Abstract
BackgroundStereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern.MethodsPatients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18–36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule.ResultsIn total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8–88.7) cc, 67.3(65.2–69.5)%, 96.6(95.5–97.7)%, 22.3(21.0–23.6) Gy and 50.3(47.7–53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients — of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints—showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation.ConclusionThe results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging.
Highlights
Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies
Median overall survival (OS) from diagnosis for all patients is less than 5 months, ~ 20% of patients overall survive more than 1 year and ~ 5% survive more than 5 years [1,2,3,4]
SABR was considered as an adjuvant when it was used within 6 months of standard therapies (14 patients)
Summary
Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. The disease is typically diagnosed at more advanced stages: ~ 45% of patients present with metastatic disease that has a median OS of ~ 2–5 months, and ~ 30% present with inoperable localized or locally advanced pancreatic cancer (LAPC) that has an intermediate status and prognosis [1,2,3,4] For the latter subset of patients, conversion to resectability currently offers the best outcome [5,6,7]: median OS reported in LAPC randomised trials remains poor at 7–15 months [8,9,10]
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