Preoperative chemo- or chemoradiotherapy is recommended for borderline-resectable pancreatic cancer. The aim of this study was to determine the impact of preoperative therapy on surgical complications in patients with resected pancreatic cancer. This systematic review and meta-analysis included studies reporting on the rate of surgical complications after preoperative chemo- or chemoradiotherapy versus immediate surgery in pancreatic cancer patients. The primary endpoint was the rate of grade B/C POPF. Pooled odds ratios were calculated using random-effects models. Forty-one comparative studies including 25,389 patients were included. Vascular resections were more often performed after preoperative therapy (29.4% vs. 15.7%, p < 0.001). Preoperative therapy was associated with a lower rate of grade B/C POPF as compared to immediate surgery (pooled OR 0.47, 95%CI 0.38-0.58). This reduction was mostly obtained by preoperative chemoradiotherapy (OR 0.46, 95%CI 0.29-0.73), but not by preoperative chemotherapy alone (OR 0.83, 95%CI 0.59-1.16). No difference was demonstrated for major morbidity, mortality, postpancreatectomy haemorrhage, delayed gastric emptying and overall morbidity. Preoperative chemo- and chemoradiotherapy in patients with pancreatic cancer appears to be safe with respect to POPF and other surgical complications as compared to immediate surgery. The reduced rate of POPF appears to be attributable to preoperative chemoradiation.

Background: Brain metastasis is considered one of the major causes of mortality in breast cancer patients. To invade the brain, tumor cells need to pass the blood-brain barrier by mechanisms that are partially understood. In primary ER-negative breast cancers that developed brain metastases, we found that some of the differentially expressed genes play roles in the T cell response. The present study aimed to identify genes involved in the formation of brain metastasis independently from the T cell response. Method: Previously profiled primary breast cancer samples were reanalyzed. Genes that were found to be differentially expressed were confirmed by RT-PCR and by immunohistochemistry using an independent cohort of samples. Results: BOC, SPOCK2, and GJD3 were overexpressed in the primary breast tumors that developed brain metastasis. BOC expression was successfully validated at the protein level. SPOCK2 was validated at both mRNA and protein levels. SPOCK2 and GJD3 mRNA overexpression were also found to be associated with cerebral metastasis in an external online database consisting of 204 primary breast cancers. Conclusion: The overexpression of BOC, SPOCK2, and GJD3 is associated with the invasion of breast cancer into the brain. Further studies to determine their specific function and potential value as brain metastasis biomarkers are required.

Objectives: Erwinia asparaginase is used as a second‐line formulation after a neutralizing hypersensitivity reaction to the first‐line formulation of asparaginase. Here, we have performed a cost‐effectiveness analysis of Erwinia asparaginase treatment.Methods: Children with acute lymphoblastic leukemia treated according to the Dutch Childhood Oncology ALL‐10 or ALL‐11 protocol were included and initially treated with PEGasparaginase in the intensification phase. The total treatment costs of this treatment phase, quality of life (QoL), and life years saved (LYS) were studied for two scenarios: (a) patients were switched to Erwinia asparaginase treatment after a hypersensitivity reaction, or (b) asparaginase would have been permanently stopped.Results: Sixty‐eight patients were included. There was no difference in QoL between patients with and without a hypersensitivity reaction. The mean costs of the intensification phase per patient were $40,925 if PEGasparaginase could be continued, $175,632 if patients had to switch to Erwinia asparaginase, and $21,190 if asparaginase would have been permanently stopped. An extrapolation of the literature suggests that the 5‐year event‐free survival would be 10.3% lower without intensive asparaginase treatment if asparaginase is stopped after a reaction. Thus, the costs per LYS were $1892 for scenario 1 and $872 for scenario 2.Conclusions: Switching to Erwinia asparaginase increases the costs per LYS by $1020, which is modest in view of the total costs. Moreover, when asparaginase treatment can be completed by switching to Erwinia asparaginase, relapses—and consequential costs—will be avoided. Therefore, from a cost perspective, we recommend a switch to Erwinia asparaginase to complete asparaginase treatment.

Postoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. All patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014-2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. Overall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03-0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25-1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P < .001). This nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.

Background: Postoperative pancreatic fistula is the main driver of morbidity and mortality after pancreatoduodenectomy. In high-risk patients, the rate of postoperative pancreatic fistula approaches 50%, whereas it is below 5% in patients with pancreatic cancer who receive neoadjuvant chemoradiotherapy. The aim of this study was to evaluate the safety, feasibility, and efficacy of preoperative stereotactic body radiotherapy on the pancreatic neck transection margin in high-risk patients undergoing pancreatoduodenectomy to prevent postoperative pancreatic fistula. Methods: In this prospective multicentre open-label single-arm trial (progressing from a safety run-in phase to a phase II design), patients undergoing pancreatoduodenectomy for neoplasms other than pancreatic ductal adenocarcinoma received a single preoperative stereotactic body radiotherapy dose of 12 Gy. Primary endpoints included safety (less than or equal to 15% grade 3–5 toxicity), feasibility (a significant change in pancreatic texture measured using a durometer), and efficacy (a 15% reduction in the grade B/C postoperative pancreatic fistula rate compared with patients from the Dutch Pancreatic Cancer Audit who were eligible but not included in this study). Secondary endpoints assessed tissue fibrosis (collagen density). Results: Overall, 38 patients were included, of whom 33 (87%) completed the study protocol and were included in the per-protocol analysis. The safety cut-off was met, with 3% grade 3–5 toxicity. Pancreatic tissue treated with stereotactic body radiotherapy showed increased firmness using a durometer (median of 47 (interquartile range 36–57) versus 37 (interquartile range 30–41) Shore OO units; P < 0.001) and a higher collagen density (median of 6.1% (interquartile range 4.4%–9.5%) versus 4.6% (interquartile range 2.5%–7.4%); P = 0.003). The grade B/C postoperative pancreatic fistula rate with stereotactic body radiotherapy was 57.6% (95% c.i. 41% to 74%), compared with 34% (95% c.i. 27% to 42%) in audit controls (P = 0.011). Conclusion: Preoperative stereotactic body radiotherapy is safe in high-risk patients undergoing pancreatoduodenectomy and increases parenchymal firmness and fibrosis, but fails to show evidence of efficacy.

Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastating loss of life. Large registry studies have begun to shed light on the epidemiological and clinical vulnerabilities of cancer patients who succumb to or endure poor outcomes of SARS-CoV-2. Specific treatment for COVID-19 infections in cancer patients is lacking while the demand for treatment is increasing. Therefore, we explored the effect of Rintatolimod (Ampligen^®) (AIM ImmunoTech, Ocala, FL, USA), a Toll-like receptor 3 (TLR3) agonist, to treat uninfected human pancreatic cancer cells (HPACs). The direct effect of Rintatolimod was measured by targeted gene expression profiling and by proteomics measurements. Our results show that Rintatolimod induces an antiviral effect in HPACs by inducing RNase-L-dependent and independent pathways of the innate immune system. Treatment with Rintatolimod activated the interferon signaling pathway, leading to the overexpression of several cytokines and chemokines in epithelial cells. Furthermore, Rintatolimod treatment increased the expression of angiogenesis-related genes without promoting fibrosis, which is the main cause of death in patients with COVID-19. We conclude that Rintatolimod could be considered an early additional treatment option for cancer patients who are infected with SARS-CoV-2 to prevent the complicated severity of the disease.