The impact of chemotherapy sequencing on resectable pancreatic cancer by stage

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m2) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P < 0.0001, P = 0.006, P < 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.

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The Impact of Resection Margin Status and Postoperative CA19-9 Levels on Survival and Patterns of Recurrence After Postoperative High-Dose Radiotherapy With 5-FU—Based Concurrent Chemotherapy for Resectable Pancreatic Cancer

American Journal of Clinical Oncology ◽

10.1097/coc.0b013e318168f6c4 ◽

2008 ◽

Vol 31 (5) ◽

pp. 446-453 ◽

Cited By ~ 55

Author(s):

Timothy J. Kinsella ◽

Yuji Seo ◽

Joseph Willis ◽

Thomas A. Stellato ◽

Christopher T. Siegel ◽

...

Keyword(s):

Pancreatic Cancer ◽

Resection Margin ◽

Concurrent Chemotherapy ◽

Margin Status ◽

High Dose ◽

Resectable Pancreatic Cancer ◽

Resection Margin Status ◽

The Impact ◽

Patterns Of Recurrence

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Propensity score matched analysis of neoadjuvant therapy for resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.381 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 381-381

Author(s):

Kenneth L Meredith ◽

Jamie Huston ◽

Anjan Jayantilal Patel ◽

Richard H. Brown ◽

Fadi Kayali ◽

...

Keyword(s):

Pancreatic Cancer ◽

Propensity Score ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Tumor Size ◽

Survival Benefit ◽

Categorical Variables ◽

Resectable Pancreatic Cancer ◽

The Impact

381 Background: Neoadjuvant therapy (NT) for resectable pancreatic cancer continues to be debated. There is little data to demonstrate survival benefit over patients who were treated with up front surgery (UFS) vs NT. We sought to examine the impact of neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and UFS on survival in pancreatic cancer patients. Methods: The NCDB was accessed to identify patients with pancreatic adenocarcinoma. Propensity score matching (PSM) was performed against age, tumor size, margin status, and institutional surgery volume. Patient characteristics (continuous and categorical variables) were compared using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α < 0.05 was considered significant. Results: After PSM, 5,034 patients (UFS 2,517; NT 2,517: 1,143 NCT and 1,374 NCRT) were included in the analysis. There was no difference in age, tumor size, or grade among cohorts. The mean nodes positive were 1.6 ± 2.6 in NT and 2 ± 3.3 in UFS, p = 0.02. In the pre-matched cohort R0 resections were performed in 75.9% UFS, 82.9% NCRT, and 79.6% NCT, p < 0.001. The median and 5 year survival for NCT, NCRT and UFS was 28.6 months and 25.2%, 25.7 months and 22.2%, and 21.3 months and 21.7%, p < 0.001. Adjuvant therapy (chemotherapy (CT) or CRT) in the UFS did demonstrate a survival benefit 22.5 months vs 18.6 months, p < 0.001, however this did not benefit NCT or NCRT, p = 0.8 and p = 0.8 respectively. Additionally survival in the UFS with adjuvant therapy either CT or CRT was still decreased compared to either NCT or NCRT, p < 0.001 and p = 0.001 respectively. MVA demonstrated that age, T-stage, lymph nodes positive, R0 resection, grade, NCT and NCRT were predictors of survival. Conclusions: Neoadjuvant therapy improves survival in resectable pancreatic cancer patients. NCT and NCRT demonstrated survival benefit compared to UFS even with adjuvant therapy. Patients with resectable pancreatic cancer should be considered for neoadjuvant therapy.

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Survival Trends for Resectable Pancreatic Cancer Using a Multidisciplinary Conference: the Impact of Post-operative Chemotherapy

Journal of Gastrointestinal Cancer ◽

10.1007/s12029-019-00303-z ◽

2019 ◽

Vol 51 (3) ◽

pp. 836-843

Author(s):

Aslam R. Syed ◽

Neil M. Carleton ◽

Zachary Horne ◽

Annika Dhawan ◽

Gurneet Bedi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Resectable Pancreatic Cancer ◽

Multidisciplinary Conference ◽

The Impact

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Mo1371 – Survival of Resectable Pancreatic Cancer: the Impact of Post-Operative Chemotherapy

Gastroenterology ◽

10.1016/s0016-5085(19)38823-7 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-755

Author(s):

Aslam Syed ◽

Neil M. Carleton ◽

Annika Dhawan ◽

Zachary Horne ◽

Gursimran Kochhar ◽

...

Keyword(s):

Pancreatic Cancer ◽

Resectable Pancreatic Cancer ◽

The Impact

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A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps516 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS516-TPS516

Author(s):

Yoshihiro Sakamoto ◽

Hiroyuki Isayama ◽

Kei Saito ◽

Junichi Arita ◽

Yousuke Nakai ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Chemotherapy ◽

Phase Ii ◽

Response Rate ◽

Phase Ii Trial ◽

Locally Advanced ◽

Resectable Pancreatic Cancer ◽

Surgical Morbidity ◽

Borderline Resectable ◽

The Impact

TPS516 Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / < 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.

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Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.409 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 409-409

Author(s):

Taylor Maramara ◽

Jamie Huston ◽

Ravi Shridhar ◽

Kenneth L Meredith

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Therapy ◽

Tumor Size ◽

Single Agent ◽

Pathologic Complete Response ◽

Multivariable Analysis ◽

Response Rates ◽

Resectable Pancreatic Cancer ◽

Multi Agent ◽

The Impact

409 Background: Neoadjuvant therapy (NT) for resectable pancreatic adenocarcinoma (PAC) continues to be debated. We sought to establish the impact of single agent (SAC) versus multi-agent chemotherapy (MAC) with or without radiation (RT) on survival in patients with resectable pancreatic cancer. Methods: Utilizing the National Cancer Database we identified patients with PAC who underwent up front surgery (UFS), SAC, or MAC ± RT followed by surgery. Patient characteristics and survival were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Multivariable analysis (MVA) was developed to identify predictors of survival. All tests were two-sided and α < 0.05 was significant. Results: We identified 26,563 patients of which, 23,877 (89.9%) UFS, 1,482 (5.6%) NT+RT (SAC+RT 768, MAC+RT 560), and 1,204 (4.5%) chemo only (SAC 262, MAC 864) with a median age of 66 (25-90). The median tumor size was smaller, p = 0.003 and Charlson/Deyo was lower, p = 0.008 in the UFS. Despite this, the 90 day mortality was higher at 8% versus 7.5% in NT+RT and 4.8% in NT, p = 0.003. There were higher R0 resections in the NT+RT versus NT-RT or UFS, 82.4%, 80.5%, and 76%, p < 0.001. Additionally, there were less N1 disease in NT+RT 35.4%, 59.5%, and 68.1%, p < 0.001. Pathologic complete response (pCR) rates were higher in the NT+RT versus NT-RT, 3.1% versus 1.7%, p < 0.001. Examining the response rates by SAC±RT and MAC±RT, pCR was 0.5% in SAC, 2.8% SAC+RT, 2.2% MAC, and 3.3 MAC+RT, p = 0.004. The median survival was 22.2 mo in UFS, 23.1 mo in SAC, 26 mo in SAC+RT, 27.9 mo in MAC+RT, and 29.8 mo in MAC, p < 0.001. On multivariable analysis, age, Chalson/Deyo score, tumor size, grade, margin status, facility volume, and MAC were predictors of survival. Conclusions: Multi-agent chemotherapy with or without radiation improves overall survival, R0 resections rates, and complete pathological response rates in patients undergoing neoadjuvant therapy for resectable pancreatic cancer.

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