Detection and segmentation of abnormalities on medical images is highly important for patient management including diagnosis, radiotherapy, response evaluation, as well as for quantitative image ...research. We present a fully automated pipeline for the detection and volumetric segmentation of non-small cell lung cancer (NSCLC) developed and validated on 1328 thoracic CT scans from 8 institutions. Along with quantitative performance detailed by image slice thickness, tumor size, image interpretation difficulty, and tumor location, we report an in-silico prospective clinical trial, where we show that the proposed method is faster and more reproducible compared to the experts. Moreover, we demonstrate that on average, radiologists & radiation oncologists preferred automatic segmentations in 56% of the cases. Additionally, we evaluate the prognostic power of the automatic contours by applying RECIST criteria and measuring the tumor volumes. Segmentations by our method stratified patients into low and high survival groups with higher significance compared to those methods based on manual contours.
•EGFR exon 20 insertion mutations occur in ~2–3% of all NSCLC cases.•Activity of 1st to 3rd generation EGFR-TKI is less in EGFR ex20ins versus common mutations.•Osimertinib might play a role in the ...treatment of EGFR ex20ins mutations.•Poziotinib, mobocertinib and amivantamab are promising new EGFR ex20ins treatments.•The specific role of EGFR ex20ins variants merits further evaluation.
Although targeted therapy is standard of care in a large subset of oncogenic addicted non-small cell lung cancers (NSCLC), until recently, this therapeutic approach has not been feasible for all genomic alterations such as for those tumors harboring Epidermal Growth Factor Receptor (EGFR) exon 20 insertion (ex20ins) mutations. Despite being the third most common EGFR mutation, a limited efficacy of first- and second-generation EGFR tyrosine kinase inhibitors (TKI) exists. This is related to the heterogeneity at the molecular level in EGFR ex20ins mutation variants and the finding that this mutation promotes active kinase conformation but does not increase the affinity for EGFR TKI. As a result, the prognosis of this population is diminished. Therefore, chemotherapy remained the most suitable strategy in this subset of EGFR mutant NSCLC patients. Recently, new treatment strategies have been reported in this landscape, either with new EGFR TKI or bispecific antibodies, which may establish a new standard of care in the coming future for these patients. Future research should focus on elucidating the oncogenic degree of all EGFR ex20ins variants, the potential role of combination strategies either with chemotherapy or immune checkpoint inhibitors, and the most appropriate first-line treatment strategy in this subgroup. Finally, the knowledge of mechanisms of acquired resistance to these new agents upon progression is a priority for personalising treatment at that time. It is in this framework, that we provide a thorough overview on this subject.
The incidence of stage I and II nonsmall cell lung cancer is likely to increase with the ageing population and introduction of screening for high-risk individuals. Optimal management requires ...multidisciplinary collaboration. Local treatments include surgery and radiotherapy and these are currently combined with (neo)adjuvant chemotherapy in specific cases to improve long-term outcome. Targeted therapies and immunotherapy may also become important therapeutic modalities in this patient group. For resectable disease in patients with low cardiopulmonary risk, complete surgical resection with lobectomy remains the gold standard. Minimally invasive techniques, conservative and sublobar resections are suitable for a subset of patients. Data are emerging that radiotherapy, especially stereotactic body radiation therapy, is a valid alternative in compromised patients who are high-risk candidates for surgery. Whether this is also true for good surgical candidates remains to be evaluated in randomised trials. In specific subgroups adjuvant chemotherapy has been shown to prolong survival; however, patient selection remains important. Neoadjuvant chemotherapy may yield similar results as adjuvant chemotherapy. The role of targeted therapies and immunotherapy in early stage nonsmall cell lung cancer has not yet been determined and results of randomised trials are awaited.
Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort.
Data from ...consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression.
A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0–1, 58.5% with a score of 1.5–2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging n = 73) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval CI: 1.5–2.1) and 2.1 (95% CI: 1.9–2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% p < 0.001). The median OS times were 8.6 months (95% CI: 6.8–12.0) with BM and 11.4 months (95% CI: 8.6–13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio HR = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48–0.52) were associated with improved OS.
In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.
Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may ...reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation.
We identified patients who were PD-(L)1-naïve with advanced non-small-cell lung cancer from two institutions-Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center-who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression.
Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P < .001).
Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non-small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended.
Synchronous oligometastatic disease (sOM) has been described as a distinct disease entity; however, there is no consensus on OM definition (OM-d) in non–small-cell lung cancer (NSCLC). A consensus ...group was formed aiming to agree on a common OM-d that could be used in future clinical trials. A European survey was circulated to generate questions and input for the consensus group meeting.
A European Organisation for Research and Treatment of Cancer Lung Cancer Group (LCG)/sOM-d consensus group survey was distributed to LCG, sOM-d consensus group, and several European thoracic oncology societies’ members.
444 responses were analysed (radiation oncologist: 55% n = 242, pulmonologist: 15% n = 66, medical oncologist: 14% n = 64). 361 physicians (81%) aimed to cure sOM NSCLC patients and 82% (n = 362) included the possibility of radical intent treatment in their sOM-d. The maximum number of metastases considered in sOM-d varied: 12% replied 1 metastasis, 42% ≤ 3, and 17% ≥ 5 metastases. 79% (n = 353) stated that number of organs involved was important for sOM-d, and most (80%, n = 355) considered that only ≤3 involved organs (excluding primary) should be included. 317 (72%) included mediastinal lymph node involvement in the sOM-d and 22% (n = 70/317) counted mediastinal lymph node as a metastatic site. Most physicians completed sOM staging with brain magnetic resonance imaging (91%, n = 403) and positron emission tomography/computed tomography (98%, n = 437). Pathology proof of metastatic disease was a requirement to define sOM for 315 (71%) physicians. The preferred primary outcome for sOM clinical trials was overall survival (73%, n = 325).
Although consensual answers were obtained, several issues remain unresolved and will require further research to agree on a sOM-d.
•The majority aimed to cure sOM NSCLC patients.•The maximum number of metastases considered in sOM-d was 42% ≤ 3 and 17% ≥ 5.•Most considered only ≤3 involved organs (excluding primary).•Few counted mediastinal lymph node as a metastatic site.•The preferred primary outcome for sOM clinical trials was overall survival.
Patients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3–9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly ...excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs).
A prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated.
Nineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval CI) PFS on ICIs was 2.0 (1.8–2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9–6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively).
Some patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival.
•Survival is poor for patients with non-small cell lung cancer (NSCLC) having leptomeningeal metastases (LM).•Some patients with NSCLC having LM do benefit from immune checkpoint inhibition.•Some, especially in the NCCN LM good prognosis group, can obtain a long survival.
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