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coated nanoparticle-containing paclitaxel or a multiple-drug regimen known as FOLFIRINOX significantly improves median survival. Prospective clinical trials are underway to determine whether these regimens can also bring beneﬁts to patients with other stages of the disease. “We hope that we can improve on the chemotherapy treatment of pancreatic cancer patients even further with time,” says Dr. Donahue. He notes that at the time of diagnosis, only 10-to-15 percent of pancreatic-cancer patients have early stage disease, for which it is clear that surgery followed by adjuvant chemotherapy is the ideal treatment approach. Of the remaining patients, about half present with metastatic disease, for which surgery is typically not considered beneﬁcial. That leaves a group of about 40 percent of patients diagnosed with locally advanced or borderline-resectable disease. In this latter group, it’s less clear whether surgery will make a diﬀerence. “Unlike the patients with early stage disease, these patients have tumors that are just a bit too large and involve the local vasculature that surrounds the pancreas,” Dr. Donahue explains. Rather than taking these patients directly to surgery and then resecting and reconstructing the local vasculature, the standard approach has been to treat them with chemotherapy plus or minus radiation therapy. The rationale is twofold: to shrink the tumor so that the blood vessels don’t have to be resected and to allow time to observe the tumor and ensure that no metastatic disease exists or develops that would preclude any surgical beneﬁt. “We believe the longer duration of preoperative therapy is a major contributor toward that improved survival.” the longer protocol before having surgery, the median survival of 45 months is approximately two years longer than similarly staged patients typically experience in other published studies. Although the better results are in part a result of the greater selectivity concerning which patients receive surgery — those found to have metastatic disease during the pre-surgical treatment are not included in the retrospective analysis — Dr. Dona hue believes t he substa ntia l improvement in survival time for these patients indicates that his team is on the right course. Timothy R. Donahue, MD As chemotherapy continues to improve, Dr. Donahue expects more patients to become surgical candidates. “Unlike in many other cancers, the majority of pancreatic-cancer patients die not from the primary tumor but from the metastasis,” Dr. Donahue explains. “Because of that, the role of surgery may not be as important But now that we have these improvements in chemotherapy that allow us to better address the systemic lesions, local therapy — surgery — can play a more prominent role.” (Below) Image at left shows patient prior to “downstaging therapy” and at right after. The patient underwent nine months of preoperative chemotherapy with a three-drug regimen (5-FU, Oxaliplatin and Irinotecan, a.k.a. FOLFIRINOX). The patient then underwent a margin-negative surgical resection. The venous segment with radiographic evidence of disease was removed and reconstructed. On pathologic analysis, the vein wall was not microscopically involved with the tumor. For more information about the UCLA Center for Pancreatic Cancer, go to: pancreas.ucla.edu Dr. Donahue and colleagues believe that taking a longer period to treat patients before deciding on surgery is a more optimal approach that allows for more shrinkage of the tumor to minimize the operation that needs to be performed. Waiting also allows selection of patients who will beneﬁt from surgery by making sure no undetectable micro-metastases will soon blossom into a larger metastasis. This approach has led to some of the best survival results ever reported for these patients. Among patients with borderline-resectable or locally advanced disease who have been treated with 9 UCLA Physicians Update