bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival benefit and optimal timing for re-resection in patients with gallbladder cancer: A National Cancer Database analysis.
Authors: Shah Shivani , Sweeney Ryan , Wegner Rodney E.
Published: January 2023

614

Background: Often times, gallbladder cancer is diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease, however overall survival (OS) benefit data in this scenario is variable. Further, limited literature regarding optimal time to re-resection exists. Prior studies found the optimal time to re-resection to be approximately 4-8 weeks after initial diagnosis; however, additional data is needed to further validate these findings. In this National Cancer Database(NCDB) analysis we compare OS in patients diagnosed with T1b – T3 gallbladder cancer who underwent re-resection and evaluate if time to resection impacts OS. Methods: We reviewed the NCDB for patients who had received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease) from 2004-2018. We excluded patients with metastatic M1 disease and T0, T1a, T1, or T4 disease. Patients with re-resection were further subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks and >12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. Results: 791 (5.82%) patients received re-resection of 13,601patients meeting inclusion and exclusion criteria. Cox proportional hazards analysis showed a Comorbidity Score of 1 was associated with worse survival. Patients with higher Comorbidity Scores (1,2, or 3) and treatment at comprehensive community, integrated or academic cancer programs were less likely to undergo re-resection (in comparison to community programs). Patients treated at an Urban facility or diagnosed from 2009-2018 were more likely to undergo re-resection. The cohort with no re-resection had the lowest median OS [17.61 months; CI 17.05- 18.20] and re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p=0.02]. Significantly improved survival was noted when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57- 0.81], 9-12 weeks [HR 0.64; CI 0.52- 0.79], or >12 weeks [HR 0.61; CI 0.47- 0.78]. Conclusions: Despite the retrospective nature and small sample size of our study, the results are consistent with prior studies depicting a survival benefit with re-resection. Additionally, optimal timing to re-resection supports previous data showing a clear benefit at any time >4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or > 12 weeks post initial cholecystectomy. Decreased post-operative inflammation and accurate staging at >4 weeks may account for improved survival with later re-resection; however, future investigations are warranted to delineate underlying causes.
Total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A real-world experience.
Authors: Ruiz-Garcia Erika , Cuervo Cmapos Rogelio , Falcon Juan Carlos , Caderillo-Ruiz German , Diaz Romero Maria del Consuelo , Herrera Marytere , Miyagui-Adame Sayako Mariana , Vela Itzel , Alvarez Nora , Lino-Silva Leonardo
Published: January 2023

62

Background: The standard treatment of locally advanced rectal cancer (LARC defined as T3-T4, N+) consists of giving chemoradiation therapy (CT/RT) followed by total mesorectal excision (TME) after 6-8 weeks followed by chemotherapy (CT) adjuvant. Recently, total neoadjuvant therapy (TNT) has shown greater efficacy in terms of increasing the rate of complete pathological response (pCR) and reducing local and systemic relapse, in addition to increasing sphincter preservation. The objective of this study was to know the percentage of pCR (ypT0N0) presented by Mexican patients with LARC treated at the National Cancer Institute (INCan) with the TNT (implemented in 2019) vs. standard treatment. Methods: An observational, analytical, and retrospective study was carried out, with a non-probabilistic sampling of patients with LARC treated at INCan from 2016 to 2021. Comparisons of continuous numerical variables for independent samples were analyzed using Student's t test or Mann-Whitney U test (depending on its distribution). To examine the association in the discrete variables, the X2 test or Fisher's exact test (according to the case) was used. The association between continuous variables was analyzed using Pearson's or Spearman's correlation coefficients according to the distribution. Statistical difference was considered significant when p < 0.05. The analysis was performed with the statistical package SPSS v26.0. Results: 286 patients were analyzed (N=76 corresponded to TNT), mean age was 57 years, 43% were female, 84% were stage III and 64% had a lower rectal tumor. Complete TME was present at 78.9%. The pCR rate was 45.16% with TNT vs. 22.39% with CT/RT (RR 0.70, 95% CI (0.56-0.90) p= 0.001). 18% recurrences and/or progressions were identified in the TNT group vs. standard treatment (28.2%) with a tendency to statistical significance (RR 0.6 95% CI (0.36-1.08) p= 0.08). 7% mortality was reported with TNT vs. 19% with standard therapy (RR of 1.15, CI 95% (1.05-1.26) p= 0.013). Conclusions: TNT was shown to increase the percentage of complete pathological responses compared to chemoradiotherapy treatment in real-world population attended at INCan. The follow-up of these patients is still short to know the final impact of TNT in terms of relapse-free survival and overall survival.
Real-world outcomes in patients with gastroenteropancreatic neuroendocrine tumors receiving somatostatin analogue: Data from a public hospital in Brazil.
Authors: Almeida Kaique Ferreira Costa de , Peria Fernanda Maris , Guimaraes Matheus , Pereira Anny Alves , Rapatoni Liane
Published: January 2023

650

Background: Neuroendocrine tumors are rare malignant neoplasms derived from endocrine cells and known for their heterogeneous behavior and histopathological characteristics; however, largely associated with a favorable clinical outcome. Somatostatin analogues (SSA) were initially used to control the symptoms of secretory neuroendocrine tumors, and later, they were considered effective as a first-line systemic treatment in unresectable or metastatic neuroendocrine tumors of the gastroenteropancreatic tract (NET-GEP). Randomized clinical trials are performed in controlled environments, with strict inclusion and exclusion criteria, and therefore, real-world studies can add to efficacy and safety data in the general population. Methods: To evaluate, in the real world scenario of a tertiary hospital of the public health system, the efficacy and toxicities of first-line treatment with somatostatin analogue in patients diagnosed with unresectable or metastatic NET-GEP, to find real-world progression free survival (rwPFS) and real-world overall survival (rwOS), in addition to the toxicity profile in our population and possible subgroups that benefit from first-line treatment, through the analysis of variables. Results: 29 patients met the study inclusion criteria, which were diagnosed in the period from 2009 to 2017. The median wrSLP and wrSG were 4.4 (95% CI 3.2 – 5.6) and 8.2 years (CI 95% 6.2 – 10.2), respectively. In an adjusted analysis of rwSLP, the HR for patients with hindgut tumors compared to midgut tumors was 4.41 with p 0.05, indicating that these patients had a 4x increased risk for disease progression (p 0 .05). In the adjusted analysis of wrSG, a trend towards a more favorable evolution was observed in the group of patients with well-differentiated tumors, with p 0.05. Assessment of toxicities revealed grade 2 and grade 3 adverse events in 34.48% of patients. Abdominal pain was the most incident toxicity, occurring in 17.24%, followed by headache (13.79%) and diarrhea (10.34%). Conclusions: Treatment with SSA was effective in our sample, with rwPFS and rwOS data above those found in randomized clinical trials. The toxicities were easily manageable and caused no documented harm to patients.
Evaluation of chromatin remodelers in pancreatic neuroendocrine neoplasms.
Authors: Ferosh Usman Khan Salma , Yadav Rajni , Dash Nihar Ranjan , Pal Sujoy , Das Prasenjit , Narayan Anand , Jyotsna V P , Shamim Shamim Ahmed , Rastogi Sameer , Agarwal Shipra , Sharma Mehar C
Published: January 2023

652

Background: Pancreatic neuroendocrine neoplasms (PanNENs) are rare entities comprising 1-2% of gastroenteropancreatic neoplasms with an annual incidence of 0.48/100,000 population in the world. The molecular pathways underpinning the entity are less explored owing to its rarity. We aimed to analyse and correlate the expression of chromatin remodelers in PanNENs from Indian subcontinent. Methods: An ambispective study (prospective 2014-2018 as well as retrospective 2018-2021) was conducted. Haematoxylin and eosin stained slides with immunohistochemistry slides (chromogranin, synaptophysin) of 73 cases of PanNENs were retrieved from archives of Department of Pathology, AlIMS, New Delhi and evaluated for assessment of histopathological parameters. Following slide review, grading and staging were done based on WHO 2017 Classification and AJCC eighth edition respectively. Representative formalin fixed paraffin embedded block was selected after slide review and retrieved for performing immunohistochemical staining with antibodies against ATRX, DAXX, SETD2, H3K36Me3 and ARID1A using Ultra Vision Quanto polymer detection system by Thermo Fisher Scientific. Data was analysed using STATA version SE14. Results: Study cohort of 73 PanNENs had a mean age of presentation 41 years (Range: 8 years -70 years) and male to female ratio of 1.43:1. Majority of the tumors in our study were non functional (63.01%). Loss of nuclear expression of ATRX/DAXX (at least one marker) was seen in 26/73 (35.62%) cases. Loss of expression had significant correlation with pathological stage of the tumor, presence of distant metastasis and adverse prognostic outcome (p value-<0.05). Lower grade tumors with low to intermediate ki67 index had higher preponderance for loss of expression of ARID1A. Loss of expression of any of the chromatin remodelers (ATRX/DAXX/ARID1A/H3K36Me3) was noted in 44/73 cases (60.27%) and was more frequently associated with advanced stage of tumor or recurrence/metastasis/death (p value-0.005). Conclusions: Loss of chromatin remodelers such as ATRX, DAXX, ARID1A, SETD2 and H3K36ME3 is involved in the pathogenesis of pancreatic neuroendocrine neoplasms and are associated with adverse outcomes, so loss or lower immunohistochemical expression for these can serve as a poor prognostic factor and guide for adjuvant therapy.
Age- and sex-based differences in the genomic profiles of patients with gastrointestinal (GI) and pancreatic neuroendocrine neoplasms (NENs).
Authors: Liu Lisa , Li Shuning , Gandhi Nishant , Farrell Alex Patrick , Lou Emil , Soares Heloisa P. , Nazha Bassel , Swensen Jeffrey , Oberley Matthew James , Nabhan Chadi , Abraham Jim , Korn Wolfgang Michael , Kunz Pamela L. , Vijayvergia Namrata
Published: January 2023

655

Background: Demographic variables such as age and sex have long been associated with risk of cancer incidence, therapeutic response, and mortality. In NENs, specifically, studies have shown differences in overall survival based on age at diagnosis and sex. However, studies investigating the molecular determinants associated with age and gender have been lacking. To delineate the mechanisms of age, gender, and outcomes, we queried a large real-world dataset of NENs originating from the GI-tract and pancreas and characterized their molecular and immune profiles. Methods: 1935 cases (GI: n=1431, Pancreas: n=504) of NENs were analyzed using Next Generation Sequencing or Whole Exome Sequencing of DNA, and 1211/1935 cases (GI: n=917, Pancreas: n=294) underwent Whole Transcriptome Sequencing at Caris Life Sciences (Phoenix, AZ). To study the age-associated effect on the molecular and immune landscapes, we applied two age cutoffs: below 50 and 70 years of age at the time of tissue collection, respectively. Significance was determined using chi-square, Fisher-Exact or Mann-Whitney U, and p-values were adjusted for multiple comparisons (q<0.05). Results: In GI-NEN, TP53, RB1 mutations and high tumor mutation burden (TMB_H; >=10 Mut/Mb) were more prevalent and KRAS mutations were less prevalent with increasing age. Interestingly, in pancreatic NENs (P-NENs), KRAS mutations were more prevalent and TMB_H were less prevalent with increasing age. Mutations specific to the sites of origin such as APC (GI) and MUTYH (pancreas) were negatively associated with age while SMAD4 (pancreas) was positively associated with age. While no differences in immune checkpoint gene (ICG) expression were associated with age, immune cell estimates of M1 macrophages (anti-tumorigenic) in GI-NENs were higher in patients above 70 and M2 macrophages (pro-tumorigenic) were higher in patients below 50 (p<0.05, q>0.05). For the analysis with gender, mutations in p53 were more prevalent among males with GI-NEN while dMMR/MSI-H were more prevalent in females with P-NENs. No significant differences in ICG expression and immune cell estimates were associated with gender. Conclusions: Our study queries one of the largest datasets of GI and P-NENs to date. We observe distinct molecular profiles associated with age and gender in both GI- and P-NENs as well as a distinct immune profile associated with age in GI-NENs. While these results are only hypothesis generating, they are suggestive of how patient demographics may be utilized for rational therapy design. [Table: see text]
The genomic landscape of advanced gastrointestinal (GI) neuroendocrine tumors (NET) and carcinomas (NEC).
Authors: Farha Nicole , Mundi Prabhjot Singh , Wei Wei , Kamath Suneel Deepak , Khorana Alok A. , Fojo Antonio Tito , Laderian Bahar
Published: January 2023

656

Background: The impact of specific genomic alterations in advanced GI neuroendocrine malignancies on prognosis and treatment decisions has not been fully characterized. In this study, we seek to evaluate next-generation sequencing (NGS) panels and corresponding clinical outcomes in patients with metastatic GI NET/NEC. Methods: Patients with GI-NET/NEC were identified from a database of NGS reports performed at the Cleveland Clinic, and clinical variables were extracted by chart review through an IRB-approved protocol. We provide an analysis of this cohort. Results: Of a total n=45 patients, 53% were male. Median age at diagnosis was 60 (range: 35-90 years) and 82% were non-Hispanic white, while 9% were black. There were n=25 GI-NETs, mostly intermediate or high grade (11 G3, 7 G2), and n=20 GI-NECs. There was a balanced distribution of primary sites, including colorectal (27%), pancreas (24%), small intestine (18%), unknown primary (24%) and a single case of biliary primary. High grade GI-NETs and GI-NECs were over-represented in the colorectal primary group vs other sites. (n=10 of 12; p=0.021). The majority of patients (73%) had at least one somatic variant, including 12 patients (27%) with one or more mutations deemed actionable, but only one patient (with MSH2 mutation) has received a mutation-matched drug (pembrolizumab). Some recurrent alterations appeared to co-segregate with aggressive histology (NEC vs NET), including 12 of 13 TP53 mutations (p<0.05 by Fisher Exact Test), 7 of 8 RB1 (p<0.05), and 5 of 6 APC (p=0.074). The most common mutations per person based on primary site is shown. Microsatellite instability high was rare (n=1) and median tumor mutational burden (TMB) was 3/mb, with TMB lower in NETs vs NECs. A number of patients (35%) underwent germline testing, with 6 of 16 having a pathogenic germline variant. Conclusions: As 42% of the 12 patients with actionable mutations were alive at time of analysis, it is possible that additional patients could be treated with mutation-matched therapies. More input will be needed from providers as to the role played by alternative effective treatments and barriers such as insurance coverage and prior authorization to implementing mutation-matched therapies. Given the overall low TMB of GI-NETs, with several tumors having zero or 1 reported mutation on targeted NGS, whole genome sequencing may prove useful. Finally, certain mutations such as RB1 and TP53 were associated with more aggressive histology (i.e. NEC). Lastly, only 9% of our cohort with NGS were black, a significant under-representation based on epidemiological data, which raises concerns about disparate accessibility and barriers to NGS testing. Further studies are needed to address any possible racial disparity.[Table: see text]
Rates of unplanned hospital care in Black Americans with pancreatic cancer.
Authors: John Kristen M , Dhillon Harkirat S , King Daniel
Published: January 2023

666

Background: Individuals with cancer are more likely to visit an emergency department (ED) for issues both related and unrelated to their cancer than individuals without cancer, but data are lacking regarding what subpopulations are most vulnerable. Here, we assessed the characteristics of patients with pancreas cancer across the Northwell Health system who had multiple ED visits. Methods: An IRB-approved retrospective chart review of patients with pancreas cancer diagnosed between 2015 through 2021 was conducted. Patients with > 3 ED visits were defined as high utilization and patients with 0 ED visits were defined as low utilization. Demographic and clinical features were recorded. Median income was extrapolated by zip code using data from the US Census Bureau. Generalized logistic regression models were constructed to analyze characteristics associated with high ED utilization. Results: The cohort consisted of 658 patients, among whom 181 individuals met criteria for high utilization and 140 met criteria for low utilization. Stage, age, gender, ethnicity, history of pancreatitis, median income, preferred language, establishment with primary care provider, and establishment with medical oncologist had no significant association with high utilization. Race (OR: 2.8; p = 0.002) and substance abuse (OR: 4.43; p = 0.02) were the strongest predictors of high ED utilization. We observed that 14% of the individuals who were Black had a history of substance abuse. Conclusions: Our analysis identified a striking and concerning association between high utilization of the ED and patients who are Black or who have a history of substance abuse. Substance abuse may contribute to high ED utilization among Black Americans, however, 86% had no history of substance abuse, suggesting that other causal factors are at play. These results compel further investigation into these casual factors to guide the development of health equity interventions to address these disparities.[Table: see text]
Adjuvant gemcitabine+S1 as adjuvant therapy for resectable pancreatic cancer: A real-world experience in a single-center retrospective study.
Authors: Lin Hsin-Chen , Shih Yu-Hsuan
Published: January 2023

673

Background: Current clinical guidelines recommended adjuvant chemotherapy for all resectable pancreatic cancer after operation. The treatment choices included Gemcitabine monotherapy, S1 monotherapy, Gemcitabine+Capecitabine or mFOLFIRINOX. However, the role of Gemcitabine+S1 combination as adjuvant chemotherapy was not clear. We aimed to investigate the benefit of adjuvant chemotherapy with Gemcitabine+S1 in resectable pancreatic cancer. Methods: We retrospectively reviewed the medical records of patients with resectable pancreatic cancer who underwent curative surgery and adjuvant treatments at Taichung Veterans General Hospital (Taichung, Taiwan) between January 2014 and July 2021. The clinical characteristics and outcomes were analyzed. Results: A total of 102 patients received operation were analyzed. 73 patients received adjuvant chemotherapy, including 35 patients received Gemcitabine+S1 combination. Median follow-up period was 22.7 months. The disease-free survival (DFS) and overall survival (OS) among patients received Gemcitabine+S1 combination were 15.5 months and 32.8 months, respectively. Compared with Gemcitabine monotherapy, there was a trend of superior DFS (10.5 months in Gemcitabine monotherapy, p = 0.071), but no OS benefits (23.1 months, p = 0.441) with Gemcitabine+S1 combination. When focusing on more advanced disease status (stage II and III), the Gemcitabine+S1 combination had statistically significant longer DFS (14.7 months vs. 8.6 months; p = 0.015) and OS (30.3 months vs. 21.7 months; p = 0.036), compared with Gemcitabine monotherapy. Conclusions: In our retrospective study, Gemcitabine+S1 combination could be another choice for resectable pancreatic cancer, especially in more advanced disease (stage II and III). Further result from prospective study (JSAP-04) is pending.
Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left-sided pancreatic ductal adenocarcinoma.
Authors: Kwon Jaewoo , Lee Sung Ryol , Shin Jun Ho , Kim Song Cheol
Published: January 2023

675

Background: The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left-sided PDAC. Methods: Patients who underwent distal pancreatectomy for PDAC at two high-volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern and survival data were collected to compare R0 resection and R1 resection. Results: Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3 cm vs. 3.7 cm, p= 0.006) and lower number of positive lymph nodes (1.3 vs. 2.0, p= 0.001). Median overall survival (37.3 months vs. 20.1 months, p< 0.001) and recurrence-free survival (14.6 months vs. 6.9 months, p< 0.001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups ( p = 0.182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence-free survival (5.6 months, p < 0.05) and overall survival (13.6 months, p < 0.05) compared with all other recurrence patterns. Conclusions: R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.
First-line chemotherapy regimens associated with survival in advanced pancreatic cancer: A Mexican single-center, real-world study.
Authors: Herrera Marytere , Maliachi Diaz Andrea , Diaz Consuelo , Salais Michaus Veronica , Ruiz Erika , Garcia Sebastian , Miyagui Adame Sayako , Calderillo Ruiz German
Published: January 2023

683

Background: Effectiveness of FOLFIRINOX and Gemcitabine – Nabpaclitaxel as first-line chemotherapy regimens in advanced pancreatic cancer has been demonstrated in phase III clinical trials. However, prospective studies directly comparing both interventions are lacking. Gemcitabine has proved effective when combined with other drugs such as Oxaliplatin. Despite GEMOX has not proved overall survival benefit over Gemcitabine and it is unclear if its effectiveness could be similar to FOLFIRINOX or Gemcitabine-Nabpaclitaxel, it is broadly used as first line chemotherapy in our center due to safety concerns and higher costs associated to FOLFIRINOX and Nabpaclitaxel. Methods: We retrospectively analyzed data of patients with stage IV Pancreatic Adenocarcinoma treated at Instituto Nacional de Cancerología from 2014 to 2021. Our aim was to compare Overall Survival (OS) in patients treated with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel, or Gemcitabine in the front-line setting. Progression Free Survival (PFS), Overall Response Rate (ORR) and Adverse Effects (AEs) were also assessed. Results: A total of 141 patients were analyzed, 72 (51.0%) were treated with GEMOX, 13 (9.2%) with FOLFIRINOX, 9 (6.4%) with Gemcitabine-Nabpaclitaxel and 47 (33.3%) with Gemcitabine. Median Overall Survival for each regimen was: 11.0, 10.7, 6.7 and 4.7 months; (p = 0.078), and median PFS was 9.2, 6.5, 5.7 and 4.0 months, respectively (p = 0.026).ORR was 21.6%, 20.0%, 11.1%, 4.8% with GEMOX, FOLFIRINOX, Gemcitabine-Nabpaclitaxel and Gemcitabine, respectively. The percentage of patients who received a second line chemotherapy after progression was 43.1%, 61.5%, 55.6% and 23.4%, (p = 0.031). Regarding AEs, G3/4 most common effects ( > 5%) were Neutropenia (9.8%, 30.0%, 55.6%, 4.8%; p = 0.001), Diarrhea (2.0%, 10.0%, 11.1%, 0.0%; p = 0.247), and Increased Liver Enzymes (7.8%, 20.0%, 0.0%, 4.8%; p = 0.371). Grade 1/2 Neuropathy was found in 43.1%, 60.0%, 44.4% and 9.5%, p = 0.018. The percentage of patients who required GCSF was 9.8%, 60.0%, 22.2% and 9.5%, P = 0.001. Conclusions: In patients with advanced pancreatic cancer treated with different chemotherapy regimens, median OS was similar in this real-world analysis. Though PFS was higher in the group of patients treated with GEMOX, a higher percentage of patients initially treated with FOLFIRINOX or Gemcitabine – Nabpaclitaxel reached 2nd line chemotherapy after progression. Percentage G3/4 Neutropenia, G1/2 Neuropathy and use of GCSF were significantly higher in patients treated with FOLFIRINOX.
Ten years of experience in patients with resected pancreatic tumors: Real-world data in a public institution in Peru.
Authors: Macetas Jackeline , Vallejos Heberth Daniel , Veramendi Cabana Eder Christian , Serrano Mariana , Pacheco Cristian , Castro Oliden Victor , Mantilla Raul , Montenegro Paola Catherine
Published: January 2023

686

Background: In Peru, the incidence of pancreatic tumors is 3.59 per 100,000 inhabitants, being the ninth cause of death. The standard of treatment in the world is surgery, achieved in 13% of patients, with overall survival (OS) and disease-free survival (PFS) at 5 years of 10% and 34%, respectively. In our study, the different subtypes of pancreatic tumors that were resected by surgery, their clinical/pathological characteristics, OS and PFS were evaluated. Methods: A retrospective review was carried out, in patients older than 18 years, diagnosed and treated with first intention surgery, during 2010 - 2019. 36.9% were adenocarcinoma (AD), 36.2% solid pseudopapillary neoplasm, 20.6% serous cystadenoma, 3.5% intraductal papillary mucinous neoplasm, 2.1% mucinous cystic neoplasm, and 0.7% acinar cell carcinoma. The Kaplan Meir method was used to estimate OS and PFS, and the log-rank test to differentiate between estimated curves. Results: 141 patients with resected pancreatic tumors; 73.8% without comorbidities and 2.1% with Diabetes Mellitus. Jaundice at debut was present in 22.7%, of whom 60% were AD; with OS at 5 years, 23.7% of patients with jaundice vs 69.9% without jaundice, 55.3% of tumors were located in the head of pancreas, 78.8% were AD; an OS at 5 years of 50.1% vs 67.3% of not located in the head of the pancreas. According to staging (S), 14.2% S I, 43.3% S IIA, 20.6% S IIB, and 22% S III; 100% were AD in S IIB-III vs 8.9% non-AD, with OS at 5 years S III of 16.2% and IIB of 39.3%. OS and PFS at 5 years, in pancreatic tumors were 57.7% and 73.5%, respectively. For patients with AD, the OS and PFS were 22.9% and 36.9%, respectively. Conclusions: The study suggests that jaundice at debut, located in head of the pancreas, S IIB-III, are worse prognostic factor in our patients with pancreatic tumors, especially in AD. And our patients with resected AD, presents greater survival compared to literature, although more evidence is still required due to the type of study.
Comparison of pancreatic cancer outcomes diagnosed in surveillance and the general population: A propensity score-matched analysis.
Authors: Klatte Derk C.F. , Boekestijn Bas , Onnekink Anke M. , Dekker Friedo W. , van der Geest Lydia G. , Wasser Martin N.J.M.M. , Feshtali Shirin , Mieog J. Sven D. , Morreau Hans , Potjer Thomas P. , Inderson Akin , Boonstra Jurjen J. , Vasen Hans F.A. , Luelmo Saskia , van Hooft Jeanin E. , Bonsing Bert A. , van Leerdam Monique E.
Published: January 2023

690

Background: Recent pancreatic cancer surveillance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) in patients with a CDKN2A/p16 pathogenic variant (PV) diagnosed during surveillance are better as compared to PDAC patients diagnosed outside surveillance. Methods: In a propensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage and survival between patients diagnosed in surveillance with non-surveillance PDAC patients. Survival analysis were repeated after adjustment for lead-time bias. Results: Between January 2000 and December 2020, 43 762 patients with PDAC were identified from the NCR. Thirty-one patients with PDAC in surveillance were matched in a 1:5 ratio with 155 non-surveillance patients based on age at diagnosis, sex, and year of diagnosis. In total, 71% of patients in surveillance, as compared to 16% of non-surveillance patients underwent a surgical resection (OR 14.03; 95% CI, 5.92 – 35.85). In surveillance, 39% of patients was diagnosed with stage I cancer, as compared to 6% of non-surveillance PDAC patients (OR 0.10; 95% CI, 0.04 – 0.21). Patients in surveillance had a better prognosis, reflected by a 3-year survival of 32.4% and a median overall survival (OS) of 26.8 months vs. 1.4% 3-year survival and 5.3 months median OS in non-surveillance patients (HR 0.22; 95% 0.14 – 0.36). After adjustment for lead time, PDAC diagnosis in surveillance remained strongly associated with improved survival. Conclusions: Surveillance for PDAC in carriers of a CDKN2A/p16 PV results in earlier detection, increased resectability and improved survival as compared to non-surveillance PDAC patients.[Table: see text]
Patterns of pancreatic enzyme replacement therapy (PERT) use among U.S. patients with pancreatic cancer.
Authors: Dang Trang Quynh , Stenehjem David D. , Gupta Arjun
Published: January 2023

696

Background: PERT is an important but costly and inconsistently used supportive care medication in PC. We sought to characterize patterns of PERT use among U.S. insured patients with PC. Methods: We conducted a retrospective observational analysis of patients with a primary diagnosis of pancreatic adenocarcinoma in the IBM MarketScan national claims database between 2013-2019. We identified pharmacy claims for PERT (Creon, Pancreaze, Pertzye, Viokace, and Zenpep) and classified patients as PERT-users (≥ 1 PERT prescription [Rx]) and non-PERT users. We used descriptive statistics for clinical, demographics, and costs. Multiple logistic regression identified predictors of PERT use. Kaplan-Meier method assessed time from PC diagnosis to first PERT Rx. Results: Of 19,866 patients with PC (median age 62 years, 49% women), 6,918 (35%) were PERT-users. The median follow-up was 11 months (PERT users: 14 months, non-PERT users: 9 months). Overall, 43% of patients received no cancer-directed treatment. PERT-users were more likely to have a history of pancreatitis (acute, odds ratio [OR] = 1.9; chronic, OR = 3.6), and received chemotherapy (OR = 1.2), surgery (OR = 2.3), and radiation (OR = 1.4). Among all PERT-users, the median time from PC diagnosis to first fill was 1.9 months (95% CI: 1.8,2.0). The median time from surgery to first fill was 1.6 months (95% CI: 1.4,1.7). The median number of PERT Rxs was 4; 22% of PERT-users received 1 Rx. A median of 150 days of PERT was supplied across all Rxs per patient. The median (IQR) cost of each PERT Rx was $25 ($0- $50). PERT accounted for 16% of all drug out-of-pocket costs (OOPC) (excluding systemic outpatient cancer-directed treatment), and 7% of all healthcare OOPC. Patients with PERT had significantly higher monthly OOPC on Rxs but lower on all other services, including inpatient and outpatient services (all p < 0.0001). Overall, PERT-users had significantly lower per-patient per-month (PPPM) OOPC vs non-PERT users ($469, vs $520, p < 0.0001). They also had fewer PPPM outpatient (0.7 vs 1.2, p < 0.0001) and ER (0.4 vs 0.5, p < 0.0001) visits. Conclusions: In this national study of insured U.S. adults with PC, only one-third received PERT. Of those receiving PERT, approximately a fifth received just a single Rx. PERT users, despite higher OOP drug spending had reduced overall OOP costs and fewer healthcare visits. These data highlight the need to explore non cost-related reasons for lack of and ways to standardize PERT use.
Prognostic role of a novel clinical-nutritional index in pancreatic ductal adenocarcinoma: The Pancreatic Adenocarcinoma Nutritional-Clinical Index (PANCIN).
Authors: Orsi Giulia , Abati Martina , Palumbo Diego , Pavarini Maddalena , Burini Alice , Cardellini Sara , Macchini Marina , Mori Martina , Fiorino Claudio , Peretti Umberto , Valente Maria Maddalena , Militello Anna Maria , Briccolani Maria Assunta , Mele Roberto , Falconi Massimo , Cascinu Stefano , Capurso Gabriele , Reni Michele
Published: January 2023

697

Background: Impaired nutritional status is often associated with Pancreatic Ductal Adenocarcinoma (PDAC) and poor prognosis. Little is known on the prognostic role of nutritional variables in PDAC patients (pts) receiving chemotherapy (CT). Methods: Locally advanced or metastatic PDAC pts enrolled at our Institute in a prospective observational study (PAC-MAIN) and treated with 1st-line CT between April 2019 and July 2021 were included in the analysis. Clinical and nutritional variables entailed biohumoral parameters, bioimpedance vector analysis (BIVA)- and Computed Tomography-derived body composition. Progression-free and Overall survival (PFS and OS) were calculated from CT start to progression or death. A Multivariate Cox proportional-hazards model for PFS prediction was generated by backward selection of features with a p-value (p) ≤ 0.06. The resultant index, named PANCIN, was calculated as linear combination of the covariates (Xi are the N) and the b Cox coefficients (bi), according to the formula: PANCIN = ∑Ni=1 bi Xi Kaplan–Meier test was performed to assess the ability of PANCIN to stratify pts according to its median value for PFS and OS prediction. Results: 74 pts were included in the study. The variables retained in the model were: serum Vitamin B12 (pg/ml) [Hazard Ratio (HR)= 1.001, 95% Confidence Interval (CI) 1.0004-1.0016, p=0.002]; BIVA-derived Body Cell Mass (%) [HR= 0.94, 95% CI 0.887-1.002, p=0.058]; ECOG Performance Status (0 vs 1-2) [HR= 3.25, 95% CI 1.048-10.077, p=0.041]; Albumin (g/L) [HR= 0.91, 95% CI 0.86-0.97, p=0.002]; FAACT Score [HR= 1.041, 95% CI 1.006-1.077, p=0.022]. Median PFS was 15.3 (95% CI 7.6-21.8) and 5.8 months (95% CI 2.7-9.0) for pts with PANCIN < or ≥ -1.7768 median value respectively [HR= 3.7, 95% CI 1.9-7.0, p=0.0001]. Median OS was 23.8 (95% CI 12.6-33.3) and 10.0 months (95% CI 5.7-12.7) for pts with PANCIN < or ≥ -1.7768 respectively [HR= 4.1, 95% CI 2.1-7.9, p<0.0001]. Conclusions: PANCIN is a novel nutritional-clinical index able to predict outcome of advanced PDAC pts receiving CT. If furtherly validated, it may represent a stratification tool both in clinical practice and in prospective trials. Our findings also support the relevance of a baseline comprehensive nutritional assessment, to define tailored nutritional interventions.[Table: see text]
Identifying predictors of on-table adaptation for pancreas stereotactic body radiotherapy (SBRT).
Authors: Wu Trudy , Yoon Stephanie , Cao Minsong , Raldow Ann C. , Xiang Michael
Published: January 2023

702

Background: There is growing interest in the use of stereotactic body radiotherapy (SBRT) to treat pancreatic cancer. The purpose of this study was to identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas SBRT with MRI-guided radiotherapy. Methods: This was a single center retrospective study of patients undergoing MRI-guided SBRT to the pancreas from 2016 to 2022. An online daily adaptive workflow was in place for all fractions according to pre-specified criteria. Pre-treatment clinical variables and dosimetric parameters on the patient’s simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted. Results: Seventy-three SBRT courses consisting of 365 fractions were included in this study. Median prescription dose was 40 Gy in five fractions (range, 33-50 Gy); 56% and 44% of courses were prescribed ≤ 40 Gy and > 40 Gy, respectively. Median gross and planning target volume (GTV and PTV) coverage were 94.7% and 84.3%, respectively. Median number of fractions adapted per course was three, with overall 58% (211 out of 365) total fractions adapted. On univariable analysis, the prescription dose ( > 40 Gy vs ≤ 40 Gy), GTV size, stomach V20 and V25, duodenum V20 and Dmax, large bowel V33 and V35, heterogeneity index, and gradient index were significant determinants of the use of on-table adaptation (all p < 0.05). On multivariable analysis, only prescription dose remained significant (adjusted odds ratio 7.66, p = 0.003). Conclusions: Prescription dose in MRI-guided pancreas SBRT is the only reliable predictor of on-table adaptation. Providers should strongly consider utilization of adaptive technology when delivering ablative doses to the pancreas.[Table: see text]
Updated results of a phase 1 study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC; SGNS40-001).
Authors: Coveler Andrew L. , Gutierrez Martin , Vaccaro Gina M. , Brown-Glaberman Ursa , Grilley-Olson Juneko E. , Kindler Hedy L. , Zalupski Mark , Heath Elisabeth I. , Piha-Paul Sarina A. , Wehr Allison , Lu Hailing , Hayman Jonathan , Bajor David L
Published: January 2023

708

Background: PDAC has a 5-year survival rate of <5% in patients with metastatic disease. Despite established frontline therapy with gemcitabine + nab-paclitaxel (GnP), outcomes remain poor and additional therapies are urgently needed. SEA-CD40 is a receptor-agonistic, nonfucosylated IgG1 antibody directed to CD40. SEA-CD40 binding to FcγRIIIa results in enhanced effector function and CD40 agonism, allowing amplification of immune stimulation and antitumor activity. In preliminary results of a phase 1 study, SEA-CD40 + GnP + pembrolizumab (pembro) showed a tolerable safety profile and evidence of immune activation in patients (pts) with PDAC. Here, we present updated clinical results for this cohort. Methods: Pts were ≥18 years old with untreated metastatic PDAC and ECOG Performance Status of 0 or 1. Gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) were given on days 1, 8, and 15 and SEA-CD40 (10 or 30 µg/kg) was given on day 3 of each 28-day cycle. Pembro (400 mg) was given every 6 weeks starting on day 8 for up to 2 years. Results: As of August 16, 2022, 61 pts were treated with 10 µg/kg (N=40) or 30 µg/kg (N=21) SEA-CD40. Median duration of exposure was 25.1 weeks. Confirmed objective responses were observed in 19 pts (48% [95% CI 31.5, 63.9]) at 10 µg/kg and 8 pts (38% [95% CI 18.1, 61.6]) at 30 µg/kg. Median duration of response (months) was 5.7 (95% CI 3.9, 7.4) and 5.7 (95% CI 2.3, 9.2) for the 10 and 30 µg/kg dose groups, respectively. Additional efficacy results are summarized. The most common treatment-emergent adverse events (TEAEs) across dose groups were fatigue (84%), nausea (74%), and neutropenia (67%). The most common grade ≥3 TEAEs across the groups were neutropenia (61%), anemia (33%), and thrombocytopenia (20%). TEAEs leading to treatment discontinuation were reported in 10% of pts, including immune-mediated lung disease (n=3) and septic shock (n=1) in the 10 µg/kg dose group, and colitis (n=1) and portal vein thrombosis (n=1) in the 30 µg/kg dose group. Conclusions: The combination of SEA-CD40 + GnP + pembro has an acceptable safety profile and shows evidence of antitumor activity in pts with PDAC. This regimen may warrant further evaluation. Clinical trial information: NCT02376699 . [Table: see text]
Screening or symptoms? Colorectal cancer diagnosis in Uruguay.
Authors: Fontes Santiago , Berry Megan , Marín-Jiménez Ana , Sánchez Juan Carlos , Krygier Gabriel David , Cuello Mauricio
Published: January 2023

71

Background: Colorectal cancer (CRC) remains a major health burden worldwide. Screening is employed due to its proven efficacy in reducing CRC incidence and mortality. In Uruguay, there is a longstanding National CRC screening program using fecal occult blood test (FOBT) as the preferred method. It is to be expected that patients with screen-detected CRC have better prognosis than those with symptoms due to earlier diagnosis and other favorable tumor/host characteristics. Beyond the well described earlier stage at diagnosis, other aspects have not been widely studied and data is sparse. An increasing proportion of CRC patients are diagnosed by screening rather than symptoms. Aim: We sought to establish and evaluate the correlation between clinicopathological features and TNM stage at diagnosis and diagnostic modality. Methods: A retrospective review of all newly diagnosed CRC patients from January 2008 to December 2021 was conducted by the authors. A total of 934 patients aged 50-80 years at diagnosis were included. Clinical, histological, diagnostic and treatment data was collected and findings were stratified and correlated according to screening detection vs symptomatic patients. Results: On one hand, 15% of patients had a positive FOBT leading up to their diagnosis. FOBT detected tumors presented a less advanced locoregional T-N staging (p = 0.001). Tumors were preferentially located in the proximal colon (33.1 vs 19.9%); p<0.001. Stage I CRC was more frequently detected in subjects with positive FOBT (14.2%) than in individuals with symptoms (5.9%); p = 0.002. Conversely, detection rates for stage IV CRC were 17.7% and 26.7% respectively; p = 0.002. A higher percentage of stage III screened patients underwent adjuvant chemotherapy when compared to their symptomatic counterparts (97.7 vs. 85.0 %, p = 0.016). On the other hand, 793 patients (85 %) were diagnosed after onset of signs or symptoms. There was a preponderance of advanced-stage disease (stages III–IV 36-27% respectively). The most common symptoms reported were change in bowel habits (52%), abdominal pain (47 %) and bleeding (45%). The most common overall sign was anemia. One hundred eighty-two patients (22.5%) required an emergency surgery mainly for obstructive colon cancer. Conclusions: Despite equal access to colorectal cancer screening, in Uruguay diagnosis after development of symptomatic cancer remains more common. FOBT detected cancers presented less advanced clinicopathological characteristics and differing management that potentially could be driving a more favorable outcome. Mode of detection is therefore an important indicator that should be taken into account when defining risk assessment in treatment decisions. These findings also support the need for continued improvement and recruitment of patients into screening programs. It must be the focus for future initiatives.
Phase II trial of maximal ablative irradiation because of encasement (MAIBE) for patients with potentially resectable locally advanced pancreatic cancer.
Authors: Reyngold Marsha , Alice Wei , O'Reilly Eileen Mary , D'Angelica Michael Ian , Drebin Jeffrey A. , Soares Kevin , Kingham T. Peter , Balachandran Vinod P. , Varghese Anna M. , Park Wungki , Khalil Danny , Yu Kenneth H. , Zinovoy Melissa , Cuaron John J , Hajj Carla , Romesser Paul Bernard , Wu Abraham Jing-Ching , Zhang Zhigang , Jarnagin William R. , Crane Christopher H.
Published: January 2023

710

Background: For patients with localized but not immediately resectable pancreatic adenocarcinoma (PDAC), the role for local therapy remains undefined. Phase II MAIBE trial studied ablative radiation (A-RT) followed by consideration of surgery for patients with locally advanced pancreatic cancer (LAPC) who remain unresectable after induction chemotherapy. Methods: Participants with histologically confirmed PDAC judged unresectable by multidisciplinary review using NCCN definition after completing 3-6 months of mFOLFIRINOX (FFX) or Gemcitabine/Nab-paclitaxel (GN) were eligible. They received hypofractionated A-RT (either 67.5Gy in 15 fractions or 75Gy in 25 fractions based on anatomy) with concurrent capecitabine followed by consideration of resection within 1-3 months. Primary endpoints included resectability (80% power to detect resectability improvement from 15% in historical controls to 30% with α = 0.05) and overall survival (OS) from A-RT. Secondary endpoints included safety of surgical resection after ablative RT using 90-day Clavien-Dindo Classification of adverse events (AE). Results: Between 6/2018 and 4/2022, 47 eligible participants underwent A-RT. Median age was 67 (range, 50-80) years, 24 (51%) were male with a median tumor size of 3.95 (1.6 – 8.3) cm and CA19-9 of 92 ( < 1-1601) U/mL. Forty-four patients (94%) received at least 1 cycle of FFX with a median duration of chemotherapy (FFX or GN) of 3.5 months (1.0 – 9.4). Sixteen (34%) underwent a laparoscopy and 12 (26%) underwent a resection (Pancreaticoduodenectomy, N = 11; distal pancreatectomy, N = 1) at a median time of 3.2 months (1.9-16.9 months) from start of A-RT. The rate of resection satisfied our prespecified boundary of 11. R0 rate was 58.3%. Two-year OS from A-RT for the entire cohort was 38.9% (95% CI, 21.9 – 55.6%), including 37.1% (18.5 - 55.8%) in non-surgical and 39.4% (7.0- 72.1%) in surgical groups. There were no deaths within 90 days of surgery and 9 surgical AEs were recorded in 6 participants, including grade 1 (n = 1), grade 2 (n = 5), grade 3 (n = 2) and grade unknown (n = 1). Conclusions: In patients with LAPC and no metastatic disease after 3-6 months of chemotherapy, A-RT results in a favorable rate of resection without excess surgical toxicity. Promising 2-year OS rates were noted in both resected and non-resected patients. Clinical trial information: NCT03523312 .