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

Download Full-text

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.

Download Full-text

Successful treatment of a locally advanced unresectable pancreatic cancer patient with interstitial pneumonitis by conversion surgery following gemcitabine plus nab‑paclitaxel chemotherapy: A case report

Molecular and Clinical Oncology ◽

10.3892/mco.2019.1807 ◽

2019 ◽

Cited By ~ 1

Author(s):

Tetsuo Yokota ◽

Shigetsugu Takano ◽

Hideyuki Yoshitomi ◽

Shingo Kagawa ◽

Katsunori Furukawa ◽

...

Keyword(s):

Pancreatic Cancer ◽

Case Report ◽

Cancer Patient ◽

Successful Treatment ◽

Interstitial Pneumonitis ◽

Locally Advanced ◽

Pancreatic Cancer Patient ◽

Unresectable Pancreatic Cancer ◽

Conversion Surgery

Download Full-text

ASO Author Reflections: Distal Pancreatectomy with Celiac Axis Resection for Locally Advanced Pancreatic Cancer—Patient Selection and Surgical Experience are Key

Annals of Surgical Oncology ◽

10.1245/s10434-018-7033-1 ◽

2018 ◽

Vol 25 (S3) ◽

pp. 828-829

Author(s):

Sjors Klompmaker ◽

Marc G. Besselink

Keyword(s):

Pancreatic Cancer ◽

Cancer Patient ◽

Distal Pancreatectomy ◽

Patient Selection ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Pancreatic Cancer Patient ◽

Celiac Axis ◽

Locally Advanced Pancreatic Cancer ◽

Surgical Experience

Download Full-text

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

Case Medical Research ◽

10.31525/ct1-nct04089150 ◽

2019 ◽

Author(s):

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Stereotactic Radiotherapy ◽

Advanced Disease ◽

Locally Advanced ◽

Locally Advanced Disease

Download Full-text

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.

Download Full-text

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.

Download Full-text

Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case Report

Oncology Research and Treatment ◽

10.1159/000517616 ◽

2021 ◽

pp. 1-7

Author(s):

Janna-Lisa Velthaus ◽

Peter Iglauer ◽

Ronald Simon ◽

Carsten Bokemeyer ◽

Peter Bannas ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patient ◽

Point Mutation ◽

Kinase Inhibitors ◽

Point Mutations ◽

Progression Free Survival ◽

Pancreatic Cancer Patient ◽

Targeted Treatment ◽

Precision Oncology ◽

Disease Stabilization

Introduction: The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking. Case Presentation: This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months. Conclusion: Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.

Download Full-text