Retrospective analysis of prognostic and predictive markers in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nabpaclitaxel: Influence of the presence of stent.

483 Background: Placement of a biliary stent is a standard measure for patients (pts) with pancreatic cancer. We evaluated prognostic/predictive factors that could predict the benefit of gemcitabine/nabpaclitaxel in pts with locally advanced unresectable and metastatic pancreatic adenocarcinoma and whether the presence of a biliary stent reduced the treatment efficacy Methods: We retrospectively analyzed 39 pts with locally advanced and metastatic pancreatic cancer treated with gemcitabine/nabpaclitaxel. Data included lactate dehydrogenase (LDH) level, alkaline phosphatase, neutrophil/lymphocyte ratio (NLR), performance status (PS), weight loss, presence of stent, analgesics use and CA 19.9 level. The correlation with response rate, progression-free survival (PFS) and overall survival (OS) was analyzed. Objective toxicities were assessed. Results: 30 pts (77%) had metastatic disease and 9 (23%) locally advanced pancreatic cancer. 46% had liver metastases and 41% lung metastases. Mean age of pts: 62 years (62% male). 20% had PS:0, 67% PS:1 and 13% PS:2. Stents were placed in 30% of pts, 69% had weight loss and 64% used analgesics at diagnosis. At the time of analysis 14 pts had died (25 alive). 56% had progressed, 3% were lost to follow-up and 41% had not progressed. A total of 54% disease stabilizations, 21% partial responses and 18% progressions were achieved (deaths: 7%). 43% required dose reduction. The main toxicity was hematologic (grade 1 anemia). Median PFS: 6 months (95%CI 4.4-7.6). Median OS: 15 months (95%CI 10.4-19.6). There was a statistically significant relationship between LDH level, NLR and PS and OS: LDH level higher than 363 increased the risk of death, NLR above 3.1 increased 1.8 times the risk of death and mean OS of pts with ECOG:0,1 was greater than that of pts with ECOG:2. No relationship between the presence of stent and PFS or OS was found, as well as with any of the other variables. Conclusions: The presence of stent did not reduce the efficacy of gemcitabine/nabpaclitaxel. Univariate analysis showed PS as a prognostic factor while multivariate showed LDH and NLR.

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Early outcomes of irreversible electroporation after stereotactic body radiation therapy for the treatment of locally advanced pancreatic adenocarcinoma (LAPC): A matched pair analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.410 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 410-410

Author(s):

Emanuel Boyer ◽

Russell Palm ◽

Jessica M. Frakes ◽

Sarah E. Hoffe ◽

Mokenge Peter Malafa

Keyword(s):

Pancreatic Cancer ◽

Radiation Therapy ◽

Pancreatic Adenocarcinoma ◽

Cohort Analysis ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Matched Pair ◽

Optimal Timing ◽

Entire Cohort

410 Background: Outcomes remain poor for those diagnosed with unresectable pancreatic cancer. SBRT and IRE have independently demonstrated high rates of local control and minimal toxicity for patients with locally advanced pancreatic cancer (LAPC). Data is limited regarding safety and efficacy in the sequential use of both therapies. Materials and Methods: A single institution retrospective matched cohort analysis was performed for patients with non-metastatic pancreatic cancer treated with induction chemotherapy and SBRT followed by IRE, compared with patients of the same cohort who did not receive IRE. Patients were paired based on age, tumor stage, GTV D95, CA19-9 prior to SBRT, and chemotherapy type to mitigate selection bias in surgical candidates. Overall survival (OS), progression free survival (PFS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were the primary outcomes compared via Kaplan-Meier survival analysis with log-rank methods. Results: From July, 2014 to February, 2020 17 patients received SBRT followed by IRE. These patients were matched with 17 patients who received SBRT from January, 2012 to March, 2019. Most patients received neoadjuvant FOLFIRINOX (82.4%) and were AJCC 8 stage III (79.4%). Median age of the overall cohort was 65.5 years and 50% were male. Median dose delivered to 95% of gross tumor volume was 32.61 Gy, and median pre SBRT CA19-9 value was 70.5 U/mL. There were no statistically significant differences in matched characteristics between the two cohorts. Among the SBRT+IRE, the median time between IRE and SBRT was 66 days (range:49-467 days). The median OS, PFS, FFLF, and FFDF for IRE+SBRT vs. SBRT alone from SBRT was 10.8 vs 15.1 months, 9.6 vs. 15.3 months, 15.7 vs. 15.3 months, 15.9 vs. 14.4 months respectively (all P > .10). 11 patients in the entire cohort experienced toxicity as a result of their radiation therapy (35%), with one G3 GIB and one patient experiencing G3 abdominal pain. Among the 17 patients who underwent IRE, nine patients experienced toxicity (53%). Most of these events were G3, with two G4 intestinal bleeds. There was zero mortality in the 90 day period post operatively. Conclusions: In a retrospective cohort,non-selective delivery ofIRE afterSBRT demonstrated no oncological benefit for patients with unresectable pancreatic adenocarcinoma compared to only SBRT. Compared to historical experiences of IRE alone, there was no increase in overall toxicity with the combination of SBRT and IRE. The optimal timing, sequencing, and indications for IRE and SBRT in LAPC remain unknown and are best assessed prospectively. [Table: see text]

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Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

10.2310/7800.16076 ◽

2017 ◽

Author(s):

Gregory C Wilson ◽

Brent T Xia ◽

Syed A Ahmed

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Treatment Strategies ◽

Ductal Adenocarcinoma ◽

Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease

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Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation

Cancers ◽

10.3390/cancers11050709 ◽

2019 ◽

Vol 11 (5) ◽

pp. 709 ◽

Cited By ~ 10

Author(s):

Patrick Naumann ◽

Jonathan Eberlein ◽

Benjamin Farnia ◽

Thilo Hackert ◽

Jürgen Debus ◽

...

Keyword(s):

Skeletal Muscle ◽

Pancreatic Cancer ◽

Weight Loss ◽

Muscle Mass ◽

Muscle Wasting ◽

Statistical Tests ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Skeletal Muscle Index ◽

Poor Outcomes

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.

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Phase II study evaluating trimodal therapy with cetuximab intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer [ISRCTN56652283]

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4100 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4100-4100 ◽

Cited By ~ 3

Author(s):

R. C. Krempien ◽

M. W. Münter ◽

C. Timke ◽

P. E. Huber ◽

H. Friess ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Phase Ii ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Intensity Modulated Radiotherapy ◽

Locally Advanced Pancreatic Cancer ◽

Trimodal Therapy ◽

Tumor Bleeding

4100 Background: The induction of EGFR targeting with cetuximab in radiation based therapy of solid tumors has yielded promising results. Thus, we initiated a prospective Phase II trial designed to analyze the feasibility and effectivity of trimodal therapy with gemcitabine-based chemoradiation and cetuximab in locally advanced inoperable pancreatic cancer. Methods: In this phase 2 study, pts with locally advanced pancreatic cancer without prior cytotoxic therapy were treated with radiotherapy (RT), gemcitabine weekly (300 mg/m2), and cetuximab weekly (loading dose 400 mg/m2 day 1, and concomitant with radiation day 8,15,22,29,36 250 mg/m2). RT was delivered by using an integrated IMRT boost concept (54 Gy GTV, 45 Gy CTV) over 5 weeks. RT was followed by gemcitabine (1000 mg/m2) weekly × 3 in 4 weeks. Response evaluation using computed tomography followed at week 12. All amenable patients were intended for surgical treatment between week 12–15. Results: 24 pts were enrolled until now. Preliminary results are presented on 20 pts with the following characteristics: pancreatic adenocarcinoma c2 T4 N1 20/20, median age = 63.5 (range 51–79); M/F = 13/7; ECOG PS 0/1/2 = 2/12/6; median days on treatment: 90 (range 70–100). Treatment-related toxicities were observed in 16 pts. Grade 3 toxicities included diarrhea (n = 4), fatigue (n = 2), nausea (n = 3), neutropenia (n = 6), thrombocytopenia (n = 2), and vomiting (n = 2). 18/20 pts developed some acneiforme rush during therapy. No omittance of cetuximab therapy was necessary. 1 patient died during RT due to tumor bleeding. Median follow-up at present is 6 month, median survival has not been reached. Partial remissions 8/20, stable disease 9/20, progressive disease 3/20. 12/20 patients were amenable for secondary potentially curative resection. 4 patients could be resected, while 3 patients were found to have abdominal metastatic spread. Conclusions: Early data from trimodal therapy in pancreatic adenocarcinoma with chemoradiation (IMRT), gemcitabine, and cetuximab indicate feasibility without increased toxicity profile. The local response appears to be very promising in pancreatic cancer, potentially allowing neoadjuvant treatment. [Table: see text]

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Phase I trial of imexon, Inj. plus gemcitabine in patients with advanced previously untreated pancreatic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15058 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15058-15058

Author(s):

S. J. Cohen ◽

M. Zalupski ◽

M. Modiano ◽

P. Conkling ◽

D. Mahadevan ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Pancreatic Adenocarcinoma ◽

Phase I Study ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Maximum Tolerated Dose ◽

Pancreatic Cancer Cells ◽

Dosing Regimens ◽

Ecog Ps

15058 Background: Imexon for inj. (Amplimexon®, AMP) is an aziridine-containing iminopyrrolidone which causes G2 arrest, accumulation of reactive oxygen species, and induction of apoptosis in pancreatic cancer cells. AMP demonstrated synergy with gemcitabine (GEM) in preclinical pancreatic cancer models. This phase I study of AMP plus GEM was undertaken to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). Secondary endpoints were pharmacokinetics for both agents (PK) and tumor response. Methods: Patients (pts) with previously untreated advanced pancreatic adenocarcinoma received one of two dosing regimens. The first 19 received 30 minute AMP IV days 1–5 and 15–19 followed by 30 minute GEM IV days 1, 8 and 15 Q4 wks (Regimen A). Dosing was modified after 19 pts to administer both AMP and GEM over 30 minutes days 1, 8 and 15 every 4 weeks (Regimen B). Dose levels (AMP/GEM, in mg/m2) for Regimen A: 200/800, 280/800, 200/1000, and 280/1000, and for Regimen B: 280/1000, 335/1000, 390/1000, 540/1000, and 750/1000. The current cohort is 1000/1000. Pts were assessed for response after cycles 2, 5 and 8. PK and pharmacodynamic (plasma thiol depletion) measurements were obtained during cycle one. Results: Forty-six pts have been treated to date, with 36 having complete toxicity data and evaluable. Pt characteristics: M/F (24/12), Age (mean 60.4 years, range 43–75), ECOG PS 0/1 (56%, 44%), metastatic/locally advanced (91%, 9%). The 36 pts have completed 122.5 cycles of therapy (median 2, range 0.5–12). Common toxicities: anemia (77%), fatigue (71%), nausea (60%), fever (54%), and leukopenia (54%). DLT were 1/6 at 280/1000 (Regimen A - febrile neutropenia), 1/6 at 280/1000 (Regimen B - gr 3 hypotension, gr 4 renal failure), and 1/9 at 390/1000 (gr 3 hyperbilirubinemia). Accrual continues at 1000/1000. Of 36 pts, 4 have had partial responses and 14 stable disease. PK and plasma thiol analysis are ongoing. Conclusions: Imexon can be administered safely with full dose gemcitabine. Accrual continues to define the combination MTD. The response rate in this phase I study compares favorably with historical gemcitabine monotherapy, and further phase II evaluation of this combination in advanced pancreatic cancer is warranted. No significant financial relationships to disclose.

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Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.326 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 326-326

Author(s):

Byung Min Lee ◽

Seung Yeun Chung ◽

Jee Suk Chang ◽

Kyong Joo Lee ◽

Si Young Song ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Cancer Patients ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Pre Treatment

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

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A phase II study of neoadjuvant gemcitabine/5-fluorouracil followed by 5-fluorouracil/oxaliplatin concurrent with radiation in patients with locally advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.259 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 259-259

Author(s):

C. Lin ◽

B. M. Kos ◽

A. R. Sasson ◽

J. L. Meza ◽

J. L. Grem

Keyword(s):

Pancreatic Cancer ◽

Continuous Infusion ◽

Pancreatic Adenocarcinoma ◽

Phase Ii ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

R0 Resection ◽

Borderline Resectable ◽

R1 Resection

259 Background: We designed this phase II trial to determine the efficacy and safety of a neoadjuvant regimen involving gemcitabine, infusional 5-fluorouracil (5-FU), oxaliplatin and radiation therapy (RT) in patients with locally advanced pancreatic adenocarcinoma Methods: Induction chemotherapy (CT) consisted of two 3-week cycles of weekly gemcitabine with 24-hour continuous infusion of 5 FU for 2 of 3 weeks. Chemoradiation (CRT) consisted of RT of 50.4 Gy in 28 fractions or 50 Gy in 25 fractions and weekly oxaliplatin with 24-hour continuous infusion of 5 FU throughout RT. The first 7 patients also received celecoxib 200 mg BID throughout induction CT and CRT. Upon completion of CRT, surgical candidates underwent a pancreatoduodenectomy. Response rate was assessed according to RECIST criteria 4 weeks after the end of CRT. CTC AE v3 was used to grade the acute side effects. The failure-free survival (FFS), overall survival (OS) and median survival were analyzed by the Kaplan Meier method. Results: Twenty-nine patients who had borderline resectable pancreatic adenocarcinoma at the UNMC were enrolled and received induction CT. Twenty-four patients completed CRT. Nineteen patients had surgical exploration: 4 were unresectable, 6 had intra-abdominal metastases, and 9 had resection (seven had R0 resection, 2 had R1 resection, and 6 had negative nodes). The median follow up was 27 months. There were maximum 48% acute grade 3-4 toxicities during induction CT and CRT. The median FFS and OS were 7 and 10 months and the 2-year FFS and OS were 17% and 28%. Median OS and FFS for patients with and without resection was 26 vs. 9 months, p=0.06; and 19 vs. 5 months, p=0.01. Patients with CA19-9 above 90 U/L throughout treatment had significantly shorter FFS and OS than patients with CA19-9 less than 90 throughout treatment or had a decline from baseline to less than 90 after treatment. Conclusions: Induction gemcitabine/5-FU followed by 5-FU/oxaliplatin concurrent with RT led to down staging in 31% patients with subsequent resection. Further innovative strategies are needed to improve the outcome of patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.

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Outcomes of neoadjuvant chemotherapy with FOLFOX/FOLFIRINOX and chemoradiotherapy in borderline resectable pancreatic cancer: Single-institution experience.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.327 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 327-327 ◽

Cited By ~ 1

Author(s):

Chang O Son ◽

Sachin Gopalkrishn Pai ◽

Suma Satti ◽

Adriana Dornelles ◽

John S. Bolton ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Chemotherapy ◽

Pancreatic Adenocarcinoma ◽

Older Patients ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Adenocarcinoma ◽

Operative Notes ◽

Advanced Pancreatic Adenocarcinoma

327 Background: The clinical benefit of neoadjuvant treatment in locally advanced pancreatic adenocarcinoma (borderline/unresectable) has not been well established. However, the challenge of managing locally advanced pancreatic adenocarcinoma has led to the incorporation of neoadjuvant treatment into clinical practice. FOLFIRINOX has been increasingly used as neoadjuvant chemotherapy, but may not be well tolerated especially in older patients due to adverse effect profile. In our institution, we have used FOLFOX as an alternative for older patients and patients with poor performance status based on our retrospective observation of FOLFOX in metastatic/advanced pancreatic adenocarcinoma. Methods: We conducted a retrospective analysis of locally advanced pancreatic cancer patients from January 1, 2011 to February 28, 2013 treated with neoadjuvant chemotherapy (FOLFOX/FOLFIRINOX) with the intention of future resection. In addition patients also received neoadjuvant chemo-radiotherapy. Imaging studies, operative notes and Pathology reports were reviewed. Results: 27 patients were analyzed, 10 received FOLFIRINOX and 17 received FOLFOX regimen. Mean age of patients were 57.28 ± 11.68 SD and 68.66± 11.21 SD in the two groups respectively. Patients received 4.2 ± 0.92 SD and 3.59 ±1.06 SD cycles of chemotherapy in FOLFIRINOX and FOLFOX groups respectively. Mean duration of follow up was similar in both groups. 5 patients on FOLFOX and 1 patient on FOLFIRINOX had disease progression thereby precluding surgery. The Rate of R0 resections was 64.7 % and 60% (P 0.27) in the two groups respectively. Overall survival was not statistically significant between the two groups. (Kaplan Meier survival graphs will accompany final presentation). Conclusions: In our study, FOLFIRINOX was administered in younger patients. However the R0 resection rates were similar in both the groups. FOLFOX may be acceptable neoadjuvant chemotherapy of choice in patients with borderline functional status. Randomized trials are needed to define this better.

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Clinical and molecular profiling of locally advanced compared with metastatic pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.747 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 747-747

Author(s):

Sarah Louise Picardo ◽

Grainne M. O'Kane ◽

Sandra Fischer ◽

Amy Zhang ◽

Robert Edward Denroche ◽

...

Keyword(s):

Pancreatic Cancer ◽

Survival Data ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Local Therapy ◽

P53 Mutation ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Metastatic Pancreatic Adenocarcinoma ◽

Lower Baseline

747 Background: It is unclear whether locally advanced pancreatic cancer (LAPC) should be treated similarly to metastatic pancreatic cancer (MPC). Clinical trials often exclude LAPC. We compare clinical and genomic characteristics of LAPC and MPC. Methods: Patients with LAPC and MPC were enrolled in the COMPASS trial (NCT02750657). Clinical, demographic and survival data was collected (cut off 8/31/19). WGS, RNAseq and modified Moffitt classification was performed. Results: Patients with LAPC (n = 28) and MPC (n = 180) did not differ in terms of age, gender, smoking or diabetes history. Patients with LAPC had lower BMI (p = 0.005) and lower baseline Ca19-9 (p = 0.02) than those with MPC. LAPC/MPC tumors had similar rates of KRAS, p53, CDKN2A and SMAD4 mutations and similar levels of ploidy, indels and neoantigens. There were increases in single nucleotide variants (p = 0.026) and structural variants (p = 0.04) in MPC compared with LAPC. No LAPC tumors were homologous recombination deficient (HRD) or KRAS wild type (WT), compared with 14 (8%) HRD and 16 (9%) KRAS-WT MPC. All LAPC were classical subtype compared with 77% MPC (p = 0.0052). OS data is shown in the table. MPC classical subtype tumors had improved OS compared with basal-like tumors (p = 0.008). Patients with MPC and p53 mutation trended towards worse OS compared with those without p53 mutation (p = 0.07); this was not seen in LAPC. There was a significant correlation between time on chemotherapy and OS in LAPC (p = 0.002) and MPC (p < 0.0001). Conclusions: Patients with LAPC have similar molecular profiles to those with MPC with similar rates of altered drivers. LAPC tumors are more likely to be Moffitt classical subtype and have similar OS to classical subtype MPC. LAPC patients benefit from local therapy; all patients benefit from increased time on chemotherapy. These data suggest that patients with LAPC should be treated similarly to those with classical subtype MPC but should be offered local therapy when possible. Clinical trial information: NCT02750657 . [Table: see text]

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