Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

Validation of the Norwegian survival prediction model in trauma (NORMIT) in Swedish trauma populations.

BACKGROUND: Trauma survival prediction models can be used for quality assessment in trauma populations. The Norwegian survival prediction model in trauma (NORMIT) has been updated recently and validated internally (NORMIT 2). The aim of this observational study was to compare the accuracy of NORMIT 1 and 2 in two Swedish trauma populations. METHODS: Adult patients registered in the national trauma registry during 2014-2016 were eligible for inclusion. The study populations comprised the total national trauma (NT) population, and a subpopulation of patients admitted to a single level I trauma centre (TC). The primary outcome was 30-day mortality. Model validation included receiver operating characteristic (ROC) curve analysis and GiViTI calibration belts. The calibration was also assessed in subgroups of severely injured patients (New Injury Severity Score (NISS) over 15). RESULTS: A total of 26 504 patients were included. Some 18·7 per cent of patients in the NT population and 2·6 per cent in the TC subpopulation were excluded owing to missing data, leaving 21 554 and 3972 respectively for analysis. NORMIT 1 and 2 showed excellent ability to distinguish between survivors and non-survivors in both populations, but poor agreement between predicted and observed outcome in the NT population with overestimation of survival, including in the subgroup with NISS over 15. In the TC subpopulation, NORMIT 1 underestimated survival irrespective of injury severity, but NORMIT 2 showed good calibration both in the total subpopulation and the subgroup with NISS over 15. CONCLUSION: NORMIT 2 is well suited to predict survival in a Swedish trauma centre population, irrespective of injury severity. Both NORMIT 1 and 2 performed poorly in a more heterogeneous national population of injured patients.

ANTECEDENTES: Los modelos de predicción de supervivencia en los traumatismos pueden ser utilizados para la evaluación de la calidad en las poblaciones con traumatismos. Recientemente, el modelo noruego de predicción de supervivencia en traumatismos (NORMIT) se ha actualizado y validado internamente (NORMIT 2). El objetivo de este estudio observacional fue comparar la precisión de los modelos NORMIT 1 y 2 en dos poblaciones suecas con traumatismos. MÉTODOS: Pacientes adultos registrados en el registro nacional de traumatismos durante 2014-2016 fueron elegibles para el estudio. Las poblaciones de estudio eran: (1) la población total nacional de traumatismos (national trauma, NT) y (2) una subpoblación de pacientes ingresados en un único centro de trauma de nivel I (trauma centre, TC). El resultado primario fue la mortalidad a los 30 días. La validación del modelo incluyó curvas de características operativas del receptor y cinturones GiViTI de calibración. La calibración también se evaluó en subgrupos de pacientes con lesiones graves (New Injury Severity Score, NISS >15). RESULTADOS: Se incluyeron un total de 26.504 pacientes. La exclusión por falta de datos fue del 18,7% en la población NT (n = 21.554) y del 2,6% en la población TC (n = 3.972). Los modelos NORMIT 1 y 2 mostraron una habilidad excelente para distinguir entre supervivientes y no supervivientes en ambas poblaciones, pero con un grado de acuerdo pobre entre el resultado predicho y el observado en la población NT, con sobreestimación de la supervivencia incluido el subgrupo de NISS >15. En la subpoblación TC, NORMIT 1 subestimó la supervivencia independientemente de la gravedad de la lesión, pero NORMIT 2 mostró una buena calibración tanto en la subpoblación total, como en el subgrupo NISS >15. CONCLUSIÓN: El modelo NORMIT 2 es muy apropiado para predecir la supervivencia en la población de un centro de traumatismos sueco independientemente de la gravedad de la lesión. Los modelos tanto NORMIT 1 como NORMIT 2 funcionan mal en una población de traumatismos nacional más heterogenea.

Analysis of preventable deaths and errors in trauma care in a Scandinavian trauma level-I centre.

BACKGROUND: The wide disparity in the methodology of preventable death analysis has created a lack of comparability among previous studies. The guidelines for the peer review (PR) procedure suggest the inclusion of risk-adjustment methods to identify patients to review, that is, exclude non-preventable deaths (probability of survival [Ps] < 25%) or focus on preventable deaths (Ps > 50%). We aimed to, through PR process, (1) identify preventable death and errors committed in a level-I trauma centre, and (2) explore the use of different risk-adjustment methods as a complement. METHODS: A multidisciplinary committee reviewed all trauma patients, which died a trauma-related death, within 30 days of admission to Karolinska University Hospital, Stockholm, in the period of 2012-2016. Ps was calculated according to TRISS and NORMIT and their accuracy where compared. RESULTS: Two hundred and ninety-eight deaths were identified and 252 were reviewed. The majority of deaths occurred between 1 and 7 days. Ten deaths (4.0%) were classified as preventable. Sixty-seven errors were identified in 53 (21.0%) deaths. The most common error was inappropriate treatment in all deaths (21 of 67) and in preventable deaths (5 of 13). Median Ps in non-preventable deaths was higher than the cut-off (<25%) and Ps-TRISS was almost twice as high as Ps-NORMIT (65% vs 33%, P < .001). Two clinically judged preventable deaths with Ps <25% would have been missed with both models. Median Ps in preventable deaths was above the cut-off (>50%) and higher with Ps-TRISS vs Ps-NORMIT (75% vs 58%, P < .001). Three and 4 clinically judged preventable deaths would have been missed, respectively, for TRISS and NORMIT, if using this cut-off. CONCLUSION: Preventable deaths were commonly caused by clinical judgment errors in the early phases but death occurred late. Ps calculated with NORMIT was more accurate than TRISS in predicting mortality, but both perform poorly in identifying preventable and non-preventable deaths when applying the cut-offs. PR of all trauma death is still the golden standard in preventability analysis.

A comparison study on three different radiation detectors used for liquid levelmetry.

In this paper, three different radiation detectors (BF3 counter, NE213 and BGO scintillators) and an (241)Am-Be isotopic neutron-gamma source have been used for a typical liquid levelmetry. The study shows that the use of the Am-Be source together with an NE213 scintillator has the best performance.