Efficacy of the Association of Fractionated SRS and Subsequent Surgery in Patients With Brain Metastases

Prospective Clinical Study on the Efficacy of the Association of Fractionated SRS and Subsequent Surgery in Patients With Brain Metastases

In this study, the possibility of performing a preoperative neoadjuvant radiotherapy dose of 27 Gy fractionated in 3 sessions is explored, to maximize the biological effect of the treatment, in patients affected by solid tumors, in particular lung, breast and melanoma, in which brain metastases have arisen, the incidence of which is constantly increasing in relation to the improvements in oncological therapies and the consequent increase in patient survival. It was demonstrated that postoperative stereotactic radiosurgery with this fractionation was effective in improving local disease control at 1 year compared to single-dose stereotactic radiosurgery (91% vs 77%) and in reducing the risk of radionecrosis for metastatic brain lesions of size.

The treatment of potentially resectable brain metastases in association with preoperative fractionated stereotactic radiotherapy (FSRT) involves the administration of radiation therapy to an intact lesion, with the advantage of presenting fewer uncertainties in terms of target definition and does not require the addition of additional irradiation margins.

Furthermore, the reduction of the dose to healthy brain tissue may lead to a lower risk of inducing subsequent radionecrosis. In fact, the volume of healthy brain tissue irradiated is a recognized predictive factor for the induction of radionecrosis. The overall reduction of treatment times (FSRT + Surgery) with higher compliance by patients and improved logistics. Furthermore, potential advantages consist in the fact that a neoadjuvant radiosurgical treatment can potentially prevent cells scattered during surgery from causing neoplastic leptomeningitis, as these would have already received ablative irradiation. That radiation treatment on a target with an intact vascular supply is potentially more effective because the irradiation bed after surgery is more hypoxic.

It has been observed that over 20% of patients undergoing surgical resection of a metastasis do not undergo the planned radiosurgery due to complications, disease progression or other reasons for delay. The treatment therefore offers the possibility of delivering a higher biological dose with a greater probability of local control and a lower risk of meningeal spread and symptomatic radionecrosis.

Inclusion Criteria:

• patients with single metastatic brain lesions with a diameter of ≥ 3 cm symptomatic / asymptomatic or with symptomatic brain lesions ≥ 2 cm < 3 cm that are surgically resectable, without or in the presence of max 3 small synchronous lesions amenable to radiosurgery treatment;
• no urgent surgical indication for neurological symptoms or worsening intracranial hypertension;
• age ≥ 18 years;
• performance status according to the Eastern Cooperative Oncology Group (ECOG) scales ≤ 2;
• Karnfosky Performance Status ≥ 60;
• life expectancy greater than 3 months;
• patients assessed as suitable for surgery (ASA score ≤ 3) and in the absence of contraindications to undergoing brain MRI examination without and with contrast medium;
• ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• contraindications to radiotherapy treatment;
• pregnancy;
• inability to follow the procedures, to fill out the questionnaires;