Neoadjuvant FOLFIRINOX versus adjuvant gemcitabine in pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4123-4123 ◽  
Author(s):  
Adam R Wolfe ◽  
Eric David Miller ◽  
Laith I. Abushahin ◽  
Jordan Cloyd ◽  
Adrei Manilchuck ◽  
...  

4123 Background: In the metastatic or adjuvant setting for pancreatic cancer, the combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in longer overall survival (OS) compared to gemcitabine therapy. We conducted an institutional study to compare the efficacy of neoadjuvant modified FOLFIRINOX (neo-mFOLFIRINOX) to adjuvant gemcitabine (adj-gem) for pancreatic cancer patients who completed resection. Methods: The study retrospectively enrolled patients from 2006 to 2017 from Ohio State University. While patients who received adjuvant gemcitabine were considered to be resectable upfront, patients who received neo-mFOLFIRINOX were either staged as borderline resectable (BR) or un-resectable (UR) by the institutional tumor board group. 111 patients received adj-gem (average cycles, 5.5) and 52 patients received neo-mFOLFIRINOX (average cycles, 3.5). The survival rates were determined by the Kaplan-Meier method and analyzed using Cox regression and log-rank test. Results: At a median follow up of 21.3 months, the median OS was 35.4 months in the neo-mFOLFIRINOX group and 21.8 months in the adj-gem group (hazard ratio, 0.56, 95% confidence interval (CI), 0.37-0.84 p = 0.005). The OS rate at 3 years was 46% in the neo-mFOLFIRINOX group and 22% in the adjuvant gemcitabine group (p = 0.001). The median disease free survival (DFS) was 18.6 months in the neo-mFOLFIRINOX group and 12.0 months in the adj-gem group (hazard ratio, 0.63, 95% CI, 0.43-0.93 p = 0.022). The DFS rate at 3 years was 17% in the neo-mFOLFIRINOX group and 11% in the adj-gem group (p = 0.02). On surgical pathological specimen review, the neo-mFOLFIRINOX group had statistically (p < 0.05) lower tumor grade, lower rates of perineural invasion and lymphovascular invasion, lower pathological T stage, lower pathological N stage, and lower number of nodes positive compared to the adj-gem group. Frequencies of obtaining R0 resections were higher in the neo-mFOLFIRINOX versus adj-gem groups but not statistically different (51.9% vs 40.4, p = 0.2). The average age and performance status were similar between the two groups. Conclusions: At our institution, BR and UR pancreatic cancer patients who received neo-mFOLFIRINOX and completed resection had longer OS, DFS, and more favorable pathological indicators compared to those patients who had upfront surgery and adjuvant gemcitabine. Randomized clinical trials comparing neoadjuvant versus adjuvant FOLFIRINOX are needed to validate these findings.

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.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 185-185
Author(s):  
M. R. Khawaja ◽  
N. Zyromski ◽  
M. Yu ◽  
H. R. Cardenes ◽  
C. M. Schmidt ◽  
...  

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 298-298
Author(s):  
Kei Saito ◽  
Yousuke Nakai ◽  
Hiroyuki Isayama ◽  
Takashi Sasaki ◽  
Naminatsu Takahara ◽  
...  

298 Background: Smoking is recognized as a risk factor for pancreatic cancer, but its associations with prognosis are not fully elucidated. Smoking was associated with poor outcomes in colon cancer, especially in patients with K-ras mutation (J Clin Oncol. 2013;31:2016-23). Therefore, we conducted this retrospective analysis of the associations of K-ras mutation, smoking and prognosis in patients with pancreatic cancer. Methods: Patients with pancreatic cancer who received surgery or chemotherapy at the University of Tokyo Hospital were retrospectively studied. The prognosis of patients with mutant and wild K-ras were compared. Overall survival was evaluated using Kaplan-Meier methods and compared by long-rank test. Cox regression models were used to calculate hazard ratios (HRs) to evaluate the prognostic factors in patients with pancreatic cancer with mutant K-ras or wild K-ras. Results: Between January 2009 and August 2013, K-ras mutation analysis was evaluated in 187 patients (47 surgical resection and 140 chemotherapy). K-ras mutation was detected in 74.3%. The rates of current-, ex- and never-smokers were 18.2%, 31.6% and 50.3%, respectively. In patients with mutant K-ras, the rate of male gender (46.0% vs. 29.0%), presence of distant metastasis (50.4% vs. 31.3%) and median CA19-9 (374 U/mL vs. 136 U/mL) were significantly higher than that in patients with wild K-ras. The rate of ever smokers (current- and ex-smokers) did not differ significantly (48.2% in mutant K-ras vs. 56.3% in wild K-ras, p=0.403). Median survival time (MST) was 16.7 (95%CI, 11.9-21.8) months in patients with mutant K-ras, compared with 20.3 (95%CI, 15.8-34.6) in patients with wild K-ras (p=0.193). Meanwhile, MST was 22.2 (95%CI, 16.9-27.9) vs. 14.8 (95%CI, 9.1-19.4) months in patients with and without smoking (p=0.024). After adjustment by age, gender, performance status, CA19-9 and treatment, HRs of smoking were 1.96 (95%CI, 1.06-3.68, p=0.032) in patients with mutant K-ras, but the association was not significant in patients with wild-K-ras (HR 1.35 [95%CI, 0.37-5.28], p=0.653). Conclusions: As previously reported in colon cancer, smoking was associated with poor prognosis in pancreatic cancer with K-ras mutation.


2020 ◽  
pp. 1-4
Author(s):  
Anuradha Kunthur ◽  
Anuradha Kunthur ◽  
Eric Siegel ◽  
Rangaswamy Govindarajan

Purpose: Gemcitabine/cisplatin (GCi) is the standard regimen used to treat stage IV urothelial bladder cancers. However, most of the bladder cancer patients are older, with poor performance status and renal dysfunction, and are not eligible for cisplatin-containing regimens. There are no randomized studies comparing gemcitabine/carboplatin (GC) and gemcitabine/cisplatin (GCi). Methods: We identified stage IV bladder cancer patients treated within the Veterans Health Administration (VHA), healthcare system between January 2000 and December 2010 from Veterans Affairs Central Cancer Registry (VACCR). Overall survival (OS) was visualized using Kaplan-Meier curves and tested for the significance of the treatment-arm difference using the log-rank test. Results: There were 196 patients with stage IV bladder cancer, out of which 78 patients were treated with GC and 118 patients treated with GCi. The median OS for all patients was 12.5 months a 95% confidence interval (CI) of 10.0-14.6 months. The median OS for patients treated with GC was 13.4 months (95% CI 9.8-17.5 months), and that of the patients treated with GCi was 11.7 months (95% CI 9.3-14.9 months). Cox regression revealed equal group mortality rates, with GC having a (hazard ratio (HR) of 0.96 (CI 0.72-1.27; P= 0.81)) compared to GCi. Conclusion: Our study is the largest comparing GC and GCi in stage IV urothelial bladder cancer patients. It showed that there is no difference in OS in patients treated with GC and GCi.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 452-452
Author(s):  
Vanessa Xu ◽  
Enid Choi ◽  
Alexandra Hanlon ◽  
William Regine ◽  
Michael David Chuong

452 Background: Higher pre-treatment neutrophil-to-lymphocyte ratio (NLR) and lower platelet-to-lymphocyte ratio (PLR) are independent predictors for worse survival in cancer patients. The effect of chemoradiation (CRT) on NLR and PLR in pancreatic cancer patients who also undergo surgical resection has not been reported. Methods: A retrospective review was performed of pancreatic cancer patients treated at our institution with CRT either prior to or after surgery with curative intent. Overall survival was evaluated using Kaplan-Meier method. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: After excluding patients who did not have surgery, who received palliative radiation doses, or who had incomplete medical records, 81 out of 282 patients remained with median age 62 years (35-86). Of these, 24 (29.6%) were borderline resectable (BR) and received preoperative CRT while 57 (70.4%) received adjuvant CRT. Median total dose and number of fractions were 50.4 Gy (30-59.4) and 28 (5-33), respectively. Median pre-CRT and post-CRT NLR were 2.9 and 7.8, respectively. Median pre-CRT and post-CRT PLR were 211.3 and 457.5, respectively. Most patients had a decrease in NLR (85.2%) and PLR (72.8%) after CRT, with median changes of -4.95 for NLR and -178.33 for PLR. Cox proportional hazards analysis showed a trend towards significance for pre-CRT NLR (p=.08) regarding OS. A significant relationship was found between relapse free survival and both pre-CRT NLR (p=0.02) and PLR (p=0.01). The difference or percent change of neither NLR nor PLR was found to correlate with clinical outcomes. Conclusions: This is the first study to evaluate the effect of CRT on NLR and PLR in resected pancreas cancer patients. Similar to other reports, our data indicate that a significant relationship exists between NLR, PLR, and clinical outcomes. Identification of clinically meaningful NLR and PLR cut-off points for resected pancreatic cancer patients who also receive CRT is needed.


Author(s):  
Li Chen ◽  
Xuantong Zhou ◽  
Xiangyi Kong ◽  
Zhaohui Su ◽  
Xiangyu Wang ◽  
...  

This study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients’ cancer tissues. The chi-square test and Fisher’s exact test were adopted to gauge the associations between breast cancer and clinicopathological variables by p-JNK expression, whereas the univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of p-JNK expression. The Kaplan-Meier plots and the log-rank test were adopted to determine patients’ disease-free survival (DFS) and overall survival (OS). Findings indicated that the p-JNK expression had prognostic significance in univariate and multivariate Cox regression survival analyses. Results of log-rank methods showed that: (1) the mean DFS and OS times in patients with high p-JNK expression were significantly longer than those in patients with low p-JNK expression (χ2 = 5.908, P = 0.015 and χ2 = 6.593, P = 0.010, respectively). p-JNK expression is a significant prognostic factor that can effectively predict the survival in breast cancer patients receiving NACT. Treatment with the JNK agonist anisomycin can induce apoptosis, lead to increased p-JNK expression and decreased p-STAT3 expression. Moreover, the p-JNK expression was inversely correlated with p-STAT3 expression.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 415-415
Author(s):  
Kajal Patel ◽  
Talha Shaikh ◽  
Lora S Wang ◽  
John Parker Hoffman ◽  
Steven J. Cohen ◽  
...  

415 Background: Sarcopenia (Sp) or severe loss of muscle mass is a prognostic factor in cancer patients. We assessed the association between Sp and outcomes in borderline resectable or locally advanced/unresectable pancreatic cancer patients undergoing chemoradiation (CRT). Methods: We reviewed all patients who underwent CRT at an NCI-designated cancer center between 2007-2012. Patients with available pre-treatment imaging were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of < 55.4 cm2/m2 for males and < 38.9 cm2/m2for females. Sp was correlated to treatment toxicity, cause specific survival (CSS), and overall survival (OS). Analysis was performed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Kaplan-Meier method and Cox regression was used for survival analysis. Results: A total of 86 patients met the inclusion criteria with 32 (37%) patients being sarcopenic. The median age was 70 (range 46-91) with a median follow-up of 14 months (3-68). The majority of patients were male (57%), had T3 disease (47%), or were borderline resectable (63%). Twenty nine (33.7%) patients underwent surgery. Sarcopenic patients were less likely to undergo surgery (p = 0.024) versus non-sarcopenic patients. Otherwise there was no difference in clinical or treatment factors. The 12-month actuarial OS for patients with and without Sp was 47.9% and 70.7%, respectively (p = 0.047). The 12-month actuarial CSS for patients with and without Sp was 48% and 76%, respectively (p = 0.007). On multivariable analysis, after controlling for T-stage, N-stage, resectability, gender, pre-treatment CA 19-9, and surgery, Sp was no longer associated with CSS (HR 0.284 95% CI 0.774-2.398) or OS (HR 1.077 95% CI 0.626-1.853). Surgery remained associated with CSS (HR 0.205 95% CI = 0.102-0.412) and OS (HR 0.187 95% CI 0.096-0.363). T-stage also remained associated with both CSS (HR 0.616 95% CI 0.410-0.925) and OS (HR 0.649 95% CI 0.440-0.957). Conclusions: The presence of Sp decreases the likelihood of undergoing curative surgery for pancreatic cancer. This may be another useful tool to identify poor prognosis patients.


2021 ◽  
Vol 38 (2) ◽  
pp. 158-165
Author(s):  
Ilaria Pergolini ◽  
I. Ekin Demir ◽  
Christian Stöss ◽  
Klaus Emmanuel ◽  
Robert Rosenberg ◽  
...  

Background: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. Methods: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. Results: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. Discussion/Conclusions: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.


2005 ◽  
Vol 23 (19) ◽  
pp. 4372-4380 ◽  
Author(s):  
Emmanuelle Boulanger ◽  
Laurence Gérard ◽  
Jean Gabarre ◽  
Jean-Michel Molina ◽  
Christophe Rapp ◽  
...  

PurposePrimary effusion lymphoma (PEL) is a rare high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV infection. The prognosis is poor, with reported median survival time shorter than 6 months. To date, no prognostic factor has been identified in this subset of lymphoma.Patients and MethodsWe describe here a large series of HIV-infected patients with PEL, including 28 cases diagnosed in six centers during an 11-year time period. Prognosis analysis was performed using a Cox proportional hazard regression model. Statistically significant covariates were further analyzed in a forward, stepwise multivariate model.ResultsAfter a median follow-up of 3.8 years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and eight of them remained progression free. The median survival was 6.2 months, and the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved complete remission, with a 1-year disease-free survival rate at 78.6%. In a multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84; 95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were found to be independent predictors for shorter survival.ConclusionBased on a retrospective series of 28 patients, two prognostic factors were identified as being independently associated with impaired clinical outcome in HIV-related PEL—(1) a poor performance status and (2) the absence of HAART before PEL diagnosis.


Author(s):  
Ru-ru Zheng ◽  
Meng-ting Cai ◽  
Li Lan ◽  
Xiao Wan Huang ◽  
Yun Jun Yang ◽  
...  

Objectives: To investigate the prognostic role of Magnetic Resonance Imaging (MRI) based radiomics signature and clinical characteristics for overall survival (OS) and disease-free survival (DFS) in the early-stage cervical cancer. Methods: A total of 207 cervical cancer patients (training cohort: n = 144; validation cohort: n = 63) were enrolled. 792 radiomics features were extracted from T2-weighted (T2W) and diffusion weighted imaging (DWI). 19 clinicopathological parameters were collected from the electronic medical record system. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select significant features to construct prognostic model for OS and DFS. Kaplan-Meier (KM) analysis and log-rank test were applied to identify the association between the radiomics score (Rad-score) and survival time. Nomogram discrimination and calibration were evaluated as well. Associations between radiomics features and clinical parameters were investigated by heatmaps. Results: A radiomics signature derived from joint T2W and DWI images showed better prognostic performance than that from either T2W or DWI image alone. Higher Rad-score was associated with worse OS (p < 0.05) and DFS (p < 0.05) in the training and validation set. The joint models outperformed both radiomics model and clinicopathological model alone for 3 year OS and DFS estimation. The calibration curves reached an agreement. Heatmap analysis demonstrated significant associations between radiomics features and clinical characteristics. Conclusions: The MRI-based radiomics nomogram showed a good performance on survival prediction for the OS and DFS in the early-stage cervical cancer. The prediction of the prognostic models could be improved by combining with clinical characteristics, suggesting its potential for clinical application. Advances in knowledge: This is the first study to build the radiomics-derived models based on T2W and DWI images for the prediction of survival outcomes on the early stage cervical cancer patients, and further construct a combined risk scoring system incorporating the clinical features.


Sign in / Sign up

Export Citation Format

Share Document