Background
The management of patients with liver and biliary malignancies is rapidly changing. Over the past year, important new studies have been published that offer new treatment options for ...patients with hepatobiliary cancers.
Methods
This article summarizes the top studies published in hepatobiliary cancer over the past year and describes how this latest evidence will impact clinical practice.
Results
Advances in systemic therapy with immune checkpoint inhibition and precision oncology approaches for primary liver cancers were reported. For colorectal liver metastases, long-term results from one large randomized trial report limited effects of chemotherapy on overall survival following liver metastasectomy.
Conclusions
Key new evidence informs that treatment strategies for hepatobiliary cancer are now available and should be incorporated into practice to improve outcomes for patients with liver and biliary malignancies.
A multimodality approach, which usually includes chemotherapy, surgery, and/or radiotherapy, is optimal for patients with localized pancreatic cancer. The timing and sequence of these interventions ...depend on anatomic resectability and the biological suitability of the tumor and the patient. Tumors with vascular involvement (ie, borderline resectable/locally advanced) require surgical reassessments after therapy and participation of surgeons familiar with advanced techniques. When indicated, venous reconstruction should be offered as standard of care because it has acceptable morbidity. Morbidity and mortality of pancreas surgery may be mitigated when surgery is performed at high-volume centers.
In a prospective, randomized trial involving patients with resected pancreatic cancer, adjuvant combination chemotherapy with FOLFIRINOX resulted in a median disease-free survival of 21.6 months, as ...compared with 12.8 months with gemcitabine therapy. Overall survival was also longer with FOLFIRINOX.
Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients
, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines
. Here in a phase I trial of adjuvant autogene ...cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8
T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.
Abstract Background Enhanced recovery after surgery (ERAS) protocols have been shown to reduce hospital stay without compromising outcomes. Attempts to apply ERAS principles in the context of ...pancreatic surgery have generated encouraging results. A systematic review of the current evidence for ERAS following pancreatic surgery was conducted. Methods A literature search of MEDLINE, CINAHL, EMBASE and the Cochrane Library was performed for articles describing postoperative clinical pathways in pancreatic surgery during the years 2000–2013. The keywords ‘clinical pathway’, ‘critical pathway’, ‘fast-track’, ‘pancreas’ and ‘surgery’ and their synonyms were used as search terms. Articles were selected for inclusion based on predefined criteria and ranked for quality. Details of the ERAS protocols and relevant outcomes were extracted and analysed. Results Ten articles describing an ERAS protocol in pancreatic surgery were identified. The level of evidence was graded as low to moderate. No articles reported an adverse effect of an ERAS protocol for pancreatic surgery on perioperative morbidity or mortality. Length of stay (LoS) was decreased and readmission rates were found to be unchanged in six of seven studies that compared these outcomes. Conclusions Evidence indicates that ERAS protocols may be implemented in pancreatic surgery without compromising patient safety or increasing LoS. Enhanced recovery after surgery programmes in the context of pancreatic surgery should be standardized based upon the best available evidence, and trials of ERAS programmes involving multiple centres should be performed.
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