Use of radiation therapy (RT) in pancreatic cancer is evolving and will likely expand as systemic therapy improves for this difficult-to-treat disease, according to a new set of guidelines from the American Society for Radiation Oncology (ASTRO).
Published in , the new guidance covers the appropriate use of RT across various clinical scenarios, and includes recommendations on sequencing with systemic agents, dosing schemes, and technical aspects (simulation, treatment planning and delivery).
"The role of radiation in the treatment of pancreatic cancer is controversial," guideline co-chair Manisha Palta, MD, of Duke University in Durham, North Carolina, told ľֱ via email. "This was recognized by the ASTRO Guidelines Subcommittee to be a topic where the development of clinical practice guidelines would be helpful for the radiation oncology and larger oncology community."
For resectable disease, ASTRO gives a "conditional" recommendation to adjuvant conventional RT for patients with high-risk clinical features such as nodal involvement or positive margins. Due to limited data, adjuvant stereotactic body radiation therapy (SBRT) is only recommended as part of a trial or multi-institutional registry. In the neoadjuvant setting, either conventional RT or SBRT are given a conditional recommendation following chemotherapy for resectable patients.
For borderline resectable disease, the guideline gives a conditional recommendation to neoadjuvant chemotherapy followed by either multi-fraction SBRT or conventional RT plus chemotherapy.
In locally advanced patients ineligible for surgery, a definitive treatment strategy of systemic chemotherapy followed by either conventional RT plus chemotherapy, dose-escalated chemoradiotherapy, or multi-fraction SBRT without chemotherapy is given a conditional recommendation.
"Any patient who is diagnosed with pancreatic cancer deserves to have a multidisciplinary evaluation," said Palta. "It's also essential that any patient who might be an appropriate candidate for radiation have access to a radiation oncologist who can provide perspective on the pros and cons of treatment, so that the patient can make an informed decision."
Prevention strategies to mitigate common radiation-induced toxicities were also evaluated by Palta's team, who examined published data on the use of RT in pancreatic cancer from 2007 to 2017 to form their new recommendations.
"The guideline strongly recommends the prophylactic use of anti-emetic medications to reduce the rate of nausea and conditionally recommends the prophylactic use of acid reducing medications," said Palta.
ASTRO's new guidelines were developed in collaboration with the American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology. Palta said that by specifically focusing on the delivery of RT, the new guidance complements ASCO's pancreatic cancer guidelines on , , and disease.
Christopher Crane, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the new recommendations seek to reconcile a confusing area in radiation oncology with a limited evidence base.
"There's a lot of people doing a lot of different things," said Crane, who was not involved in the guidelines.
"This really serves as a baseline for what we need to improve on," said Crane. "Can we do better than this? Yes."
In particular, he told ľֱ that the level of enthusiasm among radiation oncologists for low-dose SBRT for locally advanced pancreatic cancer is "disproportionate to the evidence of benefit."
For borderline resectable disease, for instance, the guidelines conditionally recommend SBRT at a dose of 30-33 Gy over five fractions, with a boost up to 40 Gy to the tumor vessel interface. For patients with locally advanced disease, SBRT at 33 to 40 Gy over five fractions is strongly recommended.
"The lower-dose SBRT that they have strongly said should be given, I have ethical reservations about recommending that to a patient because it doesn't improve survival over chemotherapy alone," said Crane. "The only thing that's promising is doubling the dose."
Delivering ablative doses of radiation using newer technologies such as MRI-guided delivery with daily adaptive planning can yield results that compete with surgery, Crane suggested.
Research from his group at Sloan Kettering was presented at the 2019 ASTRO annual meeting in Chicago. Using ablative RT doses (up to 75 Gy) in patients with locally advanced pancreatic cancer, they reported overall survival rates at 2 years of 55% in a group of 136 patients treated with definitive radiation and 67% in a group of 33 patients treated in the salvage setting.
Ultimately, Crane said there won't be a shift in practice until more data on ablative techniques from various institutions are published, more radiation oncologists are trained on these newer technologies, and its use expands.
Disclosures
The guidelines were funded by ASTRO.
Palta disclosed relevant relationships with Oakstone, Merck, Navigant, UpToDate, and Varian. Co-authors disclosed multiple relevant relationships with industry.
Primary Source
Practical Radiation Oncology
Palta M, et al "Radiation therapy for pancreatic cancer: Executive summary of an ASTRO clinical practice guideline" Pract Radiat Oncol 2019; 9(5):322-332.