bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of facility volume on outcomes in patients with pancreatic cancer treated with radiotherapy.
Authors: Rajan Arvind , Gleeson Elizabeth , Pham Veronica , Bodek Benjamin Ethan , Goodman Karyn A. 
Published: January 2024

644 Background: The impact of facility volume on overall survival (OS) outcomes in patients with pancreatic cancer (PC) treated with radiotherapy (RT), both standard chemoradiation (CRT) and stereotactic body radiation therapy (SBRT) is not well-defined. Methods: This retrospective study analyzed 16,315 patients with locally advanced (LA) or borderline resectable (BR) PC from the National Cancer Database (2004-2019) who received neoadjuvant RT or RT without surgery across RT facilities with low- (<10 cases/yr), intermediate- (10-20 cases/yr), and high-volumes (>20 cases/yr) of PC cases. Log rank and cox regression were used for univariable and multivariable survival analysis, and Kaplan-Meier curves were generated. Results: Patients were largely treated at low (n=8055) volume centers, followed by intermediate (n=3783), and high (n=4477). Approximately half of the cohort were male (51.4%), and predominantly white (82.5%), and non-Hispanic (92%). On univariable analysis (Table), high-volume centers had improved survival outcomes in the overall population, as well as in both SBRT and CRT subsets (p<0.0001). On multivariable analysis, treatment during the most recent time period: 2016-2019 (HR 0.646, p<0.001), receiving care at a high-volume center (HR 0.844, p<0.001), use of SBRT (HR 0.915, p<0.001), administration of multiagent chemotherapy (HR 0.706, p<0.001) and undergone surgical resection (HR 0.405, p<0.001) were associated with improved OS. In a subgroup analysis of patients receiving SBRT, median OS was 22.6 months for high-volume, 20.0 for intermediate-volume and 18.4 months at low-volume centers (p<0.001). Conclusions: Patients receiving RT for LAPC or BRPC at high-volume centers had longer OS compared to those receiving radiation at intermediate- or low-volume centers. In those undergoing SBRT, treatment at high-volume centers had improved OS compared to intermediate- and low-volume centers. These findings suggest that radiation oncologists’ expertise is critical for providing high-quality RT in PC, especially for SBRT.[Table: see text]
A qualitative exploration of perceptions and experiences towards physical activity among patients with pancreatic ductal adenocarcinoma undergoing treatment.
Authors: Nguyen Tyra , Gresham Gillian , Luna-Lupercio Bianca , Raines Carolina , Gong Jun , Osipov Arsen , Hendifar Andrew Eugene , Shirazipour Celina 
Published: January 2024

646 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) experience significant symptom burden due to the disease and its treatment, thus limiting their ability to participate in physical activity (PA) and engage in daily activities. PA can have many physical and psychosocial benefits, and exploring its value and how to deliver it to patients with PDAC could support their health and well-being. Therefore, the objective of this qualitative research was to explore perceptions and experiences of PA among PDAC patients undergoing active treatment. Methods: Qualitative semi-structured interviews were conducted with individuals with PDAC. Participation was optional and open to individuals in the DigiSTEPS prospective trial evaluating associations between PA measures, performance status, and patient-reported outcomes (NCT03757182). Interviews were conducted virtually. Data were analyzed using inductive thematic analysis. Results: Ten patients (50% male, 80% white, mean age=70 years) participated in the interviews. While clinical approaches may often be informational and seek to educate PDAC patients regarding the importance of PA and the benefits of PA participation, findings suggest that participants understand the benefits of PA and are interested in being active. However, cancer symptoms and treatment-related side effects are substantial barriers that are hard to surmount. A further barrier was the dissonance in self-perceptions, particularly the contrast in their functional abilities and body composition pre- to post-cancer diagnosis. We identified four action items to support patients in overcoming these barriers: clinicians can leverage trust in their team to provide evidence-based information on how to be active; distribute wearable activity monitors which can increase motivation; harness virtual PA opportunities during more symptomatic periods; and provide PA trainers with cancer knowledge to tailor programming. Conclusions: This research highlights the importance of tailoring PA discussion and approaches based on a PDAC patient’s phase in the cancer survivorship continuum, their stage at diagnosis, and treatment type. In addition, clinical teams and trainers should consider patient concerns related to body image and develop programs that address the barriers identified in this research. Clinical teams may benefit from integrating access to counselling psychologists to address these concerns and promote PA in positive and adaptive ways. Clinical trial information: NCT03757182 .
Stereotactic radiotherapy plus anti PD-1 therapy in patients with locally advanced unresectable pancreatic cancer: Results from a phase 1/2 clinical trial (CA209-9KH).
Authors: Vosmik Milan , Stanislav John , Dvorak Josef , Mohelníková-Duchoňová Beatrice , Melichar Bohuslav , Lohynska Radka , Ryška Aleš , Krempova Johana , Sirak Igor 
Published: January 2024

649 Background: The outcomes after the treatment for pancreatic ductal adenocarcinoma (PDAC) are generally disappointing. Except for MSI high tumors, PDAC is considered to be resistant to immune checkpoint inhibitors (ICI). Radiotherapy is thought to be a potential option to foster the effect of ICI. This investigator-initiated trial evaluated safety and efficacy of combining stereotactic radiotherapy (SRT) and ICI. Methods: In this open-label, multicenter phase 1/2 study, patients (pts) aged ≥ 18 years with histologically confirmed locally advanced unresectable PDAC with no distant metastases were enrolled after initial four cycles of induction chemotherapy with FOLFIRINOX. The experimental treatment consisted of SRT (32 Gy in 4 fractions/4 weeks) and sequential nivolumab (N) therapy (3mg/kg every two weeks) administered until disease progression or unacceptable toxicity. After N discontinuation pts could continue treatment with standard chemotherapy regimens. The primary end point was safety (events graded according to NCI CTCAE 4.03 criteria). The secondary objectives were progression free survival (PFS), overall survival (OS), evaluation of selected biomarkers, and quality of life (QoL; EORTC QLQ-C30 questionnaire). The PFS and OS were defined as the time from enrollment to event (i.e., did not include 3-month of ICT and screening). Results: A total of 22 pts. were screened, and 15 pts. were enrolled. Median age was 58 (range 38-74) years, and 53 % were males. All tumors were microsatellite (MS) stable or had unknown MS status. All patients underwent SRT according to the study protocol and all started N. The median number of N cycles was 11 (range 2-17). The toxicity of SRT was low and non-significant. The toxicity of N therapy was expectable. No Grade 4-5 toxicity was observed. Three pts. discontinued therapy because of toxicity (liver test elevation in two cases and unmanageable arthralgia). Median PFS and OS were 8.1 and 13.0 months, resp.; 12-month PFS and OS were 0 % and 66.7%, resp.; and 24-month OS was 8.9 %. The level of selected biomarkers correlated with clinical or radiological disease control. The QoL assessed by pts during the therapy was acceptable, deterioration of QoL in most cases occurred with tumor progression. Conclusions: The toxicity of SRT and N therapy was low and acceptable. There was no unexpected toxicity of combination of SRT of PDAC primary tumor and N, but this regimen did not lead to any long-term treatment responses. Trial registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432. The study was financially supported by Bristol-Meyer-Squibb. Clinical trial information: NCT04098432 .
Timing of primary tumor resection after systemic chemotherapy initiation among patients with metastatic colon cancer.
Authors: Buhaya Munir , Jafry Baqir , Kazmi Syed Mohammad Ali , Huang Emina 
Published: January 2024

65 Background: In patients with resectable, metastatic colon cancer, the optimal timing of definitive resection of the primary tumor after initiation of chemotherapy remains unclear. Our goal is to identify factors that influence the interval between chemotherapy and definitive surgical management, and its impact on overall survival. We hypothesize that patients with shorter chemotherapy-to-surgery intervals (less than 60 days or about 2 months) compared to 61-180 days (2-6 months) or greater than 180 days (> 6 months), will have the worst overall survival. Methods: We conducted a retrospective analysis of all patients diagnosed with metastatic colon cancer from 2004-2016 who underwent resection of both primary tumor and distant metastatic site from the National Cancer Database (NCDB). Among those who received chemotherapy prior to surgery, we calculated the interval days between initiation of chemotherapy and primary tumor resection. Descriptive analysis, logistic regression, and overall survival was performed comparing patients with chemotherapy-to-surgery intervals of <60, 60-180, and >180 days. Results: A total of 2,238 patients were included, of which 143 (6%), 1446 (65%), and 649 (29%) were in the <60, 60-180, and >180 days groups, respectively. Similar distribution of patients across groups was observed for age, gender, insurance status, income, education level, distance travel, and Charlson-Deyo scores. Poorly differentiated tumors were more frequent in the <60 days group (12% vs 2-9% for other grades, p=0.001) as well as presence of lymphovascular invasion (8% vs 4%, p = 0.006). The odds of receiving care at an academic facility were lower in the <60 days group (OR: 0.52, 95% CI 0.273-0.994). Overall survival was significantly reduced in the <60 days group compared to 60-180 days (HR= 0.562, 95% C: 0.38-0.82). Conclusions: In this retrospective study from a national database, shorter chemotherapy-to-surgery interval (<60 days) was associated with poorly differentiated tumors and lymphovascular invasion. The odds of receiving surgery in <60 days of receiving chemotherapy was lower in academic/research facilities. A reduction in overall survival was observed in the shorter interval (<60 days) group compared to longer intervals. More research is needed to define the optimal chemotherapy-surgery interval and factors that influence this.
Pharmacogenomic study of gemcitabine on the safety and efficacy in patients with metastatic pancreatic cancer (GENESECT study): Analysis of a subpopulation.
Authors: Yokokawa Takashi , Tsuji Daiki , Hatori Masahiro , Suzuki Kenichi , Kawakami Kazuyoshi , Nakao Masahiko , Yano Takuya , Arakawa Yuichiro , Matsuo Keisuke , Ohashi Yasukata , Ozaka Masato , Sasahira Naoki , Sakata Yasuhiko , Kogure Yuki , Tamaki Shinya , Wada Atsushi , Taki Yusuke , Ishii Hiroshi , Itoh Kunihiko , Yamaguchi Masakazu 
Published: January 2024

651 Background: In the GENESECT study, we examined the relationships between gemcitabine (GEM) metabolism-related germline genetic polymorphisms (GPs) and treatment efficacy and safety. However, no significant GPs were found because approximately 70% of the patients were treated with nab-paclitaxel, which has a different metabolic process than GEM. In the present study, a subanalysis including only GEM monotherapy patients was performed. Methods: Of the 159 patients analyzed in the GENESECT study, only the GEM monotherapy patients were selected. The endpoints were the carbohydrate antigen 19-9 (CA19-9) response (reduction ≥50% from the pretreatment level at 8 weeks), progression-free survival (PFS), and overall survival (OS) in relation to GPs from the viewpoint of efficacy, and neutropenia ≥Grade 3 and thrombocytopenia ≥Grade 3 in relation to GPs from the viewpoint of safety. The analyzed genes included those encoding GEM transporters and metabolic enzymes ( SLC29A1, ABCC5, CDA, DCK, RRM1/2), and a tumor cell proliferation enzyme ( COX-2). Statistical analysis included univariate and multivariate logistic regression analyses. The significance level was set to 5%. Results: Data of 50 patients were analyzed. AA genotype in ABCC5 1146A>G (rs7636910) was associated with a significantly higher percentage of CA19-9 responses compared to AG/GG (52.9% vs 21.2%, p = 0.023), and the association remained significant on multivariate analysis (OR: 6.255, p = 0.014). Patients with AA genotype in ABCC5 1146A>G tended to be associated with PFS, but this was not statistically significant (HR: 0.464, p = 0.074). On the other hand, there was no significant association between CA19-9 responses and DCK-1205C>T (rs4694362), TT/CT genotype in DCK-1205C>T was significantly associated with prolonged PFS compared to CC (median, 127 vs 48 days, p = 0.002), and the association remained significant on multivariate analysis (HR: 0.153, p = 0.028). No GPs were significantly associated with OS, and the presence of second-line chemotherapy was the only relevant factor. In terms of safety, no GPs were significantly associated with either neutropenia or thrombocytopenia. Conclusions: The results suggest that ABCC5 and DCK might be related to the efficacy of treatment with GEM, but further research is needed. Clinical trial information: UMIN000012720 .
Preliminary results of a phase II study of surufatinib plus sintilimab, nab-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with locally advanced or metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Zhang Dong-Sheng , Liu Fu-Rong , Lu Yun-Xin , Bai Bing , Zhang Yang , Wang Zhi-Qiang , Liu Yu , Chen Jian-Wen , Wang Feng , Xu Rui-Hua 
Published: January 2024

659 Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as first-line therapy for mPDAC pts. Here we report the preliminary results. Methods: Eligible pts ≥18 years old with histologically confirmed mPDAC, ECOG PS 0-1, with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m2, I.V., D1, D8, Q3W) and gemcitabine (1000mg/m2,I.V.,D1, D8, Q3W). Based on Simon’s Two-stage design, 11 patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would continue to stage 2, and additional 21 patients would be enrolled. The total sample size was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12) (95% CI: 61.5-99.8). The median time to response (TTR) was 2.95 months (95% CI: 2.79-3.06), and median PFS was not reached yet. 15 pts underwent safety evaluation. The most common AEs of all grades were white blood cell count decreased (66.7%), neutrophil count decreased (60.0%), and anemia (53.3%), and grades ≥ 3 were blood cell count decreased (33.3%), neutrophil count decreased (33.3%), and diarrhea (13.3%). Conclusions: Surufatinib plus sintilimab, along with AG showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of mPDAC. This trial is ongoing and warrants further exploration in mPDAC. Clinical trial information: NCT05481476 .
Phase II study of the safety and efficacy of discontinuing pegfilgrastim for pancreatic adenocarcinoma treated with FOLFIRINOX.
Authors: Yanagi Masahiro , Terashima Takeshi , Yamashita Tatsuya , Yamamoto Makoto , Kido Hidenori , Nakagawa Hidetoshi , Seki Akihiro , Nio Kouki , Yamashita Taro 
Published: January 2024

663 Background: The original FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) for pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of febrile neutropenia (FN), and pegfilgrastim has been used to reduce the risk. However, it remains unclear how long pegfilgrastim needs to continue. This study evaluated the safety and efficacy of FOLFIRINOX after discontinuing pegfilgrastim in PDAC patients. Methods: This prospective phase II trial included patients with PDAC who received the first three courses of FOLFIRINOX, with primary pegfilgrastim prophylaxis for FN, and did not experience FN. The patients continued on FOLFIRINOX without pegfilgrastim from the fourth course. The primary endpoint was development of FN. The secondary endpoints included relative dose intensity (RDI), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The threshold and expected development of FN were 20% and 7%, respectively, at a one-sided significance level of 0.10 and statistical power of 80%. Based on this hypothesis, we calculated the number of patients needed to be 33. Results: In total, 34 patients (20 male, median age 66 years) were enrolled from August 2017 to September 2021. Twenty-three patients were unresectable, and 11 were borderline resectable. FN developed in one patient. Grade 4 neutropenia was observed in six patients, grade 3 neutropenia in 10 (29.4%), anemia in four (11.8%), diarrhea in two (5.9%), and malaise, lung infection, peripheral sensory neuropathy, colitis, and biliary tract infection in one (2.9%) each. Twenty-two patients required dose reduction, mainly because of neutropenia. Mean RDIs at the sixth course of oxaliplatin, irinotecan, leucovorin, acute infusion of fluorouracil, and continuous infusion of fluorouracil were 77.0%, 88.2%, 81.8%, 84.4%, and 87.6%, respectively. ORR, median PFS, and median OS were 44.1%, 15.8 months, and 25.8 months, respectively. Conclusions: FOLFIRINOX can be continued safely with a low incidence of FN after discontinuing pegfilgrastim in PDAC patients who did not experience FN during the first three courses of FOLFIRINOX, if the drug dose is reduced appropriately for neutropenia from the fourth course. Clinical trial information: UMIN000028055 .
Factors associated with the receipt of surgery in acinar cell carcinoma of the pancreas.
Authors: Chaddha Jasleen Kaur , Bine Christopher Reese , Silberstein Peter T. 
Published: January 2024

668 Background: Acinar cell carcinoma of the pancreas (PACC) accounts for 1-2% of adult pancreatic tumors. Clinically, this malignancy presents as a hypersecretory syndrome as lipase is released into circulation. Median overall survival is 18 to 47 months. Aggressive surgical resection is associated with long-term survival in PACC patients. This appears to be the treatment of choice for most localized pancreatic cancers, however, there are no clear treatment guidelines or standardized protocols for PACC due to its rarity. Further, no significant study has analyzed the factors correlated with receiving this surgery. This study aims to uncover the possible factors associated with the receipt of tumor resection in patients with PACC. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PACC from 2004 to 2019 using the histology code 8550 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 1430 patients with PACC were queried. 600 (41.95%) patients received surgical resection. Surgical patients experienced longer overall survival than non-surgical patients (87.5 months vs. 25.3 months, P < 0.01). Of the surgical patients, wider surgical margins and complete tumor resection were associated with improved survival (P<0.001). Stage I and II disease, well and moderately differentiated disease, and receiving treatment at an academic/research facility were associated with an increased likelihood of receiving surgery (P<0.001). Metastasis at the time of diagnosis was associated with a decreased likelihood of receiving surgery (P<0.001). Income status, race, insurance status, and age did not appear to be significant predicting factors of surgery. Of the initial sample, 219 (15.31%) patients received adjuvant chemotherapy, 8 (0.55%) patients received adjuvant radiation, and 4 (0.28%) patients received both adjuvant chemotherapy and radiation. Adjuvant therapies did not appear to impact the overall survival of PACC patients. Conclusions: This study confirms that tumor resection is associated with increased survival in patients with PACC. Improved survival with surgery is correlated to wider surgical margins and complete tumor resection. It appears that patients with well or moderately differentiated disease, stage I or II disease, and treatment at an academic/research facility are more likely to receive surgery. PACC patients with metastasis to distant sites are less likely to receive surgery. The efficacy of adjuvant therapy remains unclear. Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of PACC treatment.