Background
Methods
- No surgery for primary tumor or metastases at any time during treatment.
- CT and/or MRI image available and sufficient to identify the primary tumor as well as distant metastases. The date of this radiological examination was defined as the timepoint of PDAC M1 diagnosis.
- Laboratory parameters of CRP, LDH, Bilirubin, CA 19–9 and CEA had to be available at the time of diagnosis.
- PDAC had to be histologically proven (via biopsy of metastases or the primary tumor).
- Therapeutic regimens the patient received during treatment of the disease had to be known.
- Time of death or last follow-up date available.
- As cholestasis can influence the CA 19–9 value, we included baseline CA 19–9 when a patient had a normalized bilirubin (< 1.2 mg/dl) after stenting.
Statistical analysis
Results
Patient data
Characterization of primary tumor and extrapancreatic tumor spread
Single organ metastasis group (SOG)
Multi-organ metastasis group
Chemotherapy
Oligometastatic disease (OMD) n = 10 | No oligometastatic disease (noOMD) n = 118 | Mann-Whitney U Test (p-value) | |
---|---|---|---|
Sex | |||
Male (%) | 7 (70) | 73 (61) | |
Female (%) | 3 (30) | 47 (39) | |
Age upon diagnosis, median (minimum; maximum) | 65 (53;89) | 66 (30;84) | 0.945 |
Primary tumor: size [cm2], median (minimum; maximum) | 14.5 (4.4;21.6) | 12.0 (0.8;68.4) | 0.758 |
Primary tumor: max. diameter [cm], median (minimum; maximum) | 4.1 (2.4;9.0) | 4.0 (1.0;10.4) | 0.348 |
Primary tumor: Location | |||
Head, n (%) | 2 (20.0) | 53 (46.5) | |
Body, n (%) | 4 (40.0) | 17 (15.8) | |
Tail, n (%) | 4 (40.0) | 42 (37.7) | |
Chemo: First line | |||
None, n (%) | 0 (0) | 17 (14.2) | |
Gemcitabine, n (%) | 3 (30.0) | 38 (31.7) | |
Gemcitabine + Erlotinib, n (%) | 2 (20.0) | 13 (10.8) | |
Gemcitabine + nab-Paclitaxel, n (%) | 2 (20.0) | 19 (15.8) | |
FOLFIRINOX, n (%) | 0 (0) | 4 (3.3) | |
5-FU, n (%) | 0 (0) | 2 (1.7) | |
Gemcitabine + Afatinib, n (%) | 1 (10.0) | 12 (10.0) | |
Capecitabin + Erlotinib, n (%) | 0 (0) | 1 (0.8) | |
Ibrutinib/Placebo + nab-Paclitaxel + Gemcitabine, n (%) | 1 (10.0) | 8 (6.7) | |
NAPOLI, n (%) | 0 (0) | 1 (0.8) | |
Capecitabine, n (%) | 1 (10.0) | 2 (1.7) | |
FOLFOX, n (%) | 0 (0) | 1 (0.8) | |
Gemcitabine + nab-Paclitaxel + Afatinib, n (%) | 0 (0) | 2 (1.7) | |
Bilirubin level [mg/dL] BL, median (minimum; maximum) | 0.3 (0.2;1.7) | 0.6 (0.2;14.2) | 0.157 |
LDH [U/L] BL, median (minimum; maximum) | 209 (179;393) | 230 (13;1870) | 0.439 |
CRP [mg/L] BL, median (minimum; maximum) | 28 (4;65) | 11 (1;348) | 0.498 |
CA 19–9 [U/mL] BL, median (minimum; maximum) | 35 (2;885) | 978 (1;938,670) | 0.003 |
CEA [μg/L] BL, median (minimum; maximum) | 4 (2;80) | 11 (0;13,006) | 0.140 |
Laboratory results and tumor markers
Survival analysis
Discussion
Palliative chemotherapy
Focus on metastasized pancreatic adenocarcinoma confined to the liver or the lung
Limited disease as a first step to approach the OMD concept
From anatomically limited disease to oligometastatic disease
# | Study participation | Overall survival [mo] | Primary tumor: Max. diameter [cm] | Primary tumor: Location | M: Liver count | Liver max metastasis [cm] | M: Liver location | M: Lung count | M: Lung max. Diameter [cm] | Chemo: First line | Bilirubin level [mg/dL] BL | LDH [U/L] BL | CRP [mg/L] BL | CA 19–9 [U/mL] BL | CEA [μg/L] BL |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | No | 16.1 | 4.1 | Tail | 4 | 4.1 | Right lobe | – | Gemcitabine + nab-Paclitacxel | 0.3 | 208 | 45.9 | 6 | 2.8 | |
2 | ACCEPT | 16.0 | 5.0 | Tail | 3 | 6.3 | Both lobes | – | Gemcitabine + Afatinib | 0.3 | 393 | 63.1 | 22 | 80.2 | |
3 | No | 22.9 | n.a. | Tail | 2 | 4.4 | Both lobes | – | Gemcitabine + Erlotinib | 1.2 | 209 | 64.9 | 33 | 1.7 | |
4 | No | 27.7 | 2.4 | Head | 4 | 1.1 | Both lobes | – | Gemcitabine + nab-Paclitacxel | 1.7 | 246 | 32.5 | 885 | 7.7 | |
5 | RESOLVE (PCYC-1137-CA) | 14.0 | 2.9 | Tail | 4 | 1.4 | Right lobe | – | Ibrutinib/Placebo + nab-Paclitacxel + Gemcitabine | 0.7 | 180 | 6.0 | 229 | 1.6 | |
6 | No | 19.4 | 4.6 | Body | 2 | 0.9 | Left lobe | – | Gemcitabine + Erlotinib | 0.2 | 198 | 4.3 | 154 | 3.8 | |
7 | No | 4.8 | 3.6 | Head | 3 | 0.9 | Both lobes | – | Gemcitabine | 0.3 | 179 | 23.1 | 2 | 3.2 | |
8 | No | 27.2 | 4.2 | Body | 4 | 1.6 | Right lobe | – | Gemcitabine | 0.3 | 230 | 5.0 | 36 | 7.6 | |
9 | No | 28.6 | 9.0 | Body | – | – | – | 4 | 4.5 | Capecitabine | 0.2 | 276 | 9.2 | 790 | 1.8 |
10 | No | 19.5 | 4.8 | Body | – | – | – | 2 | 0.5 | Gemcitabine | 0.5 | 256 | 3.0 | 148 | 2.6 |
Patient factors in metastasis surgery in PDAC
Conclusions
Criteria for Oligometastatic Disease in Pancreatic Ductal Adenocarcinoma | ||
---|---|---|
Inclusion | Exclusion | |
ECOG | 0/1 | >/= 2 |
Liver/lung only (+LN hepatoduodenal lig.) | Yes | No |
Number of hepatic or pulmonary lesions | </= 4 | > 4 |
Ascites | No | Yes |
Liver cirrhosis | No | Yes |
Lung emphysema | No | Yes |
CA 19–9 (U/mL)a | < 1000 | > 1000 |
Surgery for metastasisb | Atypical resection (+/−Ablation) | Non-resectable/major hepatic/lung surgery necessary |
Primary tumor upon diagnosisb | Resectable, borderline resectable, non-resectablec | |
Chemotherapy response | Response or stable disease | Progressive disease |