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This review summarizes the available literature on surgical and interventional treatment of metastatic pancreatic cancer in the light of modern, effective chemotherapies.
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Risk factors derived from studies are highlighted and a possible clinical algorithm is proposed.
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An outlook on future perspectives regarding multimodal treatment of metastatic pancreatic cancer is provided.
Introduction
The age of effective chemotherapies in pancreatic cancer
Influence of chemotherapy on resectable, borderline-resectable and unresectable PC
Palliative setting studies
Surgery for oligometastatic pancreatic cancer
Liver metastases
Author | Year | Inclusion period | Center |
N
| Type of metastases | Mortality (%)/morbidity (%) | Max. size (cm) | Lesions (n) | Primary tumor resected? | Median follow-up (mo) | Median OS (mo) after resection | Median RFS (mo) | Recurrence (%) | (Independent) factors for poor survival |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Zanini N et al. [14] | 2015 | 2003–2014 | Bologna | 15 | Liver | 0/60 | 3.5 | 1–3 | All | 12.6 | 9.1 | 5.2 | 93 | Timing (synchronous), >1LM |
Crippa S et al. [42] | 2016 | 2003–2013 | Milan and Ancona | 11 | Liver | 0/27 | n.a. | 1–5+ | All | n.a. | 39 (from diagnosis) | n.a. | 91 | >5LM, <50% CA 19-9 reduction, Gem monotherapy |
Wright P et al. [44] | 2016 | 2008–2013 | Pittsburgh and Baltimore | 23 | Liver, Lung, Peritoneum | 0/13 (major) | n.a. | 1–5+ | All | 30 | 18.2 | 8.6 | 74 | n.a. |
Tachezy M et al. [15] | 2016 | 1994–2014 | European Multicenter | 69 | Liver | 1/68 | n.a. | 1–11 | All | n.a. | 15 | n.a. | n.a. | Tumor located in pancreatic tail |
Frigerio I et al. [43] | 2017 | 2007–2015 | Verona | 24 | Liver (all complete hep. response) | No liver resection | n.a. | 1–2+ | All | 31 | 13 (after resection) 56 (after diagnosis) | 11 (after surgery) 21 (after diagnosis) | 75 | None |
Hackert T et al. [17] | 2017 | 2001–2014 | Heidelberg | 128 | Liver (85), ILN (43) | 2.9/45 4.3/22 (syn./met.) | 75% ≤2 cm | 1–3+ | All | n.a. | 12.3 | n.a. | n.a. | None |
Pulmonary and peritoneal metastases
Nonsurgical, local treatment of oligometastases
Author | Year | Inclusion period | Centre |
N
| Type of intervention | Mortality (%)/morbidity (%) | Max. size (cm) | Lesions (n) | Primary tumor resected? | Median follow-up (mo/range) | Median OS (mo) | Median RFS (mo) | Recurrence (%) | (Independent) factors for poor survival |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Park JB et al. [26] | 2012 | 2002–2009 | Seoul | 34 | RFA (liver) | 0/12 (all mild) | 3.2 | 1–4 | Always | 15 (3–65) | 14 | n.a. | >91 | G3, >1LM, ≥2 cm LM |
Hua Y-Q et al. [54] | 2017 | 2012–2015 | Shanghai | 102 | RFA (liver) | 0/10 (all mild) | 5.0 | 1–3+ | Never | 21 (4–43.8) | 11.4 | n.a. | 82.4 | Primary tumor location (head), ≥3 cm LM, NLR ≥2.5 |
Sun J-H et al. [55] | 2017 | 2009–2015 | Hangzhou | 18 | TACE (liver) | 0/>85 (all mild) | n.a. | n.a. | <50% of cases | n.a. | 9.2 | n.a. | n.a. | Extrahepatic disease |
Azizi et al. [52] | 2011 | 2002–2007 | Frankfurt | 32 | TACE (liver) | 0/n.a. | n.a. | 60% >5 | Some (% n.a.) | n.a. | 16 (10% 5y) | n.a. (10% 5y) | ~90 | Progressive disease during TACE, >5 LM |
Huang Z‑M et al. [56] | 2013 | 1998–2011 | Guangzhou | 71 | TACE + RFA + seeds (pancreas + liver) | 0/n.a. | n.a. | 54% >3 | Never | n.a. | 11 (6% 3y) | n.a. (no CR) | n.a. (no CR) | >3 LM |
Michl M et al. [57] | 2014 | 2004–2011 | Munich | 19 | SIRT (liver) | 11/74 | n.a. | n.a. | >70% | n.a. | 9 | 2.6 mo systemic PFS | n.a. (no CR) | Increased CA 19-9, CRP, extrahepatic disease |
Kim A et al. [53] | 2016 | 2012–2015 | Washington | 16 | SIRT (liver) | 0/13 (all < grade 4) | n.a. | n.a. | 1 patient | n.a. | 20 after LM 12.5 after SIRT | 3.4 mo systemic PFS | n.a. | n.a. |
Gibbs P et al. [58] | 2015 | 2006–2009 | Melbourne | 14 | SIRT (liver) | 7/57 (grade 3/4) | n.a. | 1–5 | 29% | n.a. | 5.5 | 4.4 mo systemic PFS | n.a. (no CR) | Primary tumor in situ |
Mahadevan A et al. [25] | 2018 | 2005–2017 | 25 centers (LM registry) | 20 | SBRT (liver) | 0/n.a. (no severe) | n.a. | n.a. | n.a. | n.a. | 6 | n.a. | All had local progress | Tumor volume <40 cm3 |
Wieners G et al. [59] | 2015 | n.a. | Berlin | 20 | HDRBT | 0/15 (severe) | 7.3 | 1–3+ | n.a. | 14 (mean) | 8.6 | 4.9 mo systemic PFS | 10% local recurrence | No chemotherapy received after HDRBT |
Liver-directed therapies
Transarterial chemoembolization
Selective internal radiation therapy
SBRT or CT-guided brachytherapy
Other nonsurgical local treatments
Prognostic factors for patient selection
Clinical factors and blood markers in mPC patients
Examples of cutoffs evaluated in studies | |
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Blood markers
| |
CA 19-9 | ≥200 or ≥626 or ≥1000 U/ml |
CEA | ≥2.9 or ≥4.5 ng/ml |
CYFRA 21-1 | ≥2.7 ng/ml |
Neutrophil–lymphocyte ratio | ≥3.75 or >5 |
CRP | ≥1 mg/dl |
Bilirubin | >1 mg/dl |
Albumin | <35 g/L |
Patient or tumor factors
| |
Poor performance index | ECOG >0 or ECOG ≥2, Karnofsky index ≤80% |
Metastatic spread | Hepatic involvement compared with isolated extrahepatic |