MR-Linac-Delivered Adaptive Radiation Therapy Promising in Pancreatic Cancer

By Marilynn Larkin

October 12, 2020

NEW YORK (Reuters Health) - Stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) delivered on an MR-Linac provided "encouraging" early local pancreatic cancer control with minimal severe treatment-related toxicity in a single-center retrospective analysis.

"Our MR-Linac was the second clinically operational unit in the U.S. starting in April 2018," Dr. Michael Chuong of the Miami Cancer Institute told Reuters Health by email. "Our treatment regimen...delivers a very high ablative dose in only five days instead of the more common five to six weeks."

While the team's initial outcomes, reported in the current analysis, are "very encouraging," he said, "there needs to be longer follow up. We are analyzing outcomes now that have a longer follow up in a larger population of patients."

"Historically, two-year overall survival is <20% with standard chemotherapy and radiation therapy, although with the use of high ablative radiation dose this may potentially be doubled to >40-50%," he suggested. "We anticipate submitting our updated results to an upcoming scientific meeting within the next month."

As reported in Practical Radiation Oncology, the retrospective analysis included 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-Linac (median age, 67; 60% men). Most (88.6%) had tumors in the head of pancreas, locally advanced disease (80%), and received induction chemotherapy (91.4%) for a median 3.9 months prior to SBRT.

As Dr. Chuong noted, all had five fractions delivered in consecutive days to a median total dose of 50 Gy, typically with a 120%-130% hotspot. About half (57.1%) had elective nodal irradiation.

The median follow-up for all patients was 10.3 months, and 12.5 months for the 21 patients (60%) who were alive at time of this analysis.

At one year, on Kaplan-Meier analysis, cause-specific survival and overall survival were 77.6% and 58.9%, respectively.

Rates of local control, distant metastasis-free survival and progression-free survival at one year in survivors were 87.8%, 63.1% and 52.4%.

After SMART, about half (48.6%) did not resume chemotherapy. Thirteen (37%) received chemotherapy due to disease progression, and five received maintenance chemotherapy due to oncologist preference.

Three patients received irreversible electroporation (IRE) at a median of 11 months after SMART. IRE was used to manage regional progression outside of the planning target volume in two patients; neither had distant metastasis. A third patient with stable disease had IRE despite lack of tumor progression; the intra-operative biopsy prior to IRE was negative for invasive adenocarcinoma.

Five patients underwent a Whipple procedure performed at a median of months after completing SMART.

Acute and late grade-3 toxicities were uncommon, at 2.9% each.

Dr. Chuong said the five-day regimen "is routinely covered by insurance and is not more expensive than stereotactic ablative radiation therapy delivered on a standard delivery machine to lower doses." No anesthesia or fiducial marker placement is required, he noted, "and most patients are able to work and carry on their normal activities throughout treatment."

Dr. Kevin Du, a radiation oncologist at NYU Langone Health's Perlmutter Cancer Center in New York City and associate professor of radiation oncology at NYU Langone, commented in an email to Reuters Health, "While this retrospective analysis adds to the promising early experience using SMART for pancreatic cancers, rigorous clinical trials are needed to get a better idea of what the real benefit of this treatment is. A multi-institutional clinical trial for SMART in pancreatic cancers is currently recruiting, he added. (https://bit.ly/3iIqYZh)

"Only about 20% of pancreatic cancer patients are candidates for curative resection, and the majority of pancreatic cancer patients will need alternative and effective treatment options," he noted. "SMART is an emerging therapy that allows the safe delivery of high, ablative, doses of radiation. This has the potential for better control of pancreatic cancers in patients who cannot have surgery."

SOURCE: https://bit.ly/3d97Kee Practical Radiation Oncology, online September 16, 2020.

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