Background:Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.Methods:Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined.Results:In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65–14.32) and PFS 6.1 months (95% CI 5.19–8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0–23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001) and fatigue (P=0.01) were significantly decreased. [18F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS.Conclusions:In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.

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Anatomical structures are rarely static during a surgical procedure due to breathing, heartbeats, and peristaltic movements. Inspired by observing an expert surgeon, we propose an intermittent synchronization with the extrema of the rhythmic motion (i.e., the lowest velocity windows). We performed 2 experiments: (1) pattern cutting, and (2) debridement. In (1), we found that the intermittent synchronization approach, while 1.8x slower than tracking motion, was significantly more robust to noise and control latency, and it reduced the max cutting error by 2.6x In (2), a baseline approach with no synchronization achieves 62% success rate for each removal, while intermittent synchronization achieves 80%.

To simulate body organ motion due to breathing, heart beats, or peristaltic movements, we designed a lowcost, miniaturized SPRK (Stewart Platform Research Kit) to translate and rotate phantom tissue. This platform is 20cm × 20cm × 10cm to fit in the workspace of a da Vinci Research Kit (DVRK) surgical robot and costs $250, two orders of magnitude less than a commercial Stewart platform. The platform has a range of motion of ± 1.27 cm in translation along x, y, and z directions and has motion modes for sinusoidal motion and breathing-inspired motion. Modular platform mounts were also designed for pattern cutting and debridement experiments. The platform's positional controller has a time-constant of 0.2 seconds and the root-mean-square error is 1.22 mm, 1.07 mm, and 0.20 mm in x, y, and z directions respectively. All the details, CAD models, and control software for the platform is available at github.com/BerkeleyAutomation/sprk.

Background: Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.

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