Radiosurgery for brain oligometastases in lung cancer

INTRODUCTION Brain metastases are a common problem in oncology patients, especially in lung cancer. The usual treatment for cerebral oligometastases is whole brain radiation therapy. Given the persistent poor prognosis of this disease, other therapeutic alternatives such as stereotactic radiosurgery have been considered. However, there is no clarity regarding the effectiveness of its addition. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified 17 systematic reviews including seven studies overall, of which four were randomized trials. All trials assessed patients with brain oligometastases, but none of them included exclusively lung cancer population. We concluded that it is not possible to clearly establish whether radiosurgery decreases neurological functionality, cognitive impairment, mortality or serious adverse effects, as the certainty of the existing evidence has been assessed as very low.

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

Purpose To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature. Results Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. Recommendations Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines.

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines .

Brain Metastases from Adult Sarcomas: A Retrospective Cohort Study from the Hellenic Group of Sarcomas and Rare Cancers (HGSRC)

Brain metastases are rare events in patients with sarcoma and the available information is relatively limited. We retrospectively reviewed medical records of patients with sarcoma who developed brain metastases between April 2010 and April 2020 in six centers. Thirty-four adult patients were included with a median age at brain metastases diagnosis of 55.5 years (range, 18–75). The primary sarcomas originated either from soft tissue (n = 27) or bone (n = 7) and the most common subtypes were leiomyosarcoma (n = 8), Ewing sarcoma/peripheral neuroectodermal tumor (PNET) (n = 7) and osteosarcoma (n = 3). Most primary tumors were of high grade and located mainly in the extremities (n = 18). The vast majority of patients at the time of brain metastasis diagnosis already had extracranial metastatic disease (n = 26). The median time from sarcoma diagnosis to cerebral metastasis diagnosis was 16 months (range, 1–136). Treatment modalities for brain metastatic disease included whole-brain radiation therapy (WBRT) (n = 22), chemotherapy (n = 17), exclusive palliative care (n = 5), surgery (n = 9), targeted therapy (n = 6) or stereotactic radiosurgery (n = 2). Most patients experienced a progression of brain metastases (n = 11). The median overall survival from brain metastasis diagnosis was 3 months (range, 0–80). OS was significantly influenced by time-to-brain metastases (p = 0.041), WBRT (p = 0.018), surgery (p = 0.002) and chemotherapy (p = 0.006). In a multivariate analysis, only the localization of the primary (p = 0.047) and WBRT (p = 0.038) were associated with survival with statistical significance. Patients with sarcoma brain metastases have a particularly poor prognosis and an appropriate therapeutic approach is yet to be defined.

Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study

Background The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs). Methods The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group. Results This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3. Conclusion The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.

MET-6 Neoadjuvant fractionated stereotactic radiotherapy followed by piecemeal resection for metastatic brain tumor

BACKGROUND: Large brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative stereotactic radiosurgery (SRS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (Na-SRS) followed by surgery was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation necrosis (RN). We treated with neoadjuvant fractionated stereotactic radiotherapy (Na-fSRT) followed by surgery for large brain metastasis with piecemeal resection. METHODS: Twelve patients received Na-fSRT followed by surgery between July 2019 and April 2021. Na-fSRT dose was based on lesion size and was standard dosing. Surgery generally followed within 7 days after radiotherapy. RESULTS: The mean age was 68 years (51–79). Sixteen men and five women. Mean follow-up period was 8.5 months (1–24.9). Primary were lung; 10 (NSCLC; 9, SCLC (recurrence); 1), esophagus; 3, colon; 2, melanoma; 2, kidney; 2 (recurrence1), uterus body; 1, and liver; 1. The median maximum tumor diameter was 3.6 cm (2.6–4.9). Median PTV, GTV volume were 21.7ml, 15.5ml, respectively. The median fSRT dose was 30Gy/5fr, and the median time from fSRT to surgery was 4 days (1–7). As preoperative adverse event, intracranial hypertension and partial seizure grade 2 (CTCAE ver.5) were occurred, but controlled with steroid and osmotic diuretics and anticonvulsant. Grade 3 and more adverse events were not occurred. Gross total removal was performed in 95.2%. Event cumulative incidence as follows: cavity local recurrence 4.8% (subtotal removal case); distant brain failure 33%; LMD 4.8%; and symptomatic RN 0%. The median intracranial progression free survival was 7 months, and median overall survival was 8.4 months. CONCLUSIONS: Na-fSRT followed by piecemeal resection is safety and feasible, and may have therapeutic value for deep large brain metastasis and eloquent lesion. Further prospective investigations in multi-institutional settings are warranted.

Advances in the diagnosis, evaluation, and management of leptomeningeal disease

Leptomeningeal metastasis (LM) is a devastating complication of cancer with variable clinical presentation and limited benefit from existing treatment options. In this review, we discuss advances in LM diagnostics and therapeutics with the potential to reverse this grim course. Emerging cerebrospinal fluid circulating tumor cell and cell-free tumor DNA analysis technologies will improve diagnosis of LM, while providing crucial genetic information, capturing tumor heterogeneity, and quantifying disease burden. Circulating tumor cells and cell-free tumor DNA have utility as biomarkers to track disease progression and treatment response. Treatment options for LM include ventriculoperitoneal shunting for symptomatic relief, radiation therapy including whole-brain radiation and focal radiation for bulky leptomeningeal involvement, and systemic and intrathecal medical therapies, including targeted and immunotherapies based on tumor mutational profiling. While existing treatments for LM have limited efficacy, recent advances in liquid biopsy together with increasing availability of targeted treatments will lead to rational multimodal individualized treatments and improved patient outcomes.