medwireNews: High-dose, twice-daily thoracic radiotherapy may improve survival among patients with limited-stage small-cell lung cancer, phase 2 study findings indicate.
“Our study shows that twice-daily thoracic radiotherapy of 60 Gy in 40 fractions is an alternative to established schedules,” write Bjørn Grønberg (Norwegian University of Science and Technology, Trondheim) and co-authors in The Lancet Oncology.
They add: “The toxicity was modest, suggesting that concerns about toxicity from twice-daily thoracic radiotherapy might be unjustified when using modern radiotherapy techniques and limiting radiotherapy fields to PET-CT [positron emission tomography-computed tomography] positive lesions.”
The trial included 170 treatment-naïve participants (median age 65 years, 57% women) from 22 hospitals in Scandinavia between 2014 and 2018 who each received four courses of intravenous cisplatin 75 mg/m2 or carboplatin (AUC 5–6 mg/mL per min) on day 1, plus intravenous etoposide 100 mg/m2 on days 1–3 of each 3-week cycle.
Between 20 and 28 days after the first course of chemotherapy, the participants received, on a randomized basis, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions (n=89) or 45 Gy in 30 fractions (n=81) to the primary lung tumor and PET-CT positive lymph node metastases. The majority (85%) of patients in each group also received prophylactic cranial irradiation.
The researchers report that at 2 years, individuals in the 60 Gy group were a significant 3.1 times more likely to be alive than those in the 45 Gy group, with overall survival (OS) rates of 74.2% and 48.1%, respectively.
Median OS was also significantly longer in the 60 Gy group than in the 45 Gy group, at 37.2 versus 22.6 months, but there was no significant difference between the two arms in median progression-free survival, at 18.6 versus 10.9 months.
There were also no significant differences between the two groups in the rates of local failure, frequency of distant metastases, or the proportion of patients receiving second-line chemotherapy.
Grønberg and team found that adverse event (AE) rates were similar between the groups. The most common grade 3 or 4 AE was neutropenia, which occurred in 81% of people in each group, followed by neutropenic infections (27% for 60 Gy vs 39% for 45 Gy), thrombocytopenia (24 vs 25%), anemia (16 vs 20%), and esophagitis (21 vs 18%).
There were three treatment-related deaths in the 60 Gy group (neutropenic fever, aortic dissection, pneumonitis) and three in the 45 Gy group (thrombocytic bleeding, cerebral infarction, myocardial infarction).
The investigators say that 5-year survival data will be available in 2023, and while “it is not yet possible to assess whether 60 Gy increases long-term survival […] the already observed survival benefit is highly relevant for patients, especially because the higher dose did not cause more toxicity, and the frequency of radiotherapy-related toxicities was among the lowest reported in studies of limited stage SCLC.”
Moreover, Grønberg et al believe, that the 2-year OS rate observed in the 60 Gy arm “is the highest reported in trials in limited stage SCLC, including all trials of high-dose, once-daily thoracic radiotherapy, and adds to the evidence suggesting that accelerated, hyperfractionated thoracic radiotherapy is the most effective approach in this disease.”
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Lancet Oncol 2021; 22: 321–331