Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Cohort Outline
2.2. The Clinical Characteristics of BR-PDAC Patients
2.3. Comparison of Prognosis of Upfront Surgery vs. Neoadjuvant Treatment by Intention to Treat Analysis
2.4. Comparison of Regimens in Neoadjuvant Treatment Induction Cases
2.5. Prognostic Factors in Patients Who Underwent Resection after NAT
2.5.1. Definition of Cutoff Values for PNI
2.5.2. Univariate and Multivariate Analyses of Prognostic Factors in BR-PDAC Patients Who Underwent Resection after Neoadjuvant Treatment
2.5.3. Prognosis of BR-PDAC Patients Who Underwent Resection after Neoadjuvant Treatment Based on PNI
3. Discussion
3.1. BR-PV
3.2. BR-A
3.3. BR-PV and BR-A
4. Materials and Methods
4.1. Study Design
- Comparison of prognosis of upfront surgery vs. NAT by intention to treat analysis;
- Comparison of regimens in patients who underwent NAT;
- Prognostic factors in patients who underwent resection after NAT.
4.2. Definitions of BR-PV PDAC and BR-A PDAC Patients
4.3. Neoadjuvant Treatment
4.4. Postoperative Adjuvant Therapy
4.5. Data Collection
4.6. Nutritional Status
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Variable | BR-PV (n = 88) | BR-A (n = 111) | Variable | BR-PV (n = 88) | BR-A (n = 111) |
---|---|---|---|---|---|
Sex (male/female) | 51/37 | 55/56 | Surgical procedures | ||
Age, years * | 66 (39–83) | 67 (42–83) | Pancreatoduodenectomy | 74 (84%) | 67 (60%) |
Body mass index * | 21.1 (15.4–43.6) | 21.2 (11.6–30.7) | Distal pancreatectomy | 1 (1%) | 13 (12%) |
Tumor location | Total pancreatectomy | 7 (8%) | 6 (5%) | ||
Head/Uncinate | 84 (95%) | 83 (75%) | Operative time, min * | 508 (308–960) | 501 (193–808) |
Body/Tail | 4 (5%) | 28 (25%) | Blood loss volume, mL * | 1075 (258–6000) | 1090 (80–9845) |
CA19-9 at diagnosis, U/mL * | 179 (1–2900) | 150 (1–6340) | Operative PRBC transfusion | 34 (41%) | 30 (34%) |
Chemotherapy | Vascular resection | ||||
no | 46 (52%) | 48 (43%) | Any venous resection | 72 (82%) | 62 (56%) |
FFX/GnP | 26 (30%) | 36 (32%) | Any arterial resection | 5 (6%) | 12 (14%) |
GS | 2 (2%) | 27 (24%) | Celiac axis | 0 | 5 |
GS + Radiation | 14 (16%) | 14 (13%) | Hepatic artery | 4 | 8 |
Length of therapy, mo * | 2.1 (1.1–6.6) | 2.7 (0.2–12.9) | Splenic artery | 1 | 0 |
Tumor size at operation, mm * | 30 (9–100) | 30 (10–100) | Both venous and arterial | 5 (6%) | 8 (9%) |
CA19-9 at operation, U/mL * | 93 (1–9869) | 102 (1–7316) | Positive lymph nodes | 54 (66%) | 58 (67%) |
in upfront surgery group | 196 (1–9869) | 321.5 (1–7316) | R0 margin status | 59 (72%) | 49 (56%) |
in resection after NAT group | 41 (1–1500) | 34 (1–2690) | 90-day operative mortality | 1 (1%) | 1 (1%) |
CA19-9 normalized | 17 (47%) | 17 (27%) | Adjuvant chemotherapy | 56 (68%) | 75 (86%) |
CA19-9 decrease rate ≥90% | 7 (19%) | 9 (19%) | Recurrent disease | 42 (51%) | 58 (67%) |
Nutrition at operation | Vital status at last follow-up | ||||
CONUT * | 2 (0–11) | 2 (0–11) | Alive, no evidence of recurrence | 32 (36%) | 34 (31%) |
GPS * | 0 (0–2) | 0 (0–2) | Alive, with recurrence | 7 (8%) | 19 (17%) |
mGPS * | 0 (0–2) | 0 (0–2) | Not alive | 49 (56%) | 58 (52%) |
NLR * | 2.4 (0.8–20.4) | 2.5 (0.7–15) | |||
PLR * | 129.2 (0.1–416.5) | 83.0 (0.05–522.5) | |||
PNI * | 46.0 (28.5–56.2) | 44.5 (26.3–55.5) | |||
LMR * | 3.6 (1.0–40.4) | 3.8 (1.0–10.9) | |||
SII * | 380.1 (0.2–2180.5) | 482.8 (0.1–3669.2) | |||
CRP/Alb * | 0.07 (0–2.0) | 0.03 (0.002–2.2) |
Variable | BR-PV (n = 82) | BR-A (n = 87) |
---|---|---|
Sex (male/female) | 47/35 | 44/43 |
Age, years * | 65 (39–83) | 67 (42–83) |
Chemotherapy | ||
no | 46 (56%) | 48 (55%) |
FFX/GnP | 26 (32%) | 36 (30%) |
GS | 2 (2%) | 27 (31%) |
GS + Radiation | 14 (17%) | 14 (16%) |
Tumor size at operation, mm * | 30 (9–100) | 30 (10–100) |
CA19-9 at operation, U/mL * | 93 (1–9869) | 102 (1–7316) |
in upfront surgery group | 196 (1–9869) | 321.5 (1–7316) |
in resection after NAT group | 41 (1–1500) | 34 (1–2690) |
CA19-9 normalized | 17 (21%) | 17 (20%) |
Surgical procedures | ||
Pancreatoduodenectomy | 74 (90%) | 67 (77%) |
Distal pancreatectomy | 1 (1%) | 13 (15%) |
Total pancreatectomy | 7 (10%) | 6 (7%) |
Operative time, min * | 508 (308–960) | 501 (193–808) |
Blood loss volume, mL * | 1075 (258–6000) | 1090 (80–9845) |
Operative PRBC transfusion | 34 (41%) | 30 (34%) |
Vascular resection | ||
Any venous resection | 72 (88%) | 62 (71%) |
Any arterial resection | 5 (6%) | 12 (14%) |
Celiac axis | 0 | 5 |
Hepatic artery | 4 | 8 |
Splenic artery | 1 | 0 |
Both venous and arterial | 5 (6%) | 8 (9%) |
Positive lymph nodes | 54 (66%) | 58 (67%) |
R0 margin status | 59 (72%) | 49 (56%) |
90-day operative mortality | 1 (1%) | 1 (1%) |
Adjuvant chemotherapy | 56 (68%) | 75 (86%) |
Variable | BR-PV (n = 88) | BR-A (n = 111) | ||
---|---|---|---|---|
UFS (n = 46) | NAT (n = 42) | UFS (n = 48) | NAT (n = 63) | |
Sex (male/female) | 27/19 | 24/18 | 27/22 | 28/35 |
Age, years * | 64 (39–83) | 66 (40–81) | 66 (42–83) | 68 (45–82) |
Body mass index * | 20.1 (15.5–32.1) | 21.4 (15.4–43.6) | 20.9 (17.1–27.5) | 21.4 (11.6–30.7) |
Tumor location | ||||
Head/Uncinate | 44 (96%) | 40 (95%) | 38 (79%) | 45 (71%) |
Body/Tail | 2 (4%) | 2 (5%) | 10 (21%) | 18 (29%) |
CA19-9 at diagnosis, U/mL * | N/A | 178.5 (1–2900) | N/A | 150 (1–6340) |
CA19-9 at operation, U/mL * | 196 (1–9869) | 41 (1–5661) | 321 (1–7316) | 65 (1–5870) |
Comorbidity (yes/no) | ||||
Diabetes | 20/26 | 11/26 | 23/25 | 13/34 |
History of other cancers | 6/40 | 1/36 | 5/43 | 8/40 |
Pancreatitis | 5/41 | 0/37 | 11/37 | 1/47 |
Hepatitis | 2/44 | 1/36 | 4/44 | 3/45 |
Hypertension | 11/35 | 12/25 | 13/35 | 19/29 |
Renal dysfunction | 1/45 | 0/37 | 0/48 | 0/48 |
Nutrition at operation | ||||
CONUT * | 1.5 (0–10) | 3 (0–11) | 2 (0–11) | 2 (0–10) |
GPS * | 0 (0–2) | 0 (0–1) | 0 (0–2) | 0 (0–1) |
mGPS * | 0 (0–2) | 0 (0–2) | 0 (0–2) | 0 (0–2) |
NLR * | 2.2 (1.1–20.4) | 2.9 (0.8–8.6) | 2.6 (1.0–9.7) | 2.5 (0.7–15) |
PLR * | 97.7 (0.1–325.5) | 166 (67.4–416.5) | 104.2 (0.05–290) | 184.9 (57.9–522.5) |
PNI * | 46.3 (29.5–56.2) | 44.8 (28.5–52.5) | 44.5 (26.3–55.5) | 43 (32–51.5) |
LMR * | 4.1 (2.2–6.5) | 3.1 (1.0–40.4) | 5.4 (1.4–10.9) | 3.5 (1–6.1) |
SII * | 300 (0.2–2180.5) | 600 (168.4–1786.9) | 376.9 (0.1–1944.4) | 530.8 (95.1–3669.2) |
CRP/Alb * | 0.07 (0–2.0) | 0.07 (0–3.3) | 0.02 (0.002–1.0) | 0.03 (0.002–2.2) |
BR-PV (n = 42) | BR-A (n = 63) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n | MST (Months) | CA19-9 Normalized | Resection | R0 Rate | Evans Grade ≥IIb | n | MST (Months) | CA19-9 Normalized | Resection | R0 Rate | Evans Grade ≥IIb | |
FFX/GnP | 26 | 32.9 | 47% | 22 (85%) | 86% | 24% | 29 | 35.4 | 40% | 17 (59%) | 71% | 21% |
FFX/GnP with RT | 0 | 7 | 18.7 | 75% | 4 (57%) | 100% | 0% | |||||
Old NAC | 2 | 10 | 0% | 2 (100%) | 50% | 0% | 10 | 43.2 | 38% | 9 (90%) | 67% | 0% |
Old NAC with RT | 14 | 20.6 | 50% | 12 (86%) | 100% | 36% | 17 | 19.7 | 20% | 9 (53%) | 100% | 33% |
BR-PV Univariate | BR-PV Multivariate | BR-A Univariate | BR-A Multivariate | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Clinical Factor | No. Patients (n = 36) | HR (95% CI) | p | HR (95% CI) | p | No. Patients (n = 39) | HR (95% CI) | p | HR (95% CI) | p |
Radiation in NAT | 12 | 0.96 (0.23–4.04) | 0.955 | 12 | 1.37 (0.38–4.87) | 0.63 | ||||
CA19-9 Before NAT >192 U/mL | 17 | 2.37 (0.58–9.64) | 0.23 | 19 | 0.41 (0.22–1.48) | 0.175 | ||||
Preoperative CA19-9 >34 U/mL | 17 | 1.05 (0.26–4.27) | 0.945 | 19 | 3.90 (0.97–15.72) | 0.056 | ||||
Tumor marker normalization | 20 | 0.16 (0.031–0.82) | 0.028 * | 0.28 (0.05–1.71) | 0.168 | 16 | 0.10 (0.01–0.83) | 0.033 * | 0.15 (0.01–1.57) | 0.064 |
Preoperative Alb >3.8 g/dL | 14 | 0.55 (0.14–2.24) | 0.404 | 17 | 0.30 (0.06–1.46) | 0.137 | ||||
Preoperative CONUT score, >4 | 5 | 3.78 (0.92–15.56) | 0.065 | 9 | 2.48 (0.66–9.34) | 0.179 | ||||
Preoperative GPS 0 | 16 | 0.15 (0.03–0.79) | 0.025 * | 0.50 (0.05–4.68) | 0.547 | 10 | 0.52 (0.07–3.78) | 0.52 | ||
Preoperative mGPS 0 | 14 | 0.25 (0.05–1.28) | 0.095 | 22 | 0.26 (0.06–1.08) | 0.064 | ||||
Preoperative NLR >2.52 | 16 | 3.17 (0.39–25.86) | 0.281 | 18 | 1.47 (0.39–5.51) | 0.571 | ||||
Preoperative PLR >184 | 11 | 0.97 (0.23–4.10) | 0.972 | 19 | 4.15 (0.85–20.26) | 0.079 | ||||
Preoperative PNI >42.5 | 16 | 0.15 (0.03–0.76) | 0.022 * | 0.32 (0.03–2.98) | 0.316 | 21 | 0.13 (0.03–0.65) | 0.013 * | 0.15 (0.02–0.85) | 0.014 * |
Preoperative LMR >3.50 | 9 | 0.19 (0.02–1.72) | 0.141 | 14 | 0.42 (0.11–1.64) | 0.214 | ||||
Preoperative SII >512 | 15 | 0.89 (0.21–3.74) | 0.873 | 19 | 4.34 (0.84–22.49) | 0.08 | ||||
Preoperative CRP/Alb >0.062 | 12 | 2.20 (0.43–11.16) | 0.341 | 10 | 1.75 (0.43–7.08) | 0.431 | ||||
Preoperative diabetes | 11 | 0.78 (0.18–3.33) | 0.739 | 13 | 0.91 (0.23–3.55) | 0.9 | ||||
Preoperative treatment period >60 day | 19 | 1.23 (0.15–10.09) | 0.844 | 29 | 0.46 (0.12–1.67) | 0.237 | ||||
Preoperative treatment period >90 day | 7 | 1.72 (0.34–8.67) | 0.509 | 14 | 1.07 (0.28–4.18) | 0.918 | ||||
Operative time >560 min | 7 | 3.12 (0.74–13.14) | 0.121 | 20 | 1.73 (0.49–6.09) | 0.396 | ||||
Intraoperative blood loss >830 ml | 21 | 1.06 (0.25–4.45) | 0.941 | 20 | 7.42 (1.53–36.1) | 0.013 * | 2.23 (0.37–13.35) | 0.358 |
Resectability | SubClass | Detail |
---|---|---|
1. Resectable (R) | No contact of the tumor with the SMV/PV. | |
Abutment/encasement of the SMV/PV of <180° circumference without occlusion (termed R-PV). | ||
No contact with any major artery (CA, SMA, or CHA). | ||
2. Borderline resectable (BR) | BR-PV | |
Tumor abutment/encasement or occlusion of the SMV/PV of ≥180°. | ||
No arterial tumor abutment/encasement (CA, SMA, or CHA). | ||
BR-A | ||
Tumor abutment/encasement of the SMA or CA of <180° without irregularity in the contour of the artery. | ||
Tumor abutment/encasement of the CHA without irregularity in the contour of the PHA or CA. | ||
3. Unresectable (UR) | UR-LA (Locally advance) | |
Tumor abutment/encasement of the SMA or CA of ≥180°. | ||
Tumor abutment/encasement of the CHA and extension of abutment/encasement to the PHA or CA. | ||
Tumor abutment/encasement of the aorta. | ||
UR-M (Metastasis) | ||
Distant metastases, including metastases to lymph nodes beyond regional lymph nodes. |
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Kimura, N.; Yamada, S.; Takami, H.; Murotani, K.; Yoshioka, I.; Shibuya, K.; Sonohara, F.; Hoshino, Y.; Hirano, K.; Watanabe, T.; et al. Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer. Cancers 2021, 13, 36. https://doi.org/10.3390/cancers13010036
Kimura N, Yamada S, Takami H, Murotani K, Yoshioka I, Shibuya K, Sonohara F, Hoshino Y, Hirano K, Watanabe T, et al. Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer. Cancers. 2021; 13(1):36. https://doi.org/10.3390/cancers13010036
Chicago/Turabian StyleKimura, Nana, Suguru Yamada, Hideki Takami, Kenta Murotani, Isaku Yoshioka, Kazuto Shibuya, Fuminori Sonohara, Yui Hoshino, Katsuhisa Hirano, Toru Watanabe, and et al. 2021. "Optimal Preoperative Multidisciplinary Treatment in Borderline Resectable Pancreatic Cancer" Cancers 13, no. 1: 36. https://doi.org/10.3390/cancers13010036