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Expert Point of View: Christopher L. Hallemeier, MD, and Andrew S. Kennedy, MD


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Christopher L. Hallemeier, MD

Christopher L. Hallemeier, MD

Andrew S. Kennedy, MD

Andrew S. Kennedy, MD

Christopher L. Hallemeier, MD, Associate Professor in Radiation Oncology at the Mayo Clinic, Rochester, and Andrew S. Kennedy, MD, Physician in Chief of Radiation Oncology at Sarah Cannon, Nashville, and Director of Radiation Oncology Research, Sarah Cannon Research Institute, commented on the trial of short-course radiation plus total neoadjuvant therapy for The ASCO Post.

“This is an important study that builds on previous work by the Washington University team in evaluating a total neoadjuvant treatment schema of short-course radiotherapy, FOLFOX (leucovorin, fluorouracil, and oxaliplatin) chemotherapy, and then surgery for patients with locally advanced rectal adenocarcinoma,”1 Dr. Hallemeier said. “As noted by the authors, this is a very appealing treatment regimen for patients, as it significantly reduces the radiotherapy schedule from 5 weeks to 1 week.”

“The authors found pathologic outcomes (pathologic complete responses and neoadjuvant rectal [NAR] score) were favorable with the short-course radiotherapy/total neoadjuvant therapy approach compared with the more traditional approach of chemoradiotherapy, surgery, and adjuvant FOLFOX. The favorable response observed supports further study of short-course radiotherapy/total neoadjuvant therapy as a regimen capable of facilitating a selective nonoperative management approach,” noted Dr. Hallemeier.

“Caution is warranted in interpreting these results, as this was a single-institution retrospective analysis,” Dr. Hallemeier added. “We await results from the RAPIDO trial, which is a large (885 patients) multicenter, phase III randomized controlled trial comparing short-course radiotherapy, CAPOX [capecitabine, oxaliplatin], and surgery versus chemoradiotherapy, surgery, and adjuvant CAPOX in patients with locally advanced rectal adenocarcinoma with adverse features.2 Initial results from this trial are expected in the next few years. If the RAPIDO trial demonstrates superiority of the short-course radiotherapy/total neoadjuvant therapy approach, it will prove practice-changing.”

Adding to the ‘Growing Medical Evidence’

According to Dr. Kennedy, a few points stand out as “reassuring and encouraging.” “First, the use of short courses (large fractions) of radiotherapy in rectal cancer originated in the mid-1990s, based on a Swedish trial that utilized large, two-field pelvic radiotherapy without chemotherapy and little time between completion and surgery—thus no downstaging effect. Concerns for excessive late radiotherapy toxicities given the 5-Gy fraction size have not been realized, and this current work using modern techniques of radiotherapy reinforces that positive result,” he said. “Second, the validated NAR score is an objective measure of success with this approach, noting equivalence with conventional chemoradiation.

“Overall, these findings add to the growing medical evidence that short-course radiotherapy provides a safe and effective alternative to conventional chemoradiation approaches in locally advanced rectal adenocarcinoma,” Dr. Kennedy concluded. 

DISCLOSURE: Drs. Hallemeier and Kennedy reported no conflicts of interest.

REFERENCES

1. Myerson RJ, Tan B, Hunt S, et al: Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. Int J Radiat Oncol Biol Phys 88:829-836, 2014.

2. Nilsson PJ, van Etten B, Hospers GA, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer—The RAPIDO trial. BMC Cancer 13:279, 2013.


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