Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy

Figures & data

Table 1. Patient characteristics, neoadjuvant therapies and pathologic response.

Characteristics, therapies, or responses	n or value
No. of patients	81
Initial resectability
BRPC	73
LAPC	8
Age (median, range)	64.9 years (33–81)
Gender
M	42
F	39
Tumor location
Head	69
Body/tail	12
Clinical N class
0	40
1	41
Chemotherapy^a
Gemcitabine	2
GTX	63
FOLFIRINOX	8
Gem + Abraxane	3
Others	5
Radiation dose^b (median, range)	37 Gy (30–50)
Time to surgery (median, range)	49 days (33–133)
Vascular resection or repair	35
Tumor regression grade
0 (complete response)	6
1 (marked response)	28
2 (moderate response)	37
3 (no or poor response)	10

^a GTX: three 21-day cycles of gemcitabine 750 mg/m² and docetaxel 30 mg/m² intravenous (IV) on Days 4 and 11, and capecitabine 750 mg/m² orally twice daily on Days 1–14. FOLFIRINOX: six 14-day cycles of FOLFIRINOX as oxaliplatin 85 mg/m², folinic acid 400 mg/m², irinotecan 180 mg/m², fluorouracil, 400 mg/m² IV bolus Day 1, and fluorouracil 1200 mg/m²/day IV continuous 46-hour infusion on Days 1–2. Gemcitabine (Gem): three 4-week cycles at 1000 mg/m² IV on Days 1, 8 and 15. Gem + Abraxane: Gemcitabine with the addition of nab-paclitaxel 125 mg/m² IV. Dose and scheduling modifications were allowed for toxicities;

^b Patients received 5-fraction dose-painted SBRT. This is the high dose prescribed to possible tumor-vessel abutment. The low dose PTV coverage was 30 Gy or lower for normal tissue constraints (see methods).

Figure 1. After multi-agent chemotherapy, SBRT and resection of pancreatic adenocarcinoma, progression-free (PFS) and overall survival (OS) are stratified by tumor regression grade (TRG) ((a) and (b), respectively) or pathologic complete response (pCR) versus partial response (pPR) ((c) and (d), respectively). PFS was better for pCR (TRG 0, median PFS not reached) compared to pPR (TRG 1-3, median PFS 13.0 months, p = .033). OS was also better for pCR (no deaths) compared to pPR (median OS 33.9 months, p = .050).

Table 2. CA19-9, SUVmax and RECIST criteria for the 81 analyzed specimens.

Response criteria	n or value
Patients with detectable CA19-9 (>1.5 U/ml)	68
Pre-therapy CA19-9 (median, range)	241.5 (22–16 600)
Post-neoadjuvant therapy CA19-9 (median, range)	23.8 (1–3200)
CA19-9 reduction (median, range)	89.7% (26–100%)
Patients with detectable SUVmax (>2.0)	70
Pre-therapy SUVmax (median, range)	5.9 (2–24)
Post-neoadjuvant therapy SUVmax (median, range)	2.8 (0–10)
SUVmax reduction (median, range)	61.1% (−108–100%)
RECIST 1.0 response to neoadjuvant therapy
Progressive disease	4
Stable disease	46
Partial response	28
Complete response	2
Unavailable	1

Figure 2. Individual data points (circles), medians (diamonds), and 95% confidence intervals (bars) for post-neoadjuvant therapy SUVmax (A), SUVmax percent reduction before and after neoadjuvant therapy (B), post-neoadjuvant therapy CA19-9 (C), and CA19-9 percent reduction before and after neoadjuvant therapy. Significance levels by ordinal logistic regression are given for each plot (p < .05 for A, C, and D, p = .095 for B).

Table 3. Correlations of TRG to CA19-9, SUVmax and RECIST response.

	Tumor regression grade
	0 (pCR)	1	2	3	1–3 (pPR)	p^a	P^b
Pre-therapy CA19-9 median U/ml (95% CI)	956 (0–2121)	167 (0–1409)	572 (0–1752)	106 (0–707)	232 (0–973)	.82	.95
Post-neoadj. tx CA19-9 median U/ml (95% CI)	8 (3–13)	21 (10–32)	33 (0–274)	23 (0–56)	26 (0–134)	.01	.42^c
CA19-9 reduction median (95% CI)	99% (82–100%)	90% (85–96%)	90% (84–97%)	76% (59–93%)	90% (85–94%)	.19	.02
Pre-therapy SUVmax median (95% CI)	5.4 (0.3–10.5)	5.5 (4.2–6.8)	6.4 (4.9–7.9)	7.4 (5.4–9.4)	6.0 (5.1–6.9)	.89	.74
Post-neoadj. tx SUVmax median (95% CI)	0.0 (0–1.6)	1.9 (0–2.9)	3.2 (2.4–4.0)	5.4 (2.8–8.0)	2.7 (2.1–3.3)	.15	.01
SUVmax reduction median (95% CI)	100% (80–100%)	69% (52–86%)	56% (41–71%)	34% (0–75%)	61% (50–72%)	.13	.10
RECIST 1.0 response
Progressive disease	0	3	0	1	4	.61	.30
Stable disease	3	15	22	6	43
Partial response	3	7	15	3	25
Complete response	0	2	0	0	2

^a p: Comparison of TRG 0 (pCR) versus TRG 1-3 (pPR);

^b P: comparison as a trend across TRG 0-3 (ordinal logistic regression);

^c due to large variations in CA19-9 (some values remain in the thousands after neoadjuvant therapy) this becomes significant for the log₁₀ transformation of CA19-9 shown in Figure 1(C).