Prediction of Recurrence with KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma

Sung Joo Kim, Mi Ju Kim, Ji Soo Han, You Na Sung, Soyeon An, Jae Hoon Lee, Ki Byung Song, Dae Wook Hwang, Sang Soo Lee, Hyung Jun Cho, Song Cheol Kim, James Eshleman, Seung Mo Hong

Research output: Contribution to journalArticle

Abstract

Objective Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. Methods KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. Results KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. Conclusions KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.

Original languageEnglish (US)
Pages (from-to)400-411
Number of pages12
JournalPancreas
Volume48
Issue number3
DOIs
StatePublished - Mar 1 2019

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Adenocarcinoma
Recurrence
Polymerase Chain Reaction
Pancreaticoduodenectomy
Pylorus
Pancreatic Neoplasms
Margins of Excision
Survival
Radiotherapy
Drug Therapy
Mutation
Mutation Rate

Keywords

  • cancer
  • KRAS
  • margin
  • pancreas
  • recurrence
  • survival

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Prediction of Recurrence with KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma. / Kim, Sung Joo; Kim, Mi Ju; Han, Ji Soo; Sung, You Na; An, Soyeon; Lee, Jae Hoon; Song, Ki Byung; Hwang, Dae Wook; Lee, Sang Soo; Cho, Hyung Jun; Kim, Song Cheol; Eshleman, James; Hong, Seung Mo.

In: Pancreas, Vol. 48, No. 3, 01.03.2019, p. 400-411.

Research output: Contribution to journalArticle

Kim, Sung Joo ; Kim, Mi Ju ; Han, Ji Soo ; Sung, You Na ; An, Soyeon ; Lee, Jae Hoon ; Song, Ki Byung ; Hwang, Dae Wook ; Lee, Sang Soo ; Cho, Hyung Jun ; Kim, Song Cheol ; Eshleman, James ; Hong, Seung Mo. / Prediction of Recurrence with KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma. In: Pancreas. 2019 ; Vol. 48, No. 3. pp. 400-411.
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abstract = "Objective Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. Methods KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. Results KRAS mutation was detected in 76 patients (94{\%}), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19{\%} or greater was observed in 18 patients (22{\%}). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. Conclusions KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.",
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T1 - Prediction of Recurrence with KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma

AU - Kim, Sung Joo

AU - Kim, Mi Ju

AU - Han, Ji Soo

AU - Sung, You Na

AU - An, Soyeon

AU - Lee, Jae Hoon

AU - Song, Ki Byung

AU - Hwang, Dae Wook

AU - Lee, Sang Soo

AU - Cho, Hyung Jun

AU - Kim, Song Cheol

AU - Eshleman, James

AU - Hong, Seung Mo

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Objective Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. Methods KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. Results KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. Conclusions KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.

AB - Objective Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. Methods KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. Results KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. Conclusions KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.

KW - cancer

KW - KRAS

KW - margin

KW - pancreas

KW - recurrence

KW - survival

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C2 - 30747828

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VL - 48

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JO - Pancreas

JF - Pancreas

SN - 0885-3177

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