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

Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC

Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58–0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47–076 and 0.48–0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients

Alectinib en osimertinib: nieuwe generatie tyrosinekinaseremmers met betere penetratie in de hersenen bij niet-kleincellig longcarcinoom

Met de komst van alectinib en osimertinib zijn de vooruitzichten voor patiënten met niet-kleincellig longcarcinoom (NSCLC), onder de vorm van adenocarcinoom met EGFR-mutaties en ALK-translocaties, verbeterd. Zowel alectinib (Alecenca®) als osimertinib (Tagrisso®) hebben in fase 3-studies aangetoond de progressievrije overleving te verlengen. Hier staat wel een forse prijs tegenover: een behandeling van zesduizend euro per maand is geen uitzondering. De nieuwe generatie tyrosinekinaseremmers, waar alectinib en osimertinib onder vallen, penetreren de bloed-hersenbarrière beter en geven derhalve een betere intracraniële respons. Aangezien een deel van de patiënten met een EGFR-mutatie, en in het bijzonder met een ALK-translocatie, bij diagnose reeds hersenmetastasen heeft of krijgt in het beloop van hun ziekte, is de verwachting dat deze nieuwe middelen eerder in de behandeling van NSCLC worden ingezet

Central nervous system metastases and oligoprogression during treatment with tyrosine kinase inhibitors in oncogene-addicted non-small cell lung cancer:how to treat and when?

Up to 70% of non-small cell lung cancer (NSCLC) patients develop central nervous system (CNS) metastases during the course of their disease, especially those with oncogenic drivers treated with a first-generation tyrosine kinase inhibitor (TKI), because of the relatively poor CNS penetration. CNS metastases are associated with a negative impact on quality of life and survival. As, with the introduction of newer generation TKIs, the survival rates are increasing in this particular population, treatment and/ or prevention of CNS metastases becomes even more relevant and the TKI with the best CNS efficacy should be selected. Unfortunately, CNS efficacy data in clinical trials are not fully comparable. Furthermore, oligoprogression to the brain without extracranial progression regularly occurs in the oncogenic driver population and both local therapy and switch of systemic therapy are possible treatment options. However, th

Unacceptable pain in oncology:The patients' perspective on reasons for absence of pain interventions

OBJECTIVE: Around 40% of oncology patients receive inadequate pain treatment. A previous study reported pain interventions for only 70% of patients who reported unacceptable pain at the self‐service registration desk. The aim of this study is to gain insight in reasons for the absence of pain intervention among oncology patients who reported unacceptable pain. METHODS: In this mixed methods study, 20 patients visiting the oncology outpatient clinic were selected via patient record assessment and interviewed about their perceived reasons for absence of pain intervention. RESULTS: The reasons mentioned by the patients for absence of pain intervention included reluctance of the patient to discuss pain, no treatment preferred by the patient, focus of the physician on treatment of the disease, pain treatment difficult or impossible, and the perception that pain is an inevitable consequence of the cancer treatment. Almost 50% of the patients considered the physician responsible for the absence of pain intervention. CONCLUSION: In conclusion, a variety of reasons for absence of pain intervention are reported by patients, including patient‐related and health professional‐related reasons. Improvements can be made by promoting regular discussion of pain during hospital visits and empowerment of patients

Screening for Brain Metastases in Patients With NSCLC:A Qualitative Study on the Psychologic Impact of Being Diagnosed With Asymptomatic Brain Metastases

Introduction: The brain is a frequent site of metastases in NSCLC, and screening for asymptomatic brain metastases (BM) is increasingly advised in NSCLC guidelines. An asymptomatic BM diagnosis may trigger anxiety for future neurologic problems and can negatively affect quality of life of patients and their relatives. Therefore, we performed this qualitative study. Methods: Three focus group discussions were organized with patients with NSCLC and asymptomatic BM (N = 3-4 per group) and separately with their relatives, to explore this psychosocial impact. Two researchers independently performed an inductive content analysis. Results: A total of 10 patients and 10 relatives participated in six focus groups. A diagnosis of BM caused feelings of distress and anxiety in both patients and relatives. These feelings diminished over time in case of a tumor responding to systemic therapy. The diagnosis of BM was not perceived as more distressful than other metastases, and scan-related anxiety was not experienced. Although magnetic resonance imaging screening and follow-up were thought of as burdensome, follow-up was valued. The coping strategies of both groups seemed related to personality and to the efficacy of the given systemic therapy. Relatives appreciated peer support of other relatives during the focus groups, and they seemed open for future psychological support. Conclusions: Asymptomatic BM diagnosis can cause anxiety and distress, but this diminishes over time with effective systemic treatment. Although patients perceive magnetic resonance imaging as burdensome, they value follow-up screening and imaging. Relatives highly appreciated peer support, and psychological distress of relatives should not be overlooked