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  • 1
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    Gender Differences in Patients with Metastatic Pancreatic Cancer Who Received FOLFIRINOX
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 2 ( 2021-01-30), p. 83-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 2 ( 2021-01-30), p. 83-
    Abstract: Background: The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effective chemotherapeutic regimen for unresectable pancreatic cancer. Previous studies have reported that female gender may be a predictor of a better response to FOLFIRINOX. This study was aimed at investigating the clinical outcomes and dose modification patterns of FOLFIRINOX by gender. Methods: Patients with metastatic pancreatic cancer (MPC) who began FOLFIRINOX as the first-line therapy at Seoul National University Bundang Hospital between 2013 and 2018 were enrolled. The patients received at least four chemotherapy cycles. Local regression and a linear mixed model were used to analyze dose modification patterns by gender. Results: Ninety-seven patients with MPC (54 men; 43 women) were enrolled. In the first FOLFIRINOX cycle, there were significant differences in age and body surface area between the genders (58.8 (men) and 64.9 years (women), p = 0.005; 1.7 (men) and 1.6 m2 (women), p 〈 0.001, respectively). The median progression-free survival (PFS) and overall survival (OS) were 10.8 and 18.0 months, respectively. There was a trend of longer PFS (10.3 (men) and 11.9 months (women), p = 0.153) and a significantly longer OS (17.9 (men) and 25.9 months (women), p = 0.019) in female patients. During the first year of FOLFIRINOX treatment, there was a significant difference of the age-corrected dose reduction pattern by gender (a mean of 95.6% dose at the initial cycle and −0.35% of dose reduction per week in men versus a mean of 90.7% dose at the initial cycle and −0.53% of dose reduction per week in women, p-value of the slope: 〈 0.001). There was no difference in the adverse event rates between the genders. Conclusions: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Gender differences should be considered during FOLFIRINOX treatment.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11020083
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 2
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    Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis
    Elsevier BV ; 2023
    In:  European Journal of Surgical Oncology Vol. 49, No. 2 ( 2023-02), p. 306-315
    Details
    In: European Journal of Surgical Oncology, Elsevier BV, Vol. 49, No. 2 ( 2023-02), p. 306-315
    Type of Medium: Online Resource
    ISSN: 0748-7983
    URL: Article
    DOI: 10.1016/j.ejso.2022.10.001
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2002481-2
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  • 3
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    NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-12-03)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-12-03)
    Abstract: According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into “highly actionable” and “modifies options” based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1 , BRCA2 , or ATM ( n  = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-24732-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 4
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    Prediction model using clinical factors for radiation exposure during endoscopic retrograde cholangiopancreatography
    Wiley ; 2022
    In:  Journal of Gastroenterology and Hepatology Vol. 37, No. 7 ( 2022-07), p. 1342-1348
    Details
    In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 37, No. 7 ( 2022-07), p. 1342-1348
    Abstract: Endoscopic retrograde cholangiopancreatography (ERCP) requires radiation. This study aimed to assess the clinical factors influencing radiation exposure and devise a scoring model for predicting high‐dose radiation exposure. Methods Endoscopic retrograde cholangiopancreatography cases recorded between 2016 and 2019 in a single tertiary teaching hospital were retrospectively reviewed. A scoring model was created by bootstrap method in a derivation cohort (2016–2018) and was assessed in a validation cohort (2019). Results Out of 4223 ERCPs, 2983 and 1240 cases were included in the derivation and validation cohorts, respectively. In the derivation cohort, 746 cases (top 25%) comprised the high‐dose exposure group, and 2237 cases (bottom 75%) comprised the low‐dose exposure group. Nine clinical parameters associated with high‐dose exposure were male, pancreatic sphincterotomy, balloon dilatation, biliary or pancreatic drainage, procedures with contrast dye, endoscopist, in‐hospital ERCP, and spot image. Stone removal was included by bootstrap analysis. As presented in a nomogram, the weight score of each variable was as follows: male, 1; pancreatic sphincterotomy, 3; balloon dilatation, 7; stone removal, 3; biliary or pancreatic drainage, 5; procedures with contrast dye, 1; endoscopist B, 4; endoscopist C, 5; in‐hospital procedure, 3; and spot image, 3. A total score ≥ 15 suggested a high‐dose radiation exposure. The sensitivity and specificity of the model for high‐dose exposure were 0.562 and 0.813, respectively. In the validation cohort, the model showed reasonable predictability. Conclusions Various factors were associated with radiation exposure. The simple scoring system in this study could guide endoscopists in predicting the risk of high‐dose radiation exposure.
    Type of Medium: Online Resource
    ISSN: 0815-9319 , 1440-1746
    URL: Issue
    URL: Article
    DOI: 10.1111/jgh.v37.7
    DOI: 10.1111/jgh.15844
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2006782-3
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  • 5
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    Comprehensive genomic analysis for homologous recombination deficiency in pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e15168-e15168
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e15168-e15168
    Abstract: e15168 Background: Although homologous recombination deficiency (HRD) has been heavily studied in oncology, HRD in pancreatic cancer remains poorly understood beyond germline alterations in BRCA1, BRCA2 and PALB2. Methods: We performed whole exome sequencing (WES) on 205 patients with pancreatic cancer. Germline and somatic mutations in HRD genes were evaluated: (1) canonical HRD mutation ( BRCA1, BRCA2 and PALB2); and (2) non-canonical HRD mutation ( ATM, ATR, ATRX, CHEK2, BAP1, BARD1, BLM, BRIP1, NBN, RAD51 genes, RAD54 genes, FANC genes and ERCC genes). In addition, signature-based HRD classifiers were also applied: (1) the genomic instability score (GIS); (2) substitution base signature 3 (SBS3); and (3) small insertion and deletions 83B (ID83B). The frequency of HRD mutations and signatures-based HRD in pancreatic cancer were evaluated and their clinical utility were assessed by confirming the association with the response to platinum-containing chemotherapy. Results: Among the 205 patients, 41 patients (20.0%) were identified to harbor HRD mutations. Germline and somatic HRD mutations were identified in 19 (9.3%) and 24 (11.7%) patients, respectively. Mutations in canonical genes and non-canonical genes were found in 12 (5.9%) and 37 (18.1%) patients, respectively. Using signature-based HRD classifier, additional 45 (22.0%) patients were determined to be HRD. Among patients who received first-line FOLFIRINOX ( N = 113), canonical HRD mutation and signature-based HRD group showed higher response rate than non-canonical HRD and non-HRD group (75.0% and 57.1% vs. 31.3% and 33.3%, respectively). In the survival analysis of patients treated with FOLFIRINOX, canonical HRD and signature-based HRD group tended to have better overall survival than non-HRD group. Conclusions: Comprehensive genomic analysis could identify a significant number of HRD pancreatic cancer beyond germline BRCA1,2 and PALB2 mutation, and it would be helpful to choose the appropriate chemotherapy regimen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e15168
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-12-14)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-14)
    Abstract: FOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC. Methods To this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival. Results Fifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3–28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4–30.3) and 16.7 months (95% CI: 13.0–20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042–3.930, p = 0.037). Conclusion Our findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.1050070
    DOI: 10.3389/fonc.2022.1050070.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 7
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    Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis
    SAGE Publications ; 2023
    In:  Therapeutic Advances in Medical Oncology Vol. 15 ( 2023-01)
    Details
    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 15 ( 2023-01)
    Abstract: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for ‘planned’ dose modification, and the ‘actually administered’ dose varied more. Objective: To map a 10-year trend for ‘planned’ and ‘actual’ doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly ‘planned’ versus ‘actual’ dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program ( www.RDI-map.com ). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of ‘planned’ dose modification in FOLFIRINOX ranging 75–100% oxaliplatin, 75–100% irinotecan, 0–100% 5-fluorouracil (5-FU) bolus, and 75–133% 5-FU continuous injection. The ‘actual’ dose further decreased to 54–96%, 61–88%, 0–92%, and 63–98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5–33.9%) and 33.8% (95% CI: 30.3–37.3%), respectively ( p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0–16.0%) and 5.5% (95% CI: 0–8.9%), respectively ( p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the ‘planned’ and ‘actual’ doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    URL: Article
    DOI: 10.1177/17588359231175441
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 8
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    Response monitoring with ctDNA in metastatic pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e16284-e16284
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e16284-e16284
    Abstract: e16284 Background: Various studies about clinical usefulness of serial monitoring with liquid biopsy are being conducted actively in many types of cancer. However, there is not much in pancreatic cancer. We explored whether serial ctDNA monitoring in metastatic pancreatic cancer (MPC) can be beneficial for evaluating treatment response and predicting prognosis. Methods: A total of 51 MPC patients were prospectively enrolled. Blood samples were collected at every response evaluation until progression of disease (PD) or 5 th evaluation. Quantitative ctDNA were measured by droplet digital polymerase chain reaction using KRAS G12/G13 screening multiplex Kit (Bio-Rad) and reported as variant allele fraction (VAF). Percent change of ctDNA VAF (DctDNA(%) = (current VAF - previous VAF)/previous VAF*100) were correlated to radiographic responses by RECIST 1.1. Furthermore, Progression free survival (PFS) and overall survival (OS) were analyzed by DctDNA. Results: Among the 51 enrolled patients, baseline ctDNA were detected in 35 patients. During a median follow-up of 9.4 months, PD by radiographic response was observed in 24 patients. As expected, PD group showed higher DctDNA compared with non-PD group (p 〈 0.001). DctDNA for PD yielded Area Under Curve of 0.914 (p 〈 0.001) with 83.3% sensitivity at 90% specificity. Patients who showed early ctDNA clearance (undetectable level at first response evaluation) had longer PFS (8.1 m vs 4.7 m; HR 0.46; 95% CI 0.20 to 1.03; p=0.059) and OS (not reached vs 8.0 m; HR 0.20; 95% CI 0.06 to 0.74; p=0.009) than those who did not. In multivariable analysis, early ctDNA clearance was still associated with significantly longer PFS (HR 0.27; 95% CI 0.08 to 0.92, p=0.036) and OS (HR 0.08; 95% CI 0.02 to 0.54, p=0.007). Conclusions: Serial monitoring with ctDNA in MPC has considerable clinical potential in monitoring treatment response and predicting prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e16284
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 9
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    Analysis of survival outcomes in patients with pancreatic cancer who underwent upfront surgery.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 679-679
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 679-679
    Abstract: 679 Background: During the last decade, the survival outcomes of patients with pancreatic cancer (PC) have improved. We aimed to establish a model of which clinical factors contributed to improved survival in PC patients who underwent upfront surgery. Methods: Public data from the KOREA Health Insurance Review and Assessment (HIRA) database were collected. Medical records in a single tertiary center were also retrospectively reviewed between 2013 and 2018. Enrolled patients were those who underwent curative upfront surgery for PC. Results: A total of 12,146 patients in HIRA data and 267 patients in single-center data were collected. The overall survival (OS) rates have improved over the years in HIRA data and were reproduced in single-center data. Dividing the patients of single-center data into two periods (2013-2015 [119] vs. 2016-2018 [148] ) based on the results of public data, the median OS was significantly different between the two periods (20.9 vs 32.1 months, p=0.003). According to multivariate regression analyses, young age (≤70 years), R0 resection, negative nodal involvement, adjuvant treatment, and palliative chemotherapy with FOLFIRINOX or gemcitabine plus nab-paclitaxel (GNP) were significantly associated with better OS. A survival prediction model was created using the beta-coefficients in cox regression analysis of the above five significant factors, and the c-index by bootstrap validation (resampling, 1500) was 0.7088. The weight scores were as follows: Age 〉 70 years, 1; R1 resection, 1; pN1, 1; pN2 stage, 3; no adjuvant treatment, 2; palliative chemotherapy with FOLFIRINOX and/or GNP, 3; without FOLFIRINOX or GNP, 5; no palliative chemotherapy, 5. Conclusions: Regarding the survival trends in patients with resected PC, we presented the recent improvement in survival over the years and suggested several clinical factors that contributed to it by different weights. Further studies are necessary for validation.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.679
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 10
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    Efficacy improvement in searching MEDLINE database using a novel PubMed visual analytic system: EEEvis
    Public Library of Science (PLoS) ; 2023
    In:  PLOS ONE Vol. 18, No. 2 ( 2023-2-9), p. e0281422-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2023-2-9), p. e0281422-
    Abstract: PubMed is the most extensively used database and search engine in the biomedical and healthcare fields. However, users could experience several difficulties in acquiring their target papers facing massive numbers of search results, especially in their unfamiliar fields. Therefore, we developed a novel user interface for PubMed and conducted three steps of study: step A, a preliminary user survey with 76 medical experts regarding the current usability for the biomedical literature search task at PubMed; step B is implementing EEEvis, a novel interactive visual analytic system for the search task; step C, a randomized user study comparing PubMed and EEEvis. First, we conducted a Google survey of 76 medical experts regarding the unmet needs of PubMed and the user requirements for a novel search interface. According to the data of preliminary Google survey, we implemented a novel interactive visual analytic system for biomedical literature search. This EEEvis provides enhanced literature data analysis functions including (1) an overview of the bibliographic features including publication date, citation count, and impact factors, (2) an overview of the co-authorship network, and (3) interactive sorting, filtering, and highlighting. In the randomized user study of 24 medical experts, the search speed of EEEvis was not inferior to PubMed in the time to reach the first article (median difference 3 sec, 95% CI -2.1 to 8.5, P = 0.535) nor in the search completion time (median difference 8 sec, 95% CI -4.7 to 19.1, P = 0.771). However, 22 participants (91.7%) responded that they are willing to use EEEvis as their first choice for a biomedical literature search task, and 21 participants (87.5%) answered the bibliographic sorting and filtering functionalities of EEEvis as a major advantage. EEEvis could be a supplementary interface for PubMed that can enhance the user experience in the search for biomedical literature.
    Type of Medium: Online Resource
    ISSN: 1932-6203
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    DOI: 10.1371/journal.pone.0281422
    DOI: 10.1371/journal.pone.0281422.g001
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    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2023
    detail.hit.zdb_id: 2267670-3
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