Immunological Impact of Neoadjuvant Chemoradiotherapy in Patients with Borderline Resectable Pancreatic Ductal Adenocarcinoma

Introduction: Evaluation of pancreatic ductal adenocarcinoma (PDAC) after chemoradiotherapy downstaging is challenging due to computed tomography (CT) overestimation of tumor extension and residual vascular involvement, limiting access to surgery to some patients with potentially resectable tumors. With this study, we wanted to assess which radiological findings are most reliable at pre-operative imaging in the evaluation of PDAC after chemoradiotherapy in order to achieve complete resection. Methods: We retrospectively enrolled 71 patients with locally advanced and borderline resectable PDAC who underwent neoadjuvant chemoradiotherapy. Pre-operative CT or magnetic resonance (MR) have been evaluated by three radiologists to assess major qualitative and quantitative parameters of lesions. Accuracy, sensitivity, and specificity compared to anatomopathological results were evaluated for each parameter. Cohen’s K-coefficient has been calculated to evaluate the inter-observer agreement (IOA). Both single and consensus lecture have been tested. Different dimensional cut-offs were tested to categorize tumors according to their major axis and to compare with anatomopathological diameter, tumor persistence, and margin infiltration. Results: A 25 mm cut-off was 67% sensitive, 90% specific, and 77% accurate in assessing real tumor dimension. 25 mm cut-off reported a 64% sensitivity, 78% specificity, and 69% accuracy in assessing R0 resection. Each 5 mm increment of major axis dimension there is an odds ratio (OR) 1.79 (95% CI 1.13–2.80, p = 0.012) for R+ resection. Imaging presence of the perivascular cuff is not associated with tumor persistence and resection margin infiltration (p = 0.362). Lesion enhancement and pattern homogeneity were not accurate in determining tumor persistence. IOA was generally poor to fair, except for >25 mm cut-off classification where IOA was moderate. Diagnostic accuracy is superior in consensus lecture rather than single lecture. Conclusion: Imaging methods tend to underestimate PDAC resectability after neoadjuvant-CRT. IOA is poor to fair in evaluating most of the qualitative parameters of downstaged pancreatic adenocarcinoma. Surgery should be considered for downstaged borderline resectable PDACs, independently from perivascular cuff presence, especially for tumors smaller than 25 mm.

Download Full-text

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Borderline Resectable Pancreatic Ductal Adenocarcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgical Resection

World Journal of Surgery ◽

10.1007/s00268-019-05159-9 ◽

2019 ◽

Vol 43 (12) ◽

pp. 3153-3160 ◽

Cited By ~ 3

Author(s):

Hirokazu Kubo ◽

Takashi Murakami ◽

Ryusei Matsuyama ◽

Yasuhiro Yabushita ◽

Nobuhiro Tsuchiya ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Surgical Resection ◽

Neoadjuvant Chemoradiotherapy ◽

Neutrophil To Lymphocyte Ratio ◽

Ductal Adenocarcinoma ◽

Prognostic Impact ◽

Borderline Resectable ◽

Lymphocyte Ratio

Download Full-text

Is surgery after neoadjuvant chemoradiotherapy feasible for elderly patients with resectable or borderline resectable pancreatic ductal adenocarcinoma?

10.21203/rs.2.21112/v1 ◽

2020 ◽

Author(s):

Hironobu Suto ◽

Keiichi Okano ◽

Minoru Oshima ◽

Yasuhisa Ando ◽

Hiroyuki Matsukawa ◽

...

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Elderly Patients ◽

Pancreatic Ductal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

The Elderly ◽

Elderly Group ◽

Ductal Adenocarcinoma ◽

Borderline Resectable ◽

Pancreas Resection

Abstract Background The benefit and safety of pancreas resection for pancreatic ductal adenocarcinoma for elderly patients, especially after preoperative adjuvant therapy, is still unknown. This study attempted to evaluate perioperative and long-term outcomes after pancreas resection in elderly patients with pancreatic ductal adenocarcinoma and to detect the potential impact of neoadjuvant chemoradiotherapy. Methods One hundred and thirty-four consecutive patients undergoing curative resection for resectable and borderline resectable pancreatic ductal adenocarcinoma between March 2008 and February 2018 at our institution were analyzed. Patients were divided into two groups: patients older than or equal to 75 years (the elderly group, n=46) and those younger than 75 years (the younger group, n= 88). Results There were no significant differences both in overall survival and relapse free survival between the two groups (P=0.270, P=0.699). Although the induction rate of adjuvant chemotherapy was not significantly different (P=0.458), the completion rate was significantly lower in elderly group than that in younger group (35% and 56%; P=0.022). Neoadjuvant chemoradiotherapy was performed for 82 patients (61%), and the induction and completion rates were not significantly different (P=0.668, P=0.794) between the two groups. The elderly patients with completion of adjuvant chemotherapy had significantly better overall survival than those without it (P=0.032). Neoadjuvant chemoradiotherapy did not significantly affect overall survival in elderly patients, however, there was a trend toward longer overall survival in patients who had neoadjuvant chemoradiotherapy (P=0.072). Conclusions Neoadjuvant chemoradiotherapy could be introduced and completed even for elderly patients without serious complications and might lead to improved prognosis for those who are difficult to complete postoperative adjuvant chemotherapy.

Download Full-text

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

The American Surgeon ◽

10.1177/00031348211011129 ◽

2021 ◽

pp. 000313482110111

Author(s):

Weizheng Ren ◽

Dimitrios Xourafas ◽

Stanley W. Ashley ◽

Thomas E. Clancy

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Univariate Analysis ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Resection Margins ◽

Borderline Resectable ◽

Stepwise Selection ◽

R1 Resection ◽

Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

Download Full-text

Changes and prognostic impact of inflammatory nutritional factors during neoadjuvant chemoradiotherapy for patients with resectable and borderline resectable pancreatic cancer

BMC Gastroenterology ◽

10.1186/s12876-020-01566-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Minoru Oshima ◽

Keiichi Okano ◽

Hironobu Suto ◽

Yasuhisa Ando ◽

Hideki Kamada ◽

...

Keyword(s):

External Beam Radiotherapy ◽

Prognostic Score ◽

Neoadjuvant Chemoradiotherapy ◽

Glasgow Prognostic Score ◽

Ductal Adenocarcinoma ◽

Prognostic Impact ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Nutritional Factors ◽

Neutrophil Lymphocyte Ratio

Abstract Background Inflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT). Methods A total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series. Results The median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p < 0.001). In multivariate analysis, high pre-NACRT mGPS (2 or 1; p = 0.0478) and significant increase in CRP/Alb ratio after NACRT (≧ 0.077; p = 0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧ 0.077) and the group with low ΔCRP/Alb ratio (< 0.077). The group with high ΔCRP/Alb ratio after NACRT (n = 13) not only had higher post-NACRT CRP levels (p < 0.001) but also had lower post-NACRT Alb levels (p = 0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p = 0.03). Conclusion In addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT.

Download Full-text