7/28/2019 SBRT is non-inferior to standard chemo-radiation for locally advanced, non-metastatic pancreas cancer: A meta-an

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2013 RSS Meeting Abstract Submission

ABSTRACT TITLE:

SBRT is non-inferior to standard chemoradiation for locally advanced, non-

metastatic pancreas cancer: A meta-analysis of published data.

AUTHOR AND CO-AUTHORS:

Jessica Varley, Thomas B. Daniels, MD, John J. Kresl, MD, PhD, FACRO, Chad L. Lee,

PhD, and Lauren D. Stegman, MD, PhD

OBJECTIVES:

Image-guided body stereotactic radiosurgery (SBRT) is an emerging treatment

option for definitive therapy of locally advanced pancreatic cancer. The objective of

this study was to assess the efficacy of this treatment by combining data from the

available small, single institution published series.

METHODS:

The MEDLINE database was searched to identify publications reporting on the

outcomes of cohorts of at least 20 patients without imaging evidence of metastatic

disease treated with body radiosurgery. The actuarial overall survival plots from

these studies were digitized. Individual patient survival data were reconstructed as

per the method of Guyot et al. (BMC Medical Research Methodology 2012, 12:9).

The accuracy of the data reconstruction process was verified by comparing the

calculated Kaplan-Meier survival probabilities from the reconstructed data with the

published results. The individual patient survival data was then aggregated to

create the combined actuarial survival data. Similar methodology was used to

reconstruct aggregate survival data from five Phase I/II prospective trials ofgemcitabine-based, standardly fractionated chemoradiation each with cohorts of 20

patients with locally advanced, non-metastatic disease.

RESULTS:

Seven studies of pancreatic radiosurgery were identified meeting the inclusion

criteria, which included a total of 274 patients. The aggregate, actuarial median

survival after radiosurgery was 12.6 months with 6 month, 1 year, and 2 year

survival probabilities of 85%, 52%, and 22%, respectively. The aggregate, actuarial

median survival of 199 patients treated on the prospective ECOG, Hoosier Oncology

Group, Israeli, and CALGB chemoradiation therapy trials was 10.8 months with 6

month, 1 year and 2 year survival probabilities of 74%, 44%, and 15 %, respectively.This represented a non-significant trend towards better survival with SBRT as

compared to chemoradiation with a HR for death of 0.89 (95% CI 0.73 1.08, p =

0.24).

For patients treated with SBRT, overall survival was statistically improved with

neoadjuvant versus adjuvant chemotherapy with a HR for death of 0.71 (95% CI

0.55 0.92, p = 0.01). The median survival was 13.7 months in the three studies in

7/28/2019 SBRT is non-inferior to standard chemo-radiation for locally advanced, non-metastatic pancreas cancer: A meta-an

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which more than 90% of patients received induction chemotherapy prior to SBRT (n

= 114 patients) versus 11.1 months in the four studies (n = 160 patients) in which

chemotherapy was given after radiosurgery. The delivered BED varied across

studies from 47.2 Gy10 - 87.5 Gy10. When treated as a continuous variable, no

radiotherapy dose response was identified (HR 1.01, 95% CI 0.997 1.013, p =

0.17).

Conclusions:

Meta-analysis of published reports of SBRT for locally advanced, non-metastatic

pancreatic adenocarcinoma using reconstructed individual patient survival data

suggests this therapy is not inferior to standard chemoradiation therapy. The

apparently equivalent outcomes indicate that future randomized trials comparing

SBRT to conventional chemoradiation may need to be conducted using a non-

inferiority design. Patients receiving induction chemotherapy prior to SBRT appear

to have more favorable outcomes than those treated with up-front radiosurgery. It

is unclear if this is due to selection of favorable prognosis patients with

chemosensitive disease or due to chemosensitization or another biologic interactionbetween the timing of systemic therapy and SBRT. There was no clear radiation

dose response, although this may be confounded by the stronger effect of

chemotherapy timing. These data support the development of prospective

randomized trials comparing induction chemotherapy followed by SBRT versus

standard chemoradiation.

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