1. Goodwin, Peter M.

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VIENNA, Austria-High doses of adjuvant radiotherapy extended median overall survival by more than a year in patients resected for their pancreatic cancers. But a subgroup treated with lower doses did not live longer. These findings from a retrospective analysis of 514 patients-led by Alessio G. Morganti, MD, of the University of Bologna in Italy-were reported at the 2017 European Society for Radiotherapy and Oncology (ESTRO) Congress.

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"What was shown was that the higher [the] dose we deliver the better we improve the survival of those patients," said study co-author Francesco Cellini, MD, Radiation Oncologist from the Fondazione Policlinico Universitario Agostino Gemelli and the Universita Cattolica del Sacro Cuore in Rome.


The team had been trying to find the best way to improve what Cellini described as "the grim prospects we still have facing this highly aggressive cancer.


"What we found was that lower dose levels of radiotherapy [were] ineffective. The higher dose levels [were] highly effective," he noted. And increasing the dose still further continued to improve survival.


Cellini suggested that, by embracing the opportunity presented by modern radiotherapy equipment to deliver higher doses safely, teams could improve survival of patients with pancreatic cancer.


He also said that, because the most common treatment aimed at increasing the curative effect of surgery had been chemotherapy-and since there was still no doubt surgery was the "cornerstone approach"-other therapies were now needed to increase the modest benefits of adjuvant chemotherapy. The study had aimed "to increase and enhance the integration of radiotherapy into the treatment approach"-even though the use of radiotherapy had been controversial.


Levels of Radiotherapy Examined

Four different radiotherapy dose levels were investigated. One group of patients received less than 45 gray (Gy) of radiation, another were treated with a dose between 45 and 50 Gy, a third group had at least 50 but not more than 55 Gy, and the final group received more than 55 Gy. "[In patients treated with] under 45 Gy, median survival was 13 months; [with] doses between 45 and 50, we [found] 21 months of survival; between 50 and 55 [Gy, patients had] 22 months of median survival overall; and over 55 Gy 28 months of median survival," Cellini explained.


When asked whether patient selection could explain the differences in survival, he stated that careful measures had been taken to avoid this. The study had been stratified to take into account covariates. And patients were certified as equivalent in terms of the common clinical and biological indicators "in line with the literature." After resection, all patients were "macroscopically negative."


Team Approach to Treatment

Cellini considered the study as potentially paradigm-changing, offering the hope that pancreatic cancer no longer be considered as relatively resistant to radiation. But he said further investigation was needed. "We don't want to be too enthusiastic. The issue is not only changing the paradigm, but starting to increase the research we have to go through including chemo-radiation in [both] post-op and, probably, preoperative settings," he noted.


In the routine clinical setting, the decision to use radiotherapy still needed to be made by multidisciplinary teams to assess whether individual patients could benefit from radiotherapy. "We need an ideal radiology staging, we-of course-need pathology, [and] we need all the efforts of nuclear medicine imaging. But we [also] need the surgeon, the radiation oncologist, and the medical oncologist to discuss-case per case-the presentation, the issues, and then to see which is the more applicable treatment approach," Cellini stated.


Even though most pancreatic cancers are not resectable on diagnosis Cellini said there was a worthwhile benefit from using radiation among those who were. "On average, we can say that usually-let's say-20 percent of patients present a resectable tumor upfront, and among them 50 percent have metastatic disease. But for the rest-[who] have locally advanced spread without any metastatic disease-we can aim for an increase of that percentage. So this is our goal," he explained.


"The main issue is that integration of chemotherapy and chemo-radiation will probably help to go for a cure for those patients. [And] the better the resection the better we understand the prognostic signature in any patient, and then we can allow for that."


The President of ESTRO, Yolande Lievens, MD, PhD, Chair of the Department of Radiation Oncology at Ghent University Hospital in Belgium, commented on the research: "This is an interesting study which raises questions about the role that radiotherapy could play in extending the lives of people diagnosed with pancreatic cancer. In this grim disease, radiotherapy has not been shown to have an impact on survival, but the current study suggests the doses previously tested may have been too low to do so. Radiotherapy has evolved and improved considerably over recent years, allowing us to deliver higher doses without increasing side effects. And for a cancer with such poor survival rates all promising new options should be explored."


Peter M. Goodwin is a contributing writer.