In a single-institution study reported in JAMA Oncology, Reyngold et al found that definitive hypofractionated ablative radiation therapy following induction chemotherapy was associated with prolonged locoregional control and favorable survival in patients with inoperable locally advanced pancreatic cancer.
As stated by the investigators, “Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease.”
Study Details
The study included 119 consecutive patients who received ablative radiotherapy using a novel radiation planning and delivery technique at a Memorial Sloan Kettering Cancer Center regional network between June 2016 and February 2019. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5-cm luminal abutment with the primary tumor were eligible.
Ablative radiation therapy was delivered in fractionation schemes consisting of 75 Gy in 25 fractions (biologically effective dose = 97.5 Gy) for tumors less than 1 cm from the stomach or intestines (n = 96) or 67.5 Gy in 15 fractions (biologically effective dose = 97.88 Gy) for tumors at a distance of ≥ 1 cm (n = 23). Respiratory gating, soft-tissue image guidance, and selective adaptive planning were used to account for organ motion and limit dose to surrounding luminal organs. The primary outcome measure was overall survival.
This cohort study of patients with inoperable locally advanced pancreatic cancer found that ablative radiation therapy following multiagent induction therapy … was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with locally advanced pancreatic cancer are warranted.— Reyngold et al
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Overall, 99 patients (83%) had T3/T4 disease and 51 (49%) were node-positive. A total of 116 (97.5%) received induction chemotherapy consisting of mFOLFIRINOX (fluorouracil, oxaliplatin, irinotecan, leucovorin; n = 66), gemcitabine/nab-paclitaxel (n = 37), or other agents (n = 13) for a median of 4 months (range = 0.5–13 months).
Key Findings
Median follow-up was 18.4 months from ablative radiation therapy and 24.5 months from diagnosis. Median progression-free survival and overall survival from time of radiation therapy were 6.3 months (95% confidence interval [CI] = 5.26–8.78 months) and 18.2 months (95% CI = 16.3–26.8 months). Median progression-free and overall survival from time of diagnosis were 13.2 months (95% CI = 11.4–15.7 months) and 26.8 months (95% CI = 21.7–35.7 months). Overall survival at 12 and 24 months from the time of radiation therapy were 74% (95% CI = 66%–83%) and 38% (95% CI = 27%–52%).
The 12- and 24-month cumulative incidences of locoregional disease progression were 17.6% (95% CI = 10.4%–24.9%) and 32.8% (95% CI = 21.6%–44.1%). At the time of reporting, 25 patients were alive without radiographic evidence of disease progression.
On univariate analysis, postinduction reduction in carbohydrate antigen 19-9 (CA19-9) vs baseline was associated with improved progression-free survival (hazard ratio [HR] = 1.36, P = .009) and reduced locoregional progression (HR = 1.86, P < .001). Using the optimal cutpoint for CA19-9, 1-year locoregional progression rates were 16.5% vs 44.5% for patients achieving the 80th percentile reduction in CA19-9 vs other patients (P = .007), with a trend observed for improved overall survival (73% vs 66%, P = .09). On multivariate analysis, only postinduction CA19-9 reduction (HR = 1.33, P = .03) and the presence of central tumor high dose (HR = 2.20, P = .02) were significantly associated with improved progression-free survival.
Grade 3 radiation therapy–related adverse events occurred in 16 patients (13%), with no grade ≥ 4 events being observed. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%), related to anticoagulation in 8 and requiring endoscopic intervention in 2.
The investigators concluded, “This cohort study of patients with inoperable locally advanced pancreatic cancer found that ablative radiation therapy following multiagent induction therapy … was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with locally advanced pancreatic cancer are warranted.”
Christopher H. Crane, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
