The impact of pancreatic cancer resection in the era of effective systemic treatment.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 722-722
Author(s):  
Yaacov Richard Lawrence ◽  
Ofer Margalit ◽  
Galia Jacobson ◽  
Liat Hamer ◽  
Uri Amit ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Phase Iii ◽  
Term Survival ◽  
Systemic Treatments ◽  
Metastatic Setting ◽  
The Impact

722 Background: Surgical resection is the only curative modality in pancreatic cancer, yet the vast majority of patients undergoing surgery succumb of their disease. No randomized studies have been performed to assess the survival impact of the procedure. We hypothesized that in the era of effective systemic treatments, the survival advantage of surgical resection would be lessened. Methods: A meta-analysis of published phase III clinical trials in pancreatic cancer in both the post resection adjuvant setting and the locally advanced metastatic setting, based upon indirect aggregate data. Data was stratified based upon the systemic agents used. Patients from trials arms for which there were not complementary data sets with/without surgical resection were excluded. Primary endpoint was 3 year overall survival (OS). Results: Trials were published between 1997 and 2018. A total of 2722 patients were included in the data analysis, of whom 1645 underwent tumor resection and 814 were metastatic. Median follow-up was 40 months. Analyses were performed of five systemic options with / without tumor resection. Across the trials averaged 3 yr OS was 0%, 0.8%, 0%, and 3.8% for 5FU, gemcitabine, gemcitabine + capecitabine, & FOLFIRINOX respectively; and 18.1%, 30.0%, 37.9%, 42.5%, and 62.5% for the same systemic treatments delivered following surgical resection. Hence the additive impact of surgical resection on absolute 3 yr OS was only 18.1% in the absence of systemic treatment, but 30.0%, 37.1%, 42.5% and 58.8% in the presence of 5FU, gemcitabine, gemcitabine + capecitabine, FOLFIRINOX respectively. Conclusions: Within the limitations of this analysis, it appears that our hypothesis was incorrect, and that the opposite is true. The introduction of effective systemic therapies has greatly increased the impact of pancreatic surgery on long-term survival in pancreatic cancer. Consequently, every effort should be made to bring patients to curative resection.

Circulating cell free tumor DNA detection as a prognostic tool in advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4130-4130
Author(s):  
Gehan Botrus ◽  
Pedro Luiz Serrano Uson Junior ◽  
Puneet Raman ◽  
Adrienne Kaufman ◽  
Heidi E. Kosiorek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Genetic Alterations ◽  
Genomic Alterations ◽  
Systemic Treatments ◽  
Investigation Methods ◽  
The Impact ◽  
Tumor Dna

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.

scholarly journals Pre-operative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER): Clinical Feasibility Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Ulrich Ronellenfitsch ◽  
Christoph W. Michalski ◽  
Patrick Michl ◽  
Sebastian Krug ◽  
Joerg Ukkat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Sample Size ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Phase Iii ◽  
Feasibility Trial ◽  
Arterial Reconstruction ◽  
Visceral Arteries

Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer.Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine–nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching.Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT04136769.

Retrospective review of FOLFIRINOX in local advanced pancreatic cancer: Single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15714-e15714
Author(s):  
Ashish Manne ◽  
Sushanth Reddy ◽  
Martin Heslin ◽  
Rojymon Jacob ◽  
Selwyn M. Vickers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Retrospective Review ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Setting ◽  
Significant Difference ◽  
One Year

e15714 Background: Although combination of fluorouracil, irinotecan, Leucovorin and oxaliplatin [FOLFIRINOX] significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine based on ACCORD trial, the efficacy and toxicities may be different in non-metastatic setting. We reviewed our institution’s experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC). Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with LAPC and receiving between June 2010 and July 2015, with at least one year of follow up from diagnosis, at University of Alabama at Birmingham. Results: Total of 41 patients with ECOG performance scale of 0 or 1, who underwent neoadjuvant chemotherapy with FOLFIRINOX were assessed for clinical and pathological characteristics. Median age was 61 years (range 38-81) with 23 (56.1%) males, 28 (68.3%) Caucasians and 16 (39.0%) underwent surgery (whipple operation) post-neoadjuvant. Median OS (time of diagnosis to last follow up/death) is 83.5 months for whole cohort, survival rates are 94.9% at 1 year, 58.4% at 2 year, and 33.3% at 5 year.Median OS for those who underwent surgical resection following the chemotherapy is 38.6 months; 100% at one year, 85.1% at 2 year, 55.3% at 5 year; while median OS for those who did not undergo surgery is 21.8 months; 91.7% at one year, 41.5% at 2 year, 20.7% at 5 years. Among those who underwent surgery, the median recurrence free survival (time from surgery to relapse/progression) is 19.9 months with liver being common recurrence site (81%). There was no post-operative mortality in 30 days. Grade 3-4 toxicity occurred in 46% ( vomiting (12%), fatigue (28%) and neutropenia (54%), febrile neutropenia (9%)). There is a significant difference between surgery and non-surgery groups (p = 0.012) for improved OS by log-rank test. Conclusions: Neoadjuvant FOLFIRINOX treatment associated with high response rates leading to surgical resection in our cohort. Patients who underwent neoadjuvant chemotherapy followed by resection for LAPC have statistically significant improved OS compared to those who did not.

Effect of time to initiation of adjuvant chemotherapy on survival in resected pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 368-368
Author(s):  
Katelin Anne Mirkin ◽  
Christopher S Hollenbeak ◽  
Joyce Wong
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Surgical Resection ◽  
Survival Benefit ◽  
Term Survival ◽  
Lower Odds ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Time To Initiation ◽  
The Impact

368 Background: Pancreatic cancer carries a grim prognosis. Surgical resection followed by adjuvant chemotherapy is standard of care, but little is known about the temporal relationship of chemotherapy initiation and survival. This study analyzed the impact of time to initiation of adjuvant chemotherapy on survival in patients with resected pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was retrospectively reviewed for patients with clinical stages 1-3 resected pancreatic carcinoma. Time to chemotherapy was stratified at the 12-week post-operative timepoint. Univariate statistics, Kaplan-Meier estimates, and Cox proportional hazard modeling were performed. Results: 5,205 patients who had undergone surgical resection alone, 3,144 patients who had undergone surgical resection and adjuvant chemotherapy initiated at or before 12 weeks, and 906 patients who had undergone surgical resection followed by adjuvant therapy started after 12 weeks were included. Patients who received chemotherapy > 12 weeks tended to be older, have more co-morbidities, receive treatment at academic centers, and undergo whipple procedures. In all pathologic disease stages, adjuvant chemotherapy conferred a significant survival benefit over surgical resection alone (p < 0.0001). However, there was no significant overall survival benefit for patients receiving adjuvant chemotherapy before 12 weeks as compared to after (p = 0.85). When stratified by pathological stage, there was still no significant survival benefit for earlier initiation of chemotherapy (£ vs. > 12 weeks): stage I, p = 0.16, stage II, p = 0.12, stage III, p = 0.38. After controlling for patient, disease, and surgery characteristics, patients who received adjuvant chemotherapy after 12 weeks had a 31% lower odds of mortality at 5 years, while those who initiated it before 12 weeks had a 34% lower odds (p < 0.0001, p < 0.0001 respectively), versus surgery-alone. Conclusions: Earlier initiation of adjuvant chemotherapy does not significantly impact long-term survival in patients with resected pancreatic cancer. However, because adjuvant chemotherapy confers a survival benefit, delayed chemotherapy should be offered when appropriate.

Treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer in the era of FOLFIRINOX and gemcitabine plus nab-paclitaxel: A multi-institutional study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Kamran Idrees ◽  
Alexander A. Parikh ◽  
Lauren McLendon Postlewait ◽  
Sharon M. Weber ◽  
Clifford Suhyun Cho ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Residual Disease ◽  
Locally Advanced ◽  
R0 Resection ◽  
Recurrence Rates ◽  
Borderline Resectable ◽  
Venous Resection ◽  
Term Survival ◽  
Treatment Protocols

451 Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high.

scholarly journals NCOG-07. FEATURES OF EPILEPTOGENIC BRAIN METASTASES AND THEIR TREATMENT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii130-ii130
Author(s):  
Nicholas Musgrave ◽  
Kristin Huntoon ◽  
Joshua Wang ◽  
Douglas Hardesty ◽  
Daniel Prevedello ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Frontal Lobe ◽  
Surgical Resection ◽  
Seizure Control ◽  
Tumor Resection ◽  
Surgical Patients ◽  
Treatment Modalities ◽  
Categorical Variables ◽  
Systemic Treatments ◽  
The Impact

Abstract Patients with brain metastases (BM) may experience seizures at diagnosis or during their treatment. Seizures are associated with decreased overall survival (OS) and poorer quality of life. Therapeutic options may include surgical resection of epileptogenic BM. This study evaluated features of epileptogenic BM and whether surgical resection of these tumors improved seizure control and OS. A retrospective single-center review between 2006-2016 identified 1581 patients with BM. Data analyzed included demographics, primary cancer, systemic treatments, radiographic features of BM, BM treatment modalities, anti-epileptic drugs (AEDs), and seizure characteristics before and after intervention for BM. Chi-squared tests were used for categorical variables. Kaplan-Meier curves and Breslow values were used to assess OS following seizure. Of 1581 patients with BM, 136 (9%) experienced one or more seizures. Seizure was the presenting symptom of BM in 74 (54.4%) patients. Melanoma metastases were most epileptogenic, causing seizure in 38 of 216 (17.6%) patients (p&lt; 0.001). Frontal lobe metastases were most common in patients with seizures (100, 73.5% p=0.033). After median follow-up of 23 months, 48 of 80 (60%) surgical patients were seizure free compared with 27 of 56 (48.2%) non-surgical patients. OS from first seizure was improved in surgical patients versus non-surgical patients (735±133 vs 447±74 days, p=0.043). Frontal lobe tumor resection (n=61) conferred improved survival compared with non-frontal lobe tumor resections (n=19) (698±323 vs 344±132 days, p=0.044). Variables such as demographics, number of BM, tumor histology, and dose of AED were not significantly different between surgical and non-surgical groups. Seizures due to BM cause significant morbidity and mortality. Frontal lobe location and melanoma histology increase seizure risk. Resection of BM was associated with improved seizure control and prolonged OS from the time of first seizure. Further studies should delineate the impact of surgery and determine if a specific constellation of variables warrants prophylactic AEDs.

QS48. The Impact of Age on Surgical Resection Rates and Long-Term Survival in Patients With Locoregional Pancreatic Cancer

2009 ◽  
Vol 151 (2) ◽  
pp. 284
Author(s):  
T.S. Riall ◽  
Y. Kuo ◽  
C.M. Townsend ◽  
J. Freeman ◽  
W. Nealon ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Term Survival ◽  
Long Term Survival ◽  
The Impact

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

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