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Hypofractionated ablative radiation tied to improved survival in pancreatic cancer

JAMA Oncology
Reuters Health - 19/03/2021 - In patients with inoperable, locally advanced pancreatic cancer (LAPC), hypofractionated ablative radiation therapy (A-RT) was associated with tumor control and favorable survival, researchers say.

"Ablative dose radiation (100 Gy equivalent) offers hope of long-term survival for patients with localized pancreatic cancer who cannot have surgery," Dr. Christopher Crane of Memorial Sloan-Kettering Cancer Center in New York City told Reuters Health by email. "Multidisciplinary feasibility is emerging using MRI adaptive technology."

"Randomized phase 3 trials will be possible in the next five years from a feasibility standpoint, but the question will require careful consideration," he said. "Most patients will not agree to a randomization of palliative dose radiation (including low-dose SBRT) to ablative dose radiation because palliative dose radiation does not improve survival."

"Likewise, even though the survival duration after ablative radiation appears to be comparable to surgery," he said, "most patients will not likely randomize to surgery versus no surgery."

"The most pressing information gap is the safety of surgery after these doses of radiation," he said. "Ideally, patients with initially unresectable locally advanced pancreatic cancer should have both definitive ablative radiation and surgery options for local tumor control."

As reported in JAMA Oncology, the single-center cohort study included 119 patients (median age, 67; about half, men) treated with A-RT between 2016-2019. All had localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor.

Ninety-nine patients had T3/T4 and 53, node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. All but three received induction chemotherapy for a median of four months.

All received ablative RT simulation, planning, and delivery according to the research team's standardized protocol: fractionation schemes included 75 Gy in 25 fractions (biologically effective dose, 97.5Gy) for tumors less than 1 cm from the stomach or intestines, and 67.5 Gy in 15 fractions (BED, 97.88 Gy) for tumors of 1 cm or further. Respiratory gating, soft tissue image guidance, and adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs.

The median overall survival from diagnosis was 26.8 months, and from A-RT, 18.4 months.

One-year OS from A-RT was 74% and two-year, 38%; incidence of locoregional failure was 17.6% and 32.8%, respectively.

A post-induction CA19-9 decline was associated with better locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%); no grade 4 to 5 events were reported.

Summing up, the authors state, "This cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

Dr. David Horowitz of Columbia University Irving Medical Center in New York City, coauthor of a related editorial, commented in an email to Reuters Health, "Ablative radiotherapy, given with the goal of destroying all cancerous cells in the treated area, has been shown to be an effective treatment in multiple diseases--notably for early-stage lung cancer and brain metastases, where tumor control with radiation rivals that seen with surgical resection."

"Due to the pancreas' location, it can be challenging to give ablative doses of radiation to pancreatic tumors while avoiding organs such as the bowel, which are sensitive to radiation," he said. "The low rates of severe side effects the authors noted with this treatment is therefore noteworthy."

"The results achieved at this single institution will need to be replicated in a large-scale study, but for patients with pancreatic cancer that cannot be removed with surgery, this is a valuable piece of evidence to suggest that a treatment we know works for other disease sites may be safely applied," he said.

"Giving patients time without the need for active treatment is beneficial," he said, "and I would encourage future studies to investigate this in order to understand better whether ablative radiotherapy can not only improve tumor control but also quality of life."

SOURCES: https://bit.ly/3c3VKfb and https://bit.ly/2Pdojh2 JAMA Oncology, online March 11, 2021.

By Marilynn Larkin

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