bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of retreatment with lutetium Lu 177 DOTATATE in patients with progressive neuroendocrine tumors in the United States: A retrospective real-world study.
Authors: Delpassand Ebrahim , Yazdi Soheil Mohammadi , Ghantoji Shashank , Nakasato Antonio Reis , Strickland Corinne Denise , Nunez Rodolfo , Shafie Afshin , Cork Susan , Byrne Clare , Tang Jackson , Runeckles Kyle , Patel Jeetvan 
Published: June 2022

e16215 Background: Advanced neuroendocrine tumors (NETs) are associated with a very poor prognosis. A regimen of 4 doses of lutetium Lu 177 (177Lu)-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. This is the first United States (US) study to evaluate the effectiveness and safety of additional doses in patients with progressive NETs. Methods: This was a retrospective chart review of 31 adults with advanced NETs who had undergone initial treatment with up to 4 doses of 177Lu-DOTATATE and who, following disease progression and a period of ≥6 months since the end of initial treatment, were re-treated with ≥1 additional dose at a single US center (2010–2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using CTCAE 5.0 criteria. Kaplan–Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE re-treatment, 19 (61%) were male and 29 (94%) were white. Overall, patients received a median of 6 doses (4 initial doses and 2 re-treatment doses) and the mean±sd administered activity was 41.9±4.4 GBq. Two patients also went on to receive additional re-treatment (1 and 2 doses, respectively) following a second period of ≥6 months and progression after re-treatment. Best responses of partial response and stable disease were observed in 11 patients (35%) and 20 patients (65%) after initial treatment, and 7 patients (23%) and 14 patients (45%) after re-treatment (Table). The median PFS after initial treatment was 20.2 months and after re-treatment was 9.6 months. The median OS after initial treatment was 42.6 months and after re-treatment was 12.6 months. Hematological parameters decreased significantly during both initial and re-treatment but recovered such that there was no significant difference between the values prior to initial treatment and prior to re-treatment. Clinically significant hematotoxicity occurred in 1 and 3 patients following initial and re-treatment, respectively. No grade 3/4 nephrotoxicity (based on creatinine levels) was observed. Conclusions: Re-treatment with 177Lu-DOTATATE after progression appeared to be well-tolerated and offered disease control in patients with progressive NETs following initial 177Lu-DOTATATE treatment.[Table: see text]
Does the primary tumor origin affect the prognosis of patients with gastrointestinal malignancies and peritoneal carcinomatosis?
Authors: Wong Krista Michelle , Patell Kanchi , Ramsawak Seshma , Abuamsha Hasan 
Published: June 2022

e16223 Background: Multiple gastrointestinal malignancies have the potential to metastasize in the peritoneal cavity. Peritoneal carcinomatosis (PC) is often associated with disease progression and poor prognosis. However, there has been limited data on the impact of tumor origin on the survival outcomes in patients with PC. We sought to examine the differences in the cancer-specific survival of gastrointestinal malignancies with PC. Methods: We performed a retrospective study of patients ≥18 years of age diagnosed with gastrointestinal malignancies (stomach, colorectal, small intestine, appendix) with PC between 2010-2016 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The study endpoint was cancer-specific mortality (CSM). We used the Kaplan-Meier method to evaluate the cancer-specific survival for each primary tumor. Cox proportional hazard regression analysis was used to examine the association between CSM and other patient characteristics. The effects were expressed as hazard ratios (HR) and 95% confidence intervals (CI). Results: We identified 7374 patients who met the inclusion criteria; 2797 (37.9%) with stomach cancer, 3274 (44.4%) with colorectal cancer, 703 (9.5%) with small intestine cancer, and 600 (8.1%) with appendiceal cancer. The median age at diagnosis was 64 (Interquartile Range (IQR), 53-75). Median follow-up was 11 months (IQR 3-22). 3709 patients (50.3%) were female. The majority was White (76.2%). 3942 (53.5%) were married. 5679 (77.0%) were insured. 4343 (58.9%) received chemotherapy and 3682 (49.9%) received surgery. Compared to PC of appendiceal cancer primary, stomach cancer primary had an increased risk of CSM (HR = 4.89; 95% CI 4.23-5.65), followed by colorectal cancer (HR = 2.78, 95% CI 2.41-3.21), and small intestine (HR = 1.17; 95% CI 0.98-1.41). Across all patients, surgery and chemotherapy were associated with a lower risk of CSM. Conclusions: Primary tumor origin significantly affects outcomes of gastrointestinal malignancies with PC. Surgery and chemotherapy were associated with decreased CSM. [Table: see text]
Real-world evaluation of AG plus PD-1 antibody in old patients with advanced unresectable pancreatic cancer.
Authors: Wang Bin , He Zenglei , Xue Liang , Mei Shengmin , Xu Li , Ling Qi 
Published: June 2022

e16226 Background: Unresectable pancreatic cancer (PC) is associated with fatal outcomes despite chemotherapy and radiation. PD-1 antibodies might provide favorable long-term survival in combination with chemotherapy according to previous clinical trials and pilot studies. In this study, we conducted a real-world evaluation of PD-1 antibody in old patients with unresectable PC. We also aimed to explore biomarkers for the early prediction of PD-1 antibodies response. Methods: This is a single-arm, single-center, real-world study. Primary Objectives: ORR. Secondary Objectives: DCR, OS, PFS, Safety(CTCAE). Exploratory Objectives: The alteration of molecular biomarkers to PD-1 antibodies treatment including IL-2, IL-4, IL-10, IL-16, TNF¦Á and IFN-¦Ã, ect. Key eligibility criteria: Histopathologically confirmed advanced unresectable PC; Without systematic treatment; ¡Ý60 years old; ECOG PS 0 or 1; Evaluated by mRECIST PD-1 plus AG, Q3W Surgery Until disease progression, unacceptable toxicity, or up to 2 years. Results: From Jan 2021 to Dec 2021, 10 unresectable PC patients were enrolled in Yuhang campus, the first affiliated hospital, Zhejiang university school of medicine, which their baseline characteristics were listed in Table. A total of 9 patients were finally included and analyzed. Clinical decisions were made by multi-disciplinary team. The treatment efficacy was evaluated by mRECIST. A total of 9 patients were assessable for response. ORR was 33.3%, with 3/9 partial response (PR). 5/9 patients were stable disease (SD), and DCR was 88.9%. Conversion therapy uses rational immunotherapy and chemotherapy and so on combined with MDT assessment to translate initial unresectable case to resectable one, which obviously prolongs survival time and improves quality of life. For patients with surgically unresectable PC 2 patients were successfully transformed. The rate of overall surgical conversions was 22.2%. The most common adverse events were anemia (6 [60%] patients). There were no treatment-related level 4 and 5 adverse events. There was no treatment-related cardiotoxicity. No patients were interrupted due to adverse events. Conclusions: PD-1 antibody plus Chemotherapy demonstrates significant clinical activity and favorable tolerability in old patients with advanced unresectable PC, and DCR was 88.9%.[Table: see text]
Adherence to genetic testing guidelines in pancreatic cancer and impact on treatment.
Authors: Crowley Fionnuala , Rudshteyn Michelle , Gandhi Sonal , Wotman Michael , Sehmbhi Mantej , Cohen Deirdre Jill 
Published: June 2022

e16238 Background: NCCN June 2019 Guidelines recommend that clinicians consider germline (GL) testing for patients(pts) diagnosed with pancreatic cancer (PDAC) and consider molecular analysis of tumors in pts with metastatic disease. Up to 25% of advanced PDAC pts have GL or somatic mutations in the DNA damage repair (DDR) pathway which are predictive of response to platinum chemotherapy (plat) and maintenance therapy with olaparib. Referral for genetic testing (GT) at our institution is currently made at provider discretion. We aimed to determine rates of GT, factors associated with GT, and outcomes of those tested. Methods: Frequency of GT testing was examined in pts with non-endocrine PDAC and >2 visits between 6/2019 and 6/2021 at Mount Sinai Health System. Clinicopathological variables and treatment outcomes were also recorded. Results: 149 pts were included. 71 pts (48%) were male. 25 pts (17%) had a personal history of cancer and 8 (5.3%) with history of DDR related cancer (prostate, breast, ovarian). 66 pts (44%) had GL testing: 42 (28%) at diagnosis with the remainder later in treatment. The rate of GL testing increased every year: 33% (2019), 44% (2020), 61% (2021). There was no statistically significant association between decision to do GL testing and age, ECOG, race, personal or family history (FH) of cancer. A FH of DDR related cancer was positively associated with GL testing (47% vs 27% p=0.039). 8 pts (12% of pts tested) had pathological gMut: BRCA1 (1), BRCA2 (1), ATM (2), PALB2 (2) , NTHL1 (1), both CHEK2 and APC (1). 6 pts (75%) had GL testing at diagnosis. One g BRCA2 pt had a plat response. Neither g BRCA pt received a PARP inhibitor. 24 pts in total had a response to plat, 16 (67%) of whom had GL testing. 94 pts (63%) had molecular tumor testing (including 65% of pts with metastases). Pathogenic mut in DDR genes were identified in 9 pts: ARID1A (2), BRCA2 (3), ATM (2), PALB2 (2), CHEK2 (1). Four of these pts had corresponding gMuts. One pt with somatic ATM mut had g BRCA1 mut. Two pts with BRCA2 somatic mut did not have GL testing. Conclusions: GT based on provider discretion resulted in suboptimal rates of GL testing. However, since inception of national guidelines, testing rates nearly doubled. Rates of GL DDR mutations were lower than previously reported, with varying response to plat in this cohort. Future studies are needed to understand barriers to GT and improve implementation.[Table: see text]
A peptide fused to CLDN18.2 antibody targeting the tumor antigen associated CD8+T cells for the treatment of pancreatic cancers.
Authors: Liu Jiajian , Luan Y. , Deng H. , Wang F. , Wang C. , Zhang Z. 
Published: June 2022

e16240 Background: PD-1/PD-L1-targeted immunotherapies have become critical roles in the treatment for many tumors. However, there is limited progress in gastrointestinal cancers, especially in pancreatic ductal adenocarcinoma (PDAC). PDAC is low immunogenicity. PDAC microenvironment is immunosuppressive. More than 70% PDACs have few or no CD8+ T cells around the tumor cell or in the tumor microenvironment. Therefore, immunotherapy like PD-1/PD-L1 antibody alone is rarely effective for PDACs. Methods: Some cytokine or analogs may activate CD8+ T cells. An analog specifically activating tumor antigen associated (TAA) CD8+ T cells was fused to anti-CLDN18.2 antibody. Results: The specific bi-functional molecule (Bis2) has high affinity to human anti-CLDN18.2 (14pM) and CD8+T cells. Bis2 shows significant in vivo efficacy at 0.1 mpk. The efficacy lasts for more than 24 days, only given two doses at day 1 and day 3, respectively. IHC shows that the tumor infiltrated CD8+T cells significantly increased and IFNγ secretion enhanced as well. The IHC results are consistent with the mechanism that Bis2 induces TAA CD8+ T cell proliferation and prevents CD8+T cells from IFNγ-mediated apoptosis. Moreover, Bis2 also shows 100% tumor inhibition in combination with either chem (L-OHP+5FU) or PD-1 antibody in vivo which is better than chem in combination with PD-1 antibody. Bis2 also shows 60% tumor inhibition at 1mpk in CLDN18.2 negative cell based in vivo model. Bis2 shows ADA in monkeys in two weeks by dosing weekly. The repeated doses toxicity study shows an increase of MONO and %MONO and decrease in RBC, HGB, HCT, and MCHC. The HNSTD was 3mpk. The T1/2 was 40h. Conclusions: The Phase I study in advanced solid tumors is ongoing. The study uses accelerated titration starting from 0.01mpk combined with a BOIN design, maximum patient size of 36. In the expansion part, two cohorts of 10 CLDN18.2+ pancreatic cancer patients are planned for the treatment of Bis2 alone or Bis2 in combination with chemotherapy, respectively.
Application of XCELSIOR, a nationwide real-world observational research protocol, to identify efficacious targeted therapy regimens in advanced pancreatic adenocarcinoma.
Authors: Stuhlmiller Timothy Joseph , Wasserman Asher , Cole Zachariah , Kesari Santosh , Shapiro Mark 
Published: June 2022

e16245 Background: The proliferation of multi-omic diagnostics, highly selective targeted therapies, multi-modal immunotherapies, and personalized vaccines has yielded many promising novel combination regimens. Still, many patients with advanced cancer are left without clear options because the clinical efficacy of these regimens is based on anecdotal evidence as collective learning from real world practice is uncoordinated across the US. XCLESIOR ( NCT03793088 ) is a nationwide observational research protocol designed to efficiently gather, centralize, and standardize electronic medical records from any institution in the country, permitting complete longitudinal histories to be compiled for individual patients and analyzed on aggregate. Methods: Patients with pancreatic carcinoma were e-consented to XCELSIOR and real world data was entered into a 21 CF Part 11-compliant database and source-verified from raw electronic medical records generated in the standard practice of medicine including physician clinic notes, radiology reports, lab testing values, and genomics reports. Time-on-treatment and overall survival (OS) were calculated for cohorts based on treatment regimens containing chemotherapy, immunotherapy, or molecularly-targeted therapy. Results: As of February 1st, 2022, a total of 330 patients (pts) with pancreatic carcinoma had consented to XCELSIOR representing 199 institutions or oncology practices. 195 pts with metastatic pancreatic adenocarcinoma had longitudinal data structured and suitable for analysis at time of writing. Median follow-up from diagnosis was 1.3 years. The most prevalent treatment regimens were FOLFIRINOX (154 pts) and gemcitabine/nab-paclitaxel (139 pts). 28 pts were treated with targeted therapies and had significantly longer OS than pts that were never treated with targeted therapies (2.6 vs. 1.1 years median OS). Targeted therapies were most commonly employed at 3rd line (15/28) and 4th line (7/28), suggesting they benefitted pts following SOC chemotherapeutic regimens. Molecular targeted therapies utilized included primarily PARP inhibitors, MAPK pathway inhibitors, and HER2-targeted therapies. Time-on-treatment for FOLFIRINOX was median 105 days (generally 1st line), for gemcitabine/nab-paclitaxel was median 143 days (generally 2nd line), and for all targeted therapies was median 106 days. Conclusions: XCELSIOR is an efficient nationwide observational research protocol designed to aggregate, structure, and analyze longitudinal clinical data. Application of this virtual platform to an emerging metastatic pancreatic adenocarcinoma dataset suggested biomarker-based molecular targeted therapies utilized at 3rd and 4th line have the potential to be efficacious. Further stratification and analyses will be performed as the data matures. Clinical trial information: NCT03793088.
Survival outcomes amongst patients with new onset diabetes preceding the diagnosis of pancreatic adenocarcinoma: Multicenter retrospective study.
Authors: Mohindroo Chirayu , Dy Paul Stendahl , Hande Suraj , Mavanur Arun A. , De Jesus-Acosta Ana , McAllister Florencia , Thomas Asha 
Published: June 2022

e16251 Background: In patients (pts) with new-onset diabetes (NOD) above the age of 50 years, 1% are diagnosed with pancreatic adenocarcinoma (PDAC) within three years. Based on this, NOD has been proposed as an important factor for early diagnosis of PDAC. Research has been directed towards investigating NOD vs Type 2 diabetes and association with PDAC. Limited data exists on its impact on the survival outcomes amongst PDAC pts. Methods: We retrospectively analyzed clinical data of 150 pts diagnosed with a pancreatic mass at three hospitals from 2014 to 2021. NOD group consisted of pts diagnosed with Diabetes or Pre-Diabetes defined as HBA1c > 6.5% and 5.7-6.4%, respectively, within the three years prior to PDAC diagnosis. Primary aim of the study was the characterization of the impact of NOD on clinical outcomes. Results: 83 pts [mean age 68.32 yrs, 58% males, 61% white] were identified with biopsy proven PDAC, out of which, 9 (11%) pts had pre-existing Diabetes, 21 (25%) pts met the criteria for NOD group. In the NOD group whose weight was available (n = 15), 11 pts (79%) had experienced weight loss within one year of the NOD diagnosis with a median age of 68.46 yrs. No significant differences were noted between race (P = 0.36), age (P = 0.9), sex (P = 0.9), tumor location (P = 0.17), and chemotherapy received (P = 0.9) between the two groups. When comparing survival outcomes, no significant differences were noted in the metastatic cohort (n = 42, PFS HR 0.77, P = 0.4, OS HR 0.9 P = 0.7) including in the subgroup analysis for pts receiving FOLFIRINOX n = 20, PFS HR 0.59, P = 0.28, OS HR 0.66 P = 0.4) or Gemcitabine based treatment (n = 9, PFS HR 1.31, P = 0.7, OS HR 0.46 P = 0.3). In the resected cohort (n = 20), pts in the NOD group did worse than pts who did not meet the criteria with PFS 10 months vs. 18.3 months (P = 0.0058, HR 7.78), a similar trend was noticed in the OS 15.2 months vs. 28.2 months (P = 0.08 HR 2.98), but it did not reach statistical significance. Conclusions: Consistent with current literature, NOD preceding PDAC is distinct from Type 2 diabetes associated NOD, characterized by weight loss and occurring at a later age. Pts with NOD preceding PDAC were shown to have worse survival outcomes in the resected cohort. Larger studies need to be conducted in this context as this could have significant implications for PDAC screening and treatment.
Neoadjuvant modified FOLFIRINOX or gemcitabine-nab paclitaxel followed by stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer and borderline pancreatic inoperable cancers.
Authors: Paluri Ravi Kumar , Manne Upender , Reddy Sushanth , Posey James , Williams Grant Richard , Gbolahan Olumide B. , Bae Sejong , Jacob Rojymon 
Published: June 2022

e16253 Background: We conducted a single center safety and feasibility trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX or Gemcitabine-nab Paclitaxel (GnP)and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancers (LAPC). Methods: Patients with biopsy proven LAPC treated between June 2017 and August 2020 were included. Patients received two months of neo-adjuvant chemotherapy with 4 cycles of FOLFIRINOX or two cycles of GnP followed by SBRT (5 fractions/6.6Gy), total 33gy over 5 days, if no tumor progression after the initial chemotherapy was observed. Patients were reassessed for resectability after SBRT. If unresectable, they were continued on systemic therapy. Primary outcome was safety measured by proportion of grade 3/4 adverse effects. The study is registered with, and is completed. Results: Twenty-five patients enrolled were treated with FOLFIRINOX (n = 16) and GnP (n = 9). Seven (28%) patients did not receive SBRT, due to disease progression (n = 6) after initial systemic therapy, and patients’ preference (n = 1). Eighteen (72%) patients received the SBRT. Thirty-five grade 3 or 4 adverse events were observed with FOLFIRINOX and twenty-five with GnP. No grade 3 or 4 adverse events after SBRT. SBRT was administered within two weeks (median 9 days) after completion of neoadjuvant therapy. Five (27%) patients underwent a resection, all resulting in a complete (R0) resection. The patients who underwent SBRT, the Median overall survival (OS) was 28.39 95%CI (26.45 46.75) and progression free survival was 26.45 95%CI 17.25 46.7. The one-year OS and PFS were 78% (95% CI: 52%-93%) and 67% (95% CI: 41%-87%), respectively. Conclusions: Neoadjuvant FOLFIRINOX or GnP followed by SBRT in patients with LAPC is feasible and shows antitumor activity. There were no safety concerns or treatment delays with incorporation of SBRT. Clinical trial information: NCT03600623.
Association of pathologic response and survival after peri-operative therapy in resected pancreatic adenocarcinoma: KU cancer center experience.
Authors: Rozeboom Brett , Martinez Maximillian , Mehta Kathan , Hamza Ameer , Chidharla Anusha , Saeed Anwaar , Al-Rajabi Raed Moh'd Taiseer , Baranda Joaquina Celebre , Kumer Sean , Schmitt Timothy , Lominska Christopher Erik , Hoover Andrew , Akhavan David , Dandawate Prasad , Anant Shrikant , Saha Subhrajit , Tiwari Ankita , Bossmann Stefan H. , Sun Weijing , Kasi Anup 
Published: June 2022

e16254 Background: Neo-adjuvant therapy (NAT) and associated pathologic complete response (pCR) rates have correlated with improved survival in resected pancreatic ductal adenocarcinoma (PDAC). In this study, we explored the relationship between pathologic response, peri-operative therapy, and survival, especially the impact of change in adjuvant therapy in patients with no/poor path response to NAT. Methods: Retrospectively reviewed 66 PDAC patients who received NAT ± radiation and underwent resection at KU Cancer Center between 2011-2022. We compared DFS and OS between Path Responders vs Non-Responders based on standard Tumor Regression Scores from pathology reports. A subanalysis was performed in path non-responders based on switch in adjuvant therapy (AT) versus not. Results: Patient characteristics are summarized in the table. Among 66 PDAC patients, 50 (75.8%) achieved a path response (G0-G2), 16 (24.2%) experienced no/poor path response (G3). Of the 50 pts who achieved a path response, 4 (8.0%) had a complete path response (pCR; G0), 5 (10%) marked response (G1), 41 (82%) moderate response (G2). Median DFS (mDFS) was 17.3 months (95% CI: 12.7-22.4) in Path Responders vs 15.9m (95% CI: 9.6-35.8) in Non-Responders [p=0.59]. Median OS (mOS) was 32.9m (95% CI: 23.4-41.5) vs 27.7m (95% CI: 15.2-38.2), respectively [p=0.39). A sub-analysis in the Non-Responders (n=16) based on switch in AT (n=8) vs not (n=3), revealed mDFS 16.4m (95% CI: 9.6-41.8) when AT was switched vs mDFS 11.3m (95% CI: 5.9-16.6) when AT was not switched [p=0.24]; and mOS 30.6m (95% CI: 15.7-60.3) vs 17.2 months (95% CI: 6.7-27.7), respectively [p=0.18]. Conclusions: Our study found no statistical difference in DFS and OS between Pathologic Responders and Non-Responders to neo-adjuvant therapy. However, a sub-analysis within Pathologic Non-Responders revealed a longer DFS and OS after switching adjuvant therapy without reaching statistical significance, likely due to small sample size. Our findings warrant validation in a larger cohort as switch in adjuvant therapy could potentially change the treatment landscape for Pathologic Non-Responders.[Table: see text]