Split-course SBRT for Borderline Resectable and Locally Advanced Pancreatic Cancer

Summary

Exploratory assessment of the efficacy and safety of gemcitabine-albumin-based paclitaxel chemotherapy combined with SBRT in the treatment of newly diagnosed borderline resectable and locally advanced unresectable pancreatic cancer patients with sequential investigator selection (IC).

Timeline

Start

2020-05-09

Primary completion

2024-05-09

Completion

2025-05-09

Publications

• Background Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
• Background Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
• Background Saif MW. Pancreatic neoplasm in 2011: an update. JOP. 2011 Jul 8;12(4):316-21.
• Background Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. doi: 10.1001/jama.2013.279201.
• Background Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. doi: 10.1245/s10434-011-1630-6. Epub 2011 Mar 10.
• Background Michelakos T, Pergolini I, Castillo CF, Honselmann KC, Cai L, Deshpande V, Wo JY, Ryan DP, Allen JN, Blaszkowsky LS, Clark JW, Murphy JE, Nipp RD, Parikh A, Qadan M, Warshaw AL, Hong TS, Lillemoe KD, Ferrone CR. Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. Ann Surg. 2019 Apr;269(4):733-740. doi: 10.1097/SLA.0000000000002600.
• Background Gao S, Zhu X, Shi X, Cao K, Bian Y, Jiang H, Wang K, Guo S, Zhang H, Jin G. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1). Radiat Oncol. 2019 Mar 27;14(1):52. doi: 10.1186/s13014-019-1254-8.
• Background Zhong J, Patel K, Switchenko J, Cassidy RJ, Hall WA, Gillespie T, Patel PR, Kooby D, Landry J. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation. Cancer. 2017 Sep 15;123(18):3486-3493. doi: 10.1002/cncr.30706. Epub 2017 May 10.
• Background Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol. 2015 Jul;54(7):979-85. doi: 10.3109/0284186X.2015.1004367. Epub 2015 Mar 3.
• Background Chuong MD, Springett GM, Weber J, Klapman J, et al. Induction gemcitabine-based chemotherapy and neoadjuvant stereotactic body radiation therapy achieve high margin-negative resection rates for borderline resectable pancreatic cancer. Journal of Radiation Oncology. 2012;1:273-281
• Background Polistina F, Costantin G, Casamassima F, Francescon P, Guglielmi R, Panizzoni G, Febbraro A, Ambrosino G. Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Ann Surg Oncol. 2010 Aug;17(8):2092-101. doi: 10.1245/s10434-010-1019-y. Epub 2010 Mar 12.
• Background Rombouts SJ, Walma MS, Vogel JA, van Rijssen LB, Wilmink JW, Mohammad NH, van Santvoort HC, Molenaar IQ, Besselink MG. Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. Ann Surg Oncol. 2016 Dec;23(13):4352-4360. doi: 10.1245/s10434-016-5373-2. Epub 2016 Jul 1.
• Background Moningi S, Dholakia AS, Raman SP, Blackford A, Cameron JL, Le DT, De Jesus-Acosta AM, Hacker-Prietz A, Rosati LM, Assadi RK, Dipasquale S, Pawlik TM, Zheng L, Weiss MJ, Laheru DA, Wolfgang CL, Herman JM. The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience. Ann Surg Oncol. 2015 Jul;22(7):2352-8. doi: 10.1245/s10434-014-4274-5. Epub 2015 Jan 7.
• Background Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, Iacobuzio-Donahue CA, Griffith ME, Pawlik TM, Pai JS, O'Reilly E, Fisher GA, Wild AT, Rosati LM, Zheng L, Wolfgang CL, Laheru DA, Columbo LA, Sugar EA, Koong AC. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015 Apr 1;121(7):1128-37. doi: 10.1002/cncr.29161. Epub 2014 Dec 23.
• Background Kharofa J, Mierzwa M, Olowokure O, Sussman J, Latif T, Gupta A, Xie C, Patel S, Esslinger H, Mcgill B, Wolf E, Ahmad SA. Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer. Am J Clin Oncol. 2019 Mar;42(3):247-252. doi: 10.1097/COC.0000000000000518.
• Background Shaib WL, Hawk N, Cassidy RJ, Chen Z, Zhang C, Brutcher E, Kooby D, Maithel SK, Sarmiento JM, Landry J, El-Rayes BF. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458). Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):296-303. doi: 10.1016/j.ijrobp.2016.05.010. Epub 2016 May 24.
• Background Bae SH, Kim MS, Kim SY, Jang WI, Cho CK, Yoo HJ, Kim KB, Lee DH, Han CJ, Yang KY, Kim SB. Severe intestinal toxicity after stereotactic ablative radiotherapy for abdominopelvic malignancies. Int J Colorectal Dis. 2013 Dec;28(12):1707-13. doi: 10.1007/s00384-013-1717-6. Epub 2013 Jun 18.
• Background Rostom AY, Tahir S, Gershuny AR, Kandil A, Folkes A, White WF. Once weekly irradiation for carcinoma of the bladder. Int J Radiat Oncol Biol Phys. 1996 May 1;35(2):289-92. doi: 10.1016/0360-3016(96)00063-6.
• Background McLaren DB, Morrey D, Mason MD. Hypofractionated radiotherapy for muscle invasive bladder cancer in the elderly. Radiother Oncol. 1997 May;43(2):171-4. doi: 10.1016/s0167-8140(97)01943-9.
• Background Scholten AN, Leer JW, Collins CD, Wondergem J, Hermans J, Timothy A. Hypofractionated radiotherapy for invasive bladder cancer. Radiother Oncol. 1997 May;43(2):163-9. doi: 10.1016/s0167-8140(96)01893-2.
• Background Jose CC, Price A, Norman A, Jay G, Huddart R, Dearnaley DP, Horwich A. Hypofractionated radiotherapy for patients with carcinoma of the bladder. Clin Oncol (R Coll Radiol). 1999;11(5):330-3. doi: 10.1053/clon.1999.9075.
• Background Hafeez S, McDonald F, Lalondrelle S, McNair H, Warren-Oseni K, Jones K, Harris V, Taylor H, Khoo V, Thomas K, Hansen V, Dearnaley D, Horwich A, Huddart R. Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment. Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):115-122. doi: 10.1016/j.ijrobp.2017.01.239. Epub 2017 Feb 9.
• Background Bledsoe TJ, Noble AR, Reddy CA, Burkey BB, Greskovich JF, Nwizu T, Adelstein DJ, Saxton JP, Koyfman SA. Split-Course Accelerated Hypofractionated Radiotherapy (SCAHRT): A Safe and Effective Option for Head and Neck Cancer in the Elderly or Infirm. Anticancer Res. 2016 Mar;36(3):933-9.
• Background Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016 Jun;17(6):801-810. doi: 10.1016/S1470-2045(16)00172-8. Epub 2016 May 6.
• Background Muranaka T, Kuwatani M, Komatsu Y, Sawada K, Nakatsumi H, Kawamoto Y, Yuki S, Kubota Y, Kubo K, Kawahata S, Kawakubo K, Kawakami H, Sakamoto N. Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer. J Gastrointest Oncol. 2017 Jun;8(3):566-571. doi: 10.21037/jgo.2017.02.02.
• Background Verma V, Lazenby AJ, Zheng D, Bhirud AR, Ly QP, Are C, Sasson AR, Lin C. Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a prospective clinical trial. Radiother Oncol. 2017 Mar;122(3):464-469. doi: 10.1016/j.radonc.2016.12.030. Epub 2017 Jan 12.
• Background Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tome WA, Verellen D, Wang L, Yin FF. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010 Aug;37(8):4078-101. doi: 10.1118/1.3438081.
• Background Blomstrand H, Scheibling U, Bratthall C, Green H, Elander NO. Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer. BMC Cancer. 2019 Jan 8;19(1):40. doi: 10.1186/s12885-018-5244-2.
• Background Gemenetzis G, Groot VP, Blair AB, Laheru DA, Zheng L, Narang AK, Fishman EK, Hruban RH, Yu J, Burkhart RA, Cameron JL, Weiss MJ, Wolfgang CL, He J. Survival in Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy and Surgical Resection. Ann Surg. 2019 Aug;270(2):340-347. doi: 10.1097/SLA.0000000000002753.
• Background Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, Oh DY, Chie EK, Lee JM, Heo JS, Park JO, Lim DH, Kim SH, Park SJ, Lee WJ, Koh YH, Park JS, Yoon DS, Lee IJ, Choi SH. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg. 2018 Aug;268(2):215-222. doi: 10.1097/SLA.0000000000002705.
• Background Bednar F, Zenati MS, Steve J, Winters S, Ocuin LM, Bahary N, Hogg ME, Zeh HJ 3rd, Zureikat AH. Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes? Ann Surg Oncol. 2017 May;24(5):1406-1413. doi: 10.1245/s10434-016-5707-0. Epub 2016 Nov 28.
• Background Conroy T, Bachet JB, Ayav A, Huguet F, Lambert A, Caramella C, Marechal R, Van Laethem JL, Ducreux M. Current standards and new innovative approaches for treatment of pancreatic cancer. Eur J Cancer. 2016 Apr;57:10-22. doi: 10.1016/j.ejca.2015.12.026. Epub 2016 Feb 4.
• Background Murphy JD, Christman-Skieller C, Kim J, Dieterich S, Chang DT, Koong AC. A dosimetric model of duodenal toxicity after stereotactic body radiotherapy for pancreatic cancer. Int J Radiat Oncol Biol Phys. 2010 Dec 1;78(5):1420-6. doi: 10.1016/j.ijrobp.2009.09.075. Epub 2010 Apr 14.
• Background Paik EK, Kim MS, Seo YS, Jang WI, Kang JK, Cho CK, Yoo HJ. Feasibility of split-course stereotactic ablative radiotherapy for oligometastases. Jpn J Clin Oncol. 2018 Jun 1;48(6):548-554. doi: 10.1093/jjco/hyy062.
• Background Gielda BT, Marsh JC, Zusag TW, Faber LP, Liptay M, Basu S, Warren WH, Fidler MJ, Batus M, Abrams RA, Bonomi P. Split-course chemoradiotherapy for locally advanced non-small cell lung cancer: a single-institution experience of 144 patients. J Thorac Oncol. 2011 Jun;6(6):1079-86. doi: 10.1097/JTO.0b013e3182199a7c.
• Background Milas L, Milas MM, Mason KA. Combination of taxanes with radiation: preclinical studies. Semin Radiat Oncol. 1999 Apr;9(2 Suppl 1):12-26.
• Background Milas L, Fujii T, Hunter N, Elshaikh M, Mason K, Plunkett W, Ang KK, Hittelman W. Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res. 1999 Jan 1;59(1):107-14.
• Background Higuchi Y, Serizawa T, Nagano O, Matsuda S, Ono J, Sato M, Iwadate Y, Saeki N. Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1543-8. doi: 10.1016/j.ijrobp.2008.10.035. Epub 2009 Jan 8.
• Background Hsieh CH, Chang HT, Lin SC, Chen YJ, Wang LY, Hsieh YP, Chen CA, Chong NS, Lin SL, Chen CY, Shueng PW. Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment--case report. BMC Cancer. 2010 Dec 31;10:696. doi: 10.1186/1471-2407-10-696.
• Background Angelov L, Mohammadi AM, Bennett EE, Abbassy M, Elson P, Chao ST, Montgomery JS, Habboub G, Vogelbaum MA, Suh JH, Murphy ES, Ahluwalia MS, Nagel SJ, Barnett GH. Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases >/= 2 cm. J Neurosurg. 2018 Aug;129(2):366-382. doi: 10.3171/2017.3.JNS162532. Epub 2017 Sep 22.
• Background Carlson DJ, Keall PJ, Loo BW Jr, Chen ZJ, Brown JM. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1188-95. doi: 10.1016/j.ijrobp.2010.10.007. Epub 2010 Dec 22.
• Background Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 2014 Feb 1;88(2):254-62. doi: 10.1016/j.ijrobp.2013.07.022.
• Background Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res. 2012 Mar;177(3):311-27. doi: 10.1667/rr2773.1. Epub 2012 Jan 9.
• Background Finkelstein SE, Timmerman R, McBride WH, Schaue D, Hoffe SE, Mantz CA, Wilson GD. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol. 2011;2011:439752. doi: 10.1155/2011/439752. Epub 2011 Nov 15.
• Background Song CW, Kim MS, Cho LC, Dusenbery K, Sperduto PW. Radiobiological basis of SBRT and SRS. Int J Clin Oncol. 2014 Aug;19(4):570-8. doi: 10.1007/s10147-014-0717-z. Epub 2014 Jul 5.
• Background Filatenkov A, Baker J, Mueller AM, Kenkel J, Ahn GO, Dutt S, Zhang N, Kohrt H, Jensen K, Dejbakhsh-Jones S, Shizuru JA, Negrin RN, Engleman EG, Strober S. Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to Induce Durable Complete Remissions. Clin Cancer Res. 2015 Aug 15;21(16):3727-39. doi: 10.1158/1078-0432.CCR-14-2824. Epub 2015 Apr 13.
• Background Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6.
• Background Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005 Jun 15;174(12):7516-23. doi: 10.4049/jimmunol.174.12.7516.
• Background Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010 Aug 15;127(4):759-67. doi: 10.1002/ijc.25429.
• Background Aryankalayil MJ, Makinde AY, Gameiro SR, Hodge JW, Rivera-Solis PP, Palayoor ST, Ahmed MM, Coleman CN. Defining molecular signature of pro-immunogenic radiotherapy targets in human prostate cancer cells. Radiat Res. 2014 Aug;182(2):139-48. doi: 10.1667/RR13731.1. Epub 2014 Jul 8.
• Zheng R, Wang C, Huang X, Lin Q, Huang D, Li XB, Huang H, Xu B. Chemotherapy-based split stereotactic body radiation therapy for borderline resectable and locally advanced pancreatic cancer: study protocol of a prospective, single-arm phase II trial. BMJ Open. 2020 Nov 5;10(11):e039900. doi: 10.1136/bmjopen-2020-039900.

Drugs

Indications