1. Samson, Kurt

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SAN DIEGO-A national survey of radiation oncologists has found a sharp decline in the use of prophylactic cranial irradiation (PCI) for extensive-stage small cell lung cancer (ES-SCLC), indicating a rapid shift in standard practice since a 2017 phase III clinical trial found little overall survival (OS) advantage with the technique.

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The findings were presented at the 2019 Multidisciplinary Thoracic Cancers Symposium by first author Olsi Gjyshi, MD, PhD, a radiation oncology resident at MD Anderson Cancer Center (Abstract 3).


PCI became widely adopted in such patients after a phase III study, published in the New England Journal of Medicine, reported that PCI decreased brain metastases and increased OS in ES-SCLC patients (2007;357:664-672). However, a 2017 study published in the Lancet Oncology, failed to find any survival advantage over observation with MRI scans (2017;18(5):663-671). One year later, National Comprehensive Cancer Network guidelines were changed to reflect the findings.


To determine whether or not the second trial had affected treatment trends, Gjyshi and his colleagues sent email questionnaires to attending radiation oncologists at academic cancer centers, asking about their awareness of the 2017 phase III trial and whether or not its findings had affected their practice. Of the 49 who responded, all of them said they were aware of the study.


While 78 percent said they had offered PCI to ES-SCLC patients prior to the 2017 study, less than half (38%) continued to do so afterwards, and two-thirds (67%) attributed the change to the trial's findings.


"Our survey indicates that most providers no longer routinely use PCI for patients with extensive-stage disease that responds to chemotherapy," Gjyshi said during a press briefing. "Unfortunately, despite recent advances in cancer medicine, small cell lung cancer continues to result in very poor outcomes, with overall 5-year survival ranging in the single digits."


Larger Survey Results

To get an even more complete prospective, the researchers conducted a nationwide survey of American Society for Radiation Oncology members. A similar shift in practice was observed among 431 respondents, with 74 percent of academic oncologists saying that they offered PCI before 2017, but only 43 percent continued to do so after the Takahashi paper. A similar decline was reported by oncologists in private or government practices where the rate fell from 69 percent to 44 percent, respectively.


In addition, one in four of the respondents reported a decline in PCI referrals for patients with ES-SCLC, and 12 percent also reported fewer referrals for PCI in patients with limited-stage SCLC.


Controversial at the time, the 2007 trial "drastically altered" treatment to the extent that most radiation oncologists accepted PCI as the standard of care for ES-SCLC patients, Gjyshi noted. The 2017 study demonstrated no OS advantage, although it did reduce the incidence of intracranial metastases.


"Small cell lung cancer has a tendency to spread past the lungs to the brain, and brain metastases substantially diminish a patient's quality of life," explained Gjyshi. One of the main reasons for this is that most ES-SCLC develop brain metastases at some point during their disease, especially those with extensive-stage disease.


"With extensive-stage disease, PCI may best be reserved for patients who are likely to benefit from it, such as those with excellent performance status, younger age (under 70 years), and excellent cognitive functions at baseline," he noted.


However, he cautioned against extrapolating the 2017 trial findings to patients with limited-stage SCLC, adding that additional research may be necessary to address the issue.


The researchers contacted 205 attending radiation oncology specialists in thoracic malignancies from 105 academic centers over a 2-week period in September 2018 and 24 percent agreed to participate in the survey. The majority were from large academic centers (67%) and 42 percent reported that more than half of their patients were lung cancer cases.


No specific trends in PCI based on geographic location, years of practice, or volume of SCC cases were observed. Individual responders also commented that close MRI surveillance is often used as an alternative to PCI. A large majority of respondents said they would be willing to enroll patients in trials testing PCI versus MRI surveillance.


"It is important to come to a consensus on how best to treat these patients," Gjyshi said.


Expert Commentary

Charles B. Simone II, MD, FASTRO, Professor and Chief Medical Director at the New York Proton Center, commented on the trial's findings.


"Now that the field is moving away from the routine use of PCI for extensive-stage small cell lung cancer patients, we need to determine the optimal method and timing for brain surveillance for these patients." he told Oncology Times. "Should a patient develop brain metastases, their prognosis is much better if the metastasis is found early and treated early. Similarly, the most effective treatment for small, asymptomatic brain metastases specifically in small cell lung cancer as opposed to non-small cell lung cancer needs to be determined."


He also noted that there has not been a randomized trial showing any survival benefit for PCI in over a decade and, at that time, MRI brain imaging after first-line chemotherapy was not a universal practice. Moreover, until the Takahashi trial, there had not been a large randomized trial using modern treatment practices of MRI imaging after first-line chemotherapy, or that assessed surveillance MRI imaging in patients not receiving prophylactic cranial irradiation.


"With better assurance that patients did not have metastatic disease on initial MRI, and with closer monitoring of patients who might develop brain metastases, patients are more closely monitored and thus are more effectively treated with early brain therapy should they development metastases," Simone explained. "Given the significant change in clinical and imaging practices for these patients, a single modern study in this population would be guideline-changing."


And although medical oncologists might now be less likely to refer patients with extensive-stage SCLC to radiation oncologists for PCI, they should still strongly consider referring these patients to radiation oncologists for thoracic consolidation of their primary tumor and residual thoracic disease following first-line therapy, Simone stated.


"With a large randomized trial suggesting that these patients can have a significant survival benefit from thoracic radiotherapy (Lancet 2015;385(9962):36-42), radiation oncologists should still be an integral part of the care of these patients. Furthermore, the Takahashi trial focused on extensive-stage small cell lung cancer, and clinicians need to be careful not to extrapolate those findings to limited-stage small cell lung cancer patients."


Kurt Samson is a contributing writer.