"Patients who received presurgical (neoadjuvant) radiation had almost double the overall survival compared with similar patients who didn't undergo radiation, and survived significantly longer than patients who received radiation after the tumour was removed," said the study's senior author, David Sherr, assistant professor of clinical radiation oncology at Weill Cornell Medical College, and a radiation oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Pancreatic cancer remains the fifth most deadly malignancy in the US, killing more than 32,000 Americans each year. It is typically not detected until it is at an advanced stage, when cure is rarely possible. In fact, the five-year survival rate for pancreatic cancer has been stalled at 5% for the past 25 years.
Because pancreatic tumours have often spread or have directly invaded critical structures by the time they are detected, just 15 to 20% of patients are deemed suitable candidates for surgical removal (resection) of the tumour. And while post-operative radiotherapy has long been used to sterilize residual cancer cells that may not have been removed by surgery, the notion of using radiation before resection has been a controversial one.
"There are potential benefits to delivering radiation before surgery rather than after," Sherr explained. "Radiation might actually increase the number of people eligible for tumour resection, by shrinking the tumour so it no longer endangers vital structures, such as the major blood vessels in close proximity to the pancreas."
In addition, neoadjuvant radiation might render cancer cells less likely to establish metastases - an important consideration, since surgery can shed stray tumour cells into the bloodstream.
Sherr added: "Radiation could also provide more benefit if given prior to surgery, since radiation therapy is more effective in well oxygenated tumour tissues. After surgery, tissue is frequently less well oxygenated due to the development of scar tissue."
Finally, patients are typically more able to tolerate radiation therapy before surgery rather than after the operation, when they are often weak and require a prolonged convalescence period before they're well enough to receive additional treatment.
In their retrospective analysis, Sherr and colleagues looked at data from 3885 cases of resected pancreatic cancer, recorded between 1994 and 2003 as part of the US Surveillance, Epidemiology and End Results (SEER) registry database. Of these cases, 2337 (60%) of patients had received surgery alone, 1478 (38%) received radiation after resection, and 70 (2%) received neoadjuvant radiation therapy.
The team found that the overall survival of patients who received neoadjuvant radiation was 23 months, compared with 17 months for those receiving post-surgical radiotherapy and 12 months for patients who received surgery alone.
Controlling for variables such as patient age, sex, cancer stage, grade and year of diagnosis, the researchers found that neoadjuvant radiation cut the death risk for patients by 45% compared with other treatment strategies, and by 37% compared with radiation performed after surgery.
Why the improvement in outcomes? "It may be that in shrinking the tumour, pre-operative radiation gives the surgeon more of a margin of healthy tissue to work with. Because of that, patients are less likely to have microscopic residual disease," said Sherr.
However, Sherr stressed that the findings need to be verified by a randomized, prospective trial before any firm recommendations can be made. "More study is needed," he concluded, "but I believe this type of research has the potential to change practice."