Oncology/Endocrine
Stereotactic Body Radiation Therapy for Nonresectable Tumors of the Pancreas

https://doi.org/10.1016/j.jss.2011.07.044Get rights and content

Background

Stereotactic body radiation therapy (SBRT) has emerged as a potential treatment option for local tumor control of primary malignancies of the pancreas. We report on our experience with SBRT in patients with pancreatic adenocarcinoma who were found not to be candidates for surgical resection.

Methods

The prospective database of the first 20 consecutive patients receiving SBRT for unresectable pancreatic adenocarcinomas and a neuroendocrine tumor under an IRB approved protocol was reviewed. Prior to SBRT, cylindrical solid gold fiducial markers were placed within or around the tumor endoscopically (n = 13), surgically (n = 4), or percutaneously under computerized tomography (CT)-guidance (n = 3) to allow for tracking of tumor during therapy. Mean radiation dose was 25 Gray (Gy) (range 22–30 Gy) delivered over 1–3 fractions. Chemotherapy was given to 68% of patients in various schedules/timing.

Results

Patients had a mean gross tumor volume of 57.2 cm3 (range 10.1–118 cm3) before SBRT. The mean total gross tumor volume reduction at 3 and 6 mo after SBRT were 21% and 38%, respectively (P < 0.05). Median follow-up was 14.57 mo (range 5–23 mo). The overall rate of freedom from local progression at 6 and 12 mo were 88% and 65%. The probability of overall survival at 6 and 12 mo were 89% and 56%. No patient had a complication related to fiducial markers placement regardless of modality. The rate of radiation-induced adverse events was: grade 1–2 (11%) and grade 3 (16%). There were no grade 4/5 adverse events seen.

Conclusion

Our preliminary results showed SBRT as a safe and likely effective local treatment modality for pancreatic primary malignancy with acceptable rate of adverse events.

Introduction

More than 40,000 individuals are diagnosed annually with tumors of the pancreas in the United States [1]. Of these, less than 20% are amenable to definitive surgical management due to advanced stage of local disease, distant metastasis, or co-morbid medical conditions [2]. Unresectable pancreatic cancer carries a poor prognosis with limited nonsurgical effective treatment options. At this time, successful systemic therapies for unresectable pancreatic cancer are poorly developed. Gemcitabine and/or 5-FU are routinely offered to patients, but have not had a significant impact on survival with a median overall survival of less than 1 y for nonsurgically removed primary tumors of the pancreas [3].

Stereotactic radiosurgery (SRS) is a technique that allows precise delivery of a large ablative radiation dose in 1 to 5 fractions to the target field (neoplasm) while sparing normal surrounding tissue. This technique allows radiation to be delivered with sub-millimeter precision and with a rapid radiation fall-off from the target field, thus sparing normal tissue from high dose of radiation. Initially developed for intracranial lesions, SRS resulted in local control rates above 80%–90% for the treatment of brain metastases [4]. When SRS is used in extracranial tumors, it is also called stereotactic body radiation therapy (SBRT). Nonetheless, its use in extracranial tumors had been limited due to the inherent movement of abdominal organs that occurs during the respiratory cycle. One such device that tracks tumors during respiration and automatically adjusts during patient positioning is the CyberKnife system, which consists of three key components: (1) an advanced, lightweight linear accelerator (LINAC), (2) a robotic arm that can point the LINAC from a wide variety of angles, and (3) a tumor tracking system. This system tracks a patient’s abdominal tumor during respiration via two simultaneous mechanisms: (a) internal fluoroscopic monitoring of fiducial markers placed in or around the tumor; and (b) external monitoring through a camera system that model the chest wall motion and adjusts the linear accelerator movement simultaneously. Thus, SBRT by the Cyberknife system uses real-time tracking of implanted fiducial markers combined with real-time respiratory motion modeling to achieve sub-millimeter accuracy by continually detecting and correcting for tumor motion throughout treatment. It was reported that the average treatment delivery precision was 0.3 ± 0.1 mm as measured at three different CyberKnife facilities [5]. We have acquired experience with SBRT in the treatment of liver malignancies, and others have shown preliminary encouraging results in the treatment of pancreatic tumors 6, 7, 8. We report our initial experience with 19 patients who underwent SBRT for unresectable pancreatic adenocarcinoma and one additional patient with a pancreatic neuroendocrine tumor (PNET).

Section snippets

Patient Population

A prospective database of 20 patients treated with SBRT at University Hospitals-Case Medical Center between November 2007 and November 2010 for nonresectable pancreatic tumors was reviewed under an IRB approved protocol. Nineteen patients met the inclusion criteria for enrolment including: (1) biopsy proven pancreatic adenocarcinoma, (2) unresectable disease, and (3) life expectancy of at least 12 wk. Two of them had localized pancreatic recurrence after pancreaticoduodenectomy and adjuvant

Results

Patient characteristics and demographics are summarized in Table 1. Our cohort of patients with pancreatic adenocarcinoma consisted of eight males and 11 females (n = 19) with a mean age of 74.5 y (range: 54–91 y). The median follow-up among survival patients was 9 mo. (range: 5.8–23.1 mo). Mean tumor volume was 57.2 cm3 (range: 10.1–118 cm3). Fourteen patients were treated with 20–25 Gray (Gy) in one fraction and five patients were treated with 24–30 Gy in three fractions. The median

Discussion

Analysis of 19 patients treated with SBRT for unresectable adenocarcinomas of the pancreas are presented. Sixty-nine percent of patients responded to SBRT as judged by >10% decrease in gross tumor volume (GTV) in 11 patients and arrest of tumor growth in two patients. No patient had local tumor recurrence on imaging 3 mo after SBRT. At 9 mo follow-up two patients recurred locally and one patient recurred locally and distally to the liver. Six patients (35%) developed distant metastasis to the

Conclusions

SBRT is a safe and effective local treatment option for unresectable pancreatic adenocarcinoma. In the multidisciplinary management of these tumors, SBRT adds to our armamentarium of local treatment modalities, especially for non-operable patients. Fiducial markers can be placed endoscopically, under CT-guidance, or surgically, for planning and treatment of pancreatic tumors with minimal adverse events. Further prospective studies are ongoing to determine long-term response and survival after

Acknowledgments

The authors are grateful to the staff and residents in the Department of Surgery, Medicine, Radiology, and Radiation Oncology, University Hospital-Case Medical Center, Cleveland, Ohio. RAI was supported by a Ruth L. Kirschstein National Research Service Award NIH/NIDDK (T32-DK007319).

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