bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of patient-derived tumor xenograft (PDX) model as artificially-created liver metastasis using cryopreserved pancreatic ductal adenocarcinoma.
Authors: Kimura Kenjiro , Tanaka Ryota , Amano Ryosuke , Kubo Shoji , Tanaka Hiroaki , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi
Published: February 2020

729

Background: Translational research using patient-derived tumor xenograft (PDX) model is progressing rapidly, and is also becoming widespread in pancreatic cancer research. The purpose of this study was to establish the liver transplant PDX model as artificially-created liver metastasis with cryopreserved primary pancreatic ductal adenocarcinoma(PDAC). Methods: The primary PDAC from 10 patients were cryopreserved and transplanted into NSG mice using liver pocket method. For engraftment and similarity evaluation, H&E staining and immunohistochemical staining such as Ki-67, p53, SMAD4, and MUC1 were performed. Results: Patient-derived xenograft was succeeded in 6 cases (60%), 10 mice (33.3%). Ki-67 index of primary PDAC and the interval of cryopreservation were significantly related to successful engraftment, respectively (p = 0.003, p = 0.007). Conclusions: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The factors such as Ki-67 index and the interval of cryopreservation would affect the successful establishment.
The incidence of peritoneal carcinomatosis and impact on outcomes in relapsed early T4 colorectal cancer.
Authors: Habib Rosemary , Gebski Val , Micklethwaite Kenneth , McLeod Duncan , Toh James , El-Khoury Toufic , Pathma-Nathan Nimalan , Ctercteko Grahame , Gowrishankar Kavitha , Wilcken Nicholas , Wong Mark , Nagrial Adnan
Published: February 2020

73

Background: There is limited data regarding the association between peritoneal carcinomatosis (PC) and clinical outcomes in colorectal cancer (CRC). We examined the incidence of PC and explored the relationship to survival (RFS & OS) in CRC. Methods: The demographic and clinical details of patients with stage II/III CRC referred to a tertiary centre in Western Sydney between 2009-2016 were obtained. Associations between clinical outcomes and baseline prognostic factors were investigated using proportional hazards regression models. The effect of prognostic factors on outcome were examined by tumour stage. Results: 495 patients were identified, 281 (57%) with stage II and 214 (43%) with stage III. Median follow-up was 38 months. 330 (67%) had T3 and 165 (33%) had T4 disease. Median age at diagnosis was 72 years (19 -94). 104 (21%) patients relapsed, 24 (23%) had PC and of those, 6 had PC as their only site of metastasis. 10% (n = 5) with T3 developed PC compared with 35% (n = 19) with T4 disease (P = 0.02). Compared with non-PC, PC was associated with poorer median OS (28 Vs 46 m; p = 0.03). Median RFS for T3 was 16 months, T4, 14 months (NS). Median OS for T3 was 34 months Vs T4 28 months (P = 0.45). Of those with PC relapse, the diagnosis of PC was highest in the first two years post-operatively (88%). 9 patients (38%) with PC died due to bowel obstruction Vs 4 (5%) patients with non-PC relapse (P < 0.01). Poorer OS was associated with PC (HR 1.74; p = 0.03), right sided primary (HR 1.602; P = 0.05), T4 stage (HR 1.69; P = 0.03), LVI (HR 1.95; p < 0.01), N stage (HR 1.51; P < 0.01), and number of metastases at baseline (HR 1.25; p = 0.04). On multivariable analysis right sided primary and T4 stage remained significant. Conclusions: Patients with PC relapse have an 18 month shorter median OS than those with non-PC relapse. Further, PC recurrence is more common in patients with T4 compared with T3 CRC and was the only site of metastatic disease in 7% of relapsed patients with T4 CRC. Consideration for peritonectomy and/or HIPEC should be given for patients with PC metastases. For patients with resected early stage T4 CRC, consideration should be given for surveillance laparoscopy.
Real-world outcomes in pancreatic adenocarcinoma (PDAC) and persona types with implications for standard of care (SOC) therapy (Tx).
Authors: Petricoin Emanuel , Pishvaian Michael J. , DeArbeloa Patricia , Barg Daniel , Thach Dzung , Brody Jonathan Robert , Matrisian Lynn McCormick , Chung Vincent , Hendifar Andrew Eugene , Mikhail Sameh , Sohal Davendra , Blais Edik Matthew
Published: February 2020

735

Background: Molecular profiling (MP) for PDAC has gained increased acceptance and we previously demonstrated that targeting actionable mutations can improve patient (pt) outcomes. However, the correlations of diverse patterns of molecular alterations with outcomes following SOC Tx are largely unknown. Methods: We analyzed longitudinal outcomes of 1355 PDAC pts who underwent MP and received SOC Tx. “Persona” types were established based on the molecular characteristics of each pt using unsupervised clustering, as well as a supervised review defined by our molecular tumor board, following classifications reported in previous studies. Progression-free survival (PFS) for each type was assessed based on the choice of first-line Tx (i.e. FOLFIRINOX [FFX] vs. gemcitabine + nab-paclitaxel [GA]). Statistical comparisons were made against all other types within a specific Tx group. Results: The prognostic/predictive value of the persona types for 1st-line Tx revealed distinct differences in outcomes (Table). As expected, the DDR deficiency type was associated with a significantly improved PFS for pts treated with FFX but not for GA. In addition, pts in the cell cycle type had a worse PFS compared to other persona types for both FFX and GA. Using this platform, we will further subdivide the persona types into molecular subtypes and associate these with pt outcomes. Conclusions: Our analyses demonstrate that specific molecular persona types exist in PDAC pts and can be linked to Tx outcomes. Ultimately, knowing the persona type/subtype early in a pt’s Tx course may help personalize Tx to improve outcomes. [Table: see text]
Gene expression profiling of unresectable pancreatic cancer patients treated with gemcitabine, nab-paclitaxel, metformin, and dietary supplements (DS).
Authors: Chung Vincent , Frankel Paul Henry , Shibata Stephen , Mambetsariev Isa , Yin Holly , Mirzapoiazova Tamara , Mambetsariev Bolot , Kulkarni Prakash , Lim Dean , Li Daneng , Chao Joseph , Fakih Marwan , Bild Andrea , Pillai Raju K. , Adalsteinsson Orn , Hirsh Steven , Salgia Ravi
Published: February 2020

736

Background: Pancreatic cancer commonly causes weight loss and many patients take supplements to improve nutrition but also for any potential anticancer properties. We conducted a pilot trial evaluating a standardized combination of dietary supplements, metformin and gemcitabine plus nab-paclitaxel chemotherapy. Methods: The supplements were custom designed by a nutritionally trained oncologist. 17 supplements were given as 12 pills and 2 smoothie packets divided twice per day. Patients began metformin on day (D)-6 to evaluate GI tolerance before starting the DS on D-3. On D1, gemcitabine and nab-paclitaxel chemotherapy was administered at standard doses. Serum samples were collected D-6, C1D1, C3D1 and at the end of treatment. RNA was extracted from PBMC samples and a total of 48 samples were analyzed from 19 patients. NanoString Human Immune Profiling and PanCancer Pathways were performed to evaluate changes in gene expression with treatment. Results: The differential expression of genes was small with dietary supplements alone and in combination with chemotherapy. After 2 months of treatment, 17 genes were upregulated while 4 genes were down regulated. At the time of tumor resistance, 33 genes were upregulated while 17 genes were downregulated. We observed downregulation of tumor suppressor gene expression with upregulation in growth factor pathways. Interestingly, SPRY2 mRNA expression was also up regulated which functions as a negative feedback regulator of multiple receptor tyrosine kinases. Conclusions: Increasing number of genes were upregulated with continued treatment. The most common pathway affected was cell cycle and apoptosis. During the initial supplement run-in period from D-6 to C1D1, IL-8 mRNA expression was upregulated the most. IL-8 is a neutrophil chemotactic factor secreted by cells involved in the innate immune response as well as pancreatic cancer cells associated with a pro-inflammatory state. Treatment with gemcitabine and nab-paclitaxel decreased the IL-8 mRNA expression. Additional studies with longer course treatment with supplements alone would be required to explore its impact on differential gene expression.
Translational analysis from SCALOP trial: CCL5 as a prognostic biomarker and a potentially actionable target in locally advanced pancreatic cancer (LAPC).
Authors: Mukherjee Somnath , Lanfredini Simone , Cox Catrin , Thapa Asmita , Hughes Sophie , Bangs Fiona , Willenbrock Frances , Wilhelm-Benartzi Charlotte , Abraham Aswin George , Owens Rob , Sabbagh Ahmad , Maughan Tim , Hurt Chris , O'Neill Eric
Published: February 2020

740

Background: SCALOP was a multi-centre phase II RCT where 114 patients with LAPC were received 3 cycles of Gemcitabine and Capecitabine (GEMCAP) and those with stable/responding disease (n = 74) were randomised to Gem-RT or Cap-RT. The trial showed superiority of Cap-RT. Baseline blood samples of randomised patients were analysed for 35 circulating biomarkers. In vivo study was undertaken with candidate biomarker (CCL5) to test actionability. Methods: Patient bloods were tested using R&D multiplexed magnetic Luminex assays and IGF-1, TGF-b1 and b-NGF DuoSet ELISA. Orthotropic KrasG12D;P53R172H;PDXcre (KPC) tumors were implanted in Bl6-mice and treated with Gem, CCR5-inhibitor (CCR5i) maraviroc (MV), PD1 inhibitor (PD1i), PD1i+MV alone and in combination with MRI guided small animal Radiotherapy (RT). Immunophenotyping was performed by IHC and Aurora Cytek spectral flow cytometry. Results: Baseline biomarker data was available on 63/74 randomised patients. Of the 35 biomarkers tested, only CCL5 was found to be significantly associated with OS with a median OS of 18.5 (95% CI: 11.76-21.32) vs 11.3 (9.86-15.51) months (low vs high), and HR 1.37 (95% CI:1.04-3.65; p = 0.037) in the Cox multivariable model. Treatment of orthotopic KPC tumors revealed that combination of MV+PD1i+RT resulted in tumour growth inhibition and a switch of tumour macrophages from M2 to M1 accompanied by increase in infiltration of cytotoxic CD8+ Tcells and NK cells. Conclusions: Previous pre-clinical studies reported CCL5-CCR5 axis as a poor prognostic marker and a possible cause of immune-resistance in pancreatic cancer. Herein we have demonstrated in prospectively collected clinical trial blood samples that high circulating CCL5 is associated with poor prognosis in LAPC. CCR5 inhibitor in combination with RT+PD1i may overcome immune-resistance, and should be tested in clinical trials. Clinical trial information: 96169987 .
Pancreatic cancer intratumoral microbiome and characteristics within paired patient samples.
Authors: Noticewala Sonal Suresh , Lin Daniel , Kouzy Ramez , Maitra Anirban , Colbert Lauren Elizabeth , Taniguchi Cullen M.
Published: February 2020

744

Background: While most studies evaluating the microbiome in gastrointestinal cancers analyze stool, little is known about the microbiota of the peri-tumoral and intra-tumoral environment. Here, we evaluated the intra-tumoral and peri-tumoral (duodenum and normal pancreas) microbiome for paired duodenal, normal pancreas and resected tumor specimens from pancreatic cancer patients. The purpose of this study was to describe the similarities and differences within patient microbiota. Methods: Fifteen specimens from 5 patients with pancreatic cancer were collected during surgical resection. Genomic bacterial DNA was extracted from these specimens and underwent 16S rRNA sequencing. Alpha (Inverse Simpson) and beta diversity were calculated, and relative abundances of individual bacterial species were compared. Sorensen distance was used the evaluate the spread in beta diversity between paired sample types. Results: Of the five patients who underwent resection, the following baseline characteristics were obtained: median age = 65 years (range 55 -80 years), 2/5 patients were treated with gemcitabine/abraxane, 3/5 patients were treated with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX); 4/5 patients received pre-operative radiation. 16s sequencing analysis of the pancreatic tumor showed the dominant genus to be Escherichia/Shigella (10.6%). Bradyrhizobium (10.1 %) was dominant in the normal pancreas . Escherichia/Shigella (14.3%) was abundant in the duodenum. There was a trend towards higher alpha diversity in tumor vs. normal duodenum/ pancreas (p = 0.12). Sorensen distance was statistically different between sample types (p = 0.004), with duodenal samples most consistent (distance = 67.82), and tumor vs. normal pancreas (81.86) and tumor vs. other tumor samples the most heterogeneous (78.5). Conclusions: This pilot data suggests that the pancreatic tumor microbiome is distinct from the normal pancreas and duodenal microbiome, which indicates tumor specific bacteria should be studied. In future studies, intra-tumoral microbiome may be more relevant to associations with outcomes and treatment response than stool or intestinal microbiome studies.
Clinical and molecular profiling of locally advanced compared with metastatic pancreatic adenocarcinoma.
Authors: Picardo Sarah Louise , O'Kane Grainne M. , Fischer Sandra , Zhang Amy , Denroche Robert Edward , Jang Gun Ho , Dodd Anna , Grant Robert C. , Grunwald Barbara , Moura Shari , Elimova Elena , Prince Rebecca M. , Zogopoulos George , Notta Faiyaz , Wilson Julie , Gallinger Steven , Knox Jennifer J.
Published: February 2020

747

Background: It is unclear whether locally advanced pancreatic cancer (LAPC) should be treated similarly to metastatic pancreatic cancer (MPC). Clinical trials often exclude LAPC. We compare clinical and genomic characteristics of LAPC and MPC. Methods: Patients with LAPC and MPC were enrolled in the COMPASS trial (NCT02750657). Clinical, demographic and survival data was collected (cut off 8/31/19). WGS, RNAseq and modified Moffitt classification was performed. Results: Patients with LAPC (n = 28) and MPC (n = 180) did not differ in terms of age, gender, smoking or diabetes history. Patients with LAPC had lower BMI (p = 0.005) and lower baseline Ca19-9 (p = 0.02) than those with MPC. LAPC/MPC tumors had similar rates of KRAS, p53, CDKN2A and SMAD4 mutations and similar levels of ploidy, indels and neoantigens. There were increases in single nucleotide variants (p = 0.026) and structural variants (p = 0.04) in MPC compared with LAPC. No LAPC tumors were homologous recombination deficient (HRD) or KRAS wild type (WT), compared with 14 (8%) HRD and 16 (9%) KRAS-WT MPC. All LAPC were classical subtype compared with 77% MPC (p = 0.0052). OS data is shown in the table. MPC classical subtype tumors had improved OS compared with basal-like tumors (p = 0.008). Patients with MPC and p53 mutation trended towards worse OS compared with those without p53 mutation (p = 0.07); this was not seen in LAPC. There was a significant correlation between time on chemotherapy and OS in LAPC (p = 0.002) and MPC (p < 0.0001). Conclusions: Patients with LAPC have similar molecular profiles to those with MPC with similar rates of altered drivers. LAPC tumors are more likely to be Moffitt classical subtype and have similar OS to classical subtype MPC. LAPC patients benefit from local therapy; all patients benefit from increased time on chemotherapy. These data suggest that patients with LAPC should be treated similarly to those with classical subtype MPC but should be offered local therapy when possible. Clinical trial information: NCT02750657 . [Table: see text]
The potential of Tenascin C in the tumor-nerve microenvironment to enhance perineural invasion and correlate with locoregional recurrence-related poor prognosis in pancreatic ductal adenocarcinoma.
Authors: Furuhashi Satoru , Sakaguchi Takanori , Muraki Ryuta , Kitajima Ryo , Fukushima Mayu , Takeda Makoto , Morita Yoshifumi , Kikuchi Hirotoshi , Setou Mitsutoshi , TAKEUCHI HIROYA
Published: February 2020

748

Background: Perineural invasion (PNI) is commonly seen in pancreatic ductal adenocarcinoma (PDAC) and worsens the postoperative prognosis. However, the detail mechanisms of PNI in PDAC remain unclear. Tenascin C (TNC), an extracellular matrix glycoprotein, is abundant in cancer stroma and modulates tumor progression. In this study, we hypothesized that TNC could enhance PNI in PDAC. The aim of this study was to investigate the roles of TNC in the tumor-nerve microenvironment of PDAC. Methods: We immunohistochemically examined TNC expression in 78 resected PDAC specimens. TNC staining intensity in perineural sites at the invasive front was classified as low or high, by comparison with adjacent non-cancerous tissues in the same section. The relationships between TNC expression and clinicopathological features were retrospectively analyzed. Furthermore, interactions between cancer cells and nerves after supplementation with TNC were investigated using in vitro co-culture model with a PDAC cell line and neonatal mouse dorsal root ganglion (DRG). Results: High perineural TNC expression at the invasive front, seen in 30 (38%) patients, was associated with the presence of PNI (p = 0.006), pathological T stage ≥ 3 (p = 0.01), and postoperative locoregional recurrence (p = 0.002). It was independently associated with postoperative, poor recurrence-free survival in multivariate analysis (p = 0.045). In the in vitro co-culture model, TNC supplementation significantly enhanced both neurotropism of PDAC cells and tumor tropism of a DRG. On the other hand, when PDAC cells and a DRG were cultured separately, TNC did not affect cancer cell proliferation or neural outgrowth. Furthermore, the knockdown of Annexin A2, which is known to be a receptor for TNC, cancelled the neurotropism of PDAC cell toward DRGs. Conclusions: Strong perineural TNC expression was a prognostic indicator of locoregional recurrence-related poor prognosis. The neurotropism of PDAC induced by TNC and TNC-Annexin A2 signaling pathway could be the potential therapeutic target for PDAC by regulating PNI.
Molecular genetic changes in solid pseudopapillary neoplasms (SPN) of the pancreas.
Authors: Rodriguez-Matta Elisa M. , Colon-Otero Gerardo , Hemmerich Amanda , Severson Eric Allan
Published: February 2020

749

Background: Solid Pseudopapillary Neoplasms (SPNs) of the pancreas are rare accounting for 1-2% of all pancreatic tumors. Previous studies had shown that a pathogenic mutation of the CTNNB1 gene is present in over 90% of the SPN tumors with very limited information available on the specific molecular changes present in SPN. Here we report the results of next generation genetic testing of a large series of SPN tumors from the Foundation Medicine database. Methods: Foundation Medicine database from 07/2012 to 04/2019 was reviewed. A total of 31 cases of SPN tumors were identified out of 12,892 cases of pancreatic cancers. Information collected included demographic information on the patients as well as tumor analysis for next generation genetic sequencing of 315 genes associated with cancer with FoundationOne or 324 genes associated with FoundationOneCDx. Microsatellite stability status and tumor mutation burden were determined. Results: Twenty nine out of 31 cases (93%) had a CTNNB1 mutation. Seventy percent of the CTNNB1 mutations were on position 32 (14 cases, 41%) or in position 37 (9 cases, 29%). Other sites of CTNNB1 mutations included position 34 (3 cases, 9.6%), position 2 (2 cases, 6.4%) and position 38 (1 case, 3.2%). Two cases did not have a CTNNB1 mutation, one had a CDKN2A mutation and the other had no detectable mutations. Most cases had additional mutations aside from the CTNNB1, the most common were TP53 (3 cases, 9.6%) and LRP1B (2 cases, 6.4%). Other accompanying mutations were seen just once. Twenty-five percent of these cases had actionable gene mutations, each found in one case including: MSH2, BRCA2, ATM, XRCC3, ATRX, PTEN, ESR1, CDKN2, and PIK3CA. Conclusions: Next generation genetic testing of SPN tumors is of clinical benefit since it identifies actionable mutations in 29% of the cases.
Pancreatic adenosquamous carcinoma: Clinical associations, treatment, and outcomes.
Authors: Hartgers Mindy L. , Bamlet William , Graham Rondell P. , Mahipal Amit , Mounajjed Taofic , Cleary Sean P. , McWilliams Robert R.
Published: February 2020

751

Background: Pancreatic adenosquamous carcinomas (PASC) are rare malignancies, with limited evidence regarding best treatment options. The Mayo Clinic Pancreatic Cancer SPORE Registry was utilized to compare/contrast outcomes for pancreatic cancers with a squamous component to pancreatic ductal adenocarcinoma (PDAC). Methods: Patients were identified from the SPORE Registry (2000-2019), were reviewed and confirmed by expert pathologists. Demographic and clinical information was ascertained from medical records and risk factor questionnaires. A case control study of patients with PASC vs PDAC was constructed. PASC patients were also followed for outcome and treatment records were extracted. Results: Of 2,584 total patients with pancreatic cancers, 45 cases of PASC and 2,438 with PDAC were identified. There were no differences in age (median 69 vs 67 years, p=0.42), sex (male 64.4vs 56.6%, p= 0.29), BMI (27.41 vs 27.78 kg/m2, P=0.50), or ever-smoking (61.0 vs 55.3%, P=0.47), with a borderline association with reported diabetes (17.8 vs 29.9%, p =0.08). Compared to PDAC, PASCs were more likely to involve the body/tail (48.9 vs 33.2%, p= 0.02) and had poorer overall survival, adjusted for age, gender, and stage (median 7.1 m vs 12.8m, HR 1.89, p=0.0004). Of 9 PASC pts treated with neoadjuvant intent, 4 were surgically resected, median survival was 7 months. Eleven pts underwent upfront surgery, with variable adjuvant treatments. Median OS post- surgery was 18m (range 7-51). Of 14 patients presenting with metastatic disease, median survival was 4.5 m (range 1-22). With regard to systemic chemotherapy, for neoadjuvant or metastatic disease median duration of treatment was 3 months (range 0.5-7m) for Gemcitabine + nab-paclitaxel (N=9) and also 3 months (range 2-6m) for FOLFIRINOX (N-13). Conclusions: The diagnosis of PASC carries an even poorer outcome than pancreatic adenocarcinoma. Tumors are more likely to arise in the distal pancreas, and patients may be less likely to report associated diabetes. Limited antitumor activity was noted with multi-agent chemotherapeutic regimens. Prospective trials will be needed to clarify choice of regimen in the future.
Exceptional responses to ipilimumab/nivolumab (ipi/nivo) in patients (pts) with refractory pancreatic ductal adenocarcinoma (PDAC) and germline BRCA or RAD51 mutations.
Authors: Terrero Gretel , Pollack Terri , Sussman Daniel A. , Lockhart Albert Craig , Hosein Peter Joel
Published: February 2020

754

Background: Immune checkpoint inhibitors (ICI’s) have not shown meaningful clinical activity in unselected pts with PDAC. BRCA-deficient tumors have increased genomic instability, including increased tumor mutation burden (TMB), more tumor-infiltrating immune cells, and enrichment of a T cell-inflamed signature. We hypothesized that pts with mutations in BRCA or other homologous recombination repair genes may be sensitive to ICI’s. Methods: Utilizing the IRB-approved PDAC database at the University of Miami, we identified pts with relapsed/refractory PDAC with pathogenic germline mutations who were treated with combination ICI’s (ipi 1mg/kg and nivo 3mg/kg every 21 days followed by nivo 240mg every 2 weeks). Results: Five pts were identified (1 BRCA1, 2 BRCA2, 1 RAD51C and 1 RAD51D). Among the 3 evaluable pts, there was one complete response (CR), one partial response (PR) and one had progressive disease (PD). The pt with a CR had BRCA1; he had resection followed by adjuvant gem/cape and had a biopsy-proven recurrence in the lung and retroperitoneum 1y after the end of adjuvant therapy. He received ipi/nivo at recurrence and achieved a CR, ongoing for 17m on nivo maintenance. The patient with a PR had RAD51C; he was diagnosed with mPDAC and received FOLFIRINOX for 6m, followed by olaparib on a trial for 12m. Upon PD, the disease quickly progressed on 5FU/liposomal irinotecan, gemcitabine/nab-paclitaxel/cisplatin and FOLFIRINOX. He then started ipi/nivo with immediate improvement in pain and tumor markers. A radiological PR was seen after 2 doses and is ongoing for 3m with continued clinical and tumor marker improvement. The 3rd evaluable pt had BRCA2 and had PD with an exponential rise in tumor markers accompanied by clinical deterioration. Response data on the final two pts were pending at the time of submission and will be presented at the meeting. Conclusions: In this biomarker selected cohort, 2 out of 3 evaluable pts with PDAC had impressive responses to ipi/nivo. PDAC has generally been refractory to ICI therapy but this series suggests that this subgroup may be responsive to ICI’s. Further evaluation is warranted.
Provider perspective: The clinical value of a novel digital medicine program in gastrointestinal oncology.
Authors: Greeno Edward , Morales Paul , Beiswenger Daniel , Wang Xue , Travis Ellen , Plowman R. Scooter
Published: February 2020

76

Background: The differences in colorectal cancer (CRC) treatment between infusion and oral chemotherapy have challenged clinical teams to maintain clinical quality and patient communications with self-administered therapies. The complexity of many regimens, such as capecitabine, creates challenges with dosing and adverse event (AE) management. The first novel Digital Medicine Program (DMP), aimed at providing support to patients and providers, was integrated into CRC treatment at Fairview Health Services and University of Minnesota Health. The DMP consists of DigiMeds (medications co-encapsulated with ingestible sensors), a wearable patch, and a mobile app to facilitate passive collection of actual medication ingestion data and biometrics over time. Methods: Beginning in September 2018, patients with CRC were offered the DMP to augment standard of care. Clinical pharmacists monitored medication adherence and biometrics in near real-time through a secure web portal. This data was used to address barriers to adherence and adjust therapy when appropriate. Qualitative data regarding provider experiences with the DMP and their interactions with patients were collected via a 5-question survey. Results: Eleven patients used the DMP (age: 66.9 ± 9.9 years (mean ± SD); patch wear: 89.9 ± 11.6%; average adherence: 91.0 ± 5.6%) for 140 ± 137 days. Providers reported that the DMP enabled data-driven decision-making by helping identify non-adherence, prompted timely dose modification for AE management, and allowed personalized care and targeted counseling. Integration of the DMP data into the Electronic Medical Record system improved utility, but providers called the DMP a “time-saver”, creating a “proactive rather than reactive” care process in “ways no other technology can do”. Providers stated patients felt more ownership of their care, and that DMP revealed newly “quantifiable positive changes” in their cancer care. Conclusions: Use of the DMP in this small cohort enabled proactive decision-making and facilitated patient-focused and efficient care. Future pragmatic, large real-world studies are underway to assess the impact of DMP on adherence, AE management, and clinical and economic outcomes.
An assessment of the total cost of pancreatic cancer using real-world evidence.
Authors: Picozzi Vincent J. , Manax Victoria G. , Feehan Kelly , Wintrob Zachary , Korfin Michele , Del Priore Giuseppe , Goldberg Robert
Published: February 2020

773

Background: The aggregate health economic implications of pancreatic cancer are poorly understood, especially from the patient perspective. As a preliminary effort, we sought to better understand changes in type and quantity of medical expenditures over time, along with quality of life related costs, from this perspective. This preliminary research is part of a larger effort to understand how the introduction of new treatments affect both the outcome and costs of pancreatic cancer associated with care, patients, survivors, their families, and their communities. Methods: We analyzed patient-level data from the Medical Expenditure Panel Survey (MEPS, 1996- 2017). All analyses were performed using R version 3.6.1 on Ubuntu 19.04. Averages were computed for the total health care costs, including prescription drug costs. Average individual annual cost estimates for the second year excluded individuals that were identified as having died prior to the first round of data collection in the second year. The individual patient level ratios of prescription drug cost to other medical expenses was also computed. All expenditures are adjusted for inflation using 2017 US dollars. Included subjects, N= 80 had a diagnosis of pancreatic cancer and available prescription data. Individual age and employment status were accounted for as covariates. Results: Between 1997 and 2017 inflation adjusted first and second year non-medication spending on pancreatic cancer care averaged $66,999.96 and $105,308.60 respectively. However, inflation-adjusted first and second year charges for hospitalizations and emergency visits fell between 2007-2017. Prescription drug as a proportion of total spending prescription drugs increased during the same time period. Lost work/school days declined between 2007 and 2017. Conclusions: Total inflation adjusted pancreatic cancer care expenses declined over the past decade even as drug costs increased. Quality of life costs declined as well. Further analysis is needed to evaluate the relationship between drug spending, total cost of care and quality of life.
Does aberrant hepatic arterial anatomy impact the complication rate or survival following resection of pancreatic adenocarcinoma?
Authors: Handy Nicketti M , Crown Angelena , Bertens Kimberly A. , Clanton Jesse , Alseidi Adnan , Biehl Thomas , Helton William Scott , Rocha Flavio G.
Published: February 2020

775

Background: Patients with aberrant hepatic arterial anatomy (AHAA) are susceptible to tumor invasion and/or ligation during resection of the pancreatic head. The purpose of this study is to determine if AHAA negatively impacts perioperative outcomes or survival. Methods: All patients who underwent either pancreaticoduodenectomy or total pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) between 2005 and 2014 at our center were retrospectively reviewed. Univariate logistic regression was used to compare outcomes between patients with conventional hepatic arterial anatomy to those with AHAA. Survival analysis was performed by Kaplan-Meier method with log rank test. Results: During the study period, 330 patients underwent resection for PDAC, 69 (20.9%) with aberrant hepatic arterial anatomy. The presence of AHAA does not significantly increase operative time (p= 0.110) or length of stay (p=0.518). The overall frequency of complications (49.3% vs 37.9%, p=0.088) was higher in the AHAA group, but not significantly so. Certain postoperative complications are more common in the AHAA group, namely superficial surgical site infection (18.8% vs. 8.8%, p=0.018) and pancreatic fistula (18.8% vs. 10.0%, p=0.042). However, deep SSI, need for blood transfusion, respiratory failure, DGE, bleed from GDA/pseudoaneurysm, biliary fistula, chyle leak, PV thrombus, fascial dehiscence, and reoperation are not statistically different between the two groups. There is a trend for reduced overall survival in the AHAA group that is not statistically significant (p=0.11). Conclusions: Aberrant hepatic arterial anatomy is encountered in greater than 20% of pancreatic surgery patients, and its presence may increase the rate of certain postoperative complications such as superficial surgical site infection and pancreatic fistula.
Retrospective analysis of institutional outcomes with FOLFIRINOX versus nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer.
Authors: Singh Amisha , Shroff Rachna T. , McBride Ali
Published: February 2020

776

Background: With an estimated six percent five-year survival, metastatic pancreatic adenocarcinoma is one of the most lethal cancers in the United States. Previously, treatments with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (G+A) have demonstrated improved overall survival versus gemcitabine alone. The purpose of this study is to compare institutional outcomes for the two regimens, FFX vs. G+A in metastatic pancreatic cancer. Methods: We conducted a retrospective review of medical records of all metastatic pancreatic cancer patients from 2010 to 2018 who received first line treatment with FFX or G+A at University of Arizona Cancer Center. Results: Thirty-five patients received combination treatment with G+A and 29 patients received FFX. Patient demographics: median age was 66 years in FFX vs 70 years in the G+A group; baseline CA-19-9 was 791 in FFX vs 738 in the G+A group. Median ECOG score was 1 for both groups. Median overall survival was 11.5 months in the FFX group (range 0-39 mos) vs 5 months in the G+A group (range 0-37 mos). Overall survival at 6 months was 75.9% vs 51.4% in FFX vs G+A groups respectively. Median progression-free survival was 6 months with FFX (range 0-25 mos) and 3 months with G+A (range 0-24 mos). Twenty-one of 29 patients in the FFX group pursued second line treatment, compared to 12 of 35 patients in the G+A group. Time to next treatment was 6 months in the FFX group vs 5 months in the G+A group. More adverse effects were noted with FFX, the most common being neuropathy and neutropenia, leading to treatment discontinuation due to adverse effects in 31% of patients, compared to 3% of patients in the G+A group. FFX patients required a higher median no. of office visits (35 visits vs 18 visits in the G+A group). Conclusions: FFX showed improved progression-free survival vs G+A; however, this could be due to more patients pursuing second line treatment in the FFX group. Compared to G+A, FFX patients had higher rates of treatment discontinuation due to adverse effects. FFX patients also required more office visits and further analysis is necessary to assess whether this resulted in poorer quality of life and increased total cost of care for patients treated with FFX.
Racial and socioeconomic disparities in overall survival in colorectal cancer (CRC) at West Cancer Center (WCC), Memphis, TN.
Authors: Wookey Vanessa , Bufalino Gabriella , Vidal Gregory A. , Somer Bradley G. , Schwartzberg Lee S. , Grothey Axel
Published: February 2020

80

Background: WCC, a comprehensive regional community oncology center in Memphis, Tennessee and the Mid-South region, serves a racially, geographically and socioeconomically diverse patient cohort. We sought to evaluate disparity of outcomes in survival by race and socioeconomic status, in addition to patient and tumor characteristics. Methods: All consecutive patients referred to and treated at WCC with colorectal adenocarcinoma from 2007-2013 were included. Individual chart review was performed to verify diagnosis, stage, and date and cause of death. Kaplan-Meier Overall Survival curves were generated for the entire cohort and by race, sex, tumor location and income derived from zip code. WCC survival data were compared to SEER data. Results: From 2007-2013, 1,176 patients were included in the analysis: 405 blacks, 757 whites, 14 others. Median age at diagnosis: Blacks 58 yrs, whites 61 yrs. Stage distribution at diagnosis: stage 1: 100, stage 2: 275, stage 3: 425, stage 4: 376. All stages combined, blacks trended towards shorter OS vs whites (5-year OS: 52.8% vs 58.3%; median survival 71.0 mos vs 98.6 mos; p= 0.095). Blacks presented at later stages (71.4% at stage 3 or 4 vs 66.3% for whites) but no statistically significant OS differences were seen when compared by stage. Patients at or below the median income of $39,590 for WCC had worse 5-year OS (51.6% vs. 61.1%; p= 0.006), as did patients without private insurance (5-year OS: uninsured: 48.0%, Medicare/Medicaid: 50.0%, private: 62.0%; p< 0.001). Adjusted for stage, 5-year OS was statistically significant for stage 4 (private: 18.0%, Medicare/Medicaid: 9.4%, uninsured: 8.3%; p= 0.020). A higher proportion of blacks were below the median income (69% vs 39%) but no statistically significant OS differences were seen when adjusted by race. Overall, cancer survival outcomes were similar to SEER results. Conclusions: At WCC, black patients with CRC presented at a later stage than whites, however, adjusted for stage, no significant racial difference in OS was found. Income and insurance status affected survival outcomes. Overall, our results reveal racial and socioeconomic disparities in colorectal cancer in a diverse US population.
The alarming rise in gastric and colorectal cancers in young adult patients: Analysis of large databases.
Authors: Khan Amir Ali , Ituarte Philip HG , Paz Isaac Benjamin , Goel Ajay , Lai Lily L. , Fong Yuman , Woo Yanghee
Published: February 2020

805

Background: The alarming rise in the incidence of gastric (GC) and colorectal (CRC) adenocarcinomas in young adults (YA) over the past three decades is not well understood. How YA populations differ from older patients with the same gastrointestinal malignancies warrants further investigation. Methods: We retrospectively analyzed the California Cancer Registry and the Office of Statewide Health Planning and Development data for all GC and CRC cases from 2000 to 2012. Pearson’s Chi-square analysis was used to analyze differences in demographic, clinical and histopathologic features and log-rank test to compare survival between young (≤ 40 years old) and older adults (40-90 years old) with GC or CRC. Results: Of the GC (n = 19,368) and CRC (n = 117,415) patients included in the study, YA accounted for 4.5% (n = 883) of GC and 3.2% (n = 3723) of CRC. Hispanic ethnicity was more common in YA for both cancers compared to older patients (50.9% vs 26.8% GC, 29.6% vs. 15.7% CRC, p < 0.0001). YA were more likely to have poorly differentiated (74.6% vs. 59.8% GC, 22.5% vs 17.5% CRC, p < 0.0001), higher grade (77.0% vs 61.6% GC, 23.9% vs 18.6 CRC, p < 0.0001), and signet ring features (44.6% vs 21.0% GC, 3.2% vs 1.1% CRC, p < 0.0001) compared to older patients. Synchronous peritoneal metastases were more common in YA compared to older patients (32.1% vs. 14.1% GC, 8.8% vs 5.4% CRC, p < 0.0001). YA with GC or CRC had a greater 5-year survival compared with older patients with the same stage of malignancy. Subgroup analysis of Stage I GC demonstrated lower survival in YA compared with adults aged 41-49 and 50-64 years (65.1% vs. 70.7% and 69.1%, 95% CI 49.7-76.9%, 62.5-77.3%, 65.2-72.7% respectively). Conclusions: GC and CRC in young adults have distinctly worse clinical and histopathologic features compared to older patients with the same malignancy. Ethnic disparity exists in the YA patients. This study contributes to improving the understanding of younger versus older GI cancer patients.
The impact of precision medicine on real-world clinical care: A single institution retrospective study.
Authors: Patel Rajvi , Quinn Ryann , Zhu Xinhua
Published: February 2020

806

Background: In Oncology, precision medicine (PM) utilizes next generation sequencing (NGS) to analyze actionable mutations (AMs) in tumors. It is commonly done for patients (pts) with advanced cancer resistant to standard treatment. FoundationOne-CDx (F1CDx) is the only FDA approved test that utilizes NGS for genomic profiling of tumors. It is necessary to report the real-world data and its impact on clinical care. Our aim was to identify pts at our institution with AMs on F1CDx testing who received non-FDA approved targeted treatments (TT) and assess objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Methods: Retrospective study of pts at our institution from 2012 and 2018 that received non-FDA approved TT based on F1CDx testing. Descriptive statistics were used to describe the demographic and clinical characteristics. ORR based on interval scans at 3 (ORR1), 6 (ORR2), and 12 (ORR3) months (mos) were estimated using standard methods for proportions. Kaplan-Meier method was used to estimate PFS and OS. Results: Of 1000 pts, 652 had tumors harboring AMs, however, only 38 pts met study criteria of receiving non-FDA approved TT with sufficient follow up time. Median age was 57.7 years and 92% of pts received at least one prior line of therapy. Majority of the pts (58%) had gastrointestinal tumors. PDL-1, microsatellite instability, and tumor mutational burden constituted 50% of AMs and 45% of pts received TT with immunotherapy. 14/38 pts had ORR1, 12/13 pts had ORR2, and 6/7 pts had ORR3. PFS was estimated to be 2.73 mos (95% CI: 2.33 to 5.39) and OS was 9.93 mos (95% CI: 4.47 to 33.68). Conclusions: The majority of pts had progression within 3 mos of initiating TT indicating a PM approach with non-FDA approved TT may not be an effective strategy. However, a minority of pts (4 with colorectal and 1 with pancreatic cancer), derived significant benefit in achieving sustained partial response and one pt with complete response at 3 years. Although genomic profiling of tumors may be a step in the right direction, we need better and more cost effective strategies to identify pts who will truly benefit from a PM approach. More PM trials are needed to establish the standard of care to guide real-world practice.
Risk factors for cancer-associated thrombosis in advanced cancer patients with chemotherapy or palliative treatment (retrospective study).
Authors: Uehara Koki , Nio Kenta , Iguchi Haruo
Published: February 2020

819

Background:Cancer-associated thrombosis (CAT) represents the second-leading cause of death in cancer patients and venous thromboembolism (VTE) occurs in about 20% of hospitalized cancer patients. CAT is important for safety cancer treatment.However, the risk factors for CAT in Japanese cancer patients have not been well studied. Methods: We retrospectively examined cases that had received chemotherapy or palliative treatment from April 2017 to February 2018 in our hospital using medical records. Results: Fifty-five cases with 37-94 years (23 males and 32 females) were examined. Primary sites of cancers were as below; pancreatic: n = 14 (25%), colorectal: n = 12 (22%), gastric: n = 7 (13%), breast: n = 4 (7%), lung: n = 3 (5%), esophageal: n = 3 (5%), head and neck: n = 3 (5%), and others: n = 9 (16%).Forty-two patients (76%) were received chemotherapy, and 12 (22%) of them were diagnosed with CAT at the beginning or during the course of chemotherapy (CAT group). The sites of CAT were as follows; lower extremity type venous thrombosis: n = 10, cerebral infarction: n = 3, pulmonary artery thromboembolism: n = 1, portal vein thrombosis: n = 1, subclavian vein thrombosis: n = 1, and others: n = 2. In 12 patients with CAT, primary sites of cancers were as below; pancreatic: n = 6 (45%), gastric cancer: n = 3 (27%), colorectal, esophageal and ovarian cancer: n = 1 (9%), and 8 patients (67%) received anticoagulant therapy, including 7 patients treated with DOACs. 3 patients (38%) discontinued anticoagulant therapy because of gastrointestinal bleeding and 2 patients (25%) had recurrence of VTE during anticoagulant therapy. Overall survival (OS) tended to be shorter in CAT groups than non-CAT group (median OS: 118 days vs 190 days; p = 0.158). Conclusions: As reported in Western countries, the incidence of CAT was about 20%, and higher in Japanese pancreatic and gastric cancer patients. As shorter overall survival in CAT group might be responsible for development of thromboembolism, thromboembolism prophylaxis for high-risk Japanese patients may be recommended. Additionally, the present study showed that recurrence rate of CAT was higher than that of previous clinical trials.
Diagnostic evaluation of immune checkpoint inhibitor (CPI) colitis: The role of CT scan.
Authors: Durbin Sienna , Mooradian Meghan , Zubiri Leyre , Allen Ian Matthew , Fintelmann Florian , Kambadakone Avinash , Pisuchpen Nisanard , Reynolds Kerry Lynn , Dougan Michael Lawrence
Published: February 2020

821

Background: CPI therapy has expanded rapidly in recent years and represents a major advancement in the treatment of many cancers, including hepatocellular carcinoma, gastric cancer, and colon cancer. However, these therapies are associated with significant toxicities. CPI colitis is one of the most common toxicities and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, an invasive procedure that is resource- and time-intensive. CT has emerged as a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of CPI colitis. Methods: With IRB approval, we conducted a retrospective cohort study of patients who received CPI therapy between 2009-2019 across a single healthcare system. Patients were included if they underwent both abdominal CT and upper/lower endoscopy with biopsy within 72 hours of each other. We reviewed the electronic medical record to identify possible cases of colitis based on either CT or pathology. All cases were labeled as either true positive or false positive based on pathology. We examined clinical characteristics, including CTCAE grade and treatment received. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for diagnosing CPI colitis when compared to the gold standard of tissue diagnosis. Results: Of the 4,474 patients screened, 141 met inclusion criteria. Average age was 63 years (23 – 91); 43% were male. Most common tumor types were melanoma (36%) and NSCLC (20%). Seventy-four percent of patients were treated with anti-PD-1/PD-L1 monotherapy. Forty percent had signs of colitis on CT scan and 59% had biopsy-proven CPI colitis. Sensitivity and specificity of CT were 51% and 74%, respectively. PPV of CT was 74% and NPV was 51%. Of those with confirmed CPI colitis, 78% had symptoms that were classified as grade 3 or above. Seventy-three percent received IV steroids and 38% received infliximab. Conclusions: CT demonstrates moderate specificity and PPV and remains an important diagnostic test but does not replace endoscopy/biopsy in the evaluation of CPI colitis.