New data may inform standard of care for limited-stage SCLC

In patients with limited-stage small-cell lung cancer (LS-SCLC), radiation oncologists have very different approaches to the dosing and fractionation of thoracic radiotherapy (TRT), according to a recent nationwide survey on practice patterns. Findings show that most oncologists preferred once-daily (QD) over twice-daily (BID) dosing, and roughly 75% administered QD more often. Results were recently published in Clinical Lung Cancer.

The National Comprehensive Cancer Network (NCCN) defines patients with LS-SCLC as those with stage I-III cancers that can be safely treated with definitive radiotherapy. Standard treatment is comprised of chemoradiotherapy and prophylactic cranial irradiation in those exhibiting good objective responses.  The addition of TRT to chemotherapy significantly improves overall survival, according to several studies, but optimal TRT dosing and fractionation schedules are—as of yet—unknown.

Guidelines from the NCCN recommend one of two TRT treatment strategies in these patients:

• BID TRT in 1.5-Gy fractions over 3 weeks to a total dose of 45 Gy, or
• QD TRT in 2.0-Gy fractions over 6-7 weeks to a total dose of 60-70 Gy

Therefore, researchers led by Matthew J. Farrell, Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, conducted this study to “broadly sample radiation oncologists in the United States on their management of LS-SCLC.”

They surveyed radiation oncologists using a questionnaire that incorporated topics such as demographics, knowledge of key clinical trials (self-rated), and treatment recommendations. In all, 309 radiation oncologists responded. Of these, 58.9% were in private practice, and 41.1% from an academic setting. More than one-half (54.4%) had been out of residency training for greater than 10 years.

Farrell and colleagues found that 60% of survey respondents preferred QD TRT, 76% reported that QD treatment was more common in their practice, and 24% reported that BID TRT was more common. Radiation oncologists in academic settings were more likely to prefer BID treatment over QD (51% vs 33%, respectively; P=0.001) and use it in their actual practice (32% vs 19%; P=0.009).

Researchers found 100% concordance between preferred QD and administering QD, but only 40% of respondents who preferred BID actually administered QD more often.

Fifteen percent of radiation oncologists reported that they were not willing to switch from QD to BID, while 3% wouldn’t be willing to switch from BID to QD, even if patients requested it. Most respondents who were unwilling to switch regimens were more likely to have more than 10 years of post-residency training (P=0.048).

Most respondents who preferred QD TRT reported that their preference was based on its greater convenience for their patients (71%), while 43% reported that their preference was based on the logistical ease of QD therapy in their clinic schedules, and 59% preferred it because it was frequently more tolerable for patients, particularly in those with low performance status.

Among radiation oncologists who preferred BID TRT, 51% did so because of its shorter treatment duration, 58% because BID dosing is established as opposed to QD dose—which is not—and 42% preferred it because the QD regimen has not been proven to be superior to BID.

Approximately 88% of respondents recommended that BID treatment be comprised of a total dose of 45 Gy, of whom 2.9% recommended ? 54 Gy, 5.9% preferred 54 Gy, 2.9% recommended 50 Gy, and 0.3% preferred 30 GY. However, for QD treatment, only 54.4% recommended 60 Gy, 20.4% preferred 66 Gy, 10% preferred 70 Gy, 9.4% recommended 63 Gy, 5.2% recommended less than 60 Gy, and 0.6% preferred greater than 70 Gy.

Interestingly, Farrell et al also found that, among clinicians who preferred QD TRT, those who had treated more patients in the past year were more likely to recommended doses of greater than 60 GY (P=0.01). Among respondents who preferred BID TRT, those with more than 10 years of experience post-residency were more likely to recommend doses of greater than 45 Gy (18% vs 4%; P=0.0004).

Respondents were also asked to rate their knowledge of three relevant studies: the Intergroup 0096 trial, the Concurrent ONce-daily VERsus Twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT) trial, and the Cancer and Leukemia Group B (CALGB) 30610 trial.

• In the CONVERT trial, presented at the 2016 American Society of Clinical Oncology Annual Meeting and published in June 2017, researchers maintained that BID TRT remain the standard of care because they failed to prove the superiority of QD treatment. They also found a nonsignificant trend toward improved survival, lower-than-expected toxicity, better compliance, and shorter treatment duration in the BID arm.
• Researchers of the Intergroup 0096trial concluded that a dose of 45-Gy BID was superior to 45-Gy QD.
• The CALGB 30610 trial is ongoing and many years from completion.

Farrell and fellow researchers found that BID TRT was more likely to be preferred by respondents who were familiar with the CALGB 30610 trial (P=0.003), but familiarity with the CONVERT trial was not associated with a preference for QD vs BID TRT (P=0.10). Among those who preferred QD TRT, those familiar with the CALGB 30610 trial only were more likely to prefer doses of greater than 60 Gy (P=0.004), as were those familiar with only the CONVERT trial (P=0.02) or with both trials (P=0.01).

“Our survey results have shown that most respondents preferred QD over BID fractionation and more than three-quarters administered QD TRT more often to their patients,” concluded Farrell and colleagues.

“Our data can be used to track changes in practice patterns in the wake of the CONVERT trial to determine whether more physicians do as the investigators of the CONVERT trial suggest and embrace 45 Gy BID as the standard of care. The ongoing CALGB 30610 trial is still many years from completion. If the results are positive, it might bring US providers to a consensus on management; however, if negative, our survey results might hold for years to come,” they added.