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Chemoradiotherapy extends survival in limited-stage small cell lung cancer

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January 18, 2019

Patients with stage I to stage II small cell lung cancer achieved long-term survival with acceptable adverse effects following chemoradiotherapy and prophylactic cranial irradiation, according to a post-hoc secondary analysis of a multicenter, randomized phase 3 trial published in JAMA Oncology.

“Limited-stage small cell lung cancer prognosis is poor, with modest survival improvement during the past decades mainly because of radiotherapy advancements and better integration of chemotherapy and radiotherapy,” Ahmed Salem, MB ChB, PGCert, MSc, PhD, FHEA, FESTRO, FRCR, senior clinical lecturer in lung cancer research in the division of cancer sciences at University of Manchester, and colleagues wrote. “To our knowledge, this is the first study reporting on stage I to II small cell lung cancer within a randomized clinical trial in the era of modern radiotherapy.”

Salem and colleagues conducted a secondary analysis of 509 patients (54% men; mean age, 61.5 years; standard deviation, 8.3) with TNM staging information from the Concurrent Once-Daily vs. Twice-Daily Radiotherapy Trial (CONVERT), which included 543 patients with limited-stage small cell lung cancer and an ECOG performance status of 0 to 1.

Participants in CONVERT were randomly assigned to either twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. When indicated, patients were offered prophylactic cranial irradiation.

OS served as CONVERT’s primary endpoint.

The researchers collected TNM staging information prospectively for the unplanned secondary analysis, hypothesizing that outcomes among patients with stage I to stage II small cell lung cancer would be significantly better than those of patients with stage III disease. Using data from CONVERT, researchers compared characteristics, interventions and outcomes of patients in both groups.

The analysis included 86 patients (16.9%) with TNM stage I (n = 4; 4.7%) or stage II (n = 82; 95.3%) disease. Node-positive disease occurred in 38 (44.2%) of those patients.

The researchers found that patients with stage I to II disease had smaller median gross tumor volume (38.4 cm3; range, 2.2-593) than patients with stage III disease (93 cm3; range, 0.5-513.4; P < .001). There were no further differences between the two groups in baseline and treatment characteristics.

Among those who received prophylactic cranial irradiation, there were no significant differences in chemoradiotherapy adherence between those with stage I/stage II vs. stage III disease (90.7% vs. 81.9%).

Patients with stage I to II disease achieved longer median OS (50 months; 95% CI, 38 to not reached) than patients with stage III disease (25 months; 95% CI, 21-29 months; HR = 0.6; 95% CI, 0.44-0.83).

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There was no significant survival difference among patients with stage I/stage II disease in the once-daily vs. twice-daily treatment arms (39 months vs. 72 months).

Rate of 2-year OS was 64% (95% CI, 54-75) among patients with stage I to II disease vs. 51% (95% CI, 46-56) among those with stage III disease.

The OS difference was consistent between trial groups.

Researchers observed no significant differences between the groups in terms of acute and late toxic effects, other than a lower prevalence of grade 3 or higher acute esophagitis among patients with stage I to II disease vs. those with stage III disease (11.3% vs. 21.1%; P < .001).

“Although our findings were expected, this analysis may benchmark chemoradiotherapy outcome and toxic effects in stage I to II small cell lung cancer, providing information that practitioners can relay to their patients to aid clinical decisions,” Salem and colleagues wrote.
These findings may support the use of more exact staging in small cell lung cancer, Howard (Jack) West, MD, medical oncologist and medical director of the thoracic oncology and genitourinary oncology programs at Seattle’s Swedish Cancer Institute, wrote in an editor’s note.

“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” West wrote. “The better outcomes in smaller-volume and earlier-stage small cell lung cancer may be attributable to greater efficacy of the same chemoradiotherapy for low-volume compared with higher-volume disease, more favorable underlying biology of these earlier-stage cancers, or a combination of these factors.” – by Jennifer Byrne

Disclosures: Salem reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. West reports no relevant financial disclosures.

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