Clinical Investigation
Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

https://doi.org/10.1016/j.ijrobp.2013.02.022Get rights and content

Purpose

Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity.

Methods and Materials

A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results

Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%).

Conclusions

SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.

Introduction

Pancreatic cancer remains a deadly disease with a poor prognosis despite continued advancements in treatment options over the past several decades. Surgical resection with negative margins (R0) remains the only means of providing long-term control and potential cure. Because the signs and symptoms are not usually clinically apparent until the advanced stages, most patients present with unresectable disease leading to dismal 5-year overall survival (OS) rates of <5%. By contrast, resectable patients have markedly improved 5-year OS of 20%. However, even these patients still have a relatively poor long-term prognosis because ultimately most will succumb to distant metastasis (1).

Early data show that patients with unresectable nonmetastatic pancreatic cancer benefit from a combination of radiation therapy (RT) and chemotherapy (2). What remains uncertain is the optimal use of these modalities with respect to sequence, technique, and dosing. One promising strategy for patients with unresectable pancreatic cancer consists of induction chemotherapy followed by chemoradiation or RT alone 3, 4. This approach allows for patients to declare themselves as metastatic and potentially avoid 5 to 6 weeks of chemoradiation (5).

Stereotactic body radiation therapy (SBRT) has been an important recent advance in RT for pancreatic cancer. Pioneered in the LAPC setting, the majority of the SBRT literature has shown SBRT to be well tolerated and effective 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. SBRT also shows promise in the BRPC setting, converting a high percentage of patients to resectability that can result in long-term results similar to those in initially resectable patients (16). This study was performed to review our institutional SBRT outcomes in BRPC and LAPC patients.

Section snippets

Patient details and staging

An institutional review board-approved database was queried to identify nonmetastatic patients with BRPC and LAPC treated with induction chemotherapy followed by SBRT between June 2009 and December 2011. Patients were not included if they underwent SBRT without first undergoing induction chemotherapy. Initial staging included physical examination, standard blood chemistries including CA 19-9, multidetector thin-section pancreatic protocol computed tomography (CT) scan, and endoscopic ultrasound

Patient and treatment characteristics

Table 1 describes the patient and treatment characteristics. A total of 73 patients (57 BRPC, 16 LAPC) were evaluated, with a median age of 64 years (range, 38-87 years). Most patients were clinically node positive (60.3%), with tumors involving the pancreatic head (86.3%). Fourteen clinically node-positive patients (31%) underwent resection. Biliary stent or drain was present in 72% of patients. GTX chemotherapy was the most commonly used induction chemotherapy regimen (65.8%). Sixty-one

Discussion

As has been previously described (16), SBRT can effectively result in tumor regression away from involved vasculature so that surgery can be performed with a high likelihood of negative surgical margins. The importance of margin status cannot be understated, given that it is related to survival outcomes in patients who have not undergone neoadjuvant therapy (17). In this study, the majority of BRPC patients underwent exploratory laparotomy. Remarkably, 3 (9.4%) of the resected patients achieved

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