Potentially Curative Surgery Achievable With Chemo/SABR Combination for Advanced Pancreatic Cancer

The combination of chemotherapy and stereotactic ablative radiotherapy (SABR) may allow patients with locally advanced pancreatic cancer to undergo surgery, a procedure that might not have otherwise been an option

The combination of chemotherapy and stereotactic ablative radiotherapy (SABR) may allow patients with locally advanced pancreatic cancer to undergo surgery, a procedure that might not have otherwise been an option, according to research presented at the ASTRO 56th Annual Meeting.

While surgery is the only potentially curative therapy for patients with pancreatic cancer, many patients are diagnosed at an advanced stage, which makes surgery a challenge, if not impossible. Also, some patients with locally advanced disease may have microscopic spread of the disease to other parts of the body.

Chemotherapy plays an important role in addressing microscopic disease while SABR is a promising treatment modality for patients with locally advanced pancreatic ductal adenocarcinoma (PDA). Since there is currently no standard of care for treating patients with pancreatic cancer for whom surgery is not an option, the combination of chemotherapy and SABR provides an option for these patients.

“This is a promising treatment option that may prove not only to be more effective than chemotherapy alone prior to surgery, it may also be better than chemotherapy and standard radiation,” lead study author Kimmen Quan, MD, a radiation oncologist at the University of Pittsburgh Medical Center, said in a statement.

In a prospective, single arm, phase II trial, researchers evaluated the safety, feasibility, and efficacy of induction chemotherapy followed by SABR in 34 patients who had biopsy-proven PDA. Of those patients, 18 had borderline resectable PDA while 16 patients had locally advanced PDA. The average patient age was 71 and 56% of the patients were women.

Ninety-one percent of the patients (n = 31) received induction chemotherapy, consisting of gemcitabine and capecitabine, over 4 cycles. Three of the patients did not complete chemotherapy—one died after consent but prior to chemotherapy; one died during chemotherapy because of an arterial occlusion; and one had a myocardial infarction prior to completion of the four courses of chemotherapy.

After receiving a CT scan to confirm that the cancer did not spread, patients went on to receive 3 SABR treatments of 36 Gy, including a 2mm expansion around the gross tumor. Four weeks after the SABR treatments, radiation oncologists, surgical oncologists and medical oncologists made a multidisciplinary decision as to whether each patient’s tumor could then be surgically removed.

Of the 31 patients, 12 (40%) underwent a pancreaticoduodenectomy, which removes the head of the pancreas, part of the small intestine, the gallbladder, the end of the common bile duct and sometimes a portion of the stomach. Ninety percent of patients who had surgery had no local disease after surgery.

These findings translate to approximately a 90% chance of local disease control at 1 year, and >20 months free of any disease recurrence.

“Patients tolerated the chemotherapy and SABR regimen quite well, with excellent quality of life during treatment,” Quan said.

The most common grade 3 side effects were GI toxicity (3%) and hematological toxicities (10%). Three percent of patients experienced grade 4 hematological toxicities following induction chemotherapy. Of the patients that underwent the pancreaticoduodenectomy, 5.8% (n = 2) saw grade 3 pseudoaneurysm and hepatic abscess, while 5.8% (n = 2) saw grade 4 ICU admission for CVA and portal vein thrombosis and post-operative toxicities (Clavien scoring).

“These results appear to translate into better control of disease in the pancreatic region and a longer freedom from disease recurrence,” Quan said. “This combination should be considered for patients with advanced pancreatic cancer, which is still treatable disease, and could potentially improve survival in this patient population.”

Quan K, Rajagopalan MS, Clump DA,et al. Interim Analysis of a Phase II Clinical Trial of Induction Gemcitabine/Capecitabine followed by SABR in Borderline/Locally Advanced Pancreatic Adenocarcinoma. Presented at: 2014 ASTRO Annual Meeting; September 14-17, 2014; San Francisco, CA. Presentation Number: 99


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