Study Evaluates Radiotherapy Dose for Brain Metastases in SCLC

Data show more than 2.2 million new cases of lung cancer were diagnosed in 2020, with small cell lung cancer (SCLC) representing approximately 15% of all lung cancers. More than 50% of patients will develop brain metastases within 2 years. Brain metastases were shown to have a negative effect on survival in patients with SCLC. The standard treatment for SCLC brain metastases remains whole brain radiotherapy (WBRT), which has an overall effective rate of 50% to 80%.

In previous studies, Liming Xu and colleagues found that WBRT with additional radiation boost is more effective than WBRT alone in prolonging overall survival (OS) in patients with SCLC with brain metastases. They noted, however, that the suitable radiotherapy dose of brain metastases and efficacy are unclear. On this basis, they conducted a retrospective study analyzing the efficacy and safety of low- or high-dose radiotherapy in patients with SCLC with brain metastases. Findings were reported in Frontiers in Oncology [published online September 15, 2023; doi;10.3389/fonc.2023.1245506].

The researchers analyzed the clinical characteristics of patients with SCLC and brain metastases who underwent brain radiation therapy from 2013 to 2023 at the Tianjin Medical University Cancer Institute and Hospital. The 121 patients were divided into two groups according to brain metastases, with 65 receiving low-dose treatment and 56 receiving high-dose treatment. All patients received first-line chemotherapy and/or combined concurrent radiotherapy/sequential thoracic radiotherapy (TRT). The first-line chemotherapy regimen included etoposide (100 mg from days 1 to 5) with either cisplatin (30 mg/m² from days 1 to 3) or carboplatin (500 mg on day 1). Eighty patients received TRT after chemotherapy.

Of the 121 patients, most were men (n=100; 82.6%), with a mean age of 61 years. The majority had severe smoking (smoking index ³400; n=90; 74.4%). Most patients also had a superior Karnofsky performance status (KPS) score (KPS score ³80; n=107; 88.4%). The biologically effective dose (BED) for radiotherapy was 48.1% for the low-dose group (BED £56 Gy) and 51.9% for the high-dose group (BED >56 Gy). The most common metastatic organs were bone metastasis (33.1%), distant lymph node metastasis (17.4%), lung metastasis (16.5%), pleural metastasis (12.4%), adrenal metastasis (11.6%), and liver metastasis (10.0%). More than 90% of patients received greater than four cycles of chemotherapy, with 71.1% of patients responding to chemotherapy.

The intracranial overall survival (iOS) and intracranial local control survival (iLC) of the two groups were analyzed after propensity score matching (PSM). The researchers defined iOS as the period from the start of brain metastases diagnosis by imaging (magnetic resonance imaging [MRI] or enhanced computed tomography [CT]) until event occurrence or the last follow-up; iLC was defined as the time from the start of brain metastases diagnosis imaging (MRI or enhanced CT) until the first event of intracranial local failure.

In all patients, the median follow-up time was 18.6 months. The 2-year incidence of iOS and iLC was 15.4% and 70.3%, respectively, and cerebral necrosis occurred in two patients. Treatment-related side effects were observed in the low- and high-dose groups, mainly nausea, vomiting, dizziness, headache, leukopenia, and radiation brain necrosis.

In a univariate analysis related to iOS, the findings showed that extracranial disease control (P=.023), diagnostic-specific Graded Prognostic Assessment (DS-GPA) ³2 (P=.016), immunotherapy (P=.049), low dose (P=.030), and WBRT plus simultaneous integrated boost (P=.009) were significantly correlated with an increase in survival rate.

Compared with the low-dose group, the high-dose group had more patients with greater weight loss >5% (9.2% vs 33.9%), a smaller maximum diameter of brain metastases (53.8% vs 73.2%), longer interval from diagnosis of SCLC to brain metastases (36.9% vs 69.9%), and WBRT plus stereotactic radiosurgery (1.5% vs 96.4%), respectively. This outcome resulted in an imbalance between the two groups.

After PSM analysis, the baseline characteristics of the two groups were well balanced. The 2-year iOS in the low-dose group (n=49) was significantly superior compared with the high-dose group (47.1% vs 30.7%, respectively; P=.025). However, the 2-year iLC was not significantly improved (65.3% vs 91.9%, respectively; P=.267).

Further analysis revealed that in the DS-GPA >2 subgroup, the 2-year iOS in the low-dose group was significantly superior compared with the high-dose group (65.3% vs 25.5%, respectively; P=.019). In the DS-GPA ³2 subgroup, there was no significant difference between the low- and high-dose groups (31.6% vs 28.8%, respectively; P=.502). Regarding the 2-year iLC in the DS-GPA ³2 subgroup, the low-dose group was significantly inferior compared with the high-dose group (52.2% vs 91.7%, respectively; P=.044).

The authors noted two study limitations. The study was a retrospective analysis, and the distribution of clinical features was not very uniform. The study was also a small retrospective analysis with choice bias, which should be verified by further prospective cohort studies.

“Our study found that the iLC was improved along with increasing radiotherapy dose, but high dose had inferior iOS compared [with] low dose, while there [was] not significantly [improved] iLC [with] BED >56 Gy. In patients [from the] DS-GPA ³2 subgroup, high dose brought better iLC benefits,” the researchers concluded. “This surprising result suggested that the iLC was not [improving] iOS along with increasing radiotherapy dose when the radiotherapy dose reached a certain extent, which needed further [observation].”