Identifying Optimal Doses and Supporting Data for IORT in Pancreatic Cancer
Investigators are assessing the use of IORT in patients with borderline resectable or unresectable pancreatic cancer as part of the phase 2 PACER trial.
Natalie A. Lockney, MD, and her colleagues spoke with CancerNetwork® about defining the optimal intraoperative radiation therapy (IORT) dose for patients with pancreatic cancer depending on the extent and resectability of their disease. The conversation also focused on prior data and ongoing research that may affirm the utility of IORT in this population.
According to Lockney, an assistant professor in radiation oncology and the program director for the radiation oncology medical residency at Vanderbilt University Medical Center, prior research conducted at Mayo Clinic1 and Massachusetts General Hospital2 demonstrate the potential local control and overall survival benefits of IORT. These data were included in a guideline published by the European Society for Radiotherapy and Oncology (ESTRO) specifying suitable conditions for using this modality.3
Transcript:
As you heard from Kamran Idrees, MD, MSCI, MMHC, FACS, the "real estate area" in the pancreas is critical to the treatment of the patient. [Although] complex surgeries and reconstructions may often be required for the vessel anatomy that he showed, the critical organs—from a radiation oncologist perspective—are the nearby bowel, such as the duodenum, remainder of the small intestine, and the stomach.
With pancreatic cancer, we have a difficult time getting a sufficient radiation dose delivered to the tumor because of those critical dose-limiting structures. We know conventional doses of external beam radiation in the range of 45 to 50 Gy do not provide durable local control. There are a lot of studies looking at use of preoperative chemoradiation, postoperative chemoradiation, and intraoperative radiation.
As we heard earlier, the benefit of intraoperative radiation is that those critical structures are either removed by the surgeon or can be manually retracted away from the field. That allow us to deliver a higher intraoperative radiation boost dose. For R0 tumors that are resected with a negative margin, our dose range for the IORT boost would typically range from 10 to 12.5 Gy. For tumors that have a microscopic positive margin, or R1 resection, the dose for the boosts will typically be 12.5 to 15 Gy. For tumors that have gross residual disease that couldn’t safely be resected, we may even escalate that IORT dose further up to 20 Gy. However, if the duodenum has not been resected and is still intact, then the dose may have to be lower. Therefore, for patients who are unresectable, we may instead pursue a high dose of ablative external beam [radiation].
To talk a little bit about the data for intraoperative radiation therapy, we know that [since the] 1980s, there have been over 30 published retrospective articles [showing] what’s been found. We know more contemporary data available from Mayo Clinic1 and Massachusetts General Hospital,2 where the local control after IORT has been reported to be in the range of 73% to 94%, with overall survival ranging from 23 to 35 months. We look forward to the completion of an ongoing, single-arm, prospective phase 2 trial that’s called the PACER trial [NCT03716531]. It’s being run out of Massachusetts General Hospital, led by Theodore Sunki Hong, MD. It’s looking at delivering intraoperative radiation in [patients with] pancreatic cancer who have either borderline resectable or unresectable disease with an intraoperative radiation therapy boost following standard preoperative radiation therapy.
It’s also important to note that we do have some guidelines available for the delivery of intraoperative radiation for pancreatic cancer. ESTRO, which is the European Society for Radiotherapy and Oncology, has an advisory committee for radiation oncology practice, and their task force did recently publish guidelines in 2020 recommending the use of IORT in certain settings for borderline resectable or unresectable pancreatic cancer.3
References
- Ashman JB, Moss AA, Rule WG, et al. Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer. J Gastrointest Oncol. 2013;4(4):352-60. doi:10.3978/j.issn.2078-6891.2013.006.
- Keane FK, Wo JY, Ferrone CR, et al. Intraoperative radiotherapy in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for pancreatic adenocarcinoma. Am J Clin Oncol. 2018;41(6):607-612. doi:10.1097/COC.0000000000000336.
- Calvo FA, Asencio JM, Roeder F, et al. ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer. Clin Transl Radiat Oncol. 2020;23:91-99. doi:10.1016/j.ctro.2020.05.005.
