Survey shows variability in thoracic radiotherapy dosing, fractionation

Issue: October 25, 2017

CHICAGO — The majority of radiation oncologists reported administering 60 Gy thoracic radiotherapy once daily for patients with limited-stage small-cell lung cancer, according to survey results presented at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.

Perspective from Steven J. Chmura, MD, PhD

However, researchers observed great variability in dosing and fractionation.

The optimal dose and fractionation schedule of thoracic radiotherapy — standard treatment for patients with limited-stage small-cell lung cancer — remain unclear.

“The benefits of radiotherapy have been demonstrated amply in this disease, but what is not as clear is how to deliver it in terms of dosing and fractionation,” Matthew J. Farrell, MD, a third-year medical student from Loyola University Chicago Stritch School of Medicine, said during the presentation.

The National Comprehensive Cancer Network guidelines recommend radiation oncologists administer either 45 Gy twice daily or 60 Gy to 70 Gy once daily.

Recent trials — including the EORTC 08072 and ongoing CALGB 30610 trials — have evaluated these regimens. However, the EORTC 08072 trial demonstrated no significant survival benefit associated with 45 Gy twice daily.

“With this fork in the road, it is unclear what radiation oncologists are actually doing with their patients. So, this is one thing our survey sought to answer,” Farrell said.

Farrell and colleagues used an Institutional Review Board-approved questionnaire to survey 309 radiation oncologists practicing in the United States to determine current practice patterns for treating patients with limited-stage small-cell lung cancer.

Questions involved background characteristics, self-rated knowledge of key trials and treatment recommendations for limited-stage small-cell lung cancer.

Results showed 60% of radiation oncologists preferred to administer thoracic radiotherapy once daily, and 76% acknowledged this treatment option to be more common in their practice.

Radiation oncologists’ stated preference of administering treatment once daily appeared to be in complete concordance with their actual administration practices. However, 40% of radiation oncologists who stated they preferred twice-daily dosing actually administered a once-daily regimen more often.

Fifteen percent of radiation oncologists were unwilling to switch from once-daily administration to twice daily, whereas 3% were unwilling to switch from twice- to once-daily administration, despite patients’ requests to switch. Of note, these physicians appeared more likely to have more than 10 years of experience following residency (P = .05).

Radiation oncologists said they preferred once-daily dosing because it is more convenient for patients (71%); is logically easier for their clinic schedule (43%); and is often more tolerable for patients, especially those with low performance status (59%).

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Conversely, radiation oncologists who preferred twice-daily therapy explained it is a shorter treatment duration for patients (51%); is more established compared with once-daily dosing (58%); and has not been proven to be inferior to once-daily dosing (42%).

Most radiation oncologists (88%) recommended a dose of 45 Gy for twice-daily treatment, whereas physicians who recommended once-daily treatment recommended a range of doses — including 60 Gy (54%), 63 Gy to 66 Gy (30%), and 70 Gy (10%).

In conjunction with self-rated knowledge of key trials, radiation oncologists who prescribed doses higher than 60 Gy once daily were more likely to be familiar with both the CALGB 30610 and EORTC 08072 trials (P = .01).

Lastly, Farrell noted the importance of the recently reported results from the open-label, randomized phase 3 CONVERT trial — designed to evaluate concurrent once-daily vs. twice-daily chemoradiotherapy in 547 patients with limited-stage smell-cell lung cancer.

The study demonstrated no significant difference in survival, nor any difference in toxicity between patients treated with 45 Gy once daily over 3 weeks compared with patients treated with 66 Gy twice daily over 6.5 weeks.

“Looking toward the future, [we will look] at how the CONVERT results change our practices compared to these pre-CONVERT data, as well as keep an eye on the ongoing [CALGB trial] in the United States comparing 45 Gy twice a day to 70 Gy once a day,” Farrell said. “Will it reach different conclusions than the CONVERT trial and, if so, how will that change things?” – by Kristie L. Kahl

Reference:

Farrell MJ, et al. Abstract OA01.05. Presented at International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.

Disclosure: Farrell reports no relevant financial disclosures.

Perspective

Steven J. Chmura, MD, PhD

The researchers show that once-daily dosing is preferred by both the patients and physicians. It makes sense, and other people have shown this. This occurred before the CONVERT trial finished, so I would assume that even fewer people now are actually going to administer radiotherapy twice a day. If, in fact, both are the same or close, we now have two effective regimens and we may not have to be so dogmatic about it.

As we go to these higher biologic doses, we cannot forget the impact on the immune system. Lower fractionated doses of 5 Gy vs. 4 Gy affect the presence of functioning T cells with little difference in terms of tumor control. The difference is dramatic as local dose increases.

My take home is that the biologic dose matters. We need to answer how high we should go because, at some point, all we are going to do is cause more acute complications. We may already be at the high point. In the absence of clear superiority, both the physician and patient preferences are going to choose the easier route.

Steven J. Chmura, MD, PhD

The University of Chicago

Disclosures: Chmura reports no relevant financial disclosures.