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Chapter 238EGFR mAbs such as cetuximab have also been evaluated as a treatment strategy for LAPC. Panitumumab and cetuximab both target the EGFR but they differ in their isotype and they might differ in their mechanism of action. An OS of 7.5 months was reported for RT in combination with single-agent cetuximab. This OS is less than for most CRT trials in LAPC but the toxicity was also very moderate (33). Crane and colleagues demonstrated a favorable OS of 19.2 months of cetuximab in combination with induction CHT (gemcitabine and oxaliplatin) in LAPC followed by capecitabine based CRT (50.4 Gy) in combination with cetuximab (34). The toxicity was comparable to this study, except an increased incidence of sensory neuropathy, which is associated with oxaliplatin. Other targeted therapies such as the VEGF mAb bevacizumab, the tyrosine kinase inhibitor sorafenib, and the cyclooxygenase-2 inhibitor, celecoxib, have also been investigated in combination with chemoradiation, but did not result in a significant improvement in OS (28, 35, 36). The combination of erlotinib, bevacizumab, and external beam radiation therapy without CHT in a phase I trial was reasonably well tolerated as presented at ASCO GI in 2011 (37). CRT trials that have been performed studying the added effect of targeted therapy are summarized in Table 4. Novel local therapies such as radiofrequency ablation (RFA) and irreversible electroporation (IRE) are used and studied in increasing frequency in the treatment of LAPC (38). RFA is a thermal local therapy based on high-frequency electrical currents. Variable outcomes of the efficacy of RFA are described in small nonrandomized trials (39, 40). IRE is a promising nonthermal ablative technique using direct current, which irreversibly damages the cell%u2019s homeostatic mechanism, causing apoptosis. Two series were reported of IRE in PDAC with promising results and manageable toxicity (41, 42). Stereotactic body RT (SBRT) is a recent advancement that allows for the precise delivery of a large ablative radiation dose to the tumor in one to five fractions. A total dose between 24 and 36 Gy in one to five fractions has been reported (43%u201345). SBRT could be delivered quickly and effectively in patients with LAPC with acceptable side effects and minimal interference with gemcitabine CHT. An advantage of IRE and stereotactic RT over RFA is that they can be used for tumors in close proximity to large vessels without risk of vascular trauma or a reduced effect of RFA due to the heat sink effect (46). No randomized studies of RFA, IRE, or stereotactic radiation have been published. These local treatment modalities in this setting are of interest because