MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease

4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p<0.001 for non-inferiority), which is consistent with prior results (HR=0.96, 97.5% CI: 0.78-1.18, p<0.001). In the GS group, median OS was 9.9 months (95% CI: 9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p=0.28 for superiority versus the GEM group). On subgroup analysis, GS was associated with a non-statistically significant trend toward better OS compared with GEM among patients with locally advanced disease and those with a PS of 1. Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and 15.9 months (95% CI: 13.0-19.7) in the GS group (HR=0.72, 95% CI: 0.51-1.03) among patients with locally advanced disease, and 6.2 months (95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9) in the GS group (HR=0.62, 95% CI: 0.46-0.83) among patients with a PS of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one of the standard treatments for advanced PC. As for GS therapy, there is room for further investigation.

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FOLFIRINOX in locally advanced or metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.313 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 313-313 ◽

Cited By ~ 4

Author(s):

Jason Edward Faris ◽

Theodore S. Hong ◽

Shaunagh McDermott ◽

Alexander R Guimaraes ◽

Dushyant Sahani ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Advanced Disease ◽

Locally Advanced ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

Clinical Trial Setting ◽

Locally Advanced Disease ◽

Grade 3 ◽

Trial Setting

313 Background: The recently published Phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability with FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX. Methods: 29 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX between July 2010 and April 2011 were used for this analysis. Clinical characteristics, and gradeable toxicities were tabulated, and formal radiographic review performed to determine best overall response rates (ORR). Results: 17 patients received FOLFIRINOX for metastatic disease and 12 patients for locally advanced disease. The median age of patients was 60 (range 39-76). 22/29 patients were men. 18/29 patients had received no prior chemotherapy. There was one patient with PS 2; all others had PS 0 or 1. 8/29 patients had biliary stents. Overall, 11 partial responses (PR) were observed (ORR 38%); 10/11 partial responses were in chemo-naïve patients, who had an ORR of 56%. In the metastatic setting, there were 6 PR, for an ORR of 35%, and 7 patients with stable disease (SD). In the locally advanced setting, there were 5 PR (ORR 42%), and 7 patients with SD. Following treatment with FOLFIRINOX, one patient with locally advanced disease has subsequently undergone R0 resection. The median number of cycles performed was 8 in both the locally advanced and metastatic settings. 12/29 patients required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 10 patients; 7/10 had not received prophylactic growth factor treatment from the start of FOLFIRINOX. 4 patients developed febrile neutropenia, 4 patients developed grade 3/4 thrombocytopenia, and 1 patient developed grade 4 anemia. Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both the metastatic and locally-advanced settings. FOLFIRINOX appears to be associated with manageable, but significant toxicities, with over 40% of patients requiring hospitalization.

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Laparoscopic radical prostatectomy for high risk localized and locally advanced disease

International braz j urol ◽

10.1590/s1677-55382012000300019 ◽

2012 ◽

Vol 38 (3) ◽

pp. 430-431 ◽

Cited By ~ 1

Author(s):

Marcos Tobias-Machado ◽

Eduardo S. Starling ◽

Alexandre Stievano Carlos ◽

Antonio C. L. Pompeo ◽

Pedro Romanelli ◽

...

Keyword(s):

High Risk ◽

Radical Prostatectomy ◽

Advanced Disease ◽

Locally Advanced ◽

Laparoscopic Radical Prostatectomy ◽

Locally Advanced Disease

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Abstract 5106: Circulating MACC1 transcripts are elevated in pancreatic cancer patient blood and correlate to locally advanced disease.

10.1158/1538-7445.am2013-5106 ◽

2013 ◽

Cited By ~ 1

Author(s):

Ulrike S. Stein ◽

Pia Herrmann ◽

Christian Fischer ◽

Peter M. Schlag ◽

Katharina Detjen

Keyword(s):

Pancreatic Cancer ◽

Cancer Patient ◽

Advanced Disease ◽

Locally Advanced ◽

Pancreatic Cancer Patient ◽

Locally Advanced Disease

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Management of High-Risk/Locally Advanced Disease

Prostate Cancer: A Comprehensive Perspective ◽

10.1007/978-1-4471-2864-9_70 ◽

2012 ◽

pp. 831-842

Author(s):

Valérie Fonteyne ◽

Piet Ost ◽

Nicolaas Lumen ◽

Geert M. Villeirs ◽

Gert O. De Meerleer

Keyword(s):

High Risk ◽

Advanced Disease ◽

Locally Advanced ◽

Locally Advanced Disease

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Washington University experience with FOLFIRINOX in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.354 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 354-354 ◽

Cited By ~ 3

Author(s):

Parvin F. Peddi ◽

Benjamin R. Tan ◽

Joel Picus ◽

Steven Sorscher ◽

Rama Suresh ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Advanced Disease ◽

Performance Status ◽

Locally Advanced ◽

Published Data ◽

Ecog Performance Status ◽

Borderline Resectable ◽

Locally Advanced Disease ◽

Grade 3

354 Background: The FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) regimen has recently been shown to be an effective treatment with a significant survival benefit in patients with metastatic pancreatic cancer. Concern for treatment-related toxicity, however, has hampered the adoption of this regimen in clinical practice. A FOLFIRINOX registry was created at our institution to document FOLFIRINOX tolerability and efficacy. Methods: Patients with pancreatic cancer who had received at least one dose of FOLFIRINOX were enrolled in the registry. Demographic information, treatment dosage, adverse events, and efficacy data were obtained. Radiographic response was independently verified by a radiologist. Results: Between January 2010 and August 2011, 29 patients were identified with a median age of 57 (range 37-71). 26 (92.8%) had ECOG performance status of 0-1. FOFIRINOX was given to 16 patients with metastatic disease, 12 with locally advanced disease, and one with borderline resectable disease. 17 (61%) received the first cycle with a dose reduction in either irinotecan and/or 5-FU dosage. UGT1A1*28/*28 homozygous genotype was found in 4 patients who all received dose reduced irinotecan. 13 patients (46%) were started on G-CSF prophylactically with the first cycle while 5 additional patients (18%) had G-CSF support added in later cycles. Main adverse events were neutropenia (grade 3-4 in 14.2%), and abdominal pain and diarrhea (grade 3-4 in 7% and 4% respectively). One incidence of neutropenic fever was observed. Four patients were hospitalized for treatment-related toxicity while three had therapy discontinued due to intolerance. At present, 19 patients have imaging available to determine efficacy: 5 (26%) had partial response, 12 (63%) stable disease, and 2 (11%) had progression of disease as their best response. For patients with locally advanced disease, 11 out of 12 had clinical benefit on FOLFIRINOX. Conclusions: In our practice, FOLFIRINOX was well tolerated and was efficacious, consistent with previously published data. It was frequently used in the setting of locally advanced disease and had similar benefit and tolerability in this setting.

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A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200902111510 ◽

2020 ◽

Vol 15 ◽

Author(s):

Amit Dang ◽

Surendar Chidirala ◽

Prashanth Veeranki ◽

BN Vallish

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Systematic Reviews ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Risk Of Bias ◽

Low Risk ◽

Locally Advanced Pancreatic Cancer ◽

Grade 3 ◽

Critical Overview

Background: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with metaanalysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities, when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had high risk of bias, with only 1/26 SR having low risk of bias. As per AMSTAR2, 25/26 SRs had critically low, and 1/26 SR had low, confidence in the results. The study which scored ‘low’ risk of bias in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=0.649, SEM=0.323, p<0.001. Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

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Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

Urologia Journal ◽

10.1177/03915603211035191 ◽

2021 ◽

pp. 039156032110351

Author(s):

Alessandro Uleri ◽

Rodolfo Hurle ◽

Roberto Contieri ◽

Pietro Diana ◽

Nicolòmaria Buffi ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Advanced Disease ◽

Independent Predictor ◽

Small Sample Size ◽

Statistical Significance ◽

Locally Advanced ◽

Small Sample ◽

Locally Advanced Disease ◽

Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

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Can 3T multiparametric magnetic resonance imaging accurately detect prostate cancer extracapsular extension?

Canadian Urological Association Journal ◽

10.5489/cuaj.245 ◽

2013 ◽

Vol 7 (11-12) ◽

pp. 699 ◽

Cited By ~ 25

Author(s):

Yannick Cerantola ◽

Massimo Valerio ◽

Aida Kawkabani Marchini ◽

Jean-Yves Meuwly ◽

Patrice Jichlinski

Keyword(s):

Magnetic Resonance Imaging ◽

Prostate Cancer ◽

Magnetic Resonance ◽

Advanced Disease ◽

Locally Advanced ◽

Resonance Imaging ◽

Extracapsular Extension ◽

Predictive Values ◽

Locally Advanced Disease ◽

Multiparametric Magnetic Resonance Imaging

Background: Accurate staging is essential to determine the correct management of patients diagnosed with prostate cancer. We assess the accuracy of 3T multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI) in detecting prostate cancer local extension.Methods: We retrospectively reviewed charts from January 2008 to July 2012 from all patients undergoing radical prostatectomy. Patients were only included if 3TemMRI and radical prostatectomywere performed at our institution. Based on the presence of extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging was then evaluated using definitive pathology as a reference.Results: Overall, 177 radical prostatectomies were performed within the timeframe. After applying exclusion criteria, 60 patients were included in the final analysis. The mean patient age was 67 ± 7 (standard deviation) years. Mean prostate-specific antigen value was 12.7 ± 12.7 ng/L. Based on preoperative characteristics, we considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an organ-confined tumour in 46 patients and locally advanced disease in 14 patients. When correlated to final pathology, 3TemMRI specificity, sensitivity, negative and positive predictive values, and accuracy in detecting locally advanced prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively.Interpretation: This study shows that the use of preoperative 3TemMRI can be used to identify organ-confined prostate cancer when locally advanced disease is suspected.

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