Patients with limited-stage small cell lung cancer treated with once-daily thoracic radiotherapy reported better quality of life and less inconvenience at three weeks compared with a standard twice-daily regimen, according to trial results presented at the 2022 American Society of Clinical Oncology Annual Meeting (Abstract 8504).
When oncologists weigh thoracic radiotherapy options for patients battling limited-stage small cell lung cancer, the choice between once-daily and twice-daily fractionation schedules involves balancing acute toxicity against long-term convenience. Data from the CALGB-70702 trial, presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8504), highlights how patients perceive these regimens differently across distinct time points.
Quality of Life and Patient Inconvenience in the CALGB-70702 Trial
The study served as a planned substudy of the CALGB 30610 study that demonstrated that 70-Gray (Gy) once-daily thoracic radiotherapy did not have superior overall survival compared with the standard 45-Gy twice-daily regimen in LS-SCLC. Because both arms provided similar clinical benefit, the researchers examined other factors like QoL to help guide decision-making. In this substudy, patients were administered several QoL questionnaires at baseline and a single item assessing difficulty swallowing at baseline and 3, 5, 7, 12, 26, and 52 weeks after radiation initiation. Inconvenience was also assessed at these timepoints, with primary endpoints including the FACT Trial Outcome Index-Lung Cancer (FACT-L TOI) and FACT eating and swallowing subscales at 12 weeks. Consent was obtained from 417 patients, with a questionnaire completion rate of 87% at baseline and 71% at week 52.
At the three-week mark, individuals on the once-daily arm experienced a significantly lower FACT-L total score mean worsening compared with the twice-daily arm, though this was only marginally less at week 5. The FACT-L TOI mean worsening was significantly less at 3 weeks (P=.003) for the once-daily arm, but was significantly greater at 12 weeks compared with the twice-daily arm. Acute esophagitis scores and difficulty swallowing were also significantly greater in the twice-daily arm at week 3 as well. Furthermore, patient convenience favored the once-daily arm: one-quarter of patients in the once-daily arm felt treatment was inconvenient compared with one-third in the twice-daily arm.
Divergent Recovery Timelines and Expert Perspectives
The quality-of-life advantage shifted as treatment progressed. Presenter Apar Kishor Ganti, MD, of University of Nebraska Medical Center in Omaha, Nebraska, noted that although QoL scores were better at 3 weeks, they were worse for the once-daily regimen at 12 weeks. However, Dr. Ganti observed that the once-a-day arm was considered to be less inconvenient by most patients and will probably end up being what is done in practice going forward.
Apar Kishor Ganti, MD, University of Nebraska Medical Center
Study discussant Kristin Ann Higgins, MD, of Emory University’s Winship Cancer Institute in Atlanta, explained that the sharp dip observed at week three in the twice-daily arm represents the last week in the twice-daily radiation treatment course, when it is expected to see a worsening of acute side effects. Dr. Higgins stated, If you consider once-daily radiation that would occur at week 7 … we do see a similar dip of quality of life at week 7 for the once-daily radiation arm,
adding that quality of life differs for the different fractionation regimens, and it differs depending on where in time you analyze quality of life.
Kristin Ann Higgins, MD, Winship Cancer Institute
Weighing the clinical implications, Joe Y. Chang, MD, PhD, of MD Anderson Cancer Center at the University of Texas in Houston, observed that both of these regimens have been used and adopted clinically. Dr. Chang noted that it is indeed difficult to say which of these is a reduced radiation schedule
because one is twice-daily but the patient only needs 3 weeks and the other is once-daily but the patient needs 7 weeks. In an email, Dr. Chang stated, In my view, the acute toxicities don’t have enough significance for clinicians to choose which regimen [to use]. Other factors, including long-term toxicity, could play more of a role in this setting.
Joe Y. Chang, MD, PhD, MD Anderson Cancer Center
Broadening Horizons in Extensive-Stage Small-Cell Lung Cancer Care
Beyond limited-stage disease, treatment paradigms continue to evolve for extensive-stage small-cell lung cancer. Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC), though only 0.8%–2.5% of patients presented complete response after chemoimmunotherapy. Because ES-SCLC is highly sensitive to radiotherapy, prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy, helping address residual thoracic lesions that commonly recur within the first year. Small-cell lung cancer accounts for 13%–15% of all lung cancers as a particularly malignant neuroendocrine carcinoma characterized by rapid growth and trend toward early widespread diffusion, with extensive-stage SCLC accounting for 65% of all newly diagnosed cases.
At the same time, managing brain metastasis risks remains a critical component of small-cell lung cancer care, given that prior studies have demonstrated that 50% of patients with SCLC are at risk of evolving to brain metastases after systemic therapy. While prophylactic cranial irradiation has historically been shown to decrease brain metastasis and prolong survival in patients with limited-stage SCLC in previous reports, current guidelines note that PCI is not commonly recommended for ES-SCLC.
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