas: 449 - 458
Recibido: 18 may 2021
Aceptado: 16 jul 2021
DOI: https://doi.org/10.2478/raon-2021-0039
© 2021 Suzana Stojanovic-Rundic, Mladen Marinkovic, Milena Cavic, Vesna Plesinac Karapandzic, Dusica Gavrilovic, Radmila Jankovic, Richarda M. de Voer, Sergi Castellvi-Bel, Zoran Krivokapic, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) for the whole patient group.
Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) for the whole patient group.

Figure 2

(A) Kaplan-Meier plots for Disease-free survival (DFS), (B) progression-free survival (PFS), and (C) overall survival (OS) in relation to response to treatment after 6 months.
(A) Kaplan-Meier plots for Disease-free survival (DFS), (B) progression-free survival (PFS), and (C) overall survival (OS) in relation to response to treatment after 6 months.

Figure 3

Receiver Operating Characteristics (ROC) curve for the platelet-to-lymphocyte ratio (PLR) in relation to response to treatment after 6 months.
Receiver Operating Characteristics (ROC) curve for the platelet-to-lymphocyte ratio (PLR) in relation to response to treatment after 6 months.

Results of the ROC analysis for neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and relevant events

Characteristics NLR PLR
AUC ROCa (95% CI) 65.2% (45.3–85.2%) 76.2% (59.5–92.9%)
Likelihood ratio testb ns p < 0.05
ROC-cut-off valuec - 145.2
Sensitivity (95% CI) - 68.7% (43.7–87.5%)
Specificity (95% CI) - 75.0% (56.1–93.7%)

Patients’ disease, treatment and outcomes characteristics

Characteristics N (%) Characteristics N (%)
Age (years) NLR
    Mean (SD) 61.9 (10.0)     Mean (SD) 2.7 (1.7)
    Median (Range) 63.0 (40.0–81.0)     Median (Range) 2.1 (0.8–7.0)
Gender PLR
    Female 36 (76.6%)     Mean (SD) 159.4 (92.1)
    Male 11 (23.4%)     Median (Range) 132.9 (51.7–401.2)
Performance status (PS)1 RT technique
    ECOG 0 13 (27.7%) 2D 23 (48.9%)
    ECOG 1 33 (70.2%) 3D 24 (51.1%)
    ECOG 2 1 (2.1%) The first RT part-dose (Gy)
T in clinical TNM     Mean (SD) 36.1 (1.6)
    T2 18 (38.3%)     Median (Range) 36 (30–45)
    T3 24 (51.1%) The second RT part-dose (Gy)
    T4 5 (10.6%)     Mean (SD) 22.8 (2.5)
N in clinical TNM     Median (Range) 23.4 (9–26)
    N0 17 (36.2%) Total dose (Gy)
    N1 30 (63.8%)     Mean (SD) 58.9 (1.6)
UICC staging     Median (Range) 59.4 (52–59.4)
    IIA 10 (21.3%) OTT (days)
    IIB 7 (14.9%)     Mean (SD) 74.7 (14.2)
    IIIA 8 (17.0%)     Median (Range) 77 (51–134)
    IIIC 22 (46.8%) Acute toxicity-first part
Tumour differentiation     Without or gr. I/II 26 (55.3%)
    well 24 (51.1%)     Grade III/IV 21 (44.7%)
    moderate 13 (27.7%) Acute toxicity-second part
    poor 4 (8.5%)     Without or gr. I/II 32 (68.1%)
    without data 6 (12.8%)     Grade III/IV 15 (31.9%)
Tumour size (cm) Tumour response at 6 months
    Mean (SD) 5.2 (2.0)     CR 30 (63.8%)
    Median (Range) 5.4 (2.1–10.0)     PR 15 (31.9%)
Initial haemoglobin level (g/L)     SD 1 (2.1%)
    Mean (SD) 116.3 (20.3)     PD 1 (2.1%)
    Median (Range) 124 (66–154) Follow-up period (months)
Pretreatment colostomy     Mean (SD) 53.0 (30.9)
    No 42 (89.4%)     Median (Range) 44 (11–136)
    Yes 5 (10.6%) Total 47 (100%)

Comparison of characteristics of complete responders (CR) and non-complete responders (non-CR) to chemoradiotherapy

Characteristic The response to treatment after 6 months
CR non-CR rank Wilcoxon sum test
Age (years)
    Mean (SD) 60 (10.7) 65.1 (7.8) ns
    Median (Range) 59.5 (40.0–80.0) 65.0 (52.0–81.0)
Gender
    Male 6 (20%) 5 (29.4%) ns*
    Female 24 (80%) 12 (70.6%)
T in clinical TNM
    T2 13 (43.3%) 5 (29.4%)
    T3 14 (46.7%) 10 (58.2%) ns#
    T4 3 (10.0%) 2 (11.8%)
N in clinical TNM
    N0 15 (50.0%) 2 (11.8%)
    N1 15 (50.0%) 15 (88.2%) p* < 0.05
Tumour size (cm)
    Mean (SD) 4.7 (1.8) 6.0 (2.1) p < 0.05
    Median (Range) 4.9 (2.1–8.0) 5.8 (2.3–10.0)
Initial haemoglobin level (g/L)
    Mean (SD) 124.2 (16.9) 103.0 (18.8) p < 0.01
    Median (Range) 127.0 (66.0–154.0) 101.0 (68.0–132.0)
Pretreatment colostomy
    No 28 (93.3%) 14 (82.3%)
    Yes 2 (6.7%) 3 (17.6%) ns#
Neutrophil-to-lymphocyte ratio
    N (%) 16/30 (50%) 16/17 (50%)
    Mean (SD) 2.4 (1.8) 3.1 (1.6) ns
    Median (Range) 1.9 (0.8–7.0) 3.2 (0.9–5.6)
Platelet-to-lymphocyte ratio
    N (%) 16/30 (50%) 16/17 (50%)
    Mean (SD) 118.3 (54.9) 200.5 (104.4)
    Median (Range) 108.3 (51.7–256.6) 158.9 (79.5–401.2) p < 0.05
DFS (months)
    Median (95% CI) NR NR p$ < 0.05
PFS (months)
    Median (95% CI) NR 26 (> 17) p$ < 0.01
OS (months)
    Median (95% CI) NR 71 (> 33) p$ < 0.01
ACSOS (months)
    Median (95% CI) NR NR p$ < 0.05
CFS (months)
    Median (95% CI) NR 11 (> 10) p$ < 0.01
Total 30 (100%) 17 (100%) -

The value of neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) in prediction of CR vs. non-CR

Characteristic The response to treatment after 6 months
CR non-CR Fisher Exact Test
NLR (literature cut-off value)
    < 3.0 13 (81.2%) 7 (43.8%)
    ≥ 3.0 3 (18.8%) 9 (56.2%) p = 0.06
PLR (literature cut-off value)
    < 160.0 13 (81.2%) 9 (56.2%)
    ≥ 160.0 3 (18.8%) 7 (43.8%) p = 0.25
PLR (ROC cut-off value)
    < 145.2 12 (75%) 5 (31.3%)
    ≥ 145.2 4 (25%) 11(68.7%) p = 0.03
Total 16 (100%) 16 (100%) -

Logistic regression analysis of the response to treatment after 6 months

Characteristic Logistic regression
Univariate
 Multivariate
OR (95%CI) Wild test OR (95%CI) Likelihood Ratio test
Age
    > 63 y vs. ≤ 63 y 1.7 (0.4–6.6) p = 0.213 - p = 0.884
Gender
    Male vs. Female 2.1 (0.6–7.2) p = 0.468 - p = 0.082
T in clinical TNM
    T3 vs. T2 T4 vs. T2 1.9 (0.5–6.9) 1.7 (0.2–13.7) p = 0.634 - p = 0.940
N in clinical TNM
    N1 vs. N0 7.5 (1.4–38.7) p = 0.006 - p = 0.133
Tumour size (cm)
    > 4 cm vs. ≤ 4 cm 6.6 (1.3–33.8) p = 0.011 - p = 0.602
Initial haemoglobin level (g/L)
    < 120 g/L vs. ≥ 120 g/L 8.9 (2.2–35.6) p = 0.001 13.4 (2.4–74.3) p* = 0.003
RT technique
    2D vs. 3D 1.3 (0.4–4.2) p = 0.679 - p = 0.784
Treatment break
    > 10 days vs. ≤ 10 days 6.0 (1.6–22.3) p = 0.005 9.6 (1.7–52.5) p* = 0.009
Completed chemotherapy
    No vs. Yes 2.0 (0.4–9.3) p = 0.379 - p = 0.555
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Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
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