ALK inhibitors in ALK-positive NSCLC with central nervous system metastases

In anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer, brain metastases occur in 22–33% of cases at diagnosis and could reach up to 70% after crizotinib failure. Next-generation ALK inhibitors (ngALKi) have superior intracranial activity and prolonged responses compared with crizotinib and chemotherapy, as was shown in treatment-naïve or crizotinib pre-treated patients, irrespective of prior brain irradiation. Nevertheless, central nervous system relapse is also seen with ngALKi. Tailored treatment is necessary to obtain long-term survival without detrimental effects on cognition. Possible options include profiling secondary mutations to select sequential ngALKi, stereotactic radiotherapy and/or surgery, with the aim to avoid/deter whole brain irradiation

The Current Role of Whole Brain Radiation Therapy in Non–Small Cell Lung Cancer Patients

The incidence of brain metastases has increased in patients with NSCLC as a result of better systemic disease control and advances in imaging modalities. Whole brain radiotherapy (WBRT) has been the mainstay treatment of multiple symptomatic brain metastases for years. A number of recent publications have questioned its place in the absence of a survival and quality of life benefit and the possible risk for long-term neurotoxicity. Omission or deferral of WBRT and strategies consisting of stereotactic radiosurgery or delivery of systemic therapies alone are being proposed more and more. However, critical analysis of the literature shows that WBRT still has relevant indications in well-selected patients. Within this review, we discuss the place of WBRT in the modern management of patients with NSCLC. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.</p

Combination of Immunotherapy and Radiotherapy-The Next Magic Step in the Management of Lung Cancer?

none4sinoneHendriks L.E.L.; Menis J.; De Ruysscher D.K.M.; Reck M.Hendriks, L. E. L.; Menis, J.; De Ruysscher, D. K. M.; Reck, M

The electronic nose : emerging biomarkers in lung cancer diagnostics

Lung cancer is very common and the most common cause of cancer death worldwide. Despite recent progress in the systemic treatment of lung cancer (checkpoint inhibitors and tyrosine kinase inhibitors), each year, >1.5 million people die due to this disease. Most lung cancer patients already have advanced disease at the time of diagnosis. Computed tomography screening of high-risk individuals can detect lung cancer at an earlier stage but at a cost of false-positive findings. Biomarkers could lead towards a reduction of these false-positive findings and earlier lung cancer diagnosis, and have the potential to improve outcomes and treatment monitoring. To date, there is a lack of such biomarkers for lung cancer and other thoracic malignancies, although electronic nose (e-nose)-derived biomarkers are of interest. E-nose techniques using exhaled breath component measurements can detect lung cancer with a sensitivity ranging from 71% to 96% and specificity from 33 to 100%. In some case series, such results have been validated but this is mostly using internal validation and hence, more work is needed. Furthermore, standardised sampling and analysis methods are lacking, impeding interstudy comparison and clinical implementation. In this narrative review, we provide an overview of the currently available data on E-nose technology for lung cancer detection

Non-small cell lung cancer with a single metastasis, the new stage M1b; does the site matter?

Non-small cell lung cancer (NSCLC) patients with a solitary metastasis are considered to have a more favourable prognosis compared to those with multiple metastases. This is also shown in the 8th tumor, node, metastases edition for lung cancer (TNM8): patients with M1b (single extrapulmonary metastasis) have a superior prognosis than those with M1c disease (multiple metastases). Although not described in the TNM8, site of single metastatic disease may reflect tumour biology and may be of important prognostic value. We report a case of a patient with squamous cell NSCLC and a single skeletal muscle metastasis with a remarkably aggressive disease course

In-depth Analysis of Lorlatinib-related neurocognitive Adverse Events in Patients With Non–small-cell Lung Cancer

Introduction: Lorlatinib is a potent, brain penetrant, next-generation ALK/ROS1 TKI, with high response rates and durable responses, including the brain. However, a significant drawback is the manifestation of neurocognitive adverse events (NCAEs). Despite being generally low-grade in severity, these NCAEs can be physically and mentally disabling. Extensive neurocognitive testing in this group of patients is lacking; therefore we conducted this study. Patients and methods: This observational prospective study was conducted across 3 Dutch university hospitals. Patients with metastatic NSCLC with an ALK- or ROS1-rearrangement and having an indication to start lorlatinib in daily clinical practice were eligible. The primary endpoints were to identify changes in neurocognitive functioning, measured through neurocognitive assessment at intervals of 2 weeks and 2 months after starting lorlatinib, in comparison to baseline. As a secondary endpoint, the correlation between neurocognitive impairment and self-reported neurocognitive dysfunction was examined. Results: Between June 2019 and October 2022, 22 patients were included. Among the various neurocognitive tests administered, only the Hopkins Verbal Learning Test-Revised parts b and c demonstrated a significant and clinically relevant decrease in scoring 2 weeks post initiation of lorlatinib (P = .036 and P = .003, respectively). However, these returned to baseline at the 2-month evaluation. The questionnaires did not result in significantly different outcomes over time.Conclusion: Lorlatinib treatment did not result in a sustained and significant decline within any of the specified neurocognitive domains.</p

In-depth Analysis of Lorlatinib-related neurocognitive Adverse Events in Patients With Non–small-cell Lung Cancer

Introduction: Lorlatinib is a potent, brain penetrant, next-generation ALK/ROS1 TKI, with high response rates and durable responses, including the brain. However, a significant drawback is the manifestation of neurocognitive adverse events (NCAEs). Despite being generally low-grade in severity, these NCAEs can be physically and mentally disabling. Extensive neurocognitive testing in this group of patients is lacking; therefore we conducted this study. Patients and methods: This observational prospective study was conducted across 3 Dutch university hospitals. Patients with metastatic NSCLC with an ALK- or ROS1-rearrangement and having an indication to start lorlatinib in daily clinical practice were eligible. The primary endpoints were to identify changes in neurocognitive functioning, measured through neurocognitive assessment at intervals of 2 weeks and 2 months after starting lorlatinib, in comparison to baseline. As a secondary endpoint, the correlation between neurocognitive impairment and self-reported neurocognitive dysfunction was examined. Results: Between June 2019 and October 2022, 22 patients were included. Among the various neurocognitive tests administered, only the Hopkins Verbal Learning Test-Revised parts b and c demonstrated a significant and clinically relevant decrease in scoring 2 weeks post initiation of lorlatinib (P = .036 and P = .003, respectively). However, these returned to baseline at the 2-month evaluation. The questionnaires did not result in significantly different outcomes over time.Conclusion: Lorlatinib treatment did not result in a sustained and significant decline within any of the specified neurocognitive domains.</p