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Published in: Annals of Surgical Oncology 1/2018

01-01-2018 | Pancreatic Tumors

Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Surgical Resection of Pancreatic Ductal Adenocarcinoma Appears to be Safe and Effective

Authors: John F. Ryan, BS, Vincent P. Groot, MD, Lauren M. Rosati, BS, Amy Hacker-Prietz, MS, PA-C, Amol K. Narang, MD, Todd R. McNutt, MS, PhD, Juan F. Jackson, CMD, Dung T. Le, MD, Elizabeth M. Jaffee, MD, Lei Zheng, MD, PhD, Daniel A. Laheru, MD, Jin He, MD, PhD, Timothy M. Pawlik, MD, MPH, PhD, Matthew J. Weiss, MD, Christopher L. Wolfgang, MD, PhD, Joseph M. Herman, MD, MSc

Published in: Annals of Surgical Oncology | Issue 1/2018

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Abstract

Background

A standardized treatment regimen for unresectable isolated local recurrence (ILR) of pancreatic ductal adenocarcinoma has not been established. This study evaluated the outcomes for patients with ILR who underwent stereotactic body radiation therapy (SBRT).

Methods

The records of patients with ILR who underwent SBRT between 2010 and 2016 were retrospectively reviewed. Symptom palliation and treatment-related toxicity were recorded. Associations between patient or treatment characteristics and overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were assessed.

Results

The study identified 51 patients who received SBRT for ILR. Of the 51 patients, 26 (51%) had not received radiation therapy before SBRT. The median OS was 36 months after diagnosis. From the first day of SBRT, the median OS, PFS, and LPFS were respectively 16, 7, and 10 months. Patients with a recurrence-free interval of 9 months or longer after surgery had superior OS (P = 0.019). Maintenance chemotherapy after SBRT was associated with superior OS (P < 0.001) and LPFS (P = 0.027). In the multivariable analysis, poorly differentiated tumor grade [hazard ratio (HR) 11.274], positive surgical margins (HR 0.126), and reception of maintenance chemotherapy (HR 0.141) were independently associated with OS. Positive surgical margins (HR 0.255) and maintenance chemotherapy (HR 0.299) were associated with improved LPFS. Of 16 patients, 10 (63%) experienced abdominal pain relief after SBRT. Four patients (8%) experienced grade 3 gastrointestinal toxicity, and one patient experienced grade 4 gastrointestinal toxicity.

Conclusions

Use of SBRT for ILR improved pain for a majority of the patients with acceptable acute and late toxicity. The findings show that SBRT is a feasible treatment for select patients with ILR. For those who receive SBRT, maintenance chemotherapy should be considered.
Literature
2.
go back to reference Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival: a prospective, single-institution experience. Ann Surg. 1997;225:621–36.CrossRefPubMedPubMedCentral Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival: a prospective, single-institution experience. Ann Surg. 1997;225:621–36.CrossRefPubMedPubMedCentral
3.
go back to reference Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.CrossRefPubMed Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.CrossRefPubMed
4.
go back to reference Hartwig W, Werner J, Jager D, Debus J, Buchler MW. Improvement of surgical results for pancreatic cancer. The Lancet Oncology. 2013;14:476–85.CrossRef Hartwig W, Werner J, Jager D, Debus J, Buchler MW. Improvement of surgical results for pancreatic cancer. The Lancet Oncology. 2013;14:476–85.CrossRef
5.
go back to reference Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.CrossRefPubMed Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.CrossRefPubMed
6.
go back to reference Asiyanbola B, Gleisner A, Herman JM, Choti MA, Wolfgang CL, Swartz M, et al. Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph nodes and lymph node ratio. J Gastrointest Surg. 2009;13:752–759.CrossRefPubMed Asiyanbola B, Gleisner A, Herman JM, Choti MA, Wolfgang CL, Swartz M, et al. Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph nodes and lymph node ratio. J Gastrointest Surg. 2009;13:752–759.CrossRefPubMed
7.
go back to reference Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600–4.CrossRefPubMed Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600–4.CrossRefPubMed
8.
go back to reference Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995;221:721–33.CrossRefPubMedPubMedCentral Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995;221:721–33.CrossRefPubMedPubMedCentral
9.
go back to reference Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2017. doi:10.1097/SLA.0000000000002234. Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2017. doi:10.​1097/​SLA.​0000000000002234​.
10.
go back to reference Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806–13.CrossRefPubMedPubMedCentral Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806–13.CrossRefPubMedPubMedCentral
11.
go back to reference Ogawa K, Shibuya H, Uchida N, Onishi H, Okuno Y, Myojin M, et al. Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival. Anticancer Res. 2010;30:2959–67.PubMed Ogawa K, Shibuya H, Uchida N, Onishi H, Okuno Y, Myojin M, et al. Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival. Anticancer Res. 2010;30:2959–67.PubMed
12.
go back to reference Rudra S, Narang AK, Pawlik TM, Wang H, Jaffee EM, Zheng L, et al. Evaluation of predictive variables in locally advanced pancreatic adenocarcinoma patients receiving definitive chemoradiation. Pract Radiat Oncol. 2012;2:77–85.CrossRefPubMed Rudra S, Narang AK, Pawlik TM, Wang H, Jaffee EM, Zheng L, et al. Evaluation of predictive variables in locally advanced pancreatic adenocarcinoma patients receiving definitive chemoradiation. Pract Radiat Oncol. 2012;2:77–85.CrossRefPubMed
13.
go back to reference Groot VP, van Santvoort HC, Rombouts SJ, Hagendoorn J, Rinkes IH, van Vulpen M, et al. Systematic review on the treatment of isolated local recurrence of pancreatic cancer after surgery; re-resection, chemoradiotherapy, and SBRT. HPB (Oxford). 2017;19:83–92.CrossRef Groot VP, van Santvoort HC, Rombouts SJ, Hagendoorn J, Rinkes IH, van Vulpen M, et al. Systematic review on the treatment of isolated local recurrence of pancreatic cancer after surgery; re-resection, chemoradiotherapy, and SBRT. HPB (Oxford). 2017;19:83–92.CrossRef
14.
go back to reference Chang DT, Schellenberg D, Shen J, Kim J, Goodman KA, Fisher GA, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed Chang DT, Schellenberg D, Shen J, Kim J, Goodman KA, Fisher GA, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed
15.
go back to reference Didolkar MS, Coleman CW, Brenner MJ, Chu KU, Olexa N, Stanwyck E, et al. Image-guided stereotactic radiosurgery for locally advanced pancreatic adenocarcinoma results of first 85 patients. J Gastrointest Surg. 2010;14:1547–59.CrossRefPubMed Didolkar MS, Coleman CW, Brenner MJ, Chu KU, Olexa N, Stanwyck E, et al. Image-guided stereotactic radiosurgery for locally advanced pancreatic adenocarcinoma results of first 85 patients. J Gastrointest Surg. 2010;14:1547–59.CrossRefPubMed
16.
go back to reference Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.CrossRefPubMed Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.CrossRefPubMed
17.
go back to reference Koong AC, Christofferson E, Le QT, Goodman KA, Ho A, Kuo T, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63:320–3.CrossRefPubMed Koong AC, Christofferson E, Le QT, Goodman KA, Ho A, Kuo T, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63:320–3.CrossRefPubMed
18.
go back to reference Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker‐Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121:1128–37.CrossRefPubMed Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker‐Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121:1128–37.CrossRefPubMed
19.
go back to reference Schellenberg D, Goodman KA, Lee F, Chang S, Kuo T, Ford JM, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72:678–86.CrossRefPubMed Schellenberg D, Goodman KA, Lee F, Chang S, Kuo T, Ford JM, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72:678–86.CrossRefPubMed
20.
go back to reference Moningi S, Dholakia AS, Raman SP, Blackford A, Cameron JL, Le DT, et al. The role of stereotactic body radiation therapy for pancreatic cancer: a single-institution experience. Ann Surg Oncol. 2015;22:2352–8.CrossRefPubMedPubMedCentral Moningi S, Dholakia AS, Raman SP, Blackford A, Cameron JL, Le DT, et al. The role of stereotactic body radiation therapy for pancreatic cancer: a single-institution experience. Ann Surg Oncol. 2015;22:2352–8.CrossRefPubMedPubMedCentral
21.
go back to reference Wild AT, Hiniker SM, Chang DT, Tran PT, Khashab MA, Limaye MR, et al. Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions. J Gastrointest Oncol. 2013;4:343–51.PubMedPubMedCentral Wild AT, Hiniker SM, Chang DT, Tran PT, Khashab MA, Limaye MR, et al. Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions. J Gastrointest Oncol. 2013;4:343–51.PubMedPubMedCentral
25.
go back to reference Hosmer DW, Lemeshow S. Applied Survival analysis: regression modeling of time-to-event data. Wiley, New York, 1999. Hosmer DW, Lemeshow S. Applied Survival analysis: regression modeling of time-to-event data. Wiley, New York, 1999.
26.
27.
go back to reference Strobel O, Hartwig W, Hackert T, Hinz U, Berens V, Grenacher L, et al. Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol. 2013;20:964–72.CrossRefPubMed Strobel O, Hartwig W, Hackert T, Hinz U, Berens V, Grenacher L, et al. Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol. 2013;20:964–72.CrossRefPubMed
28.
go back to reference Wilkowski R, Thoma M, Bruns C, Duhmke E, Heinemann V. Combined chemoradiotherapy for isolated local recurrence after primary resection of pancreatic cancer. JOP. 2006;7:34–40.PubMed Wilkowski R, Thoma M, Bruns C, Duhmke E, Heinemann V. Combined chemoradiotherapy for isolated local recurrence after primary resection of pancreatic cancer. JOP. 2006;7:34–40.PubMed
29.
go back to reference Habermehl D, Brecht IC, Bergmann F, Welzel T, Rieken S, Werner J, et al. Chemoradiation in patients with isolated recurrent pancreatic cancer: therapeutical efficacy and probability of re-resection. Radiat Oncol. 2013;8:27.CrossRefPubMedPubMedCentral Habermehl D, Brecht IC, Bergmann F, Welzel T, Rieken S, Werner J, et al. Chemoradiation in patients with isolated recurrent pancreatic cancer: therapeutical efficacy and probability of re-resection. Radiat Oncol. 2013;8:27.CrossRefPubMedPubMedCentral
30.
go back to reference Nakamura A, Itasaka S, Takaori K, Kawaguchi Y, Shibuya K, Yoshimura M, et al. Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer: prolonged disease-free interval associated with favorable prognosis. Strahlenther Onkol. 2014;190:485–90.CrossRefPubMed Nakamura A, Itasaka S, Takaori K, Kawaguchi Y, Shibuya K, Yoshimura M, et al. Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer: prolonged disease-free interval associated with favorable prognosis. Strahlenther Onkol. 2014;190:485–90.CrossRefPubMed
31.
go back to reference Xue P, Kanai M, Mori Y, Nishimura T, Uza N, Kodama Y, et al. Comparative outcomes between initially unresectable and recurrent cases of advanced pancreatic cancer following palliative chemotherapy. Pancreas. 2014;43:411–6.CrossRefPubMed Xue P, Kanai M, Mori Y, Nishimura T, Uza N, Kodama Y, et al. Comparative outcomes between initially unresectable and recurrent cases of advanced pancreatic cancer following palliative chemotherapy. Pancreas. 2014;43:411–6.CrossRefPubMed
32.
go back to reference Zhang Y, Frampton AE, Kyriakides C, Bong JJ, Habib N, Ahmad R, et al. Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy. J Cancer Res Clin Oncol. 2012;138:1063–71.CrossRefPubMed Zhang Y, Frampton AE, Kyriakides C, Bong JJ, Habib N, Ahmad R, et al. Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy. J Cancer Res Clin Oncol. 2012;138:1063–71.CrossRefPubMed
33.
go back to reference Hashimoto D, Chikamoto A, Ohmuraya M, Sakata K, Miyake K, Kuroki H, et al. Pancreatic cancer in the remnant pancreas following primary pancreatic resection. Surg Today. 2014;44:1313–20.CrossRefPubMed Hashimoto D, Chikamoto A, Ohmuraya M, Sakata K, Miyake K, Kuroki H, et al. Pancreatic cancer in the remnant pancreas following primary pancreatic resection. Surg Today. 2014;44:1313–20.CrossRefPubMed
34.
go back to reference Suzuki S, Furukawa T, Oshima N, Izumo W, Shimizu K, Yamamoto M. Original scientific reports: clinicopathological findings of remnant pancreatic cancers in survivors following curative resections of pancreatic cancers. World J Surg. 2016;40:974–81.CrossRefPubMed Suzuki S, Furukawa T, Oshima N, Izumo W, Shimizu K, Yamamoto M. Original scientific reports: clinicopathological findings of remnant pancreatic cancers in survivors following curative resections of pancreatic cancers. World J Surg. 2016;40:974–81.CrossRefPubMed
35.
go back to reference Murphy JD, Chang DT, Abelson J, Daly ME, Yeung HN, Nelson LM, et al. Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer. Cancer. 2012;118:1119–29.CrossRefPubMed Murphy JD, Chang DT, Abelson J, Daly ME, Yeung HN, Nelson LM, et al. Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer. Cancer. 2012;118:1119–29.CrossRefPubMed
36.
go back to reference Seo Y, Kim MS, Yoo S, Cho C, Yang K, Yoo H, et al. Stereotactic body radiation therapy boost in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2009;75:1456–61.CrossRefPubMed Seo Y, Kim MS, Yoo S, Cho C, Yang K, Yoo H, et al. Stereotactic body radiation therapy boost in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2009;75:1456–61.CrossRefPubMed
37.
go back to reference Zeng XL, Wang HH, Meng MB, Wu ZQ, Song YC, Zhuang HQ, et al. Stereotactic body radiation therapy for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph nodes or postoperative stump including pancreatic stump and other stump. Onco Targets Ther. 2016;9:3985–92.CrossRefPubMedPubMedCentral Zeng XL, Wang HH, Meng MB, Wu ZQ, Song YC, Zhuang HQ, et al. Stereotactic body radiation therapy for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph nodes or postoperative stump including pancreatic stump and other stump. Onco Targets Ther. 2016;9:3985–92.CrossRefPubMedPubMedCentral
38.
go back to reference Dagoglu N, Callery M, Moser J, Tseng J, Kent T, Bullock A, et al. Stereotactic body radiotherapy (SBRT) reirradiation for recurrent pancreas cancer. J Cancer. 2016;7:283–8.CrossRefPubMedPubMedCentral Dagoglu N, Callery M, Moser J, Tseng J, Kent T, Bullock A, et al. Stereotactic body radiotherapy (SBRT) reirradiation for recurrent pancreas cancer. J Cancer. 2016;7:283–8.CrossRefPubMedPubMedCentral
39.
go back to reference Lominska CE, Unger K, Nasr NM, Haddad N, Gagnon G. Stereotactic body radiation therapy for re-irradiation of localized adenocarcinoma of the pancreas. Radiat Oncol. 2012;7:74.CrossRefPubMedPubMedCentral Lominska CE, Unger K, Nasr NM, Haddad N, Gagnon G. Stereotactic body radiation therapy for re-irradiation of localized adenocarcinoma of the pancreas. Radiat Oncol. 2012;7:74.CrossRefPubMedPubMedCentral
Metadata
Title
Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Surgical Resection of Pancreatic Ductal Adenocarcinoma Appears to be Safe and Effective
Authors
John F. Ryan, BS
Vincent P. Groot, MD
Lauren M. Rosati, BS
Amy Hacker-Prietz, MS, PA-C
Amol K. Narang, MD
Todd R. McNutt, MS, PhD
Juan F. Jackson, CMD
Dung T. Le, MD
Elizabeth M. Jaffee, MD
Lei Zheng, MD, PhD
Daniel A. Laheru, MD
Jin He, MD, PhD
Timothy M. Pawlik, MD, MPH, PhD
Matthew J. Weiss, MD
Christopher L. Wolfgang, MD, PhD
Joseph M. Herman, MD, MSc
Publication date
01-01-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 1/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-6134-6

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