Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results
Marsha Reyngold, Parag Parikh, Christopher H Crane, Marsha Reyngold, Parag Parikh, Christopher H Crane
Abstract
Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.
Keywords: Ablative radiation; CBCT guided radiation therapy; Hypofractionated ablative radiation; IGRT; MRI guided radiation therapy; Pancreatic adenocarcinoma.
Conflict of interest statement
PJP receives clinical trial funding from Viewray, Inc.; CHC and MR declare that they have no competing interests.
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References
- Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–810. doi: 10.1016/S1470-2045(16)00172-8.
- 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(11):1806–1813. doi: 10.1200/JCO.2008.17.7188.
- Crane Christopher H., Varadhachary Gauri R., Yordy John S., Staerkel Gregg A., Javle Milind M., Safran Howard, Haque Waqar, Hobbs Bridgett D., Krishnan Sunil, Fleming Jason B., Das Prajnan, Lee Jeffrey E., Abbruzzese James L., Wolff Robert A. Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation ofSmad4(Dpc4)Immunostaining With Pattern of Disease Progression. Journal of Clinical Oncology. 2011;29(22):3037–3043. doi: 10.1200/JCO.2010.33.8038.
- Anonymous Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988;80(10):751–755. doi: 10.1093/jnci/80.10.751.
- Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592–1599. doi: 10.1093/annonc/mdn281.
- Klaassen DJ, MacIntyre JM, Catton GE, et al. Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil-an eastern cooperative oncology group study. J Clin Oncol. 1985;3:373–378. doi: 10.1200/JCO.1985.3.3.373.
- Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, et al. Effect of Chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without Erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844–1853. doi: 10.1001/jama.2016.4324.
- Loehrer PJ, Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105–4112. doi: 10.1200/JCO.2011.34.8904.
- Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825. doi: 10.1056/NEJMoa1011923.
- Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703. doi: 10.1056/NEJMoa1304369.
- 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(3):678–686. doi: 10.1016/j.ijrobp.2008.01.051.
- Hoyer M, Roed H, Sengelov L, Traberg A, Ohlhuis L, Pedersen J, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76(1):48–53. doi: 10.1016/j.radonc.2004.12.022.
- 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(7):1128–1137. doi: 10.1002/cncr.29161.
- Park JJ, Hajj C, Reyngold M, Shi W, Zhang Z, Cuaron JJ, et al. Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. Acta Oncol. 2017;56(12):1746–1753. doi: 10.1080/0284186X.2017.1342863.
- Zhong J, Patel K, Switchenko J, Cassidy RJ, Hall WA, Gillespie T, et al. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation. Cancer. 2017;123(18):3486–3493. doi: 10.1002/cncr.30706.
- Krishnan Sunil, Chadha Awalpreet S., Suh Yelin, Chen Hsiang-Chun, Rao Arvind, Das Prajnan, Minsky Bruce D., Mahmood Usama, Delclos Marc E., Sawakuchi Gabriel O., Beddar Sam, Katz Matthew H., Fleming Jason B., Javle Milind M., Varadhachary Gauri R., Wolff Robert A., Crane Christopher H. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. International Journal of Radiation Oncology*Biology*Physics. 2016;94(4):755–765. doi: 10.1016/j.ijrobp.2015.12.003.
- Bohoudi O, Bruynzeel AME, Senan S, Cuijpers JP, Slotman BJ, Lagerwaard FJ, et al. Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer. Radiother Oncol. 2017;125(3):439–444. doi: 10.1016/j.radonc.2017.07.028.
- Henke L, Kashani R, Robinson C, Curcuru A, DeWees T, Bradley J, et al. Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen. Radiother Oncol. 2018;126(3):519–526. doi: 10.1016/j.radonc.2017.11.032.
- Rudra S, Jiang N, Rosenberg SA, Olsen JR, Parikh PJ, Bassetti MF, et al. High dose adaptive MRI guided radiation therapy improves overall survival of inoperable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2017;99(2):E184. doi: 10.1016/j.ijrobp.2017.06.1042.
- Kelly P, Das P, Pinnix CC, Beddar S, Briere T, Pham M, et al. Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2013;85(3):e143–e1e9. doi: 10.1016/j.ijrobp.2012.09.035.
Source: PubMed