A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate. RESULTS: Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Prevalence of radiologic evidence of metastatic pancreatic ductal adenocarcinoma (PDAC) at first post-operative restaging studies in patients (pts) undergoing pancreatic cancer surgery with curative intent

225 Background: Surgical resection is the only potentially curative modality for PDAC. However, even after a successful surgical resection outcomes are poor due to both local and distant disease recurrence. Patients with early recurrence likely derive no benefit from surgery and could be considered for a non-surgical approach as initial therapy. Since the incidence of recurrent/metastatic disease at first post-operative staging scan is not well documented, our aim was to determine this incidence. Methods: This IRB-approved analysis identified all pts diagnosed with resectable PDAC that underwent surgery with intent to cure at the University of Miami/Sylvester Comprehensive Cancer Center between 2010 and 2012. Patients with imaging before and within 6 months after surgery were included. All post-operative CT scans performed within 3 months after surgery were reviewed for the presence of recurrent and/or metastatic disease. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: Data from105 pts were analyzed. Mean age was 61, 63% were male, 91% had adenocarcinoma, 84% had disease in the head of the pancreas. 11 out of 85 (13%) pts had recurrent/metastatic disease detected on first post-operative CT scan; 64% stage IIB and 73% had positive lymph nodes. 54 out of 105 (51%) had disease progression. 60% had local recurrence, 40% had distant metastasis. The mean time from preoperative CT scan to surgery was 35 days. Patients with early and late recurrence had similar OS from diagnosis (median 27.7 and 27.1 months, respectively) but worse than those with no disease recurrence (median not reached, OS rate 78% at 36 months). Conclusions: The relatively high incidence (13%) of early recurrence in this retrospective cohort suggests that further studies aimed at improving patient selection for surgery are warranted and provides a strong rationale for the use of neoadjuvant therapy to select patients with early disease progression who would not have benefitted from surgery

Successful use of Trastuzumab with anthracycline-based chemotherapy followed by trastuzumab maintenance in patients with advanced HER2-positive gastric cancer

There is no standard chemotherapy regimen that is universally accepted for the treatment of advanced gastric cancer. Trastuzumab added to chemotherapy improves survival in patients with metastatic human epidermal growth factor receptor-2 (Her2/neu)-overexpressing gastric cancer. Data are lacking for the combination of trastuzumab with other chemotherapy regimens, apart from the cisplatin/fluorouracil backbone used in the pivotal TOGA trial. In this retrospective analysis, we included patients with gastric cancer with HER2 overexpression who received trastuzumab in addition to their first-line chemotherapy, with or without trastuzumab maintenance therapy. The end-points were response and tolerance to treatment. We identified seven patients who met the search criteria; six had metastatic disease and one had locally advanced unresectable disease. Four patients received epirubicin/oxaliplatin/capecitabine/trastuzumab, and the others had non-anthracycline-based chemotherapy with trastuzumab. All patients had radiological responses to treatment - one had a complete response and six had partial responses. Among the four patients who received anthracycline-based chemotherapy with trastuzumab, there was a transient decline in cardiac ejection fraction in three, but all resolved without sequelae. All patients received a period of chemotherapy induction followed by trastuzumab monotherapy for maintenance. The median progression-free survival was 14.6 months and median overall survival was 16.4 months. Trastuzumab is an important agent for the treatment of HER2-overexpressing gastric cancer. We recorded an acceptable safety and efficacy profile in this small cohort treated with anthracycline-based chemotherapy with trastuzumab followed by trastuzumab maintenance

Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma

Purpose To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC). Materials and Methods This retrospective study included 50 patients (23 women, 27 men; age range, 46–91 y; median age, 62.5 y) with biopsy-proven, unresectable LAPC who received percutaneous computed tomography (CT)–guided IRE. The primary objective was to assess the safety profile of the procedure; the secondary objective was to determine overall survival (OS). All patients had prior chemotherapy (1–5 lines, median 2), and 30 (60%) of 50 patients had prior radiation therapy. Follow-up included CT at 1 month and at 3-month intervals thereafter. Results There were no treatment-related deaths and no 30-day mortality. Serious adverse events occurred in 10 (20%) of 50 patients (abdominal pain [n = 7], pancreatitis [n = 1], sepsis [n = 1], gastric leak [n = 1]). Median OS was 27.0 months (95% confidence interval [CI], 22.7–32.5 months) from time of diagnosis and 14.2 months (95% CI, 9.7–16.2 months) from time of IRE. Patients with tumors ≤ 3 cm (n = 24) had significantly longer median OS than patients with tumors > 3 cm (n = 26): 33.8 vs 22.7 months from time of diagnosis (P =.002) and 16.2 vs 9.9 months from time of IRE (P =.031). Tumor size was confirmed as the only independent predictor of OS at multivariate analysis. Conclusions Percutaneous image-guided IRE of unresectable LAPC is associated with an acceptable safety profile