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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.
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Carcinoma Pulmonar de Células não Pequenas , Lactamas , Neoplasias Pulmonares , Pirazóis , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Proteínas Tirosina Quinases/uso terapêutico , Estudos Prospectivos , Quinase do Linfoma Anaplásico/uso terapêutico , Proteínas Proto-Oncogênicas/uso terapêutico , Aminopiridinas/efeitos adversos , Lactamas Macrocíclicas/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
PURPOSE: Despite the inconclusiveness regarding health effects of cannabinoids among cancer patients, studies from non-European countries suggest that the medical-intended consumption of such products by this patient group is significant. The current study analyses cannabinoid usage among oncology patients receiving systemic treatment in the Netherlands. METHODS: The current study included adult patients receiving intravenous systemic therapy at Maastricht Comprehensive Cancer Centre, for a solid malignancy. Participants were asked to complete an anonymous questionnaire including questions on demographic variables, clinical variables and cannabinoid consumption. RESULTS: A total of 153 patients with solid cancer were included in this study. Almost 25% reported usage of cannabinoids for medical purposes, with 15% of the patients currently using the substance. Additionally, 18% of non-users considered future medical usage. In 48% of the cases, consumption was reported by the oncologist. The proposed anti-cancer effect was reported by 46% of the users as motivation for consumption. Current users were mainly palliative patients and 54% of the users were undergoing immunotherapy. Intention of treatment and type of therapy were predictive factors for consumption. Cannabinoid-oil was the most frequently used way of consumption. CONCLUSION: This study underlines the high number of cannabinoid users among oncology patients in the Netherlands in presumed absence of clinical guidance. It highlights the essence of a pro-active role of the clinician, assessing cannabinoid usage and educating the patients on the most recent evidence regarding its potential benefits and risks. Further studies on clinical decision making and efficacy of cannabinoids are recommended, to improve clinical guidance.
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Canabinoides , Neoplasias , Adulto , Humanos , Canabinoides/uso terapêutico , Países Baixos/epidemiologia , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , OncologiaRESUMO
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.
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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.
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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.
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Neoplasias , Dor , Humanos , Oncologia , Neoplasias/complicações , Neoplasias/terapia , Dor/etiologia , Manejo da Dor/métodos , Medição da DorRESUMO
Although central nervous system (CNS) metastases frequently occur in patients with non-small cell lung cancer (NSCLC), historically these patients have been excluded from clinical trials. However, due to improving NSCLC prognosis, time to develop CNS metastases increases and information on CNS efficacy of systemic treatment is important. We performed a systematic PubMed review (2000-2020) to describe CNS related eligibility and screening criteria over time. Randomized phase III, and for tyrosine kinase inhibitors (TKIs) also randomized phase II trials enrolling advanced/metastatic NSCLC patients were included. 256/1195 trials were included. In 71 %, CNS metastases were eligible, but in only 3% regardless of symptoms/treatment. Only 37 % required baseline CNS screening (most often TKI and immunotherapy trials), without significant increase over time. A CNS endpoint was pre-specified in 4%. CONCLUSION: CNS screening and eligibility criteria are heterogenous across trials, and CNS related endpoints are rare. These criteria and endpoints should be improved and harmonized.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistema Nervoso Central , Ensaios Clínicos Fase II como Assunto , Receptores ErbB , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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, the best order of systemic and local therapy is still not precisely known. In this narrative review, we will summarize incidence and treatment of CNS metastases in oncogene driven NSCLC, including the optimal treatment of CNS oligometastatic disease (synchronous as well as oligoprogressive).
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INTRODUCTION: Non-small-cell lung cancer (NSCLC) guidelines advise to screen stage III NSCLC patients for brain metastases (BMs), preferably by magnetic resonance imaging (MRI) or when contraindicated or not accessible a dedicated contrast enhanced-computed tomography (dCE-CT), which can be incorporated in the staging 18Fluodeoxoglucose-positron emission tomography (18FDG-PET-CE-CT). In daily practice, often a dCE-CT is performed instead of a MRI. The aim of the current study is to evaluate the additive value of MRI after dCE-CT, incorporated in the 18FDG-PET-CE-CT. PATIENTS AND METHODS: It is an observational prospective multicentre study (NTR3628). Inclusion criteria included stage III NSCLC patients with a dCE-CT of the brain incorporated in the 18FDG-PET and an additional MRI of the brain. Primary end-point is percentage of patients with BM on MRI without suspect lesions on dCE-CT. Secondary end-points are percentage of patients with BM on dCE-CT and percentage of patients with BM ≤ 1 year of a negative staging MRI. RESULTS: Sixteen (7%) patients with extracranial stage III had BM on dCE-CT and were excluded. One hundred forty-nine patients were enrolled. 7/149 (4.7%) had BM on MRI without suspect lesions on dCE-CT. One hundred eighteen patients had a follow-up of at least 1 year (four with BM on baseline MRI); eight of the remaining 114 (7%) patients developed BM ≤ 1 year after a negative staging brain MRI. CONCLUSION: Although in 7% of otherwise stage III NSCLC patients, BMs were detected on staging dCE-CT, MRI brain detected BMs in an additional 4.7%, which we consider clinically relevant. Within 1 year after a negative staging MRI, 7% developed BM.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Progressão da Doença , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Países Baixos , Valor Preditivo dos Testes , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Brain metastases (BM) frequently occur in non-small cell lung cancer (NSCLC) patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT) has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.
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Recently, non-small cell lung cancer (NSCLC) has been partly subclassified into molecularly-defined oncogene "addicted" tumors for which targeted agents are available. Tyrosine kinase inhibitors (TKI) are currently approved for patients with an activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. In these patients, brain metastases are often the first site of progression while on TKI treatment. The TKI may however still be active on extra-cranial sites and clinicians are thus faced with the question if the TKI may be continued during cranial radiotherapy. Advantages of combining TKI with cranial radiotherapy would be a possible synergistic effect on the brain metastases and the prevention of a systemic disease flare-up. A disadvantage is the possibly increased risk of (neuro)toxicity. The present systematic review addresses the toxicity of combining TKI with cranial radiotherapy in NSCLC patients.