Introduction
Patients and methods
Patient selection
Treatments
Measurements
Follow-up
Statistical analysis
Results
Patient characteristics and cutoff point for weight loss
Factors |
N (%) | Pre-CRT | Post-CRT | Relative change (median, range) | Variation (95 % CI) |
P value |
---|---|---|---|---|---|---|
Pre-CRT BMI (mean ± SD, kg/m2) | ||||||
Total | 364 | 22.4 ± 3.1 | 22.3 ± 3.1 | −0.71 % (−25.97 to 30.91 %) | −0.163 (−0.295 to −0.030) | 0.02 |
≤18.5 | 40 (11.0) | 17.2 ± 1.3 | 17.4 ± 1.6 | 0 (−9.96 to 22.08 %) | 0.257 (−0.143 to 0.657) | 0.20 |
18.5–24 | 216 (59.3) | 21.6 ± 1.5 | 21.5 ± 1.8 | 0 (−14.29 to 30.91 %) | −0.077 (−0.240 to 0.086) | 0.35 |
>24 | 108 (29.7) | 26.1 ± 1.7 | 25.6 ± 2.0 | −1.29 % (−12.70 to 25.97 %) | −0.489 (−0.754 to −0.225) | <0.001 |
PreCRT body weight (mean ± SD, kg) | ||||||
Total | 364 | 60.5 ± 9.7 | 60.1 ± 9.8 | −0.71 % (−25.97 to 30.91 %) | −0.418 (−0.771 to −0.056) | 0.02 |
≤50 | 50 (13.7) | 45.5 ± 4.1 | 45.7 ± 5.1 | −1.10 % (−11.46 to 22.08 %) | 0.224 (−0.724 to 1.172) | 0.64 |
50–70 | 256 (70.3) | 60.1 ± 5.7 | 59.7 ± 6.2 | 0 (−17.07 to 30.91 %) | −0.330 (−0.731 to 0.071) | 0.11 |
>70 | 58 (15.9) | 75.4 ± 4.2 | 74.1 ± 5.8 | −1.32 % (−25.97 to 8.97 %) | −1.333 (−2.458 to −0.207) | 0.02 |
Variables | All patients
n = 364 (%) | BMI loss <7 %
n = 325 (%) | BMI loss ≥7 %
n = 39 (%) |
P value |
---|---|---|---|---|
Clinical variables
| ||||
Age, median (range) | 56 (15–80) | 55 (15–80) | 62 (33–76) | 0.007 |
Gender (male: female) | 259:115 | 224:101 | 25:14 | 0.54 |
Mean preCRT BMI (kg/m2) | 22.5 ± 3.1 | 22.4 ± 3.1 | 22.6 ± 2.9 | 0.72 |
Mean inferior tumor margin from anal verge, cm (SD) | 4.9 ± 2.2 | 4.9 ± 2.1 | 5.2 ± 2.7 | 0.35 |
cT stage | 0.46 | |||
3 | 216 (59.3) | 195 (60.0) | 21 (53.8) | |
4 | 148 (40.7) | 130 (40.0) | 18 (46.2) | |
cTNM stage | 0.12 | |||
II | 127 (34.9) | 109 (33.5) | 18 (46.2) | |
III | 237 (65.1) | 216 (66.5) | 21 (53.8) | |
Pathological variables
| ||||
Mean size of tumor after CRT, cm (SD) | 3.0 ± 1.6 | 3.0 ± 1.5 | 3.4 ± 1.9 | 0.14 |
Tumor differentiation | 0.90 | |||
Well and moderate | 283 (77.7) | 253 (77.8) | 30 (76.9) | |
Poor | 81 (22.3) | 72 (22.2) | 9 (23.1) | |
Median number of lymph nodes examined (range) | 6 (0–37) | 6 (0–37) | 6 (0–21) | 0.99 |
Median number of positive lymph nodes (range) | 0 (0–12) | 0 (0–12) | 0 (0–4) | 0.42 |
ypT stage | 0.42 | |||
0–2 | 181 (49.7) | 164 (50.5) | 17 (43.6) | |
3–4 | 183 (50.3) | 161 (49.5) | 22 (56.4) | |
ypN stage | 0.50 | |||
0 | 283 (77.7) | 251 (77.2) | 32 (82.1) | |
1–2 | 81 (22.3) | 74 (22.8) | 7 (17.9) | |
ypTNM stage | 0.87 | |||
0 | 85 (23.4) | 76 (23.4) | 9 (23.1) | |
I | 77 (21.2) | 69 (21.2) | 8 (20.5) | |
II | 121 (33.2) | 106 (32.6) | 15 (38.5) | |
III | 81 (22.2) | 74 (22.8) | 7 (17.9) | |
Achievement of pCR | 0.97 | |||
Yes | 85 (23.4) | 76 (23.4) | 9 (23.1) | |
No | 279 (76.6) | 249 (76.6) | 30 (76.9) |
Treatment characteristics and chemoradiotherapy toxicity
Variables | BMI loss <7 %
n = 325 (%) | BMI loss ≥7 %
n = 39 (%) |
P value |
---|---|---|---|
Preoperative chemoradiotherapy
| |||
Chemotherapy regimen | 0.25 | ||
XELOX | 273 (84.0) | 32 (82.1) | |
FOLFOX | 38 (11.7) | 7 (17.9) | |
Capecitabine | 14 (4.3) | 0 | |
Duration of chemotherapy, cycles (median, range) | 2 (1–4) | 2 (1–4) | 0.27 |
Completion of chemotherapy | 258 (79.4) | 28 (71.8) | 0.26 |
Completed dose of chemotherapy >50 % | 298 (91.7) | 37 (94.9) | 0.49 |
Dose of radiotherapy, Gy (range) | 46 (30–50) | 46 (30–50) | 0.32 |
Completion of radiotherapy | 317 (97.5) | 37 (94.9) | 0.35 |
Surgical operation
| |||
Interval from the completion of radiation to surgery, weeks (range) | 6.8 (1–12) | 7 (4–11) | 0.99 |
Surgical procedure | 0.66 | ||
Anterior resection | 187 (57.5) | 21 (53.8) | |
Abdominal perineal resection | 138 (42.5) | 18 (46.2) | |
Postoperative treatment
| |||
Adjuvant chemotherapy | 0.030 | ||
Yes | 271 (83.4) | 27 (69.2) | |
No | 54 (16.6) | 12 (30.8) | |
Duration of postoperative chemotherapy, weeks (median, range) | 12 (0–18) | 10.5 (0–18) | 0.019 |
Toxicity | BMI loss <7 %
n = 235 (%) | BMI loss ≥7 %
n = 39 (%) |
P value | Toxicity | BMI loss <7 %
n = 235 (%) | BMI loss ≥7 %
n = 39 (%) |
P value |
---|---|---|---|---|---|---|---|
Leucopenia
|
Rash
| ||||||
Total | 190 (58.5) | 26 (66.7) | 0.33 | Total | 40 (12.3) | 3 (7.7) | 0.40 |
Grade 1–2 | 176 (54.2) | 25 (64.1) | 0.24 | Grade 1–2 | 36 (11.1) | 1 (2.6) | 0.13 |
Grade 3–4 | 14 (4.3) | 1 (2.6) | 0.61 | Grade 3–4 | 4 (1.2) | 2 (5.1) | 0.10 |
Thrombocytopenia
|
Urination disorder
| ||||||
Total | 72 (22.2) | 9 (23.1) | 0.90 | Total | 10 (3.1) | 1 (2.6) | 0.86 |
Grade 1–2 | 62 (19.1) | 9 (23.1) | 0.55 | Grade 1–2 | 10 (3.1) | 1 (2.6) | 0.86 |
Grade 3–4 | 10 (3.1) | 0 | 1 | Grade 3–4 | 0 | 0 | |
Nausea/vomiting
|
Renal disorder
| ||||||
Total | 150 (46.2) | 19 (48.7) | 0.76 | Total | 2 (0.6) | 2 (5.1) | 0.033 |
Grade 1–2 | 149 (45.8) | 19 (48.7) | 0.73 | Grade 1–2 | 2 (0.6) | 2 (5.1) | 0.033 |
Grade 3–4 | 1 (0.3) | 0 | 1 | Grade 3–4 | 0 | 0 | |
Diarrhea
|
Hepatic disorder
| ||||||
Total | 102 (31.4) | 19 (48.7) | 0.033 | Total | 44 (13.5) | 7 (17.9) | 0.46 |
Grade 1–2 | 91 (28.0) | 16 (41.0) | 0.09 | Grade 1–2 | 42 (12.9) | 7 (17.9) | 0.39 |
Grade 3–4 | 11 (3.4) | 3 (7.7) | 0.20 | Grade 3–4 | 2 (0.6) | 0 | 1 |
Hand-foot syndrome
|
Neurotoxicity
| ||||||
Total | 225 (69.2) | 27 (69.2) | 1 | Total | 53 (16.3) | 5 (12.8) | 0.58 |
Grade 1–2 | 216 (66.5) | 25 (64.1) | 0.77 | Grade 1–2 | 53 (16.3) | 5 (12.8) | 0.58 |
Grade 3–4 | 9 (2.8) | 2 (5.1) | 0.42 | Grade 3–4 | 0 | 0 | |
Radiation proctitis
| |||||||
Total | 198 (60.9) | 24 (61.5) | 0.94 | ||||
Grade 1–2 | 192 (59.1) | 21 (53.8) | 0.53 | ||||
Grade 3–4 | 6 (1.8) | 3 (7.7) | 0.041 |
Survival outcomes and severe weight loss
Variable | Univariate | Multivariate | ||
---|---|---|---|---|
HR (95 % CI) |
P value | HR (95 % CI) |
P value | |
Age >60 year | 1.360 (0.856–2.162) | 0.19 | ||
Gender (female) | 1.139 (0.702–1.847) | 0.60 | ||
PreCRT BMI ≤18.5 kg/m2
| 1.248 (0.640–2.436) | 0.52 | ||
PreCRT weight ≤50 kg | 1.430 (0.784–2.607) | 0.24 | ||
cT stage 4 | 1.439 (0.867–2.387) | 0.16 | ||
cTNM stage III | 1.269 (0.734–2.193) | 0.39 | ||
DAV ≤ 5 cm | 1.158 (0.947–1.417) | 0.15 | ||
Tumor size ≥3 cm | 1.158 (0.701–1.915) | 0.57 | ||
Histopathology (poor grade) | 1.175 (0.689–2.002) | 0.55 | ||
Number of retrieved LNs ≥12 | 0.776 (0.456–1.322) | 0.35 | ||
ypT stage 3–4 | 2.411 (1.462–3.976) | 0.001 | 1.781 (1.054–3.010) | 0.031 |
ypN stage 1–2 | 3.227 (2.031–5.126) | <0.001 | 2.571 (1.576–4.192) | <0.001 |
Preoperative CRT with oxaliplatin | 0.466 (0.202–1.075) | 0.07 | ||
Completed dose of preoperative chemotherapy >50 % | 0.470 (0.253–0.874) | 0.017 | 0.532 (0.284–0.997) | 0.049 |
Radiotherapy completion | 0.627 (0.195–2.015) | 0.43 | ||
Anterior resection | 0.694 (0.438–1.100) | 0.12 | ||
Acceptance of postoperative chemotherapy | 0.798 (0.457–1.393) | 0.43 | ||
Duration of postoperative chemotherapy ≥12 weeks | 0.843 (0.489–1.453) | 0.45 | ||
BMI loss ≥7 % during preoperative CRT | 1.961 (1.055–3.647) | 0.030 | 1.984 (1.061–3.709) | 0.032 |