Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
Statistics
3. Results
3.1. Patient Characteristics
3.2. Clinical Factors and pCR
3.3. Univariate and Multivariate Analyses for pCR
3.4. Predictive Model for pCR
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Treatment | scRT | CRT | scRT/CRT + CTX | All Patients | p-Value | |
---|---|---|---|---|---|---|
n = 435 (44%) | n = 358 (36%) | n = 201 (20%) | n = 994 (100%) | |||
Age | Median (range) | 73 (43–91) | 64 (31–81) | 64 (23–82) | 66 (23–91) | 0.003 |
≤70 years | 183 (42%) | 287 (80%) | 156 (78%) | 626(63%) | <0.001 | |
>70 years | 252 (58%) | 71 (20%) | 45 (22%) | 368 (37%) | ||
Sex | Female | 173 (40%) | 150 (42%) | 85 (42%) | 408 (41%) | 0.768 |
Male | 262 (60%) | 208 (58%) | 116 (58%) | 586 (59%) | ||
MRI T-stage | cT1-2 | 50 (12%) | 10 (3%) | 2 (1%) | 62 (6%) | <0.001 |
cT3 | 260 (60%) | 170 (47%) | 102 (51%) | 532 (54%) | ||
cT4 | 125 (28%) | 178 (50%) | 96 (48%) | 399 (40%) | ||
Missing | 0 (0%) | 0 (0%) | 1 (0.5%) | 1 (0.1%) | ||
MRI N-stage | cN0 | 124 (29%) | 37 (10%) | 10 (5%) | 171 (17%) | <0.001 |
cN1-2 | 309 (71%) | 321 (90%) | 191 (95%) | 821 (83%) | ||
Missing | 2 (0.5%) | 0 (0%) | 0 (0%) | 2 (0.2%) | ||
MRI Mesorectal | No | 254 (58%) | 86 (24%) | 61 (30%) | 401 (40%) | <0.001 |
fascia engagement | Yes | 175 (40%) | 272 (76%) | 139 (69%) | 586 (59%) | |
Missing | 6 (2%) | 0 (0%) | 1 (0.5%) | 7 (0.7%) | ||
MRI Extramural | No | 296 (68%) | 201 (56%) | 94 (47%) | 591 (60%) | <0.001 |
vascular invasion | Yes | 129 (30%) | 157 (44%) | 105 (52%) | 391 (39%) | |
Missing | 10 (2%) | 0 (0%) | 2 (1%) | 12 (1%) | ||
MRI Mucinous tumour | No | 369 (85%) | 301 (84%) | 142 (71%) | 812 (82%) | <0.001 |
Yes | 55 (13%) | 57 (16%) | 56 (28%) | 168 (17%) | ||
Missing | 11 (2%) | 0 (0%) | 3 (1%) | 14 (1%) | ||
MRI Lateral lymph nodes | No | 242 (56%) | 202 (56%) | 52 (26%) | 496 (50%) | <0.001 |
Yes | 44 (10%) | 68 (19%) | 27 (13%) | 139 (14%) | ||
Missing | 149 (34%) | 88 (25%) | 122 (61%) | 359 (36%) | ||
MRI Tumour length | ≤3.5 cm | 87 (20%) | 27 (8%) | 22 (11%) | 136 (14%) | <0.001 |
>3.5 cm | 320 (74%) | 319 (89%) | 173 (86%) | 812 (82%) | ||
Missing | 27 (6%) | 12 (3%) | 6 (3%) | 45 (4%) | ||
Distance anal verge | 0–5 cm | 179 (41%) | 144 (40%) | 64 (32%) | 387 (39%) | 0.050 |
6–10 cm | 164 (38%) | 147 (41%) | 80 (40%) | 391 (39%) | ||
11–15 cm | 92 (21%) | 67 (19%) | 57 (28%) | 216 (22%) | ||
Weeks from end of RT | ≤8 | 244 (56%) | 141 (39%) | 29 (14%) | 414 (42%) | <0.001 |
to surgery | 8–11 | 92 (21%) | 133 (37%) | 18 (9%) | 243 (24%) | |
>11 | 99 (23%) | 84 (24%) | 154 (77%) | 337 (34%) | ||
Haemoglobin | >110 g/L | 291 (67%) | 327 (91%) | 179 (89%) | 797 (80%) | 0.100 |
≤110 g/L | 54 (12%) | 30 (8%) | 21 (10%) | 105 (11%) | ||
Missing | 90 (21%) | 1 (0.2%) | 1 (0.5%) | 92 (9%) | ||
Leucocytes | ≤109/L | 257 (59%) | 302 (84%) | 155 (77%) | 714 (72%) | 0.122 |
>109/L | 63 (15%) | 49 (14%) | 28 (14%) | 140 (14%) | ||
Missing | 115 (26%) | 7 (2%) | 18 (9%) | 140 (14%) | ||
Thrombocytes | ≤4009/L | 176 (41%) | 239 (67%) | 69 (34%) | 484 (49%) | 0.598 |
>4009/L | 19 (4%) | 31 (9%) | 10 (5%) | 60 (6%) | ||
Missing | 240 (55%) | 88 (24%) | 122 (61%) | 450 (45%) | ||
C-reactive protein | ≤10 mg/L | 186 (43%) | 251 (70%) | 108 (54%) | 545 (55%) | <0.001 |
>10 mg/L | 86 (20%) | 47 (13%) | 45 (22%) | 178 (18%) | ||
Missing | 163 (38%) | 60 (17%) | 48 (24%) | 271 (27%) | ||
Carcinoembryonic antigen | ≤5 µ/L | 198 (45%) | 187 (52%) | 119 (59%) | 504 (51%) | 0.441 |
>5 µ/L | 107 (25%) | 124 (35%) | 76 (38%) | 307 (31%) | ||
Missing | 130 (30%) | 47 (13%) | 6 (3%) | 183 (18%) | ||
Pathologic | Non-pCR | 402 (92%) | 310 (87%) | 158 (79%) | 870 (87%) | <0.001 |
complete response | pCR | 33 (8%) | 48 (13%) | 43 (21%) | 124 (13%) |
Non-pCR | pCR | p-Value | ||
---|---|---|---|---|
n = 870 (Row%) | n = 124 (Row%) | |||
Age | Median (range) | 68 (23–91) | 65 (38–84) | 0.003 |
≤70 years | 531 (85%) | 95 (15%) | 0.001 | |
>70 years | 339 (92%) | 29 (8%) | ||
Sex | Female | 351 (86%) | 57 (14%) | 0.234 |
Male | 519 (89%) | 67 (11%) | ||
MRI T-stage | cT1-2 | 48 (77%) | 14 (23%) | 0.027 |
cT3 | 464 (87%) | 68 (13%) | ||
cT4 | 357 (90%) | 42 (10%) | ||
Missing | 1 | 0 | ||
MRI N-stage | cN0 | 152 (89%) | 19 (11%) | 0.546 |
cN1-2 | 716 (87%) | 105 (13%) | ||
Missing | 2 | 0 | ||
MRI Mesorectal fascia | No | 346 (86%) | 55 (14%) | 0.366 |
engagement | Yes | 517 (88%) | 69 (12%) | |
Missing | 7 | 0 | ||
MRI Extramural | No | 513 (87%) | 78 (13%) | 0.190 |
vascular invasion | Yes | 348 (89%) | 43 (11%) | |
Missing | 9 | 3 | ||
MRI Mucinous tumour | No | 713 (88%) | 99 (12%) | 0.456 |
Yes | 144 (86%) | 24 (14%) | ||
Missing | 13 | 1 | ||
MRI Lateral lymph nodes | No | 441 (89%) | 55 (11%) | 0.083 |
Yes | 116 (84%) | 23 (17%) | ||
Missing | 313 | 46 | ||
MRI Tumour length | ≤3.5 cm | 109 (80%) | 27 (20%) | 0.010 |
>3.5 cm | 716 (88%) | 96 (12%) | ||
Missing | 44 | 1 | ||
Distance anal verge | 0–5 cm | 332 (86%) | 55 (14%) | 0.414 |
6–10 cm | 347 (89%) | 44 (11%) | ||
11–15 cm | 191 (88%) | 25 (12%) | ||
Weeks from end of RT | ≤8 | 371 (90%) | 43 (10%) | 0.110 |
to surgery | 8–11 | 214 (88%) | 29 (12%) | |
>11 | 285 (85%) | 52 (15%) | ||
Haemoglobin | >110 g/L | 689 (86%) | 108 (14%) | 0.088 |
≤110 g/L | 97 (92%) | 8 (8%) | ||
Missing | 84 | 8 | ||
Leucocytes | ≤109/L | 614 (86%) | 100 (14%) | 0.014 |
>109/L | 131 (94%) | 9 (6%) | ||
Missing | 125 | 15 | ||
Thrombocytes | ≤4009/L | 418 (86%) | 66 (14%) | 0.023 |
>4009/L | 58 (97%) | 2 (2%) | ||
Missing | 394 | 56 | ||
C-reactive protein | ≤10 mg/L | 468 (86%) | 77 (14%) | <0.001 |
>10 mg/L | 160 (90%) | 18 (10%) | ||
Missing | 242 | 29 | ||
Carcinoembryonic antigen | ≤5 µ/L | 424 (84%) | 80 (16%) | 0.001 |
>5 µ/L | 281 (92%) | 26 (8%) | ||
Missing | 165 | 18 | ||
Treatment group | scRT | 402 (92%) | 33 (8%) | <0.001 |
CRT | 310 (87%) | 48 (13%) | ||
scRT/CRT + CTX | 158 (79%) | 43 (21%) | ||
Cohort | A Uppsala/Dalarna | 313 (87%) | 46 (13%) | 0.808 |
B Stockholm | 557 (88%) | 78 (12%) |
scRT | CRT | scRT/CRT + Chemo | Total | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Total | pCR | Total | pCR | Total | pCR | Total | pCR | ||||||
435 | 33 | Row % | 358 | 48 | Row % | 201 | 43 | Row % | 994 | 124 | Row % | ||
Sex | Female | 173 | 10 | 6% | 150 | 23 | 15% | 85 | 24 | 28% | 408 | 57 | 14% |
Male | 262 | 23 | 9% | 208 | 25 | 12% | 116 | 19 | 16% | 586 | 67 | 11% | |
Age | ≤70 years | 183 | 19 | 10% | 287 | 42 | 15% | 156 | 34 | 22% | 626 | 95 | 15% |
>70 years | 252 | 14 | 6% | 71 | 6 | 8% | 45 | 9 | 20% | 368 | 29 | 8% | |
MRI T-stage | cT1-2 | 50 | 9 | 18% | 10 | 5 | 50% | 2 | 0 | 0% | 62 | 14 | 23% |
cT3 | 260 | 19 | 7% | 170 | 23 | 14% | 102 | 26 | 25% | 532 | 68 | 13% | |
cT4 | 125 | 5 | 4% | 178 | 20 | 11% | 96 | 17 | 18% | 399 | 42 | 11% | |
Missing | 0 | 0 | 0 | 0 | 1 | 0 | 0% | 1 | 0 | 0% | |||
MRI N-stage | cN0 | 124 | 12 | 10% | 37 | 5 | 14% | 10 | 2 | 20% | 171 | 19 | 11% |
cN1-2 | 309 | 21 | 7% | 321 | 43 | 13% | 191 | 41 | 21% | 821 | 105 | 13% | |
Missing | 2 | 0 | 0% | 0 | 0 | 0 | 0 | 2 | 0 | 0% | |||
MRI Mesorectal fascia | MRF- | 254 | 26 | 10% | 86 | 14 | 16% | 61 | 15 | 25% | 401 | 55 | 14% |
MRF+ | 175 | 7 | 4% | 272 | 34 | 13% | 139 | 28 | 20% | 586 | 69 | 12% | |
Missing | 6 | 0 | 0% | 0 | 0 | 1 | 0 | 0% | 7 | 0 | 0% | ||
MRI Extramural | EMVI- | 296 | 28 | 9% | 201 | 30 | 15% | 94 | 20 | 21% | 591 | 78 | 13% |
vascular invasion | EMVI+ | 129 | 4 | 3% | 157 | 18 | 11% | 105 | 21 | 20% | 391 | 43 | 11% |
Missing | 10 | 1 | 10% | 0 | 0 | 2 | 2 | 100% | 12 | 3 | 25% | ||
MRI Mucinous tumour | Non-mucinous | 369 | 30 | 8% | 301 | 40 | 13% | 142 | 29 | 20% | 812 | 99 | 12% |
Mucinous | 55 | 2 | 4% | 57 | 8 | 14% | 56 | 14 | 25% | 168 | 24 | 14% | |
Missing | 11 | 1 | 9% | 0 | 0 | 3 | 0 | 0% | 14 | 1 | 7% | ||
MRI Lateral lymph | No lat. nodes | 242 | 18 | 7% | 202 | 26 | 13% | 52 | 11 | 21% | 496 | 55 | 11% |
nodes | Lateral nodes | 44 | 5 | 11% | 68 | 11 | 16% | 27 | 7 | 26% | 139 | 23 | 17% |
Missing | 149 | 10 | 7% | 88 | 11 | 13% | 122 | 25 | 20% | 359 | 46 | 13% | |
MRI Tumour length | ≤3.5 cm | 87 | 10 | 11% | 27 | 9 | 33% | 22 | 8 | 36% | 136 | 27 | 20% |
>3.5 cm | 320 | 23 | 7% | 319 | 38 | 12% | 173 | 35 | 20% | 812 | 96 | 12% | |
Missing | 27 | 0 | 0% | 12 | 1 | 8% | 6 | 0 | 0% | 45 | 1 | 2% | |
Distance anal verge | 0–5 cm | 179 | 16 | 9% | 144 | 22 | 15% | 64 | 17 | 27% | 387 | 55 | 14% |
6–10 cm | 164 | 10 | 6% | 147 | 17 | 12% | 80 | 17 | 21% | 391 | 44 | 11% | |
11–15 cm | 92 | 7 | 8% | 67 | 9 | 13% | 57 | 9 | 16% | 216 | 25 | 12% | |
Weeks from RT to | ≤8 | 244 | 22 | 9% | 141 | 17 | 12% | 29 | 4 | 14% | 414 | 43 | 10% |
surgery | 8–11 | 92 | 7 | 8% | 133 | 20 | 15% | 18 | 2 | 11% | 243 | 29 | 12% |
>11 | 99 | 4 | 4% | 84 | 11 | 13% | 154 | 37 | 24% | 337 | 52 | 15% | |
Haemoglobin | >110 g/L | 291 | 22 | 8% | 327 | 47 | 14% | 179 | 39 | 22% | 797 | 108 | 14% |
≤110 g/L | 54 | 3 | 6% | 30 | 1 | 3% | 21 | 4 | 19% | 105 | 8 | 8% | |
Missing | 90 | 8 | 9% | 1 | 0 | 0% | 1 | 0 | 0% | 92 | 8 | 9% | |
Leucocytes | ≤109/L | 257 | 19 | 7% | 302 | 44 | 15% | 155 | 37 | 24% | 714 | 100 | 14% |
>109/L | 63 | 3 | 5% | 49 | 3 | 6% | 28 | 3 | 11% | 140 | 9 | 6% | |
Missing | 115 | 11 | 10% | 7 | 1 | 14% | 18 | 3 | 17% | 140 | 15 | 11% | |
Thrombocytes | ≤4009/L | 176 | 13 | 7% | 239 | 35 | 15% | 69 | 18 | 26% | 484 | 66 | 14% |
>4009/L | 19 | 0 | 0% | 31 | 2 | 6% | 10 | 0 | 0% | 60 | 2 | 3% | |
Missing | 240 | 20 | 8% | 88 | 11 | 13% | 122 | 25 | 20% | 450 | 56 | 12% | |
C-reactive protein | ≤10 mg/L | 186 | 14 | 8% | 251 | 36 | 14% | 108 | 27 | 25% | 545 | 77 | 14% |
>10 mg/L | 86 | 4 | 5% | 47 | 5 | 11% | 45 | 9 | 20% | 178 | 18 | 10% | |
Missing | 163 | 15 | 9% | 60 | 7 | 12% | 48 | 7 | 15% | 271 | 29 | 11% | |
Carcinoembryonic | ≤5 µ/L | 198 | 18 | 9% | 187 | 32 | 17% | 119 | 30 | 25% | 504 | 80 | 16% |
antigen | >5 µ/L | 107 | 3 | 3% | 124 | 11 | 9% | 76 | 12 | 16% | 307 | 26 | 8% |
Missing | 130 | 12 | 9% | 47 | 5 | 11% | 6 | 1 | 17% | 183 | 18 | 10% |
Univariate Analyses n = 994 | Multivariable Model n = 735 | ||||
---|---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | p-Value | ||
Age | Continuous | 0.97 (0.95–0.99) | 0.002 | ||
>70 years | 1.00 | 1.00 | |||
≤70 years | 2.09 (1.35–3.23) | 0.001 | 1.35 (0.77–2.37) | 0.291 | |
Sex | Male | 1.00 | |||
Female | 1.25 (0.86–1.83) | 0.234 | |||
MRI T-stage | cT4 | 1.00 | 1.00 | ||
cT3 | 1.24 (0.82–1.87) | 0.292 | 1.38 (0.85–2.28) | 0.193 | |
cT1-2 | 2.47 (1.26–4.87) | 0.008 | 3.37 (1.30–8.78) | 0.013 | |
MRI N-stage | cN1-2 | 1.00 | |||
cN0 | 1.173 (0.70–1.97) | 0.546 | |||
MRI Mesorectal fascia | MRF+ | 1.00 | |||
engagement | MRF- | 1.19 (0.81–1.74) | 0.367 | ||
MRI Extramural vascular | EMVI+ | 1.00 | |||
invasion | EMVI- | 1.23 (0.82–1.82) | 0.305 | ||
MRI Mucinous tumour | Mucinous | 1.00 | |||
Non-mucinous | 1.20 (0.72–1.94) | 0.456 | |||
MRI Lateral lymph nodes | Lateral lymph nodes | 1.00 | |||
No lateral lymph nodes | 0.62 (0.37–1.06 | 0.085 | |||
MRI Tumour length | >3.5 cm | 1.00 | 1.00 | ||
≤3.5 cm | 1.84 (1.15–2.96) | 0.011 | 2.27 (1.24–4.18) | 0.008 | |
Distance anal verge | 0–5 cm | 1.00 | |||
6–10 cm | 0.76 (0.50–1.17) | 0.217 | |||
11–15 cm | 0.79 (0.47–1.30) | 0.154 | |||
Weeks from RT to Surg. | ≤8 | 1.00 | 1.00 | ||
8–11 | 1.16 (0.70–1.92) | 0.540 | 1.61 (0.87–2.98) | 0.131 | |
>11 | 1.57 (1.02–2.42) | 0.040 | 1.45 (0.79–2.67) | 0.227 | |
Haemoglobin | ≤110 g/L | 1.00 | |||
>110 g/L | 1.90 (0.89–4.01) | 0.093 | |||
Leucocytes | >109/L | 1.00 | 1.00 | ||
≤109/L | 2.37 (1.16–4.81) | 0.017 | 2.02 (0.93–4.37) | 0.075 | |
Thrombocytes | >4009/L | 1.00 | |||
≤4009/L | 4.57 (1.09–19.2) | 0.037 | |||
C-reactive protein | ≤10 mg/L | 1.00 | |||
>10 mg/L | 1.46 (0.85–2.52) | 0.171 | |||
Carcinoembryonic antigen | >5 µ/L | 1.00 | 1.00 | ||
≤5 µ/L | 2.03 (1.27–3.25) | 0.003 | 1.73 (1.04–2.90) | 0.034 | |
Treatment group | scRT | 1.00 | 1.00 | ||
CRT | 1.89 (1.18–3.01) | 0.008 | 2.621 (1.34–5.14) | 0.005 | |
scRT/CRT + CTX | 3.32 (2.03–5.41) | <0.001 | 4.70 (2.23–9.93) | <0.001 |
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Karimi, M.; Osterlund, P.; Hammarström, K.; Imam, I.; Frodin, J.-E.; Glimelius, B. Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters. Cancers 2022, 14, 6238. https://doi.org/10.3390/cancers14246238
Karimi M, Osterlund P, Hammarström K, Imam I, Frodin J-E, Glimelius B. Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters. Cancers. 2022; 14(24):6238. https://doi.org/10.3390/cancers14246238
Chicago/Turabian StyleKarimi, Masoud, Pia Osterlund, Klara Hammarström, Israa Imam, Jan-Erik Frodin, and Bengt Glimelius. 2022. "Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters" Cancers 14, no. 24: 6238. https://doi.org/10.3390/cancers14246238
APA StyleKarimi, M., Osterlund, P., Hammarström, K., Imam, I., Frodin, J. -E., & Glimelius, B. (2022). Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters. Cancers, 14(24), 6238. https://doi.org/10.3390/cancers14246238