Tu1465 – The Effect of Neoadjuvant Therapy on Overall Survival in Resected Pancreatic Cancer

2019 ◽  
Vol 156 (6) ◽  
pp. S-1490-S-1491
Author(s):  
William Lancaster ◽  
David Adams ◽  
Katherine A. Morgan
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy

scholarly journals Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma—Who Will Benefit from a Secondary Resection?

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 77
Author(s):  
Nathalie Rosumeck ◽  
Lea Timmermann ◽  
Fritz Klein ◽  
Marcus Bahra ◽  
Sebastian Stintzig ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Induction Therapy ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Comprehensive Cancer Center ◽  
Secondary Resection ◽  
Number Of Patients

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

Predictors of recurrence and implications for overall survival in borderline resectable pancreatic cancer patients treated with total neoadjuvant therapy: A retrospective cohort study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16781-e16781
Author(s):  
Jori Lee Kaplan ◽  
Benjamin Powers ◽  
Wenyi Fan ◽  
Michael J. Schell ◽  
Barbara Centeno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Treatment Effect ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Borderline Resectable ◽  
Risk Of Recurrence ◽  
Predictors Of Recurrence ◽  
Increased Risk

e16781 Background: Borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) is a subset of pancreatic cancer with unique prognostic implications. A multimodality, neoadjuvant therapy (NAT) approach has known benefits such as downstaging tumors, reducing the risk of a positive margin, and treating micrometastatic disease. Patient selection and therapy sequencing are controversial owing to the high risk of recurrence. Therefore, we aimed to identify factors predicting recurrence and overall survival (OS) in BR PDAC patients undergoing NAT. Methods: We identified BR PDAC patients treated with NAT followed by surgery at Moffitt Cancer Center between 2008-2015. We evaluated clinical, demographic, and perioperative factors to identify predictors of recurrence and OS. Statistical analyses were performed with univariate and multivariable Cox regression models. Results: 117 patients with BR PDAC who received NAT were evaluated; 53 (45%) were female and 64 (55%) were male. Of those, 91 (78%) received gemcitabine/xeloda/taxotere and the remainder received other gemcitabine or 5FU regimens. 107 (91%) patients received neoadjuvant radiation, mainly 5-day dose painted SBRT. Post- NAT CA 19-9 normalized in 39 (33%) and 11 (9%) additional patients normalized after surgery. Pathologic treatment effect was appreciated in 85 (73%) patients and pathologic complete response (pCR) was seen in 18 (15%). 95 (81%) patients initiated adjuvant therapy. In multivariable analysis, the strongest predictor of recurrence was higher log(10) post-operative CA 19-9 (HR 2.29; 95% CI, 1.40-3.75). Time from initiation of NAT to surgery ≥ 5 months also predicted recurrence (HR 2.08; 95% CI, 1.16-3.72). In OS analysis, 71 patients had recurrence after multimodality treatment; 61 (86%) died and 10 (14%) were alive. In multivariable analysis, the strongest predictors of prolonged OS from recurrence were female gender (HR 0.47; 95% CI, 0.26-0.84) and presence of a treatment effect (HR 0.37; 95% CI, 0.15-0.93). Conclusions: We observed treatment effects and pCR comparable to other institutions, supporting a multimodality approach to BR PDAC. Higher post-operative CA 19-9 and time to surgery ≥ 5 months from initiation of NAT were associated with an increased risk of recurrence. These data suggest that timely receipt of surgery after completion of NAT may impact recurrence and OS in BR PDAC.

ABO blood group and survival in pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 380-380
Author(s):  
Christina Wai ◽  
Karthik Devarajan ◽  
John Parker Hoffman
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Blood Group ◽  
Blood Groups ◽  
Prognostic Indicators ◽  
Rank Test ◽  
Cancer Center ◽  
Abo Blood Group ◽  
Survival Difference

380 Background: ABO blood group has been shown to be a risk factor in many gastrointestinal cancers. Recent studies have shown that patients with non-O blood groups have a higher risk of pancreatic adenocarcinoma compared to those with blood group O. Based on this finding, we were interested in seeing if a particular ABO blood group would have an impact on survival outcomes in pancreatic cancer. Methods: A retrospective chart review of 236 pancreatic patients who underwent surgical resection at a major cancer center from January 1998 to July 2011 was performed. Data were collected for demographics, ABO blood group, Rh factor, CA 19-9 level, use of neoadjuvant therapy, pathological stage, surgical margins and peritoneal washings. Overall survival (OS) was compared amongst the different blood groups. Results: There were 118 male and 118 female patients. The median age at diagnosis was 68. Of the 236 patients, 80 (33.9%) were blood group O, 108 (45.8%) were blood group A, 32 (13.6%) were blood group B and 16 (6.8%) were blood group AB. For all patients, there was no statistically significant association between ABO blood group and OS (log rank test p = 0.7). Furthermore, no survival difference was seen between O and non-O blood groups when the data was stratified by stage and neoadjuvant therapy. Conclusions: Like other GI malignancies, ABO groups have been shown to be linked to the risk of pancreatic cancer. The mechanism by which this occurs is not completely clear. In our analysis of ABO blood groups, they were not shown to be prognostic indicators. There does not appear to be a difference in overall survival between patients with O blood group and those with non-O blood groups.

Impact of G-CSF during neoadjuvant therapy on outcomes of operable pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4126-4126
Author(s):  
Pranav Murthy ◽  
Mazen S Zenati ◽  
Samer S. AlMasri ◽  
Aatur D. Singhi ◽  
Annissa DeSilva ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Tumor Staging ◽  
Neutrophil Extracellular Trap ◽  
Oncologic Outcomes ◽  
Ductal Adenocarcinoma ◽  
Common Side Effect ◽  
Interleukin 17 ◽  
The Impact

4126 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. Neutropenia is a common side effect of cytotoxic chemotherapy, managed with administration of recombinant granulocyte-colony stimulating factor (G-CSF, Filgrastim). The interleukin 17 – G-CSF – neutrophil extracellular trap (NET) axis promotes oncogenesis and progression of PDAC, inhibiting adaptive immunity. We evaluated the impact of G-CSF administration during neoadjuvant therapy (NAT) on oncologic outcomes in patients with operable pancreatic cancer. Methods: A retrospective review of all patients with localized PDAC treated with NAT prior to pancreatic resection between 2014 – 2020 was completed at a single institution. G-CSF administration, type, and dose were collected from inpatient and outpatient medical records. Results: Of 351 patients treated, 138 (39%) received G-CSF during NAT with a median follow-up of 45.8 months. Patients who received G-CSF were younger (64.0 vs 66.7, p = 0.008), had lower BMI (26.5 vs 27.9, p = 0.021), and were more likely to receive 5-FU based chemotherapy (42% vs 28.2%, p < 0.0001), NAT dose reduction (40.6% vs 25.4%, p = 0.003), or experience febrile neutropenia (8.7% vs 3.3%, p = 0.029). No differences were observed in baseline or pathologic tumor staging. In patients who received G-CSF, 130 (94%) received Pegfilgrastim with a median cumulative dose of 12 mg (IQR 6-12). Patients who received G-CSF were more likely to have an elevated post-NAT neutrophil to lymphocyte ratio (45% vs 29.6%, p = 0.004) and systemic immune-inflammation index (39.5% vs 29.6%, p = 0.061). Receiving G-CSF was an independent predictor of perineural invasion (HR 2.4, 95 CI [1.08, 5.5], p = 0.031) and margin positive resection (HR 1.69, 95 CI [1.01, 2.83], p = 0.043). Patients who received G-CSF had decreased overall survival compared to patients who did not receive G-CSF (median OS: 29.2 vs 38.7 months, p = 0.0001). Receiving G-CSF during NAT was an independent negative predictor of progression free (HR 1.38, 95 CI [1.04, 1.83], p = 0.022) and overall survival (HR 2.02, 95 CI [1.45, 2.79], p < 0.0001). In a subset of patients with available pre- and post-NAT serum specimens (n = 28), G-CSF administration resulted in an increased number of citrullinated histone H3 complexes following NAT (+1378±1502 vs -300.7±1147 pg/ml, p = 0.007), indicative of enhanced peripheral NET formation. Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration is associated with worse oncologic outcomes and should be administered with caution. Prospective randomized as well as confirmatory clinical studies are in order.

Effect of Perioperative Transfusions on Overall Survival among Patients with Localized Pancreatic Cancer Receiving Neoadjuvant Therapy

2016 ◽  
Vol 223 (4) ◽  
pp. e135
Author(s):  
Grace Blitzer ◽  
Moha Aldakkak ◽  
Kathleen K. Christians ◽  
Ben George ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy

260 T cell infiltrating repertoire diversity is associated with enhanced survival following neoadjuvant therapy in patients with resectable pancreatic cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A284-A284
Author(s):  
Pranav Murthy ◽  
Pragosh Saini ◽  
Kira Russell ◽  
Wenjing Pan ◽  
Daniel Weber ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Dendritic Cells ◽  
T Cell ◽  
Neoadjuvant Therapy ◽  
Cell Receptor ◽  
Tumour Microenvironment ◽  
Resectable Pancreatic Cancer ◽  
Histopathologic Response ◽  
Autophagy Inhibition

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, characterized by a desmoplastic stromal reaction and an immunosuppressive tumor microenvironment (TME)1. The metabolic stress within the PDAC TME promotes autophagy, a form of programmed cell survival associated with chemotherapeutic resistance and immune evasion.2, 3MethodsWe conducted a randomized phase II study of preoperative gemcitabine and nab-paclitaxel with or without autophagy inhibition with oral hydroxychloroquine (HCQ) in patients with resectable PDAC. Autophagy inhibition increased Evans Grade histopathologic response and immune infiltrate.4Utilizing multiplex immunohistochemistry and dimer avoidance multiplex PCR-NGS5 in a subset of RNA extracted FFPE tumor specimens, we evaluated the adaptive immune response and immune correlates of response.ResultsPatients receiving HCQ had a greater CD4/CD8 immune infiltration (p = 0.033). Independent of treatment, a higher tumor immune infiltration score,6 was associated with improved overall survival (p = 0.035). Bulk tumor immunosequencing revealed a clonally expanded T cell receptor (TCR) Vβ (115±84 unique CDR3s (uCDR3s) of 3.3 × 104±2.4 total CDR3s) and B cell receptor (BCR) IgH (9.8 × 104±5.2 uCDR3s of 1.4 × 105±0.76 total CDR3s) repertoire compared to a paucity of TCR Vδ clones (2±1 uCDR3s of 43±60 total CDR3s). Patients with a higher than median TCR Vβ Diversity 50 Index (D50, proportion of uCDR3s that make up 50% of the total CDR3s) had significantly higher tumor CD4 (p = 0.003) and CD8 (p = 0.031) counts. Patients with a higher than median TRC Vβ D50 also had a reduced lymph node ratio (p = 0.039) and greater overall survival (p = 0.037, figure 1). Conversely, patients with a higher than median BCR IgH D50 had worse overall survival (p = 0.0241). Given the dichotomy of the TCR and BCR repertoire diversity and association with clinical outcome, we further analyzed the individual ratio of TRC Vβ:BCR IgH CDR3s and found that patients with a higher than median TRC Vβ:BCR IgH ratio had a greater Evan’s Grade histopathologic response (p = 0.069).Abstract 260 Figure 1Following neoadjuvant therapy, patients with resectable pancreatic cancer with a higher than median intratumoral TCR Vβ Diversity 50 (n=9, 4.624 HR; 95 CI [0.971, 21.83]) have greater overall survival compared to patients with lower than median intratumoral TCR Vβ Diversity 50 (n=10, 0.2163 HR; 95 CI [0.458, 1.021]). Representative tree maps of high and low TRC Vβ D50, where each rounded rectangle represents a unique CDR3, with the size of the rectangle corresponding to the relative frequency of the CDR3 clones across the entire repertoireConclusionsPDAC TIL repertoire with high TCR Vβ diversity is associated with decreased positive lymph node ratio and greater overall survival following neoadjuvant therapy. The divergent outcomes associated with increased intratumoral TCR and BCR diversity suggest a host response that may favor opposing T and B cell lymphocytic expansion. Regulation of this relationship may be explained by tumor MHC class I expression[3] or the presence of CD141+ cross presenting dendritic cells7, 8 and tertiary lymphoid structures,9 currently under investigation. Examination of repertoire modulating therapies is warranted.Trial RegistrationThis trial (NCT01978184) was approved by the protocol review committee and IRB 13–074 at the University of Pittsburgh and performed in full accordance with the guidelines for good clinical practice and the Declaration of Helsinki. Written informed consent was obtained from all patients prior to any protocol treatment.ReferencesHo WJ, Jaffee EM, Zheng L. The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities. Nat Rev Clin Oncol 2020;17(9):527–540.Boone BA, Zeh HJ, 3rd, Bahary N. Autophagy inhibition in pancreatic adenocarcinoma. Clin Colorectal Cancer 2018;17(1):25–31.Yamamoto K, Venida A, Yano J, et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature 2020;581(7806):100–105.Zeh HJ, Bahary N, Boone BA, et al. A Randomized phase ii preoperative study of autophagy inhibition with high-dose hydroxychloroquine and gemcitabine/nab-paclitaxel in pancreatic cancer patients. Clin Cancer Res 2020;26(13):3126–3134.Han J, Lotze MT. The adaptome as biomarker for assessing cancer immunity and immunotherapy. Methods Mol Biol2020; 2055:369–397.Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):192–198.Spranger S, Dai D, Horton B, Gajewski TF. Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell 2017;31(5):711–723 e714.Jang JE, Hajdu CH, Liot C, Miller G, Dustin ML, Bar-Sagi D. Crosstalk between regulatory T cells and tumor-associated dendritic cells negates anti-tumor immunity in pancreatic cancer. Cell Rep 2017;20(3):558–571.Bruno TC. New predictors for immunotherapy responses sharpen our view of the tumour microenvironment. Nature 2020;577(7791):474–476.

scholarly journals Factors Associated with Overall Survival in Pancreatic Cancer Treated with Neoadjuvant Therapy and Surgery

HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S60
Author(s):  
R. Kim ◽  
S. Tsai ◽  
M. Aldakkak ◽  
B. George ◽  
M. Kamgar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Factors Associated

Association of decline in serum Ca19-9 after neoadjuvant therapy with improved survival among borderline resectable pancreatic cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15082-e15082 ◽  
Author(s):  
Susan Tsai ◽  
Anna Mahmoud ◽  
Ben George ◽  
Tracy R. Kelly ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Response To Therapy ◽  
Proportional Hazard ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Cox Proportional Hazard ◽  
Localized Disease

e15082 Background: Serum Ca19-9 (19-9) decline in response to therapy has been associated with an increased overall survival in metastatic pancreatic cancer patients (pts). However, the prognostic value of a 19-9 decline after neoadjuvant therapy in pts with localized disease is less well defined. Methods: We evaluated 73 pts with NCCN defined BRPC who received neoadjuvant therapy with induction chemotherapy (CRX) followed by chemoradiation (CRT). Staging with CT and 19-9 was obtained at three defined time points: baseline (bilirubin normal), after CRX, and following CRT (pre-surgical). Change in 19-9 (δ19-9) was defined as: (baseline 19-9- pre-surgical 19-9)/baseline 19-9. δ19-9 was classified as: absent (δ19-9<0) or minimal (0 <δ19-9<0.25), low (0.25<δ19-9<0.50), moderate (0.50<δ19-9<0.75), high (δ19-9> 0.75). Results: Of the 73 pts, 20 pts had normal/undetectable 19-9 and were excluded from the analysis. Of the remaining 53 pts, mean 19-9 levels at baseline, after CRX, and after CRT were 956, 164, and 139 U/mL, respectively. The mean change in 19-9 after CRX was 44%. Changes in 19-9 after CRX correlated with continued decline in 19-9 after CRT (Spearman rho = 0.81, p<0.001). δ19-9 was high in 38 (71%), moderate in 9 (17%), min/low in 1 (2%), and absent in 5 (9%). Of the 53 pts, 49 (92%) were considered for surgery after neoadjuvant therapy and 38 (72%) underwent pancreatectomy. In a multivariate logistic regression, higher δ19-9 was associated with a 5.4 fold increased odds of completing all neoadjuvant therapy including surgery as compared to pts with no change in 19-9 (absent δ19-9; HR 5.4, p=0.12). Patients with absent δ19-9 had a worse overall survival than pts with minimal to high δ19-9 (median survival 11.5 mo vs. 30.1 mo, p = 0.0002). In a multivariate Cox proportional hazard, a decline in pre-surgical 19-9 from baseline was associated with improved survival (HR 0.21, p =0.02). Conclusions: Following neoadjuvant therapy, a decline in 19-9 is associated with surgical resection and improved overall survival. An increase in 19-9 above baseline (the absent δ19-9 group) prior to surgery is a poor prognostic marker and such patients may benefit from additional systemic therapy.

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