Shorter Radiation Course May Benefit Patients With Locally Advanced Rectal Cancer


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Krzysztof Bujko, MD

Smitha Krishnamurthi, MD

The new regimen has similar efficacy but causes fewer side effects and is more convenient for patients. It is also less costly compared to standard chemoradiation, so it may be especially valuable in limited-resource settings.

Lucjan Wyrwicz, MD, PhD

As neoadjuvant treatment for locally advanced rectal cancer, a shorter course of radiation therapy followed by chemotherapy may be as good as, or better than, standard chemoradiotherapy, according to a study from the Polish Colorectal Study Group presented at the 2016 Gastrointestinal Cancers Symposium.1

The short-course therapy delivers radiation over 5 days, then gives three cycles of chemotherapy. This regimen is better tolerated and much more convenient for patients, according to the researchers, who also reported that 3-year overall survival was higher with the short-course approach (73% vs 65%; P = .046).

Lucjan Wyrwicz, MD, PhD, presented the findings in a press briefing, and Krzysztof Bujko, MD, delivered the oral presentation. Both physicians are at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

ASCO spokesperson Smitha
Krishnamurthi MD
, of Seidman Cancer Center and the Case Comprehensive Cancer Center in Cleveland, Ohio, explained in a press briefing that short-course radiotherapy has been more widely used in Europe than in the United States, largely because of conflicting findings when it has been compared with conventional chemoradiation therapy. Although in the current study many patients received oxaliplatin, which is not the standard of care, she considered the findings to be relevant.

“The study still provides important information. There is interest in incorporating short-course radiation because it is more convenient and less expensive,” said Dr. Krishnamurthi. “These results may lead to increased use of this method in the United States.”

Short-Course vs Conventional Treatment

The Polish Colorectal Study Group compared outcomes and toxicity with short-course radiation therapy/chemotherapy vs conventional chemoradiotherapy in this phase III study of 515 patients with stage cT3 or cT4 rectal cancer. Patients were assigned to standard chemoradiotherapy or the short-course radiation regimen.

In the control arm, patients received radiotherapy at 50.4 Gy given concurrently over approximately 5 weeks with bolus fluorouracil (5-FU) and leucovorin during the first and fifth weeks, plus oxaliplatin at 50 mg/m2 once weekly. The experimental arm received 5 days of radiation (5 x 500 cGy) followed by three cycles of FOLFOX4 (5-FU, leucovorin, oxaliplatin) every 2 weeks.

When evidence emerged that oxaliplatin was associated with toxicity without additional benefit, the protocol was amended to allow physicians to use the drug at their discretion. Roughly 70% of each arm did receive oxaliplatin.

In both arms, surgery was performed approximately 12 weeks after patients started radiotherapy. Adjuvant therapy was not specified.

Comparable Outcomes

The treatments offered the same opportunity for radical resection and achieved similar disease-free survival. The short-course radiation approach, however, was associated with less toxicity, Dr. Wyrwicz reported.

“The new regimen has similar efficacy but causes fewer side effects and is more convenient for patients. It is also less costly compared to standard chemoradiation, so it may be especially valuable in limited-resource settings,” Dr. Wyrwicz said.

R0 resection, the primary endpoint, was achieved in 77% of the experimental arm and 71% of the control arm (P = .07), indicating a trend in favor of the short-course approach. Pathologic complete responses were achieved by 16% and 12%, respectively (P = .17).

The hypothesis was that the experimental arm would produce higher R0 rates. Therefore, the study was technically “negative,” he pointed out, “but we showed for the first time that there is an alternative to standard chemoradiation lasting more than 5 weeks.”

Chemoradiotherapy Regimens in Rectal Cancer

  • A short course of radiation (5 days) followed by 3 cycles of chemotherapy yielded outcomes as good as those with conventional radiation (> 5 weeks) plus chemotherapy, in a study reported by the Polish Colorectal Study Group.
  • R0 resection, the primary endpoint, was achieved in 77% of the short-course arm and 71% of the control arm—a positive trend for short-course treatment.
  • Three-year disease-free survival was over 50% in each arm, and local failure rates were 22% per arm.
  • Acute toxicities were significantly less with the short course (75%) than conventional treatment (83%).

Rates of disease-free survival at 3 years were similar: 53% for the experimental arm and 52% for the control arm (P = .85). Local failure rates were 22% and 21% (P = .82), respectively.

Rates of acute toxicities, however, favored the short course, with 75% in the experimental arm and 83% in the control arm (P = .006). Rates of grade 3+ toxicities, however, were essentially the same, 23% and 21%. Late toxicities were also similar, the investigators reported.

Overall survival also appeared to favor the short-course approach. The Kaplan-Meier curves for overall survival separated at about 2 years and plateaued thereafter, with 3-year survival rates of 73% with the short-course modality and 65% with chemoradiotherapy (P = .046).

“This preliminary observation of an 8% absolute survival benefit warrants a closer look for factors that may be contributing to a survival benefit,” Dr. Wyrwicz said. ■

Disclosure: Dr. Bujko reported no potential conflicts of interest.

Reference

1. Bujko K, on behalf of the Polish Colorectal Study Group: Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study. 2016 Gastrointestinal Cancers Symposium. Abstract 489. Presented January 21, 2016.


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Claus Rödel, MD, of the Department of Radiotherapy, University of Frankfurt, Germany, discussed the study at the 2016 Gastrointestinal Cancers Symposium.

“The main strength of the Polish II study is clearly its innovative design,” he said. “It sequentially combines effective local radiotherapy and ...


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