Skip to main content
Top
Published in: Radiation Oncology 1/2017

Open Access 01-12-2017 | Research

Quantification of renal function following stereotactic body radiotherapy for pancreatic cancer: secondary dosimetric analysis of a prospective clinical trial

Authors: Vivek Verma, Abhijeet R. Bhirud, Kyle A. Denniston, Nathan R. Bennion, Chi Lin

Published in: Radiation Oncology | Issue 1/2017

Login to get access

Abstract

Background

This is the first known study examining renal function following stereotactic body radiotherapy (SBRT) for pancreatic head adenocarcinoma.

Methods

Thirty-eight borderline-resectable/unresectable patients, part of an ongoing prospective trial, underwent 3 cycles of gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5/6/7/8 Gy) and concurrent nelfinavir. Thereafter, in resectable cases, surgery was performed within 4–8 weeks. The last available pre-SBRT creatinine was recorded, along with the highest post-SBRT value. Glomerular filtration rate (GFR) was calculated by the commonly-utilized Modification of Diet in Renal Disease formula. GFR decline was defined as the post-SBRT nadir GFR minus the pre-SBRT GFR. Correlations with the V5–V30, and mean/maximum kidney doses was performed. Statistics included Pearson correlation, Mann-Whitney, and Fisher’s exact tests.

Results

The median total kidney volume was 355 cm3. Median dosimetric values were as follows: V5 (209 cm3), V10 (103 cm3), V15 (9 cm3), V20 (0 cm3), V25 (0 cm3); and mean (6.7 Gy) & maximum kidney dose (18.3 Gy). Median GFR change was −23 (range, −105 to 25) mL/min/1.73 cm2. Of all dosimetric parameters, only V5 was significantly associated with changes in GFR (Pearson r = −0.40, p = 0.012). In patients with V5 < 210 cm3, median GFR change was −11.8 mL/min/1.73 cm2, as compared with −37.1 mL/min/1.73 cm2 change in those with V5 ≥ 210 cm3 (p = 0.02). A GFR change < −23 mL/min/1.73 cm2 was observed in 6/20 (30%) patients with V5 < 210 cm3, versus 15/18 (83%) of those with V5 ≥ 210 cm3. Patients with V5 ≥ 210 cm3 were over ten times as likely to have GFR change < −23 mL/min/1.73 cm2 (p = 0.003). Using linear regression, GFR change ≈ −0.1748 × V5(cm3) + 8.63.

Conclusions

In the first known analysis of renal function after pancreatic SBRT, evaluating patients on a prospective study, V5 ≥ 210 cm3 was associated with a post-SBRT GFR decline of >23 mL/min/1.73 cm2. If V5 is kept <210 cm3, median GFR decline was only 11.8 mL/min/1.73 cm2. Further validation is needed to ascertain definite dose-volume parameters and examine late renal decline.
Literature
1.
go back to reference Verma V, Li J, Lin C. Neoadjuvant Therapy for Pancreatic Cancer: Systematic Review of Postoperative Morbidity, Mortality, and Complications. Am J Clin Oncol. 2016;39:302–13. Verma V, Li J, Lin C. Neoadjuvant Therapy for Pancreatic Cancer: Systematic Review of Postoperative Morbidity, Mortality, and Complications. Am J Clin Oncol. 2016;39:302–13.
2.
go back to reference Marks LB, Yorke ED, Jackson A, et al. The use of normal tissue complication probability (NTCP) models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S10–9.CrossRefPubMedPubMedCentral Marks LB, Yorke ED, Jackson A, et al. The use of normal tissue complication probability (NTCP) models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S10–9.CrossRefPubMedPubMedCentral
3.
go back to reference Dawson LA, Kavanagh BD, Paulino AC, et al. Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S108–15.CrossRefPubMed Dawson LA, Kavanagh BD, Paulino AC, et al. Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S108–15.CrossRefPubMed
4.
go back to reference Siva S, Jackson P, Kron T, et al. Impact of stereotactic radiotherapy on kidney function in primary renal cell carcinoma: establishing a dose-response relationship. Radiother Oncol. 2016;118:540–6.CrossRefPubMed Siva S, Jackson P, Kron T, et al. Impact of stereotactic radiotherapy on kidney function in primary renal cell carcinoma: establishing a dose-response relationship. Radiother Oncol. 2016;118:540–6.CrossRefPubMed
5.
go back to reference Koong AC, Christofferson E, Le QT, 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, 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
6.
go back to reference Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed
7.
go back to reference Chuong MD, Springett GM, Freilich JM, et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well-tolerated. Int J Radiat Oncol Biol Phys. 2013;86:516–22.CrossRefPubMed Chuong MD, Springett GM, Freilich JM, et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well-tolerated. Int J Radiat Oncol Biol Phys. 2013;86:516–22.CrossRefPubMed
8.
go back to reference Su TS, Liang P, Lu HZ, et al. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. World J Gastroenterol. 2015;21:8156–62.PubMedPubMedCentral Su TS, Liang P, Lu HZ, et al. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. World J Gastroenterol. 2015;21:8156–62.PubMedPubMedCentral
9.
go back to reference Herman JM, Chang DT, Goodman KA, 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, 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
10.
go back to reference Gupta AK, Cerniglia GJ, Mick R, et al. HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo. Cancer Res. 2005;65:8256–65.CrossRefPubMed Gupta AK, Cerniglia GJ, Mick R, et al. HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo. Cancer Res. 2005;65:8256–65.CrossRefPubMed
11.
go back to reference Brunner TB, Geiger M, Grabenbauer GG, et al. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J Clin Oncol. 2008;26:2699–706.CrossRefPubMed Brunner TB, Geiger M, Grabenbauer GG, et al. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J Clin Oncol. 2008;26:2699–706.CrossRefPubMed
12.
go back to reference Wilson JM, Fokas E, Dutton SJ, et al. ARCII: a phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer. Radiother Oncol. 2016;119:306–11.CrossRefPubMedPubMedCentral Wilson JM, Fokas E, Dutton SJ, et al. ARCII: a phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer. Radiother Oncol. 2016;119:306–11.CrossRefPubMedPubMedCentral
14.
go back to reference Verma V, Lazenby AJ, Zheng D, et al. Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: secondary analysis of a prospective clinical trial. Radiother Oncol. 2017;122:464-69. Verma V, Lazenby AJ, Zheng D, et al. Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: secondary analysis of a prospective clinical trial. Radiother Oncol. 2017;122:464-69.
16.
go back to reference Jabbour SK, Hashem SA, Bosch W, et al. Upper abdominal normal organ contouring guidelines and atlas: a Radiation Therapy Oncology Group consensus. Pract Radiat Oncol. 2014;4:82–9.CrossRefPubMed Jabbour SK, Hashem SA, Bosch W, et al. Upper abdominal normal organ contouring guidelines and atlas: a Radiation Therapy Oncology Group consensus. Pract Radiat Oncol. 2014;4:82–9.CrossRefPubMed
17.
go back to reference Grimm J, LaCouture T, Croce R, et al. Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys. 2011;12:267–92.CrossRef Grimm J, LaCouture T, Croce R, et al. Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys. 2011;12:267–92.CrossRef
19.
go back to reference Boubaker K, Sudre P, Bally F, et al. Changes in renal function associated with indinavir. AIDS. 1998;12:F249–54.CrossRefPubMed Boubaker K, Sudre P, Bally F, et al. Changes in renal function associated with indinavir. AIDS. 1998;12:F249–54.CrossRefPubMed
20.
go back to reference Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62:968–74.CrossRefPubMed Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62:968–74.CrossRefPubMed
21.
go back to reference Broce JC, Price LL, Liangos O, et al. Hospital-acquired acute kidney injury: an analysis of nadir-to-peak serum creatinine increments stratified by baseline estimated GFR. Clin J Am Soc Nephrol. 2011;6:1556–65.CrossRefPubMedPubMedCentral Broce JC, Price LL, Liangos O, et al. Hospital-acquired acute kidney injury: an analysis of nadir-to-peak serum creatinine increments stratified by baseline estimated GFR. Clin J Am Soc Nephrol. 2011;6:1556–65.CrossRefPubMedPubMedCentral
24.
go back to reference Weber CL, Beaulieu M, Karr G, Levin A. Demystifying chronic kidney disease: clinical caveats for the family physician. BC Med J. 2008;50:304–9. Weber CL, Beaulieu M, Karr G, Levin A. Demystifying chronic kidney disease: clinical caveats for the family physician. BC Med J. 2008;50:304–9.
25.
go back to reference Koong AC, Le QT, Ho A, 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, 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
26.
go back to reference Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–70.CrossRefPubMed Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–70.CrossRefPubMed
27.
go back to reference Chronic Kidney Disease Prognosis Consortium, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81.CrossRef Chronic Kidney Disease Prognosis Consortium, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81.CrossRef
28.
go back to reference Teh B, Bloch C, Galli-Guevara M, et al. The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Intervion J. 2007;3:1–9. Teh B, Bloch C, Galli-Guevara M, et al. The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Intervion J. 2007;3:1–9.
29.
go back to reference Elhammali A, Patel M, Weinberg B, et al. Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas. Radiat Oncol. 2015;10:186.CrossRefPubMedPubMedCentral Elhammali A, Patel M, Weinberg B, et al. Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas. Radiat Oncol. 2015;10:186.CrossRefPubMedPubMedCentral
Metadata
Title
Quantification of renal function following stereotactic body radiotherapy for pancreatic cancer: secondary dosimetric analysis of a prospective clinical trial
Authors
Vivek Verma
Abhijeet R. Bhirud
Kyle A. Denniston
Nathan R. Bennion
Chi Lin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-017-0798-8

Other articles of this Issue 1/2017

Radiation Oncology 1/2017 Go to the issue