Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
Definitions
3. Results
3.1. Resection
3.1.1. Primary Pancreatic Tumor Resection
3.1.2. Hepatic Metastasectomy
3.1.3. Pulmonary Metastasectomy
3.2. Ablation
3.2.1. Radiofrequency Ablation (RFA)
3.2.2. Irreversible Electroporation (IRE)
3.2.3. Stereotactic Body Radiotherapy (SBRT)
3.2.4. High-Intensity Focused Ultrasound (HIFU)
3.3. Embolization
3.3.1. Selective Internal Radiation Therapy (SIRT)/Transarterial Radioembolization (TARE)
3.3.2. Transarterial Chemoembolization (TACE)
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Authors | Year | Design | Nr. of Patients (mPDAC) | Study Details | Synchronous/Metachronous | Morbidity, Grade 3+ | Mortality | Chemotherapy | Median Overall Survival (Months) |
---|---|---|---|---|---|---|---|---|---|
McKenzie [19] | 2010 | R | 4649 | 92 P 4557 NR | 92/0 | NS | P: 0–17.5 NR: 5.8–34.1% | P: 36% NR: 38.4% | From primary res: P: 6.3 NR: 4.9 |
Tao [20] | 2017 | R | 28,918 | 467 P 28,451 NR | NS | NS | NS | P: 53% NR: 45% | From primary diagnosis: P: 7 NR: 2 |
Oweira [21] | 2017 | R | 13,233 | 160 P 504 M 14,812 NR | NS | NS | NS | NS | NS |
Wang [22] | 2019 | R | 2694 | 365 P 2329 NR | NS | NS | NS | PSM 1: P: 69% NR: 66% | From primary res (PSM 1): P: 11.6 NR: 9 |
Liu [23] | 2020 | R | 11,541 | 133 P 24 PM 6999 NR | NS | NS | NS | NS | From primary diagnosis: P: 10–14 NR: 4–6 |
Treatment | Positive Prognostic Factors— Patient Characteristics | Positive Prognostic Factors— Disease Characteristics (Primary Tumor) | Positive Prognostic Factors— Disease Characteristics (Metastases) | Positive Prognostic Factors—Treatment(s) |
---|---|---|---|---|
Primary resection | Younger age [20,21] Caucasian ethnicity [20,21] Married [20,21] Female [20,21] Later era of diagnosis [22] | Tumor in pancreatic head [20] Well/moderate differentiation of tumor (histological grade) [20,22,23] | Longer DFI [23] Single-organ metastatic disease [23] | Chemotherapy (pre- and/or post local treatment) [20,22] Primary tumor resection [20,21,22,23] Local metastatic treatment [21] |
Hepatic resection | Lower tumor stage [24,25] Tumor in pancreatic body/tail [26] Smaller primary tumor size [27] Well/moderate differentiation of tumor (histological grade) [25] Lower tumor marker CA19-9 levels pre- or post-treatment(s) [25,28,29] | Fewer and/or smaller liver lesions [28] Metachronous (instead of synchronous) [30] Absence of lymph node status [25,31] | Chemotherapy (pre- and/or post local treatment) [25,28,29] Primary tumor resection [28,29] Better primary resection status [24,31] Better liver resection status [25] | |
Pulmonary resection | Well/moderate differentiation of tumor (histological grade) [32] Lower tumor marker CA19-9 levels pre- and/or post-treatment(s) [33,34] | Fewer and/or smaller lung lesions [34,35] Longer DFI [32,34,36] | ||
Ablation | Younger age [37] Performance status 0–1 [37] | Lower tumor stage [38] Tumor in pancreatic body/tail [39] Well/moderate differentiation of tumor (histological grade) [37,38,40] Neutrophil-to-lymphocyte ratio (NLR) < 2.5 [38] | Fewer and/or smaller liver/lung lesions [37,38,39,40,41] Longer DFI [38,42] Single-organ metastatic disease [38] | |
Embolization | Male [43] | Smaller primary tumor size [44] Lower tumor marker CA19-9 levels pre- or post-treatment(s) [45] Absence of ascites [44] Decreased albumin and bilirubin prior to local treatment [46] | Fewer and/or smaller liver/lung lesions [47] Single-organ metastatic disease [48] | Primary tumor resection [46] Local metastatic treatment [44] |
Authors | Year | Design | Nr. of Patients (Hepatic mPDAC) | Study Details | Resection Details | Synchronous/Metachronous | Morbidity, Grade 3+ | Peri-Procedural Mortality | Chemotherapy, Neoadjuvant/Adjuvant | Median Overall Survival (Months), Hepatic mPDAC Only |
---|---|---|---|---|---|---|---|---|---|---|
Yamada [49] | 2006 | R | 6 | 6 Primary + liver res (PM) | NS | 5/1 | NS | NS | NS | NS |
Gleisner [50] | 2007 | R | 68 | 17 Primary + liver res (PM) 66 Palliative bypass (control) | NS | 88/0 | NS | 9% | N: NS A: 32% | From primary/meta res: -PM: 5.9 -Control (PB): 5.6 |
Shrikhande [31] | 2007 | R | 10 | 29 Primary res ± ILN res or liver res or multi-organ res (PM) | R0: 86% R1: 14% | 29/0 | NS | 0% | N: 3% A: 69% | From primary/meta res: -PM: 11.4 -Control (SE/PB): 5.9 |
De Jong [51] | 2010 | Pro | 42 | 126 Primary res + LDT (incl. liver res, ablation, embolization) (PM) | NS | 15/28 | Sc: 12.4% Mc: 20.3% | Sc: 2% Mc: 3% | NS | From primary/meta diagnosis or resection (unknown): -PM: 13.6 |
Dünschede [52] | 2010 | Pro | 23 | 13 Primary + liver res (PM) 10 Chemotherapy (control) | R0 pancreas: 100% R0 liver: Sc: 89% Mc: 100% | 14/9 | NS | Sc: 0% Mc: 0% | N: NS A: -PM: 50% -Control: 100% | Sc, from primary/meta diagnosis: -PM: 8 -Control (chemo): 11 Mc, from meta diagnosis: -PM: 31 -Control (chemo): 11 |
Klein [53] | 2012 | R | 22 | 22 Primary + liver res (PM) 22 Primary res only (M0) | Liver: R0: 32% R1: 46% R2: 23% | 22/0 | 18% | 0% | N: NS A: 100% | From primary/meta diagnosis or resection (unknown): -PM: 7.5 |
Zanini [30] | 2015 | R | 15 | 15 Primary + liver res (PM) | R0: 47% R1: 53% | 11/4 | Sc: 9% Mc: 25% | 0% | N: NS A: 100% | From meta res: -Sc PM: 8.3 -Mc PM: 11.4 |
Bahra [54] | 2015 | R | 29 | 21 Primary + liver res (PM) 24 Primary res only (control) 45 Chemotherapy (control) | R0M1: 27% R1M1: 27% R2M1: 13% R2M0: 33% | PM: 29/0 Control: NS | 20% | 2% | N: NS A: -PM: 98% -Control: 100% | From primary/meta res: -PM: 10.4 -Control (chemo): 7.2 |
Tachezy [24] | 2016 | R | 138 | 69 Primary + liver res (PM) 69 Liver res only (control, M) | R0: 58% R1: 32% R2: 10% | 138/0 | PM: 7% SE: 5% | PM: 1% SE: 1% | N: -PM: 14% -Control: 1% A: -PM: 80% -Control: 82% | From primary/meta treatment: -PM: 14.5 -Control (M): 7.5 |
Hackert [55] | 2016 | Pro | 85 | 85 Primary + liver res (PM) 43 Primary + ILN res | Liver: R0: 19% R1: 60% Rx: 21% | Liver: 62/23 | NS | Sc: 3% Mc: 4% | N: 16% A: 75% | From meta res: -Sc + Mc PM: 12.3 |
Crippa [28] | 2016 | R | 127 | 11 Primary ± liver res (PM) 116 Chemotherapy (control) | R0: 82% R1: 18% | 3/8 | NS | PM: 0% Control: NS | N: 100% A: -PM: 82% | From primary diagnosis: -Sc + Mc PM: 39 -Control (chemo): 11 |
Wright [56] | 2016 | R | 16 | 23 Primary ± liver/lung res (PM) | R0: 91% R1: 9% | 23/0 | 13% | 0% | N: 100% A: NS | NS |
Kim [29] | 2016 | R | 45 | 35 Primary res ± metastasectomy (PM) 35 No res (matched controls) | NS | 70/0 | PM: 20% Control: 6% | 0% | N: NS A: -PM: 83% -Control: 57% | NS |
Andreou [25] | 2018 | R | 76 | 76 Primary + liver res (PM) | R0: 82% R1: 18% | 76/0 | 16% | 5% | N: 5% A: 72% | NS |
Kandel [57] | 2018 | R | 18 | 6 M1PDAC: Primary res + meta res/RFA/embolization (PM) 18 M1PDAC: No res, chemo | M1R0: 83% M1R1: 17% | NS | NS | NS | N: -PM: 100% -Control: 44% A: 100% all groups | NS |
Yang [26] | 2020 | R | 89 | 48 Primary + liver res (PM) 10 Surgical exploration, chemo (control) 31 No res, chemo (control) | R0: 100% | 89/0 | NS | PM: 4% | N: 27% A: -PM: 79% -Control (SE): 100% -Control: 100% | From primary/meta res: -PM: 7.8 -Control (SE, chemo): 4.3 -Control (chemo): 7.6 |
Gu [27] | 2020 | R | 73 | 36 Primary + meta res (PM) 60 Surgical exploration (control) 54 Palliative bypass (control) | R0: 94% R1: 6% | 150/0 | PM: 3% SE: 0% PB: 2% | PM: 0% SE: 3% PB: 4% | N: 0% A: -PM: 19% -Control (SE): NS -Control (PB): NS | NS |
Schwarz [58] | 2020 | R | 33 | 25 Primary + liver res (PM) 8 Primary res + chemo (matched controls) | Liver: R0: 96% R1: 4% | 0/33 | 12% | 0% | N: NS A: -PM: 88% -Control: 100% | From meta diagnosis: -PM: 36.8 -Controls (P + chemo): 9.2 |
Authors | Year | Design | Nr. of Patients (Pulmonary mPDAC) | Study Details | Synchronous/Metachronous | Morbidity, Grade 3+ | Peri-Procedural Mortality | Chemotherapy *, Neoadjuvant/Adjuvant | Median Overall Survival (Months), Pulmonary mPDAC Only |
---|---|---|---|---|---|---|---|---|---|
Arnaoutakis [59] | 2011 | R | 31 | 9 Primary res + CRT + lung res (PM) 22 Primary res + CRT (control) | 0/31 | NS | Lung res: 0% Control: NS | N: 100% A: NS | From primary res: -PM: 51 -Control (P + chemo): 23 |
Thomas [36] | 2012 | R | 7 | 14 Primary + meta res/RFA (7 lung, PM) 405 Primary res only (incl. lung, other sites) | 0/7 | NS | 0% | N: 76% A: 29% | From primary res: -PM: 92.3 |
Downs-Canner [60] | 2015 | R | 58 | Data available on 41 patients: 8 Primary res/SBRT + lung res (PM) 23 Primary res + chemo (control) 10 Primary res + BSC (control) | 0/58 | NS | NS | N: 88% A: 50% | From primary diagnosis: -PM: 67.5 -Control (P + chemo): 33.8 -Control (P + BSC): 29.9 From meta diagnosis: -PM: 27 -Control (P + chemo): 18.9 -Control (P + BSC): 11.5 |
Robinson [33] | 2016 | R | 16 | 15 Primary res + lung res (PM) 1 Primary SBRT + lung res (PM) | 1/15 | NS | 0% | N: 88% A: 56% | From primary res: -PM: 52 From meta res: -PM: 28 |
Kruger [35] | 2016 | R | 40 | 13 S Primary res + lung res (PM) 22 M Primary res + lung res (PM) 5 M CRT primary + lung res (LAPC, M) | 13/27 | NS | NS | N: 71% A: NS | From meta diagnosis: -Sc PM: 22.8 -Mc PM: 31.3 -Mc M: 10.7 |
Nakajima [61] | 2017 | R | 16 | 16 Primary res + lung res (PM) | 0/16 | NS | 0% | N: 59% A: 71% | From primary res: -PM: 92 From meta res: -PM: 37 |
Okui [62] | 2017 | R | 6 | 6 Primary + lung res (PM) | 0/6 | NS | NS | N: 100% A: NS | Median follow-up, since all patients were alive From primary res: -PM: 81.7 From meta res: -PM: 37.3 |
Yasukawa [63] | 2017 | R | 12 | 11 Primary res + lung res (PM) 1 CRT + lung res | 0/12 | NS | 0% | N: 100% A: 100% | From primary res: -PM: 121 From meta res: -PM: 47 |
Ilmer [32] | 2019 | R | 11 | 11 Primary + lung res (PM) | 0/11 | 0% | 0% | N: 91% A: 100% | From primary res: -PM: 37.7 From meta res: -PM: 26 |
Groot [34] | 2019 | R | 96 | 19 Primary + lung res (PM) 77 Primary res only (controls): -45 CRT -32 BSC | 0/96 | Lung res: 0% | 0% | N: -PM: 5% A: -PM: 53% | From primary res: -PM: 68.9 -Control (P + CRT): 34.2 -Control (P + BSC): 24.5 From meta res: -PM: 35 -Control (P + CRT): 20.2 -Control (P + BSC): 8.1 |
Kaiho [64] | 2019 | R | 12 | Primary + lung res (PM) | NS | NS | 0% | N: -mPDAC: 75% A: -mPDAC: 75% | NS |
Shimizu [65] | 2020 | R | 13 | 6 Primary + lung res (PM) 7 Primary res only (control) | 0/13 | NS | 0% | N: -PM: 100% -Control: 71% A: -PM: 50% -Control: 0% | From primary res: -PM: 39 -Control (P + BSC): 33 |
Authors | Year | Design | Nr. of Patients (mPDAC) | Study Details | Synchronous/Metachronous | Morbidity, Grade 3+ | Peri-Procedural Mortality | Chemotherapy, Neoadjuvant/Adjuvant | Median Overall Survival (Months), mPDAC Only |
---|---|---|---|---|---|---|---|---|---|
RFA | |||||||||
Park [40] | 2012 | R | 34 liver | 34 Primary res + liver RFA (PM) | 6/28 | NS | 0% | N: 68% A: 62% | From primary res: -PM: 18 From meta RFA: -PM: 14 |
Hua [39] | 2017 | R | 102 liver | 102 no primary res (unresectable) + liver RFA (M) | 102/0 | 0% | 0% | N/A: 100% Unclear whether prior to or after liver RFA | From primary/meta diagnosis: -M: 11.4 |
Lee [38] | 2020 | R | 126 liver | 60 Primary res + liver RFA (PM) 66 Primary res + chemo for meta (control, P) | 0/126 | 13% | 0% | N: 80% A: NS | From meta RFA: -PM: 12 -Control (P + chemo): 9.1 |
IRE | |||||||||
Hong [67] | 2018 | R | 7 liver, peritoneum, omentum | Primary res + meta IRE (PM) or Primary IRE + metastasectomy (PM) | 7/0 | NS | 0% | N: 100% A: 57% | From initial local treatment: -PM: 16 |
Authors | Year | Design | Nr. of Patients (mPDAC) | Study Details | Synchronous/Metachronous | Morbidity, acute/late, Grade 3+ | Peri-Procedural Mortality | Chemotherapy, Neoadjuvant/Adjuvant | Median Overall Survival (Months), mPDAC Only |
SBRT | |||||||||
Chang [68] | 2009 | R | 15 Metastatic sites not specified | 15 primary SBRT only (P) | 15/0 | Ac: 1% | 0% | Prior: 19% Concurrent: 77% | From primary SBRT: -P: 10.5 |
Su [69] | 2015 | R | 16 Metastatic sites not specified | 16 Primary SBRT only (P) | 16/0 | Ac: 0% L: NS | 0% | N: 8% A: 8% | From primary SBRT: -P: 8.5 |
Gkika [70] | 2017 | R | 14 liver, LN | -5 Primary res + primary SBRT (P) -9 Primary res + meta SBRT (PM) -2 Primary SBRT + meta SBRT (PM) -2 Primary SBRT (P) | Sc + Mc Numbers not specified | Ac: 6% L: 6% | 0% | N: NS A: 78% | NS |
Lischalk [41] | 2018 | R | 20 Metastatic sites not specified | 20 Primary SBRT only (P) | 20/0 | Ac: NS L: 0% | 0% | N: 60% A: 100% | From primary SBRT: -P: 13.6 |
Scorsetti [42] | 2020 | R | 41 liver, lung, LN | 33 Primary res (± CRT) + meta SBRT (PM) 8 Meta SBRT only (M) | 2/39 | NS | NS | N: 83% A: 22% | From SBRT: -M ± P: 23 |
HIFU | |||||||||
Li [37] | 2016 | R | 120 liver, lung, LN | 61 HIFU meta + chemo ± primary res (M ± P) 59 Chemo ± primary res (control, ± P) | NS | 0% | 0% | Concomitant: 100% | From meta HIFU/chemo: -M ± P: 10.3 -Control (chemo ± P): 6.6 |
Authors | Year | Design | Nr. of Patients (mPDAC) | Study Details | Synchronous/Metachronous | Morbidity, Grade 3+ | Peri-Procedural Mortality | Chemotherapy, Neoadjuvant/Adjuvant | Median Overall Survival (Months), mPDAC Only |
---|---|---|---|---|---|---|---|---|---|
SIRT/TARE | |||||||||
Cao [71] | 2010 | Pro | 7 liver (±EHD) | 3 Primary res + liver SIRT (PM) 4 liver SIRT only (M) | 6/1 | Ac: 0% L: 0% | 0% | N: 100% A: NS | NS |
Michl [45] | 2014 | R | 19 liver (±EHD) | 15 Primary res + liver SIRT (PM) 4 liver SIRT only (M) | 9/10 | Ac: 9% L: 43–64% | 16% (likely TARE related) | N: 84% A: 47% | From meta SIRT: -M ± P: 9 |
Gibbs [72] | 2015 | Pro | 14 liver (±EHD) | 4 Primary res + liver SIRT (PM) 10 liver SIRT only (M) | Sc + Mc Numbers not specified | Ac: 36% L: 50% | 14% | Concomitant: 100% | From enrolment/SIRT: -PM: 13.6 -M: 4.2 |
Kim [73] | 2016 | R | 16 liver (±EHD) | 6 Primary res/SBRT + liver SIRT (PM) 10 liver SIRT only (M) | NS | 6% | 0% | Concomitant: 94% | From meta diagnosis: -M ± P: 22 From meta SIRT: -M ± P: 12.5 |
Kim [46] | 2019 | R | 33 liver (±EHD) | 23 Primary res/SBRT + liver SIRT (PM) 10 liver SIRT only (M) | NS | Clinical: 15% Lab: 9% | 3% (likely TARE related) | N: 82% A: 30% | From primary diagnosis: -M ± P: 20.8 From meta SIRT: -M ± P: 8.1 |
Nezami [74] | 2019 | Pro | 3 liver | 3 Primary treatment NS + liver SIRT (M ± P) | NS | Clinical: 38.5% Lab: 38.5% | 0% | Concomitant: 100% | NS |
Kayaleh [47] | 2020 | R | 26 liver (±EHD) | 8 Primary res + liver SIRT (PM) 18 no primary res + liver SIRT (M) | 13/13 | Clinical: 3 in 77 pts Lab: 9 in 77 pts | 0% | N: 100% A: 73% | From primary diagnosis: -M ± P: 33 From meta diagnosis: -M ± P: 21.8 From meta SIRT: -M ± P: 7 |
TACE | |||||||||
Kim [75] | 2010 | R | 15 liver | 15 Primary res + liver TACE (PM) | 0/15 | 13% | 0% | N: 13% A: NS | From meta diagnosis: -PM: 9.6 From meta TACE: -PM: 7.5 |
Azizi [43] | 2011 | R | 32 liver | 32 Primary res + liver TACE (PM) | NS | 0% | 0% | N: 100% A: NS | From meta TACE: -PM: 16 |
Kotoyan [76] | 2012 | Pro | 6 liver (± EHD) | 6 Primary NS + liver TACE (M ± P) | NS | 30% | 0% | N: 100% A: NS Concomitant: 100% | From unknown: -M ± P: 9.3 |
Sun [48] | 2017 | R | 18 liver (± EHD) | 18 liver TACE ± primary res (M ± P) | NS | 0% | 0% | N: 44% A: NS | NS |
Vogl [77] | 2018 | R | 112 liver | 112 Primary res + liver TACE (PM) | NS | 0% | 0% | N: 100% A: NS | From TACE: -PM: 19 |
Das [78] | 2019 | R | 182 liver | -84 RFA/ISI + TACE -59 TACE -123 matched control: syst chemo All groups include M1 and M0 disease | NS | RFA/ISI + TACE: 13 in 75 pts TACE only: 16 in 143 pts Controls: 28 in 123 pts | 0% | N: NS A: NS Control: 100% | NS |
TARE/TACE | |||||||||
Ouyang [44] | 2018 | R | 184 liver (±EHD) | No primary resection, some pts may have received primary SIRT -64 LDT + systemic chemo (M):
| 184/0 | M: 30% Control (chemo): 18% | TACE: 1 pt | N: 100% A: NS | From primary/meta diagnosis: -M: 8.7 -Control (chemo): 6.3 |
(Locoregional) Treatments | Hepatic mPDAC mOS from Metastatic Diagnosis/Treatment | Pulmonary mPDAC mOS from Metastatic Diagnosis/Treatment |
---|---|---|
P + M | 7.8–19 (Sc + Mc) | 22.8–47 (Sc + Mc) |
P only | 9.1–9.2 (Mc) | 8.1–20.2 (Mc) |
M only | 7.5 (Sc) | 10.7 (Mc) |
CRT/BSC | 4.3–7.6 (Sc + Mc) | 11.8 * (Sc + Mc) |
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Timmer, F.E.F.; Geboers, B.; Nieuwenhuizen, S.; Schouten, E.A.C.; Dijkstra, M.; de Vries, J.J.J.; van den Tol, M.P.; Meijerink, M.R.; Scheffer, H.J. Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review. Cancers 2021, 13, 1608. https://doi.org/10.3390/cancers13071608
Timmer FEF, Geboers B, Nieuwenhuizen S, Schouten EAC, Dijkstra M, de Vries JJJ, van den Tol MP, Meijerink MR, Scheffer HJ. Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review. Cancers. 2021; 13(7):1608. https://doi.org/10.3390/cancers13071608
Chicago/Turabian StyleTimmer, Florentine E. F., Bart Geboers, Sanne Nieuwenhuizen, Evelien A. C. Schouten, Madelon Dijkstra, Jan J. J. de Vries, M. Petrousjka van den Tol, Martijn R. Meijerink, and Hester J. Scheffer. 2021. "Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review" Cancers 13, no. 7: 1608. https://doi.org/10.3390/cancers13071608