No abstract

In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

Neoplasms of the central nervous system (CNS) are the most frequently encountered solid tumors of childhood, but are less common in adolescents and young adults (AYA), aged 15–39 years. Gliomas account for 29%–35% of the CNS tumors in AYA, with approximately two-thirds being low-grade glioma (LGG) and the remaining being high-grade glioma (HGG). We review the epidemiology, work-up, and management of LGG and HGG, focusing on the particular issues faced by the AYA population relative to pediatric and adult populations. Visual pathway glioma and brainstem glioma, which represent unique clinical entities, are only briefly discussed. As a general management approach for both LGG and HGG, maximal safe resection should be attempted. AYA with LGG who undergo gross total resection (GTR) may be safely observed. As age increases and the risk factors for recurrence accumulate, adjuvant therapy should be more strongly considered with a strong consideration of advanced radiation techniques such as proton beam therapy to reduce long-term radiation-related toxicity. Recent results also suggest survival advantage for adult patients with the use of adjuvant chemotherapy when radiation is indicated. Whenever possible, AYA patients with HGG should be enrolled in a clinical trial for the benefit of centralized genetic and molecular prognostic review and best clinical care. Chemoradiation should be offered to all World Health Organization grade IV patients with concurrent and adjuvant chemotherapy after maximal safe resection. Younger adolescents with GTR of grade III lesions may consider radiotherapy alone or sequential radiotherapy and chemotherapy if unable to tolerate concurrent treatment. A more comprehensive classification of gliomas integrating pathology and molecular data is emerging, and this integrative strategy offers the potential to be more accurate and reproducible in guiding diagnostic, prognostic, and management decisions.

Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.