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2. Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer

Author

Lee, B., Lipton, L., Cohen, J., Tie, J., Javed, A.A., Li, L., Goldstein, D., Burge, M., Cooray, P., Nagrial, A., Tebbutt, N.C., Thomson, B., Nikfarjam, M., Harris, M., Haydon, A., Lawrence, B., Tai, D.W.M., Simons, K., Lennon, A.M., Wolfgang, C.L., Tomasetti, C., Papadopoulos, N., Kinzler, K.W., Vogelstein, B., and Gibbs, P.

Published
2019
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5. Surgery following observation of branch-duct IPMN reveals dynamic predictors of malignancy: Significance of cyst stability vs. progression. Results of the “CrOS” multicentric study

Author

Pollini, T., primary, Marchegiani, G., additional, Andrianello, S., additional, Tomasoni, G., additional, Biancotto, M., additional, Javed, A.A., additional, Kinny-Koster, B., additional, Amini, N., additional, Han, Y., additional, Kim, H., additional, Kwon, W., additional, Kim, M., additional, Perri, G., additional, He, J., additional, Bassi, C., additional, Goh, B., additional, Katz, M., additional, Jang, J.-., additional, Wolfgang, C., additional, and Salvia, R., additional

Published
2021
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6. Accuracy of grading pancreatic neuroendocrine tumors on endoscopic ultrasound-guided fine needle aspiration: a multi-institutional study

Author

Javed, A.A., primary, Razi, S., additional, Michelakos, T., additional, Pulvirenti, A., additional, Zheng, J., additional, Sekigami, Y., additional, Burns, W.R., additional, Burkhart, R.A., additional, Cameron, J.L., additional, Weiss, M.J., additional, Wolfgang, C.L., additional, Wei, A.C., additional, Zureikat, A.H., additional, Ferrone, C.R., additional, and He, J., additional

Published
2021
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8. Impact of liver disease and parenchymal changes on patterns of liver recurrence in patients with resected PDAC: a new insight into the biological behavior of this lethal disease

Author

Javed, A.A., primary, Baig, E., additional, Habib, J.R., additional, C, Correa, additional, Lafaro, K., additional, Greer, J.B., additional, Burkhart, R.A., additional, Burns, W.R., additional, Cohen, S.M., additional, Fishman, E.K., additional, Cameron, J.L., additional, He, J., additional, Weiss, M.J., additional, and Wolfgang, C.L., additional

Published
2021
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13. Presence Of Transitional Circulating Tumor Cells Following Resection Is Associated With Worse Survival In Patients With Delayed Initiation Of Adjuvant Therapy

Author

Hasanain, A., primary, Javed, A.A., additional, van Oosten, F., additional, Gemenetzis, G., additional, Groot, V.P., additional, Ding, D., additional, Teinor, J.A., additional, Wright, M.J., additional, Yu, J., additional, Cameron, J.L., additional, Weiss, M.J., additional, Burns, W.R., additional, Burkhart, R.A., additional, Zheng, L., additional, He, J., additional, and Wolfgang, C.L., additional

Published
2020
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14. Systemic therapy in pancreatic ductal adenocarcinoma: Does drug selection, sequence, and duration impact survival

Author

Javed, A.A., primary, Noor, A., additional, Sham, J.G., additional, Hasanain, A., additional, Blair, A.B., additional, Wright, M.J., additional, Rozich, N., additional, Ho, D., additional, Cameron, J.L., additional, He, J., additional, Burkhart, R.A., additional, Zheng, L., additional, Wolfgang, C.L., additional, and Weiss, M.J., additional

Published
2020
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15. Persistent Circulating Tumor Cells At One Year After Oncologic Resection Of Pancreatic Cancer Predict Recurrence

Author

Wolfgang, C.L., primary, Ding, D., additional, Hasanain, A., additional, Oosten, F.V., additional, Gemenetzis, G., additional, Groot, V., additional, Tenior, J., additional, Javed, A.A., additional, Wright, M., additional, Yu, J., additional, Cameron, J., additional, Weiss, M., additional, Burns, W.R., additional, Burkhart, R., additional, Zheng, L., additional, and He, J., additional

Published
2020
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16. Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer.

Author

Gibbs P., Simons K., Lennon A.M., Wolfgang C.L., Tomasetti C., Papadopoulos N., Kinzler K.W., Vogelstein B., Lee B., Lipton L., Cohen J., Tie J., Javed A.A., Li L., Goldstein D., Burge M., Cooray P., Nagrial A., Tebbutt N.C., Thomson B., Nikfarjam M., Harris M., Haydon A., Lawrence B., Tai D.W.M., Gibbs P., Simons K., Lennon A.M., Wolfgang C.L., Tomasetti C., Papadopoulos N., Kinzler K.W., Vogelstein B., Lee B., Lipton L., Cohen J., Tie J., Javed A.A., Li L., Goldstein D., Burge M., Cooray P., Nagrial A., Tebbutt N.C., Thomson B., Nikfarjam M., Harris M., Haydon A., Lawrence B., and Tai D.W.M.

Abstract

Background: In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. Material(s) and Method(s): Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. Result(s): Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P = 0.002)] and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. Conclusion(s): ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment int

Published
2019

17. Circulating tumor DNA as a prognostic biomarker in early stage pancreatic cancer.

Author

Harris M., Tomasetti C., Papadopoulos N., Kinzler K.W., Vogelstein B., Gibbs P., Lee B., Lipton L.R., Cohen J., Tie J., Javed A.A., Li L., Goldstein D., Cooray P., Nagrial A., Burge M.E., Tebbutt N.C., Nikfarjam M., Lennon A.M., Wolfgang C.L., Harris M., Tomasetti C., Papadopoulos N., Kinzler K.W., Vogelstein B., Gibbs P., Lee B., Lipton L.R., Cohen J., Tie J., Javed A.A., Li L., Goldstein D., Cooray P., Nagrial A., Burge M.E., Tebbutt N.C., Nikfarjam M., Lennon A.M., and Wolfgang C.L.

Abstract

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Published
2019

18. Circulating tumor cells dynamics in pancreatic adenocarcinoma correlate with disease status: Results of the prospective cluster study

Author

Gemenetzis, G., primary, Groot, V.P., additional, Yu, J., additional, Ding, D., additional, Teinor, J.A., additional, Javed, A.A., additional, Wood, L.D., additional, Burkhart, R.A., additional, Cameron, J.L., additional, Makary, M.A., additional, Weiss, M.J., additional, He, J., additional, and Wolfgang, C.L., additional

Published
2019
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24. Recurrent or metachronous adenocarcinoma of the pancreatic remnant: long-term survival after completion pancreatectomy

Author

Tran, T.B., primary, Norton, J.A., additional, Maker, A.V., additional, Krasnick, B.A., additional, Ethun, C.G., additional, Cameron, J.L., additional, Maithel, S.K., additional, Rocha, F.G., additional, He, J., additional, Javed, A.A., additional, Fields, R.C., additional, Wolfgang, C.L., additional, Weiss, M.J., additional, and Poultsides, G.A., additional

Published
2018
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37. Inter-observer variability for pancreatic surgery-specific complications as defined by ISGPS after pancreatoduodenectomy: an international cross-sectional multicenter study.

Author

Hendriks, T.E., Balduzzi, A., van Dieren, S., Suurmeijer, J.A., Salvia, R., Del Chiaro, M., Stoop, T.F., Mieog, S.D., Nielen, M., Zani, S., Nussbaum, D., Hackert, T., Hewitt, D.B., Javed, A.A., Koerkamp, B. Groot, de Wilde, R.F., Miao, Y., Jiang, K., Nakata, K., and Nakamura, M.

Published
2024
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