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Patterns of Failure Following Preoperative Chemotherapy and Stereotactic Body Radiation Therapy and Resection for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer

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Abstract

Background

The role of neoadjuvant stereotactic body radiation therapy (SBRT) in the treatment of pancreatic adenocarcinoma (PDAC) is controversial and the optimal target volumes and dose-fractionation are unclear. The aim of this study is to report on treatment outcomes and patterns of failure of patients with borderline resectable (BL) or locally advanced (LA) pancreatic cancer following preoperative chemotherapy and SBRT.

Methods

We conducted a single-institution, retrospective study of patients with BL or LA PDAC. Patients received neoadjuvant chemotherapy and SBRT was prescribed to 30 Gy over 5 fractions to the pancreas planning tumor volume (PTV). A subset of patients received a simultaneous integrated boost to the high risk vascular PTV and/or elective nodal irradiation (ENI). Following neoadjuvant chemoradiation, all patients underwent subsequent resection. Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMPFS), and locoregional control (LRC) estimates were obtained using Kaplan-Meier analysis.

Results

Twenty-two patients with BL (18) or LA (4) PDAC were treated with neoadjuvant chemotherapy and SBRT followed by resection from 2011–2022. Following neoadjuvant treatment, 5 patients (23%) achieved a pathologic complete response (pCR) and 16 patients (73%) had R0 resection. At 24 months, there were no isolated locoregional recurrences (LRRs), 9 isolated distant recurrences (DRs), and 5 combined LRRs and DRs. Two LRRs were in-field, 2 LRRs were marginal, and 1 LRR was both in-field and marginal. 2-year median LRC, LRRFS, DMPFS, PFS, and OS were 77.3%, 45.5%, 31.8%, 31.8%, and 59.1%, respectively. For BL and LA cancers, 2-year LRC, DMPFS, and OS were 83% vs. 75%, (p = 0.423), 39% vs. 0% (p = 0.006), and 61% vs. 50% (p = 0.202), respectively. ENI was associated with improved LRC (p = 0.032) and LRRFS (p = 0.033). Borderline resectability (p = 0.018) and lower tumor grade (p = 0.027) were associated with improved DMPFS.

Conclusions

Following preoperative chemotherapy and SBRT, locoregional failure outside of the target volume occurred in 3 of 5 recurrences; ENI was associated with improved LRC and LRRFS. Further studies are necessary to define the optimal techniques for preoperative radiation therapy.

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Availability of Data and Materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

SBRT:

Stereotactic body radiation therapy

BL:

Borderline resectable

LA:

Locally advanced

PTV:

Planning tumor volume

ENI:

Elective nodal irradiation

OS:

Overall survival

LRRFS:

Locoregional recurrence-free survival

DMPFS:

Distant metastasis free survival

LRC:

Locoregional control

pCR:

Pathologic complete response

LRR:

Locoregional recurrences

DR:

Distant recurrences

PDAC:

Pancreatic adenocarcinoma

CT:

Computed tomography

GTV:

Gross tumor volume

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Authors and Affiliations

  1. Georgetown University School of Medicine, Washington, DC, USA

    Nicole Libbey & Lindsey Gallagher

  2. Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA

    Jonathan Cantalino, Benjamin A. Weinberg, Marcus S. Noel, Aiwu R. He, John L. Marshall, Louis M. Weiner, Abdul Rashid & Keith R. Unger

  3. Department of Surgery, MedStar Georgetown University Hospital, Georgetown University, Washington, DC, USA

    Pejman Radkani, Patrick G. Jackson, Thomas M. Fishbein & Emily R. Winslow

  4. Department of Gastroenterology, Medstar Georgetown University Hospital, Washington, DC, USA

    Nadim Haddad

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Contributions

N.L. and L.G. share first authorship and made substantial contributions to the analysis and interpretation of data, wrote the main manuscript text, and prepared all tables/figures. J.C. and K.U assisted in the design of the study and drafting/revising the work. B.W., N.M., A.H., J.M., L.W., P.J., T.F., E.W., N.H., and A.R. contributed this study’s conception and data acquisition. All authors reviewed the manuscript.

Corresponding author

Correspondence to Lindsey Gallagher.

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This study was reviewed and approved by Georgetown – MedStar IRB Committee.

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Not applicable.

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The authors declare no competing interests.

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Libbey, N., Gallagher, L., Cantalino, J. et al. Patterns of Failure Following Preoperative Chemotherapy and Stereotactic Body Radiation Therapy and Resection for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-023-00996-3

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