scholarly journals Competing Risk Analysis of Outcomes of Unresectable Pancreatic Cancer Patients Undergoing Definitive Radiotherapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Yi-Lun Chen ◽  
Chiao-Ling Tsai ◽  
Jason Chia-Hsien Cheng ◽  
Chun-Wei Wang ◽  
Shih-Hung Yang ◽  
...  

PurposeWe investigated potential factors, including clinicopathological features, treatment modalities, neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen (CA) 19-9 level, tumor responses correlating with overall survival (OS), local progression (LP), and distant metastases (DMs), in patients with locally advanced pancreatic cancer (LAPC) who received definitive radiotherapy (RT).MethodsWe retrospectively analyzed demographic characteristics; biologically effective doses (BED10, calculated with an α/β of 10) of RT; and clinical outcomes of 57 unresectable LAPC (all pancreatic adenocarcinoma) patients receiving definitive RT using modern techniques with and without systemic therapy between January 2009 and March 2019 at our institution. We used Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate the radiographic tumor response after RT. The association between prognostic factors and OS was assessed using the Kaplan–Meier analysis and a Cox regression model, whereas baseline characteristics and treatment details were collected for competing-risk regression of the association with LP and DM using the Fine–Gray model.ResultsA median BED10 of 67.1 Gy resulted in a disease control rate of 87.7%, and the median OS was 11.8 months after a median follow-up of 32.1 months. The 1-year OS rate, cumulative incidences of LP, and DM were 49.2%, 38.5%, and 62.9%, respectively. Multivariate analyses showed that pre-RT NLR ≥3.5 (adjusted hazard ratio [HR] = 8.245, p < 0.001), CA19-9 reduction rate ≥50% (adjusted HR = 0.261, p = 0.005), RT without concurrent chemoradiotherapy (adjusted HR = 5.903, p = 0.004), and administration of chemotherapy after RT (adjusted HR = 0.207, p = 0.03) were independent prognostic factors for OS. Positive lymph nodal metastases (adjusted subdistribution HR [sHR] = 3.712, p = 0.003) and higher tumor reduction after RT (adjusted sHR = 0.922, p < 0.001) were significant prognostic factors for LP, whereas BED10 ≥ 67.1 Gy (adjusted sHR = 0.297, p = 0.002), CA19-9 reduction rate ≥50% (adjusted sHR = 0.334, p = 0.023), and RT alone (adjusted sHR = 2.633, p = 0.047) were significant prognostic factors for DM.ConclusionOur results indicate that pre-RT NLR and post-RT monitoring of CA19-9 and tumor size reduction can help identify whether patients belong to the good or poor prognostic group of LAPC. The incorporation of new systemic treatments during and after a higher BED10 RT dose for LAPC patients is warranted.

2019 ◽  
Vol 36 (05) ◽  
pp. 386-391
Author(s):  
Gregory T. Frey ◽  
Carlos A. Padula ◽  
John A. Stauffer ◽  
Beau B. Toskich

AbstractEfforts to improve mortality associated with locally advanced pancreatic cancer (LAPC) have shown minimal gains despite advances in surgical technique, systemic treatments, and radiation therapy. Locoregional therapy with ablation has not been routinely adopted due to the high risk of complications associated with thermal destruction of the pancreas. Irreversible electroporation (IRE) is an emerging, nonthermal, ablative technology that has demonstrated the ability to generate controlled ablation of LAPC while preserving pancreatic parenchymal integrity. IRE may be performed percutaneously or via laparotomy and will commonly involve multidisciplinary treatment teams. This article will describe the technical aspects of how multidisciplinary IRE is performed during laparotomy at a single tertiary care institution.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 326-326
Author(s):  
Byung Min Lee ◽  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.


2018 ◽  
pp. 1-4 ◽  
Author(s):  
Yu-Fei Fan ◽  
Yuan Qin ◽  
Ding-Gang Li ◽  
David Kerr

Purpose Hyperthermia is a mechanistically plausible partner with chemotherapy, although many of the underlying molecular mechanisms of this combination treatment are not yet properly understood. Preclinical studies suggest that there is potential synergy with gemcitabine and that provides the basis for retrospective analysis of a clinical series combining these treatment modalities for patients with advanced pancreatic cancer. Patients and Methods Twenty-nine chemotherapy-naive patients with locally advanced or metastatic pancreatic carcinoma with malignant ascites were treated with intraperitoneal cisplatin 30 mg/m2 and gemcitabine 800 to 1,000 mg/m2 intravenously on days 1, 8, and 15 every 28 days until tumor progression. Patients also received regional hyperthermia treatment (41 to 42°C) on the upper abdomen two times per week from days 1 to 21. Results In all, 83 cycles of chemotherapy were administered and were generally well tolerated. No patients had a complete response, 13 had a partial response, seven had stable disease, and 9 had progressive disease. Mean progression-free survival and overall survival were 119 ± 61days and 195 ± 98 days, respectively. Conclusion This study provides preliminary evidence that the treatment approach of combined systemic and intraperitoneal chemotherapy plus hyperthermia is well tolerated, is active, and has an acceptable survival profile for patients with stage IV pancreatic cancer and ascites.


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