Does irradiation dose escalation to doses known to cure other cancers improve local tumor control and survival for patients with localized pancreatic cancer?
Ablative radiation therapy after induction chemotherapy in 119 patients with locally advanced unresectable pancreatic cancer was associated with a 2-year local tumor progression rate of only 32.8% and a 2-year overall survival rate of 38% from the time of irradiation.
Hypofractionated ablative radiation therapy was associated with durable control of the primary tumor leading to favorable survival outcomes.
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.
To determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique.
Design, Setting, and Participants
This cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. 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 RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs.
Main Outcomes and Measures
The primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival.
Between 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12- and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve- and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events.
Conclusions and Relevance
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.
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Reyngold M, O’Reilly EM, Varghese AM, et al. Association of Ablative Radiation Therapy With Survival Among Patients With Inoperable Pancreatic Cancer. JAMA Oncol. Published online March 11, 2021. doi:10.1001/jamaoncol.2021.0057
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