Stereotactic Body Radiation Therapy: A New Standard Option for Pancreatic Cancer?
Authors: Joseph M. Herman, Albert C. Koong
Journal: Journal of the National Comprehensive Cancer Network (2014)

For many patients, a pancreatic cancer diagnosis involves a dismal (<6%) chance of survival beyond 5 years, and little progress has been made in terms of prevention and early detection of this disease. As a result, most patients present with advanced disease and a poor performance status that often precludes them from receiving aggressive therapy or surgery. Advances in imaging technology, such as multidetector CT, high-field MRI, and PET, have improved staging for patients with pancreatic cancer. In addition, multiagent chemotherapy regimens such as FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin) and gemcitabine with nab-paclitaxel have resulted in significant improvements in survival when compared to gemcitabine monotherapy. Nonetheless, these multiagent regimens can cause more toxicity than single-agent chemotherapy, including nausea, vomiting, infection, and severe neuropathy. These toxicities can be debilitating, particularly with chronic administration. Efforts to include targeted therapies have not been very effective and, unfortunately, often increase rates of treatment-related toxicity. Radiation therapy has been shown to improve local control, stability of disease progression, and pain control in many stages of pancreatic cancer. However, these clinical benefits have historically been limited by (1) the relatively long courses of therapy, which often exceed 5 to 6 weeks; (2) the associated toxicity resulting from a lack of dose conformality; and (3) the fact that concurrent chemoradiation often decreases the ability to give patients full-dose systemic therapy. Recently, however, advances in radiation therapy techniques, including image guidance, target delineation (ie, fiducial markers, dose constraints), and motion management (ie, active breathing control, respiratory gating, respiratory tracking) now allow for very precise irradiation of pancreatic tumors, with an accuracy of 1 mm. This form of therapy, otherwise known as stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR), has now been used in several malignancies, including those of the lung, liver, brain, spine, and prostate. However, its integration into the treatment paradigm of pancreatic cancer has been limited thus far. This slow integration primarily stems from the requirement for increased physical support and findings of several early studies in which SBRT resulted in increased rates of late gastrointestinal toxicity (ie, ulcers, gastrointestinal bleeding). 1–3 More recently, however, single-institution studies and a multi-institution prospective study with SBRT 4–7 have shown acceptable levels of late toxicity with minimal acute toxicity when treatment is delivered over 3 to 5 days as opposed to 1 day. Additionally, SBRT is typically delivered without the need for concurrent chemotherapy, resulting in improved quality of life, less delay in the administration of full-dose systemic therapy, and enhanced integration with other cancer treatment modalities. To date, more than 600 patients with pancreatic cancer have been treated with SBRT, and reports suggest an improvement in pain scores and quality of life. Furthermore, the efficacy and toxicity data compare favorably with those on conventional chemoradiotherapy. Nonetheless, evaluation of SBRT in a prospective randomized trial is necessary to define its role in the management of pancreatic cancer and to ensure its safe implementation for treating patients. Precise delivery of SBRT is particularly important because errors involving any dimension of the planning and treatment process (ie, contouring, target delineation, breathing motion) can significantly increase the risk of toxicity due to the close proximity of adjacent radiosensitive organs (ie, bowel and stomach).