Citations

687 Background: The NAPOLI 3 study (NCT04083235, N = 770) reported that NALIRIFOX improved overall survival (OS) vs Gem+NabP with manageable toxicity in 1L treatment of metastatic pancreatic adenocarcinoma. We explored changes in CA19-9 levels and their potential associations with efficacy as an important tumor marker in pancreatic adenocarcinoma. Methods: In NAPOLI 3, CA19-9 was evaluated at baseline and every 8 weeks until patients discontinued study treatment. The detection limit of CA19-9 was 8000 kU/L in this study. The Cox proportional hazards regression and logistic regression were employed to investigate the relationship between CA19-9 decrease and OS, progression-free survival (PFS), and overall response rate (ORR). Results: Patients with evaluable CA19-9 (levels =< 8000) at baseline and additional measurements at weeks 8 and 16 were included in the analysis (NALIRIFOX, n = 179; Gem+NabP, n = 194). The median baseline CA19-9 level was 378.0 and 409.7 kU/L for the NALIRIFOX and Gem+NabP arms, respectively. Overall, patients with (vs without) any CA 19-9 decrease by week 16 had a higher ORR (59.9% vs 35.2%; p = 0.002), a longer median PFS (9.2 vs 6.2 months; p < 0.001) and a longer median OS (14.2 vs 8.7 months; p = 0.005), respectively in a pooled analysis of the treatments. In the NALIRIFOX arm, patients with any CA19-9 decrease by week 16 had a higher confirmed ORR of 65.1% compared with those without at 42.4% ( p < 0.001), a median PFS of 9.5 vs 7.1 months ( p < 0.001) and a median OS of 15.4 versus 8.4 months ( p = 0.004), respectively. In the Gem+NabP arm, patients with CA19-9 decrease by week 16 had a higher ORR of 55.5% compared with those without at 23.8% ( p = 0.012), a median PFS of 7.6 versus 5.8 months ( p < 0.001) and a median OS of 13.7 versus 11.9 months ( p = 0.235), respectively. Conclusions: CA19-9 decrease by week 16 has the potential to be an early prognostic factor for OS, PFS and ORR. The results should be interpreted with caution as a considerable percentage of patients were excluded due to non-evaluable CA19-9 that exceeded the lab detection limit of 8000 kU/L. Clinical trial information: NCT04083235 .

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p<0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

283 Background: The randomized phase II CALGB 80803 trial evaluated use of PET imaging for early assessment of induction chemotherapy (iCT) responsiveness to tailor therapy for patients with esophageal and gastroesophageal junction adenocarcinomas (EC) undergoing trimodality therapy. The primary endpoint of improving pathologic complete response rates using PET-adapted therapy was met. A companion QOL study aimed to characterize patients’ experience through iCT, chemoradiation (CRT) and surgery (S). Methods: Between 11/2011 and 5/2015, 241 eligible patients were randomized to an iCT regimen: modified oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) or carboplatin/paclitaxel (CP), followed by PET scan then CRT, either continuing on the same CT for PET-responders (PET-R) or crossing over to the alternative CT for PET-nonresponders (PET-NR). We prospectively collected QOL domains and symptoms at baseline (T1), after iCT (T2), after CRT (T3), and 3- (T4) and 6- months (T5) after S using the EORTC QLQ-C30, The Esophageal Cancer subscale (EORTC OES18), FACT Neurotoxicity Scale (FACT-NTX), and 6 questions from the PRO-CTCAE. QOL scores were compared between iCT groups and between PET-R and PET-NR at each time point using mixed models. The association of QOL scores at enrollment with overall survival (OS) was tested using Cox regression. Results: 189 patients enrolled on the QOL sub-study, 92 received induction FOLFOX and 97 induction CP. Of those, 110 were PET-R and 79 were PET-NR. 97.9% went on to CRT, and 83.6% underwent S. Global QOL and symptoms statistically significantly worsened from T1 to T2 in 14 of 25 domains, and remained significantly worsened from T1 at: T3 for 19 of 25 domains, T4 for 17 of 25 domains, and T5 for 6 of 25 domains. Changes from T1 significantly favored iFOLFOX (vs iCP) for ability to eat (at T3 and T4), GI symptoms (at T3 and T4), and talking (at T5). Changes from T1 significantly favored iCP (vs iFOLFOX) for neuropathy (at T2, T3, and T4) and coughing (at T5). Proportion of patients reporting worsened PRO-CTCAE scores did not differ between PET-R or PET-NR groups . Multiple QOL domains and symptoms were associated with OS including role functioning, global health status/QOL, appetite loss, pain, dysphagia, and ability to eat (all p<0.002). Conclusions: QOL was impacted most by CRT but returned to baseline 6 months after surgery for most domains. Observed symptom differences did not consistently favor one iCT regimen. Early interventions such as nutritional support and prehabilitation should be studied to improve QOL and OS. Clinical trial information: NCT01333033 .

The role of informatics in public health has increased over the past few decades, and the coronavirus disease 2019 (COVID-19) pandemic has underscored the critical importance of aggregated, multicenter, high-quality, near-real-time data to inform decision-making by physicians, hospital systems, and governments. Given the impact of the pandemic on perioperative and critical care services (eg, elective procedure delays; information sharing related to interventions in critically ill patients; regional bed-management under crisis conditions), anesthesiologists must recognize and advocate for improved informatic frameworks in their local environments. Most anesthesiologists receive little formal training in public health informatics (PHI) during clinical residency or through continuing medical education. The COVID-19 pandemic demonstrated that this knowledge gap represents a missed opportunity for our specialty to participate in informatics-related, public health-oriented clinical care and policy decision-making. This article briefly outlines the background of PHI, its relevance to perioperative care, and conceives intersections with PHI that could evolve over the next quarter century.

Epicardial pulsed field ablation (PFA) of ganglionated plexi (GPs) is being explored as a potential treatment for atrial fibrillation. Initial work using open-chest access with a monopolar ablation device has been completed. This study describes the early development work for a device that can be used with subxiphoid access and deliver bipolar ablation pulses. Electric field computational models have been used for the initial guidance on pulse parameters. An in vivo assessment of these ablation parameters has been performed in an open-chest canine study, while subxiphoid access and navigation of the device has been demonstrated in a porcine model. Results from this acute study have demonstrated the promising potential of this approach.