This study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS as first-line treatment for SCLC patients with brain metastases.
At present, the standard treatment for SCLC brain metastases is whole brain radiotherapy (WBRT). However, WBRT is palliative in nature due to its low dose and poor long-term control rate of intracranial lesions. At the same time, with the advent of the era of immunotherapy, a variety of PD-1/PD-L1 monoclonal antibodies combined with chemotherapy have become the standard first-line treatment for extensive-stage SCLC(ES-SCLC). Studies have shown that the survival time of SCLC patients with brain metastases is expected to be further prolonged in the era of chemotherapy and immunotherapy. Therefore, it is particularly important to further improve the control rate of intracranial lesions. It has been confirmed in previous studies that WBRT combined with stereotactic radiotherapy for visible intracranial lesions (SRS/SRT) can effectively improve the control rate of intracranial lesions. However, most of the previous studies of WBRT combined with SRT for brain metastases did not include or only included a very small number of patients with SCLC. Studies on thoracic radiotherapy for limited-stage small cell lung cancer have found that an increase in radiotherapy dose can significantly improve the prognosis of patients with SCLC, which was previously considered to be highly radiosensitive. It is reasonable to think that SRS combined with WBRT for SCLC brain metastases may improve the prognosis of patients. WBRT is known to cause severe cognitive impairment, which has also led to the reluctance of some patients to undergo WBRT. In the era of chemotherapy, the NRG-CC001 study showed that Hippocampal avoidance WBRT (HA-WBRT) could better protect the cognitive function of patients without affecting the prognosis of patients. The 2022 ASTRO guidelines have clearly recommended the use of hippocampal protection techniques in WBRT. Considering the lack of previous literature on the use of SRS combined with WBRT in SCLC patients in the chemo-immunotherapy era, The aim of this study is to adopt the dose fractionation of SRS combined with WBRT, which has been proven to be safe in the treatment of brain metastases from NSCLC, and to evaluate the safety of this treatment mode in SCLC patients with brain metastases receiving standard first-line chemoimmunotherapy. In summary, this study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS in the first-line treatment of SCLC patients with baseline brain metastases who are suitable for SRS treatment during the standard first-line chemotherapy combined with immunotherapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
hippocampal-avoidance whole brain radiotherapy (WBRT) followed by stereotactic body radiotherapy (SBRT)
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGdose-limiting toxicities rate
dose-limiting toxicities(DLTs) were assessed according to CTCAE 5.0 criteria and included the following three conditions, with the exception of asymptomatic biochemical abnormalities: (1) grade 3 toxicity lasting for more than 7 consecutive days; (2) Grade 4 toxicity excluding neutropenia and thrombocytopenia; (3) Treatment-related grade 5 adverse events could not be excluded.
Time frame: 30 days since the final day of radiotherapy
1-year intracranial progression-free survival rate
1-year intracranial progression-free survival (iPFS) rate was defined as proportion of patients without intracranial disease progression or death at 1 year of follow-up
Time frame: one year
overall survival
overall survival(OS) was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
Time frame: one year
time to intracranial progression
Time to intracranial progression was defined as the time from enrollment for treatment to the observation of progression of intracranial disease.
Time frame: one year
Changes in learning and memory function
learning and memory function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the Hopkins Verbal Learning Test (HVLT-R)
Time frame: one year
processing speed and executive function
processing speed and executive function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the trail making test (TMT-Part A, to assess processing speed, and TMT-Part B, to assess executive function).
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Time frame: one year