Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Staging Evaluations
2.3. Definitive Chemoradiotherapy and Surgery
2.4. Statistics
3. Results
3.1. Clinicopathological Characteristics of the Study Patients
3.2. Survival and Prognostic Factors for Patients Receiving Surgical and Non-Surgical Treatment
3.3. Risk Factors for Incomplete Definitive Chemoradiotherapy
4. Discussion
4.1. Survival and Prognosticators of Patients Receiving Definitive Chemoradiotherapy
4.2. Prognostic Effect of Salvage Esophagectomy
4.3. Optimization of Treatment Plans
4.4. Brief Summary
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All Patients (N = 273) | dCRT Incomplete (N = 90) | dCRT Complete (N = 183) | |||||
---|---|---|---|---|---|---|---|
p * | Total | Total | Salvage Operation | p ** | |||
Group 1 | No (N = 166) Group 2 | Yes (N = 17) Group 3 | |||||
Age (years; median, IQR) | 59.0 (52.0–67.0) | 0.282 | 61.0 (52.0–68.0) | 58.0 (52.0–66.0) | 58.0 (51.8–66.3) | 60.0 (54.0–66.5) | 0.886 |
Sex (%) | 0.287 | 0.611 | |||||
Male | 251 (91.9) | 85 (94.4) | 166 (90.7) | 150 (90.4) | 16 (94.1) | ||
Female | 22 (8.1) | 5 (5.6) | 17 (9.3) | 16 (9.6) | 1 (5.9) | ||
BMI (median, IQR) | 21.0 (19.0–23.7) | 0.087 | 20.4 (17.9–23.2) | 21.2 (19.3–23.8) | 21.1 (19.2–23.8) | 23.2 (20.3–25.2) | 0.091 |
Smoking (%) | 0.065 | 0.883 | |||||
Never | 53 (20.2) | 23 (25.8) | 30 (16.4) | 27 (16.3) | 3 (17.6) | ||
Former/current | 219 (79.6) | 66 (74.2) | 153 (83.6) | 139 (83.7) | 14 (82.4) | ||
ECOG (%) | <0.001 | 0.580 | |||||
0 | 142 (52.0) | 29 (32.2) | 113 (61.7) | 101 (60.8) | 12 (70.6) | ||
1 | 106 (38.8) | 43 (47.8) | 63 (34.4) | 58 (34.9) | 5 (29.4) | ||
≥2 | 25 (9.2) | 18 (20.0) | 7 (3.8) | 7 (4.2) | 0 (0) | ||
Cirrhosis (%) | 0.007 | 0.355 | |||||
Child–Pugh A | 10 (11.2) | 8 (4.4) | 8 (4.8) | 0 (0) | |||
Child–Pugh B | 2 (2.2) | 0 (0) | 0 (0) | 0 (0) | |||
Charlson comorbidity index | 3.0 (2.0–4.0) | 0.131 | 3.0 (2.0–4.3) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) | 2.0 (2.0–3.5) | 0.703 |
Laboratory data (median, IQR) | |||||||
Hemoglobin (g/dL) | 12.4 (10.9–13.6) | 0.003 | 11.9 (10.1–13.3) | 12.6 (11.3–13.8) | 12.6 (11.2–13.8) | 13.5 (12.3–14.1) | 0.150 |
Albumin (g/dL) | 3.7 (3.3–4.0) | <0.001 | 3.5 (3.0–3.9) | 3.8 (3.4–4.1) | 3.8 (3.4–4.0) | 3.9 (3.6–4.3) | 0.017 |
Neutrophil (cells/µL) | 5427.1 (4126.0–7392.6) | 0.109 | 5505.2 (4203.7–8296.7) | 5217.2 (4002.3–7145.7) | 5544.0 (4301.5–7204.4) | 3938.7 (2989.2–5036.8) | 0.018 |
Lymphocyte (cells/µL) | 1504.4 (1124.3–1850.0) | 0.009 | 1354.2 (1024.6–1731.3) | 1572.6 (1163.6–1894.8) | 1548.6 (1153.1–1862.3) | 1674.8 (1405.9–2154.4) | 0.136 |
Monocyte (cells/µL) | 633.2 (490.2–861.6) | 0.509 | 636.0 (463.3–910.6) | 629.9 (501.0–846.3) | 633.9 (520.4–859.5) | 555.0 (458.3–763.4) | 0.692 |
Platelet (counts/µL) | 279,000.0 (217,000.0–342,000.0) | 0.191 | 285,000.0 (186,500.0–346,000.0) | 277,000.0 (227,000.0–341,000.0) | 279,000.0 (228,000.0–345,000.0) | 248,000.0 (222,000.0–383,000.0) | 0.081 |
NLR (IQR) | 3.7 (2.6–5.5) | 0.001 | 4.5 (2.9–7.2) | 3.5 (2.6–4.9) | 3.6 (2.7–5.0) | 2.2 (1.7–3.4) | 0.002 |
LMR (IQR) | 2.2 (1.6–3.0) | 0.009 | 1.9 (1.4–2.8) | 2.4 (1.7–3.2) | 2.2 (1.7–3.1) | 3.5 (2.3–3.8) | 0.012 |
PLR (IQR) | 184.1 (134.2–255.4) | 0.376 | 190.9 (131.2–277.8) | 178.3 (135.6–238.9) | 184.5 (139.6–252.0) | 147.8 (100.2–182.4) | 0.008 |
Tumor location (%) | 0.610 | 0.867 | |||||
Cervical | 24 (8.8) | 8 (8.9) | 16 (8.7) | 15 (9.0) | 1 (5.9) | ||
Upper | 69 (25.3) | 26 (28.9) | 43 (23.5) | 40 (24.1) | 3 (17.6) | ||
Middle | 99 (36.3) | 32 (35.6) | 67 (36.6) | 59 (35.5) | 8 (47.1) | ||
Lower | 72 (26.4) | 23 (25.6) | 49 (26.8) | 45 (27.1) | 4 (23.5) | ||
EGJ | 9 (3.3) | 1 (1.1) | 8 (4.4) | 7 (4.2) | 1 (5.9) | ||
cT stage (%) | 0.004 | 0.758 | |||||
1 | 5 (1.8) | 0 (0) | 5 (2.7) | 4 (2.4) | 1 (5.9) | ||
2 | 30 (11.0) | 8 (8.9) | 22 (12.0) | 20 (12.0) | 2 (11.8) | ||
3 | 146 (53.5) | 39 (43.3) | 107 (58.5) | 96 (57.8) | 11 (64.7) | ||
4 | 87 (31.9) | 42 (46.7) | 45 (24.6) | 42 (25.3) | 3 (17.6) | ||
Cannot be assessed | 5 (1.8) | 1 (1.1) | 4 (2.2) | 4 (2.4) | 0 (0) | ||
cN stage (%) | 0.648 | 0.511 | |||||
0 | 17 (6.2) | 6 (6.7) | 11 (6.0) | 11 (6.6) | 0 (0) | ||
1 | 61 (22.3) | 20 (22.2) | 41 (22.4) | 38 (22.9) | 3 (17.6) | ||
2 | 74 (27.1) | 26 (28.9) | 48 (26.2) | 41 (24.7) | 7 (41.2) | ||
3 | 120 (44.0) | 37 (41.1) | 83 (45.4) | 76 (45.8) | 7 (41.2) | ||
Cannot be assessed | 1 (0.4) | 1 (1.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
cM stage (%) | 0.567 | 0.766 | |||||
0 | 67 (24.5) | 24 (26.7) | 43 (23.5) | 40 (24.1) | 3 (17.6) | ||
1 | 206 (75.5) | 66 (73.3) | 140 (76.5) | 126 (75.9) | 14 (82.4) | ||
Histology (%) | 0.621 | 0.715 | |||||
SCC | 249 (91.2) | 81 (90.0) | 168 (91.8) | 152 (91.6) | 16 (94.1) | ||
ADC | 24 (8.8) | 9 (10.0) | 15 (8.2) | 14 (8.4) | 1 (5.9) | ||
MDT conference (%) | <0.001 | <0.001 | |||||
0 | 109 (39.9) | 46 (51.1) | 63 (34.4) | 62 (37.3) | 1 (5.9) | ||
1 | 112 (41.0) | 39 (43.3) | 73 (39.9) | 70 (42.2) | 3 (17.6) | ||
≥2 | 52 (19.1) | 5 (5.6) | 47 (25.7) | 34 (20.5) | 13 (76.5) | ||
Radiation dose (cGy) (%) | |||||||
≤5040 | 125 (45.8) | <0.001 | 59 (65.6) | 66 (36.1) | 59 (35.5) | 7 (41.2) | 0.792 |
>5040 | 148 (54.2) | 31 (34.4) | 117 (63.9) | 107 (64.5) | 10 (58.8) | ||
Chemotherapy regimen (%) | 0.192 | 0.800 | |||||
CDDP + 5-FU | 230 (84.2) | 77 (85.6) | 153 (83.6) | 138 (83.1) | 15 (88.2) | ||
CDDP + 5-FU + Taxane | 10 (3.7) | 1 (1.1) | 9 (4.9) | 9 (5.4) | 0 (0) | ||
Tegafur–Uracil | 7 (2.6) | 1 (1.1) | 6 (3.3) | 5 (3.0) | 1 (5.9) | ||
5-FU | 6 (2.2) | 3 (3.3) | 3 (1.6) | 3 (1.8) | 0 (0) | ||
Carboplatin + Taxane | 4 (1.5) | 3 (3.3) | 1 (0.5) | 1 (0.6) | 0 (0) | ||
Others *** | 16 (5.9) | 5 (5.6) | 11 (6.0) | 10 (6.0) | 1 (5.9) | ||
Clinical response to therapy (%) | <0.001 | <0.001 | |||||
CR | 16 (5.8) | 0 (0) | 16 (8.7) | 11 (6.6) | 5 (29.4) | ||
PR | 112 (41.0) | 58 (64.4) | 54 (29.5) | 43 (25.9) | 11 (64.7) | ||
SD | 23 (8.4) | 13 (14.4) | 10 (5.5) | 10 (6.0) | 0 (0) | ||
PD | 119 (43.6) | 19 (21.1) | 100 (54.6) | 99 (59.6) | 1 (5.9) | ||
Undefined | 3 (1.1) | 0 (0) | 3 (1.6) | 3 (1.8) | 0 (0) | ||
Follow-up time (month; median, IQR) | 8.1 (3.9–16.1) | <0.001 | 2.6 (1.1–4.4) | 11.4 (7.7–21.7) | 10.2 (7.4–18.2) | 26.5 (18.5–33.3) | 0.071 |
Variable | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p Value | HR | 95% CI | p Value | |
Age (years; ≥60 vs. <60) | 0.84 | 0.65–1.08 | 0.181 | |||
Sex (male vs. female) | 1.69 | 1.04–2.74 | 0.033 | 1.70 | 0.99–2.91 | 0.051 |
Smoking (ever vs. never) | 0.77 | 0.56–1.05 | 0.102 | |||
BMI (≥21 vs. <21) | 0.94 | 0.73–1.21 | 0.630 | |||
ECOG (≥2 vs. 0–1) | 2.13 | 1.40–3.23 | <0.001 | 1.58 | 0.95–2.65 | 0.081 |
CCI score (≥4 vs. <4) | 1.04 | 0.80–1.35 | 0.777 | |||
Liver cirrhosis (yes vs. no) | 1.20 | 0.75–1.93 | 0.452 | |||
Laboratory data | ||||||
Hemoglobin (g/dL; ≥10 vs. <10) | 0.80 | 0.57–1.11 | 0.180 | |||
Albumin (g/dL; ≥3.5 vs. <3.5) | 0.69 | 0.54–0.90 | 0.005 | 0.85 | 0.63–1.14 | 0.273 |
NLR (≥3.4 vs. <3.4) | 1.41 | 1.09–1.82 | 0.009 | 1.02 1.23 | 0.98–1.06 0.93–1.63 | 0.295 0.152 |
LMR (<2.4 vs. ≥2.4) | 1.23 | 0.96–1.59 | 0.109 | |||
PLR (≥170 vs. <170) | 1.23 | 0.96–1.59 | 0.106 | |||
Tumor location (Ce vs. Ut/Mt/Lt/EGJ) | 0.94 | 0.60–1.47 | 0.776 | |||
c T stage (4b vs. 1/2/3/4a) | 1.48 | 1.12–1.96 | 0.005 | |||
c N stage (3 vs. 0/1/2) | 1.35 | 1.05–1.75 | 0.020 | 1.38 | 1.06–1.80 | 0.019 |
c M stage (1 vs. 0) | 0.83 | 0.62–1.10 | 0.190 | |||
cT4b | ||||||
Aorta | 1.41 | 0.88–2.25 | 0.152 | |||
Airway | 1.65 | 1.23–2.21 | 0.001 | 1.63 | 1.17–2.25 | 0.003 |
Distant metastasis | ||||||
Retroperitoneal LN | 1.24 | 0.93–1.65 | 0.149 | |||
Liver | 1.38 | 1.01–1.90 | 0.045 | 1.66 | 1.18–2.33 | 0.004 |
Bone | 1.75 | 1.29–2.38 | <0.001 | 1.71 | 1.23–2.38 | 0.002 |
Lung | 0.94 | 0.72–1.23 | 0.647 | |||
Adrenal | 1.42 | 0.73–2.76 | 0.308 | |||
Histopathology (SCC vs. ADC) | 1.24 | 0.80–1.93 | 0.341 | |||
MDT (yes vs. no) | 0.82 | 0.63–1.05 | 0.117 | |||
Clinical response | ||||||
PD | 1 | 1 | ||||
PR | 0.80 | 0.61–1.06 | 0.120 | 0.82 | 0.61–1.10 | 0.190 |
SD | 1.06 | 0.67–1.67 | 0.807 | 1.05 | 0.60–1.83 | 0.863 |
CR | 0.05 | 0.01–0.16 | <0.001 | 0.05 | 0.02–0.17 | <0.001 |
Variable | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p Value | HR | 95% CI | p Value | |
Age (years; ≥60 vs. <60) | 1.51 | 0.91–2.50 | 0.114 | |||
Sex (male vs. female) | 1.74 | 0.62–4.88 | 0.292 | |||
Smoking (ever vs. never) | 0.56 | 0.30–1.04 | 0.067 | |||
BMI (≥21 vs. <21) | 0.76 | 0.46–1.27 | 0.299 | |||
ECOG (≥2 vs. 0–1) | 6.29 | 2.52–15.70 | < 0.001 | 5.23 | 1.95–14.02 | 0.001 |
CCI score (≥4 vs. <4) | 1.55 | 0.92–2.63 | 0.102 | |||
Laboratory data | ||||||
Hemoglobin (g/dL; ≥10 vs. <10) | 0.44 | 0.23–0.84 | 0.014 | 0.64 | 0.31–1.34 | 0.236 |
Albumin (g/dL; ≥3.5 vs. <3.5) | 0.49 | 0.29–0.82 | 0.006 | |||
NLR (≥3.4 vs. <3.4) | 1.78 | 1.05–3.03 | 0.033 | 1.06 | 0.97–1.17 | 0.202 |
LMR (<2.4 vs. ≥2.4) | 1.77 | 1.04–3.00 | 0.034 | 1.01 | 0.73–1.37 | 0.993 |
PLR (≥170 vs. <170) | 1.44 | 0.85–2.42 | 0.174 | |||
Tumor location (Ce vs. Ut/Mt/Lt/EGJ) | 1.02 | 0.42–2.48 | 0.968 | |||
c T stage (4b vs. 1/2/3/4a) | 2.08 | 1.20–3.61 | 0.009 | |||
c N stage (3 vs. 0/1/2) | 0.86 | 0.51–1.43 | 0.556 | |||
c M stage (1 vs. 0) | 0.85 | 0.47–1.51 | 0.568 | |||
cT4b | ||||||
Aorta | 1.58 | 0.64–3.91 | 0.319 | |||
Airway | 2.48 | 1.39–4.42 | 0.002 | 2.90 | 1.53–5.51 | 0.001 |
Distant metastasis | ||||||
Retroperitoneal LN | 1.25 | 0.71–2.22 | 0.443 | |||
Liver | 1.72 | 0.92–3.20 | 0.089 | |||
Bone | 2.40 | 1.32–4.36 | 0.004 | 2.18 | 1.11–4.30 | 0.024 |
Lung | 1.08 | 0.63–1.86 | 0.786 | |||
Adrenal | 1.37 | 0.38–4.99 | 0.631 | |||
Histopathology (SCC vs. ADC) | 0.80 | 0.34–1.91 | 0.621 | |||
MDT (yes vs. no) | 0.50 | 0.30–0.84 | 0.009 | 0.65 | 0.37–1.15 | 0.139 |
Liver cirrhosis (yes vs. no) | 3.41 | 1.34–8.67 | 0.010 | 3.20 | 1.15–8.91 | 0.026 |
dCRT Incomplete (N = 90) | dCRT Complete (N = 183) | |||
---|---|---|---|---|
Grade 3 | Grade 4 | Grade 3 | Grade 4 | |
Hematological (%) | ||||
Leukopenia | 15 (16.7) | 18 (20.0) | 48 (26.2) | 20 (10.9) |
Anemia | 23 (25.6) | 2 (2.2) | 33 (18.0) | 2 (1.1) |
Thrombocytopenia | 9 (10.0) | 14 (15.6) | 22 (12.0) | 5 (2.7) |
Non-hematological (%) | ||||
Respiratory system | 20 (22.2) | 13 (14.4) | 22 (12.0) | 9 (4.9) |
Gastrointestinal tract | 23 (25.6) | 5 (5.5) | 12 (6.6) | 4 (2.2) |
Renal insufficiency | 2 (2.2) | 2 (2.2) | 0 (0) | 1 (0.5) |
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Pai, C.-P.; Chien, L.-I.; Huang, C.-S.; Hsu, H.-S.; Hsu, P.-K. Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer. Cancers 2023, 15, 5421. https://doi.org/10.3390/cancers15225421
Pai C-P, Chien L-I, Huang C-S, Hsu H-S, Hsu P-K. Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer. Cancers. 2023; 15(22):5421. https://doi.org/10.3390/cancers15225421
Chicago/Turabian StylePai, Chu-Pin, Ling-I Chien, Chien-Sheng Huang, Han-Shui Hsu, and Po-Kuei Hsu. 2023. "Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer" Cancers 15, no. 22: 5421. https://doi.org/10.3390/cancers15225421