Joseph Herman

Purpose/Objective: This purpose of this study is to report on a cohort of patients with Early-onset pancreatic cancer (EOPC) (age < 55 years) who were treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) with or without surgical resection. Materials/Methods: This was a single-institution, retrospective review of patients with EOPC that was staged as either borderline resectable (BRPC) or locally advanced (LAPC) based on NCCN criteria and who were treated with upfront chemotherapy followed by SBRT, with or without subsequent surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Results: From 2016 to 2021, 47 patients met the inclusion criteria. The median age was 50.4 years (range, 36.4–54.7 years). The median duration of induction chemotherapy was 4 months (range, 2.5–9.0 months). The SBRT dose for the majority (46/47, 97.9%) of patients was 33 Gy in five fractions. Surgical resection was performed in 33 patients (70.2%). The median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (≥4 months) was associated with improved median OS (16.5 vs. 10.1 months, p = 0.005), LPFS (10.1 vs. 4.9 months, p = 0.002), DMFS (9.7 vs. 5.2 months, p = 0.014), and PFS (9.7 vs. 5.2 months, p = 0.020). The normalization of CA 19-9 (≤34 vs. >34 U/mL) after chemotherapy was associated with improved median DMFS (not reached vs. 5.6 months, p = 0.003) and PFS (11.3 vs. 5.6 months, p = 0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. The Clavien–Dindo 3b toxicity rate was 3.0%. Conclusions: In EOPC, an induction chemotherapy duration ≥4 months and the normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population.

Intrahepatic abscess is an exceedingly rare complication of locoregional therapy for patients with liver cancer. However, in patients who underwent prior hepatobiliary intervention, the incidence of liver abscess increases significantly, causing morbidity and even mortality in such patients. Here, we will review the relative risk of developing a liver abscess after intraarterial and ablative locoregional therapies in patients with liver cancer depending on whether they underwent any kind of prior hepatobiliary procedures that resulted in violation of the Ampulla of Vater. As a result, patients deemed at high risk of developing a liver abscess were treated prophylactically, with the combination of bowel preparation and antibiotics nearly eliminating the occurrence of a liver abscess after locoregional therapy. Therefore, given the significant risk of developing a liver abscess in patients with prior hepatobiliary procedures, management consisting of prophylactic bowel preparation with antibiotic coverage followed by antibiotics post-locoregional therapy is recommended.

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. Most patients included in the study had either locally advanced disease (32 patients, 39%) or borderline resectable disease (29 patients, 35%). Eighty-two PC patients underwent the placement of 230 fiducial markers under EUS guidance. The technical success rate of the fiducial placement was 98%. No immediate EUS-related adverse events were reported. The average time to the simulation CT after fiducial placement was 3.1 days. Of the 216 fiducial markers used for the SBRT delivery, 202 fiducial markers were visible on both the simulation CT and the cone beam CT scan. A median dose of 40cGY was given to all the patients in five fractions. Of these, 41% of the patients reported no SBRT-related toxicities during the follow-up. Fatigue and nausea were the most reported SBRT-related toxicities, which were seen in 35% of the patients post-SBRT. Our results demonstrate that EUS-guided fiducial placement is safe and effective in target volume delineation, facilitating SBRT delivery in PC patients. Further clinical trials are needed to determine the SBRT-related survival benefits in patients with pancreatic cancer.

We aimed to evaluate the impact of time from stereotactic body radiation therapy (SBRT) to surgery on treatment outcomes and post-operative complications in patients with borderline resectable or locally advanced pancreatic cancer (BRPC/LAPC). We conducted a single-institutional retrospective analysis of patients with BRPC/LAPC treated from 2016 to 2021 with neoadjuvant chemotherapy followed by SBRT and surgical resection. Covariates were stratified by time from SBRT to surgery. A Cox regression model was used to identify variables associated with survival outcomes. In 171 patients with BRPC/LAPC, the median time from SBRT to surgery was 6.4 (range: 2.7–25.3) weeks. Hence, patients were stratified by the timing of surgery: ≥6 and p = 0.042), pathologic node positivity, elevated baseline CA19-9, and inferior LC if of the male sex. In multivariable analysis, surgery ≥6 weeks (p = 0.013; HR 0.46, 95%CI 0.25–0.85), node positivity (p = 0.019; HR 2.09, 95% CI 1.13–3.88), and baseline elevated CA19-9 (p = 0.002; HR 2.73, 95% CI 1.44–5.18) remained independently associated with LC. Clavien–Dindo Grade ≥3B complications occurred in 4/63 (6.3%) vs. 5/99 (5.5%) patients undergoing surgery p = 0.7). In summary, the timing of surgery ≥6 weeks after SBRT was associated with improved local control and low post-operative complication rates, irrespective of the surgical timing. Further investigation of the influence of surgical timing following radiotherapy is warranted.

Optimal management of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) is controversial and variation exists within/across academic and healthcare systems. Herein we describe the initial results of a neoadjuvant therapy (NAT) pathway across one of New York’s largest, most diverse health care systems. The NATP was established at Northwell Health in June 2019, consisting of an initial, single-day pancreas multi-disciplinary clinic (PMDC) visit, followed by NAT, interval scans and PMDC re-reviews at two and four months, prior to consideration of radiation and of surgical resection. We conducted an IRB-approved retrospective analysis of patients enrolled to this pathway. Primary endpoints included completion of NAT pathway and overall survival (OS). Kaplan-Meier analysis was used to estimate OS. The cohort consisted of 55 patients: 44% men, mean age 69.7 years, and 48% non-White. Surgical stage at diagnosis was locally advanced (LAPC; 49%), borderline resectable (BRPC; 35%) and resectable (RPC; 16%). NAT consisted of gemcitabine/nab-paclitaxel (GnP, 41%; 147 total cycles), FOLFIRINOX (36%; 167 total cycles), and a combination of both regimens (23%). Eighteen (33%) received radiotherapy (94%, SBRT) and 72% received >=50 Gy. Average duration of NAT pathway (from biopsy to surgery) was 5.9 mo (IQR 4.7-7.6 mo): average time from biopsy to C1 of NAT was 25 days (IQR 18-39 days), from C1 to post NAT completion imaging was 3.9 mo (IQR 3.5-4.8 mo) and from RT to surgery was 36.0 days (IQR 30.5-43.8 days). Of 55 patients who began the pathway, 24 (44%; 6% RPC, 53% BRPC, 41% LAPC) completed the pathway and underwent surgical exploration; 22 did not complete the pathway and 9 are currently undergoing NAT. Reasons for not completing NAT included metastasis (24%), transfer of care (12%), local progression (5.5%), and death (3.6%). Out of 24 patients who were surgically explored, 71% underwent successful resection (53% R0, 18% R1<1mm and 30% R1) compared to prior institutional resection rate in NAT patients of 17% (p=0.015). There were 11 deaths (20%) and median OS was reached at 17.7 mo (95% CI 7.9, 27.6): 16.3 mo 95% CI 7.2, 25.4) and 26.1 mo (95% CI 3.2, 49) for GnP and FOLFIRINOX, respectively. Patients enrolled in the NAT pathway had a higher rate of germline mutation testing (52% vs 30%, p=0.002). The percentage of patients that remained within the Northwell Health system for their post-NAT was higher among patients in the pathway, compared to prior (87% versus 44%). Implementation of a standardized NAT approach at a large diverse healthcare system increased the percentage of PDAC patients who underwent surgical resection and improved patient retention rate. Citation Format: Ruwan Parakrama, Baho Sidiqi, Lyudmyla Demyan, Shamsher Pasha, Danielle Pinto, Tiffany Zavadsky, Xianghui Zhou, Sunita Patruni, Adrianna Kapusta, Oliver Standring, Matthew J. Weiss, Joseph M. Herman, Daniel A. King. Standardization of a neoadjuvant therapy (NAT) pathway for pancreatic cancer across a geographically large and diverse healthcare system improves patient outcomes and successful completion of NAT [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A022.

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.