Citations

e16752 Background: Undifferentiated osteoclast-like giant cell carcinoma of the pancreas is an aggressive malignancy only described by a few case reports in the literature. In this study, we sought to better characterize this entity by examining patients seen at Mayo Clinic. Methods: This study identified patients with osteoclast-like giant cell carcinoma of the pancreas using Mayo Clinic databases (MN, AZ, FL) from the year 2000 to present. Patient demographics, genetic data, and treatment modalities were reviewed. Kaplan-Meier analysis was used to evaluate median overall survival (mOS) for the cohort as well as mOS and mPFS for treatment subgroups. Results: 15 patients were identified (9 female, 6 male). Median age at diagnosis was 59 years and mOS for all patients was 11.0 mos (95% CI 6.2-15.7 mos). 3 patients (20%) had metastatic disease at diagnosis with the liver being the most common site (n = 3). Metastatic disease was associated with significantly shorter OS (3.5 vs. 14.1 mos, p = 0.005; HR 7.98 [95% CI 1.43-44.4]) compared to locoregional disease (LRD). 4 patients underwent genetic testing. The most common mutation was CDKN2A (n = 3), followed by TP53 (n = 2) and KRAS (n = 2). 13/15 patients had detailed follow-up information. 6/7 patients undergoing chemotherapy received a gemcitabine-based regimen as first line: with capecitabine (n = 2), with nab-paclitaxel (n = 2), or as monotherapy (n = 2). 1 patient received FOLFIRINOX. In patients with LRD and adequate follow-up (n = 11), 8/11 underwent surgical resection and had longer OS compared to those without resection (17.0 vs. 8.4 mos, p = 0.09). No surgical patients received neoadjuvant chemotherapy. 5/8 received adjuvant chemotherapy, 2 did not undergo chemotherapy, and 1 was lost to follow-up after surgery. PFS from time of surgery was 15.3mos (95% CI 5.0-25.6mos). 6 patients (40%) were alive at time of analysis; all 6 underwent surgical resection. Conclusions: Osteoclast-like giant cell carcinoma of the pancreas is a rare malignancy with a poor prognosis, even when diagnosed at an early stage. OS for patients of all stages in this study was less than 1 year suggesting prognosis may be even worse than that of pancreatic adenocarcinoma. The optimal therapy remains unknown but most patients received similar chemotherapy as in adenocarcinoma. Patients with LRD amenable to surgical resection experienced a PFS over 1 year from surgery, possibly associated with OS benefit, however overall prognosis is poor. Further study is warranted on a larger scale to better understand disease course and treatment options.

e16702 Background: There are only a few reports examining the treatment patterns for poorly differentiated rectal/anal NEC. In this study, we sought to report treatment and survival outcomes for patients with NEC of the anus and rectum seen at Mayo Clinic. Methods: We identified patients with a primary NEC of the anus or rectum using Mayo Clinic databases (Minnesota, Arizona, Florida) from the year 2000 to present. NEC identified within polyps on colonoscopy was excluded from this study. Patients’ demographics were compiled. Kaplan Meier analyses were performed to evaluate overall survival (OS) for all patients, as well as subgroups with locoregional disease (LRD) and metastatic disease at diagnosis. Progression free survival (PFS) was also evaluated for patients with LRD treated with chemoradiation therapy (CRT). Results: 38 patients with NEC of the anus/rectum were identified with a median age of 55.5 years. 23 patients (61%) had metastatic disease at diagnosis and 15 (39%) had LRD. The most common site of metastasis was the liver (n = 20). Patients with metastatic disease at presentation had significantly shorter OS compared to patients with LRD (median OS 10.4 vs. 18.9 months, p = 0.039; HR 2.46, 95% CI [1.001-6.050]). 34 total patients received chemotherapy (ORR 11.8%), with platinum + etoposide (EP) being the most common first-line chemotherapy (n = 26). 10 of 15 patients with LRD received CRT (9 with EP and 1 with 5-FU) with median PFS of 6.3 months (95% CI 2.3-16.5 months), a 1-year PFS rate of 20%, and median OS of 18.6 months (95% CI 13.5-23.7 months). 2/10 received induction chemotherapy prior to CRT with 6/10 undergoing primary tumor resection (1 prior to CRT and 5 after CRT). Only 3 CRT patients were living at time of analysis (all underwent surgical resection), 2 without any active disease, 1 who achieved complete response with CRT then suffered recurrence and is still undergoing treatment. Conclusions: NEC of the anus and rectum is an aggressive malignancy with most patients experiencing metastatic disease at presentation and poor response to chemotherapy at all stages. Even those with LRD experience a very poor prognosis with OS of 18.9 months from diagnosis. For LRD, most patients underwent CRT with only a short-lived response (median PFS 6.3 months). Those achieving sustained response also underwent surgical resection. Overall, prognosis is poor for all stages and further study on a large scale is warranted to better characterize this rare, aggressive malignancy.

e16691 Background: Recent WHO classification of NET has defined high-grade well-differentiated NET (NET G3) as a distinct entity that is clinically different from neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aims to evaluate NET G3 response to different treatment regimens. Methods: This is a retrospective study of NET G3 patients within the Mayo Clinic database (Arizona, Florida, and Minnesota). Patient demographics along with treatment responses and survival were assessed. Primary end points were progression-free survival (PFS) and objective response rate (ORR) by RECIST 1.1 criteria. Results: 71 patients with NET G3 were identified. Systemic treatment data was available in 30 patients who had a median age of 59.5 years at time of diagnosis. The primary tumor was most commonly pancreatic (73.3%). Ki 67 index was ≥55% in 26.7% of cases. 56.7% of cases had > 1 metastatic site. Treatment regimens included: capecitabine+temozolomide (CAPTEM) (n = 20), somatostatin analog (SSA) (n = 14), carboplatin/cisplatin+etoposide (EP) (n = 7), everolimus (n = 2), FOLFOX (n = 7), and lutetium Lu 177 DOTATATE (PRRT) (n = 10). CAPTEM was the most commonly used regimen (10 first-line, and 10 second-line) with ORR of 35%, disease control rate (DCR) of 65%, and median PFS of 9.4 months. The table summarizes the treatment data and responses rates for the various therapies used. Conclusions: Among NET G3 patients treated at Mayo Clinic, CAPTEM was found to be the most commonly used treatment with reasonable efficacy and disease control. Other treatment options include SSA, PRRT, FOLFOX, and EP. Prospective studies evaluating different treatments effects in NET G3 patients are needed to determine an optimal treatment strategy. [Table: see text]

4003 Background: Aspirin and cyclooxygenase-2 (COX-2) inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. CALGB/SWOG 80702 tested the effect of celecoxib, a COX-2 inhibitor, on reducing the risk of recurrence in stage III CC. Methods: CALGB/SWOG 80702 is a 2x2 randomized controlled phase III trial of 3 v 6 months of adjuvant FOLFOX (data previously reported as part of the IDEA collaboration) with concurrent celecoxib (400 mg daily) v placebo x 3 yrs for patients (pts) with resected stage III CC. The primary endpoint of the trial is disease-free survival (DFS), defined as time from randomization to recurrence or death from any cause. The trial was designed to provide 91% power to detect a hazard ratio (HR) of 0.79 in favor of celecoxib with 2-sided alpha = 0.05 (775 events required); due to slowing accumulation of events 4 years after complete accrual, power was lowered to 85% with same HR and alpha assumptions (696 events required). The DSMB released data on February 24, 2020 at median f/u of 5.6 yrs with 689 DFS events. Results: Between June 2010 and November 2015, 2,526 pts were consented and randomized to the trial. Treatment arms were well balanced by patient and tumor prognostic features, as well as low-dose aspirin use. Baseline characteristics included 45% female, 18% non-White, 8% Hispanic, 15% T4, 26% N2. 3-yr DFS for celecoxib was 76.3% v 73.3% for placebo (HR 0.89 [95% CI 0.77-1.04]; P = 0.14). 5-yr overall survival (OS) was 83.9% for celecoxib v 81.7% for placebo (HR 0.87 [95% CI 0.72-1.05]; P = 0.14). When considering the 4 treatment arms separately, 3-yr DFS was 77.0% for 12 months FOLFOX + celecoxib, 74.9% for 12 months FOLFOX + placebo, 75.5% for 6 months FOLFOX + celecoxib, and 71.9% for 6 months FOLFOX + placebo (log rank P = 0.22; P interaction = 0.64). There were no significant differences in grade 3-4 toxicity with celecoxib v placebo. Compliance with protocol celecoxib treatment, defined as 3 yrs of therapy completion or recurrence/death while on treatment, was 58.1% pts on celecoxib and 60.2% pts on placebo. Conclusions: The addition of celecoxib to standard chemotherapy did not significantly improve DFS or OS. Clinical trial information: NCT01150045 .

3594 Background: Selpercatinib (LOXO-292) is a highly selective and potent small molecule RET kinase inhibitor. Here we report an update on the efficacy and safety of selpercatinib in RET-mutant medullary thyroid cancer (MTC). Methods: Patients with RET-mutant MTC were enrolled to the Phase 1/2 LIBRETTO-001 trial (NCT03157128), a global, multicenter trial (16 countries, 89 sites). Following the Phase 1 dose escalation portion of the trial, patients received the recommended dose of 160 mg orally twice daily. Each cycle was 28 days. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included duration of response (DoR) and safety. Per health authority agreement, the primary analysis set was defined as the first 55 consecutively enrolled patients previously treated with multikinase inhibitors cabozantinib and/or vandetanib. Patients naïve to cabozantinib and vandetanib treatment were analyzed separately. All analyses were based on a 16-Dec-2019 data cutoff date. Results: In the primary analysis set of prior cabozantinib and/or vandetanib-treated patients with MTC (n = 55), the ORR by investigator assessment was 62% (95% CI 47.7–74.6, n = 34/55) and the median DoR was not reached (95% CI 18.4 months–not estimable) despite a median follow-up of 14.8 months. In cabozantinib/vandetanib treatment-naïve patients (n = 88), the ORR by investigator assessment was 69% (95% CI 58.6–78.7, n = 61/88, including 2 responses pending confirmation). Of the 59 confirmed responding patients, with a median follow-up of 8 months, responses were ongoing for 57 responders at the time of the analysis. In the safety analysis set consisting of all selpercatinib dosed patients (N = 702), the most common treatment-related adverse events (TRAEs) that occurred in ≥15% of patients were dry mouth (33.3%), increased AST (24.5%), increased ALT (23.8%), hypertension (23.2%), diarrhea (19.7%), and fatigue (16.8%). Only 2% (14 of 702) of patients discontinued selpercatinib for TRAEs. Conclusions: Selpercatinib use was associated with marked and durable antitumor activity in prior cabozantinib and/or vandetanib-treated patients and in cabozantinib/vandetanib-naïve patients with RET-mutant MTC, with the majority of responses ongoing in both cohorts. Selpercatinib was well tolerated. Efficacy data assessed by independent review committee based on the 16-Dec-2019 data cutoff date will be presented. Clinical trial information: NCT03157128 .

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

OBJECTIVEPlatelet-rich plasma (PRP) is a biological agent obtained by centrifuging a sample of blood and retrieving a high concentration of platelets and plasma components. The concentrate is then stimulated for platelet secretion of various growth factors and cytokines. Although it is not widely used in clinical practice, its role in augmenting bony union among patients undergoing spinal fusion has been assessed in several clinical studies. The objective of this study was to perform a systematic review and meta-analysis of the existing literature to determine the efficacy of PRP use in spinal fusion procedures.METHODSA comprehensive literature search was conducted using PubMed, Scopus, and EMBASE for studies from all available dates. From eligible studies, data regarding the fusion rate and method of assessing fusion, estimated blood loss (EBL), and baseline and final visual analog scale (VAS) scores were collected as the primary outcomes of interest. Patients were grouped by those undergoing spinal fusion with PRP and bone graft (PRP group) and those only with bone graft (graft-only group).RESULTSThe literature search resulted in 207 articles. Forty-five full-text articles were screened, of which 11 studies were included, resulting in a meta-analysis including 741 patients. Patients without PRP were more likely to have a successful fusion at the last follow-up compared with those with PRP in their bone grafts (OR 0.53, 95% CI 0.34–0.84; p = 0.006). There was no statistically significant difference with regard to change in VAS scores (OR 0.00, 95% CI −2.84 to 2.84; p > 0.99) or change in EBL (OR 3.67, 95% CI −67.13–74.48; p = 0.92) between the groups.CONCLUSIONSThis study found that the additional use of PRP was not associated with any significant improvement in patient-reported outcomes and was actually found to be associated with lower fusion rates compared with standard grafting techniques. Thus, PRP may have a limited role in augmenting spinal fusion.

Extraocular muscle (EOM) entrapment with resulting reduction in motility and diplopia is a known complication of orbital fractures. Less commonly, transection of the EOMs due to trauma, iatrogenic injury, or intentional myotomy may lead to persistent diplopia. The inferior oblique (IO) is often encountered during orbital surgery along the medial wall and floor, and may be disinserted to aid in visualization. The authors present a case of IO entrapment which occurred during zygomaticomaxillary fracture reduction. Intraoperatively, an IO transection was performed and the muscle was reattached within the orbit. Postoperatively, the patient did not develop diplopia or motility disruption. This technique may provide a useful solution to an unusual problem during orbital fracture repair.

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking. Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type. Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients’ median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years). Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

Abstract Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.Results: Although no differences were observed between groups in CT fusion rates or fusion mass volumes, iliac allografts displayed a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.