The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

Dongen, Jelle C van; Wismans, Leonoor V.; Suurmeijer, J Annelie; Besselink, Marc G.; Wilde, Roeland F. de; Koerkamp, Bas Groot; Eijck, Casper H.J. van

doi:10.1016/j.hpb.2021.04.027

Cited by 21 publications

(12 citation statements)

References 72 publications

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“…Neoadjuvant therapy could impact the texture of pancreatic tissue, which has been associated with reduced rates of POPF. 32 The results of the present study should be interpreted considering several limitations. First, there was potential information bias regarding the lack of information on patient's preoperative nutritional status as no data on nutritional status are available in the nationwide, prospectively recorded DPCA.…”

Section: Discussionmentioning

confidence: 87%

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Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

et al. 2022

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Background Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. Methods After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien–Dindo grade III or higher) was assessed via multivariable regression analysis. Results Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p < 0.001), postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grade B/C; 23.1% vs. 13.4%; p < 0.001), complication-related intensive care admission (14.3% vs. 10.3%; p = 0.046), re-interventions (39.8% vs. 26.6%; p < 0.001), in-hospital mortality (5.7% vs. 3.1%; p = 0.025), and longer hospital stay (15 days vs. 11 days; p < 0.001) compared with pancreatoduodenectomy for other cancers. In multivariable analysis, duodenal adenocarcinoma was independently associated with major complications (odds ratio 1.14, 95% confidence interval 1.03–1.27; p = 0.011). Conclusion Pancreatoduodenectomy for duodenal adenocarcinoma is associated with higher rates of major complications, pancreatic fistula, re-interventions, and in-hospital mortality compared with patients undergoing pancreatoduodenectomy for other cancers. These findings should be considered in patient counseling and postoperative management.

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Section: Discussionmentioning

confidence: 87%

“…Neoadjuvant therapy could impact the texture of pancreatic tissue, which has been associated with reduced rates of POPF. 32 …”

Section: Discussionmentioning

confidence: 99%

Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

et al. 2022

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“…An interesting and less radical concept in high-risk patients is one-time preoperative radiotherapy, aiming to obtain local fibrosis in the pancreatic neck where the future pancreatico-enterostomosis will be created (FIBROPANC study) [ 44 ]. Hence, pancreatic cancer patients who are treated with chemo(radio)therapy have a lower chance to develop clinically relevant POPF, with radiotherapy as independent predictor [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Surgical management of severe pancreatic fistula after pancreatoduodenectomy: a comparison of early versus late rescue pancreatectomy

Stoop

Fröberg

Sparrelid

et al. 2022

Langenbecks Arch Surg

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Background Rescue pancreatectomy for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) is associated with high mortality. However, in-depth literature is scarce and hard to interpret. This study aimed to evaluate the indications, timing and perioperative outcomes of rescue pancreatectomy for severe POPF after PD. Methods Retrospective single-centre study from all consecutive patients (2008–2020) with POPF-C after PD (ISGPS 2016 definition). Major morbidity and mortality during hospitalization or within 90 days after index surgery were evaluated. Time from index surgery to rescue pancreatectomy was dichotomized in early and late (≤ 11 versus > 11 days). Results From 1076 PDs performed, POPF-B/C occurred in 190 patients (17.7%) of whom 53 patients (4.9%) with POPF-C were included. Mortality after early rescue pancreatectomy did not differ significantly compared to late rescue pancreatectomy (13.6% versus 35.3%; p = 0.142). Timing of a rescue pancreatectomy did not change significantly during the study period: 11 (IQR, 8–14) (2008–2012) versus 14 (IQR, 7–33) (2013–2016) versus 8 days (IQR, 6–11) (2017–2020) (p = 0.140). Over time, the mortality in patients with POPF grade C decreased from 43.5% in 2008–2012 to 31.6% in 2013–2016 up to 0% in 2017–2020 (p = 0.014). However, mortality rates after rescue pancreatectomy did not differ significantly: 31.3% (2008–2012) versus 28.6% (2013–2016) versus 0% (2017–2020) (p = 0.104). Conclusions Rescue pancreatectomy for severe POPF is associated with high mortality, but an earlier timing might favourably influence the mortality. Hypothetically, this could be of value for pre-existent vulnerable patients. These findings must be carefully interpreted considering the sample sizes and differences among subgroups by patient selection.

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“…To date, only one randomized phase II trial has been presented that directly compared neoadjuvant multiagent chemotherapy with or without RT. 23,24 The ALLIANCE A021501 trial compared neoadjuvant mFOLFIRINOX (8 cycles) versus mFOLFIRINOX (7 cycles) followed by SBRT (33)(34)(35)(36)(37)(38)(39)(40) Gy in 5 fractions) or hypofractionated image-guided RT (25 Gy in 5 fractions). After inclusion of 56 patients, the RT arm was closed due to futility regarding the R0 resection rate.…”

Section: Discussionmentioning

confidence: 99%

“…Two recent studies, however, have found no difference in postoperative complications between patients with and without preoperative Moreover, the rate of postoperative pancreatic fistula was lower in patients who received preoperative RT. 37,38 Currently, 3 randomized trials are assessing the role of neoadjuvant RT for BR PDAC. The 3-arm BRPCNCC-1 trial is comparing neoadjuvant gemcitabine plus nab-paclitaxel with or without SBRT with S1 plus nab-paclitaxel with SBRT in 150 patients.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study

Janssen¹,

Prakash²,

Doppenberg³

et al. 2022

Journal of the National Comprehensive Cancer Network

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Background: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012–2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0–20 vs 21–40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1–4 vs 5–8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score–matched. After matching, median OS was 26.2 months (95% CI, 24.0–38.4) with RT versus 32.8 months (95% CI, 25.3–42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with <5% tumor viability (24.7% vs 8.3%; P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.

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The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

Abstract: The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

Cited by 21 publications

References 72 publications

Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

Surgical management of severe pancreatic fistula after pancreatoduodenectomy: a comparison of early versus late rescue pancreatectomy

Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study

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