Publications
637 results found
Eastwood M, Marc ST, Gao X, et al., 2023, Malignant Mesothelioma subtyping via sampling driven multiple instance prediction on tissue image and cell morphology data., Artif Intell Med, Vol: 143
Malignant Mesothelioma is a difficult to diagnose and highly lethal cancer usually associated with asbestos exposure. It can be broadly classified into three subtypes: Epithelioid, Sarcomatoid, and a hybrid Biphasic subtype in which significant components of both of the previous subtypes are present. Early diagnosis and identification of the subtype informs treatment and can help improve patient outcome. However, the subtyping of malignant mesothelioma, and specifically the recognition of transitional features from routine histology slides has a high level of inter-observer variability. In this work, we propose an end-to-end multiple instance learning (MIL) approach for malignant mesothelioma subtyping. This uses an adaptive instance-based sampling scheme for training deep convolutional neural networks on bags of image patches that allows learning on a wider range of relevant instances compared to max or top-N based MIL approaches. We also investigate augmenting the instance representation to include aggregate cellular morphology features from cell segmentation. The proposed MIL approach enables identification of malignant mesothelial subtypes of specific tissue regions. From this a continuous characterisation of a sample according to predominance of sarcomatoid vs epithelioid regions is possible, thus avoiding the arbitrary and highly subjective categorisation by currently used subtypes. Instance scoring also enables studying tumor heterogeneity and identifying patterns associated with different subtypes. We have evaluated the proposed method on a dataset of 234 tissue micro-array cores with an AUROC of 0.89±0.05 for this task. The dataset and developed methodology is available for the community at: https://github.com/measty/PINS.
Krebs MG, Popat S, 2023, RETaliation-Tackling Rare Resistance Alterations to Osimertinib., Clin Cancer Res, Vol: 29, Pages: 2951-2953
RET fusions occur as a rare mechanism of acquired resistance to osimertinib in patients with EGFR mutation-positive non-small cell lung cancer. Inhibiting RET alongside osimertinib shows promising clinical activity, but innovative approaches are needed to seek regulatory approvals in these rare treatment resistance settings. See related article by Rotow et al., p. 2979.
Yang JC-H, Liu G, Lu S, et al., 2023, Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial., J Thorac Oncol
INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib. METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events. RESULTS: The population (N = 248; brigatinib, n = 125; alectinib, n = 123) was notable for long median duration of prior crizotinib (16.0-16.8 mo) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78 of 232 [34%]). Median blinded independent review committee-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio = 0.97 [95% confidence interval: 0.66-1.42], p = 0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across the treatment groups revealed median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% confidence interval: 0.32-0.71]). Treatment-related adverse events in more than 30% of patients (brigatinib, alectinib) were elevated levels of blood creatine phosphokinase (70%, 29%), aspartate aminotransferase (53%, 38%), and alanine aminotransferase (40%, 36%). CONCLUSIONS: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3.
Hasan AMM, Cremaschi P, Wetterskog D, et al., 2023, Copy number architectures define treatment-mediated selection of lethal prostate cancer clones, Nature Communications, Vol: 14, Pages: 1-16, ISSN: 2041-1723
Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10-8 and 6.4 × 10-4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories.
O'Sullivan H, Popat S, 2023, Atezolizumab in patients with advanced non-small-cell lung cancer who are platinum-doublet ineligible., Lancet, Vol: 402, Pages: 426-427
Garon EB, Reck M, Nishio K, et al., 2023, Ramucirumab plus erlotinib versus placebo plus erlotinib in previously untreated EGFR-mutated metastatic non-small-cell lung cancer (RELAY): exploratory analysis of next-generation sequencing results., ESMO Open, Vol: 8
BACKGROUND: Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identify clinically relevant alterations in circulating tumor DNA (ctDNA) and explore their impact on treatment outcomes. PATIENTS AND METHODS: Eligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks. Liquid biopsies were to be prospectively collected at baseline, cycle 4 (C4), and postdiscontinuation follow-up. EGFR and co-occurring/treatment-emergent (TE) genomic alterations in ctDNA were analyzed using Guardant360 NGS platform. RESULTS: In those with valid baseline samples, detectable activating EGFR alterations in ctDNA (aEGFR+) were associated with shorter PFS [aEGFR+: 12.7 months (n = 255) versus aEGFR-: 22.0 months (n = 131); hazard ratio (HR) = 1.87, 95% confidence interval (CI) 1.42-2.51]. Irrespective of detectable/undetectable baseline aEGFR, RAM + ERL was associated with longer PFS versus PBO + ERL [aEGFR+: median PFS (mPFS) = 15.2 versus 11.1 months, HR = 0.63, 95% CI 0.46-0.85; aEGFR-: mPFS = 22.1 versus 19.2 months, HR = 0.80, 95% CI 0.49-1.30]. Baseline alterations co-occurring with aEGFR were identified in 69 genes, most commonly TP53 (43%), EGFR (other than aEGFR; 25%), and PIK3CA (10%). PFS was longer in RAM + ERL, irrespective of baseline co-occurring alterations. Clearance of baseline aEGFR by C4 was associated with longer PFS (mPFS = 14.1 versus 7.0 months, HR = 0.481, 95% CI 0.33-0.71). RAM + ERL improved PFS outcomes, irrespective of aEGFR mutation clearance. TE gene alterations were most commonly in EGFR [T790M (29%), other (19%)] and TP53 (16%). CONCLUSIONS: Baseline
Meunier A, Longworth L, Gomes M, et al., 2023, Distributional Cost-Effectiveness Analysis of Treatments for Non-Small Cell Lung Cancer: An Illustration of an Aggregate Analysis and its Key Drivers., Pharmacoeconomics, Vol: 41, Pages: 1011-1025
BACKGROUND AND OBJECTIVE: Distributional cost-effectiveness analysis (DCEA) facilitates quantitative assessments of how health effects and costs are distributed among population subgroups, and of potential trade-offs between health maximisation and equity. Implementation of DCEA is currently explored by the National Institute for Health and Care Excellence (NICE) in England. Recent research conducted an aggregate DCEA on a selection of NICE appraisals; however, significant questions remain regarding the impact of the characteristics of the patient population (size, distribution by the equity measure of interest) and methodologic choices on DCEA outcomes. Cancer is the indication most appraised by NICE, and the relationship between lung cancer incidence and socioeconomic status is well established. We aimed to conduct an aggregate DCEA of two non-small cell lung cancer (NSCLC) treatments recommended by NICE, and identify key drivers of the analysis. METHODS: Subgroups were defined according to socioeconomic deprivation. Data on health benefits, costs, and target populations were extracted from two NICE appraisals (atezolizumab versus docetaxel [second-line treatment following chemotherapy to represent a broad NSCLC population] and alectinib versus crizotinib [targeted first-line treatment to represent a rarer mutation-positive NSCLC population]). Data on disease incidence were derived from national statistics. Distributions of population health and health opportunity costs were taken from the literature. A societal welfare analysis was conducted to assess potential trade-offs between health maximisation and equity. Sensitivity analyses were conducted, varying a range of parameters. RESULTS: At an opportunity cost threshold of £30,000 per quality-adjusted life-year (QALY), alectinib improved both health and equity, thereby increasing societal welfare. Second-line atezolizumab involved a trade-off between improving health equity and maximising health; it improved
Yang M, Vioix H, Hook ES, et al., 2023, Health Utility Analysis of Tepotinib in Patients With Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping., Value Health, Vol: 26, Pages: 1155-1163
OBJECTIVES: The VISION trial showed durable activity of tepotinib in MET exon 14 (METex14) skipping non-small cell lung cancer. We analyzed health state utilities using patient-reported outcomes from VISION. METHODS: 5-level version of EQ-5D (EQ-5D-5L) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 responses were collected at baseline, every 6 to 12 weeks during treatment, and at the end of treatment and safety follow-up. EQ-5D-5L and European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D) utilities were derived using United States, Canada, United Kingdom, and Taiwan value sets, where available. Utilities were analyzed with linear mixed models including covariates for progression or time-to-death (TTD). RESULTS: Utilities were derived for 273/291 patients (EQ-5D-5L, 1545 observations; QLU-C10D, 1546 observations). Mean (± SD) US EQ-5D-5L utilities increased after tepotinib initiation, from 0.687 ± 0.287 at baseline to 0.754 ± 0.250 before independently assessed progression, and decreased post progression (0.704 ± 0.288). US QLU-C10D utilities showed similar trends (0.705 ± 0.215, 0.753 ± 0.195, and 0.708 ± 0.209, respectively). Progression-based models demonstrated a statistically significant impact of progression on utilities and predicted higher utilities pre versus post progression. TTD-based models showed statistically significant associations of TTD with utilities and predicted declining utilities as TTD decreased. Prior treatment (yes/no) did not significantly predict utilities in progression- or TTD-based models. Utilities for Canada, United Kingdom, and Taiwan showed comparable trends. CONCLUSIONS: In this first analysis of health state utilities in patients with METex14 skipping non-small cell lung cancer, who received tepotinib, utilities were significantly associated with progression a
Aboagye E, Aravind P, Popat S, et al., 2023, A subset of non-small cell lung cancer patients treated with pemetrexed show 18f-fluorothymidine ‘flare’ on positron emission tomography, Cancers, Vol: 15, Pages: 1-14, ISSN: 2072-6694
Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the
Nishio M, Paz-Ares L, Reck M, et al., 2023, RELAY, Ramucirumab Plus Erlotinib (RAM+ERL) in Untreated Metastatic EGFR-Mutant NSCLC (EGFR+ NSCLC): Association Between TP53 Status and Clinical Outcome., Clin Lung Cancer, Vol: 24, Pages: 415-428
BACKGROUND: Ramucirumab plus erlotinib (RAM+ERL) demonstrated superior progression-free survival (PFS) in RELAY, a randomised Phase III trial in patients with untreated, metastatic, EGFR-mutated, non-small-cell lung cancer (EGFR+ NSCLC). Here, we present the relationship between TP53 status and outcomes in RELAY. MATERIALS AND METHODS: Patients received oral ERL plus intravenous RAM (10 mg/kg IV) or placebo (PBO+ERL) every 2 weeks. Plasma was assessed by Guardant 360 next-generation sequencing and patients with any gene alteration detected at baseline were included in this exploratory analysis. Endpoints included PFS, overall response rate (ORR), disease control rate (DCR), DoR, overall survival (OS), safety, and biomarker analysis. The association between TP53 status and outcomes was evaluated. RESULTS: Mutated TP53 was detected in 165 (42.7%; 74 RAM+ERL, 91 PBO+ERL) patients, wild-type TP53 in 221 (57.3%; 118 RAM+ERL, 103 PBO+ERL) patients. Patient and disease characteristics and concurrent gene alterations were comparable between those with mutant and wildtype TP53. Independent of treatment, TP53 mutations, most notably on exon 8, were associated with worse clinical outcomes. In all patients, RAM+ERL improved PFS. While ORR and DCR were comparable across all patients, DoR was superior with RAM+ERL. There were no clinically meaningful differences in the safety profiles between those with baseline TP53 mutation and wild-type. CONCLUSION: This analysis indicates that while TP53 mutations are a negative prognostic marker in EGFR+ NSCLC, the addition of a VEGF inhibitor improves outcomes in those with mutant TP53. RAM+ERL is an efficacious first-line treatment option for patients with EGFR+ NSCLC, independent of TP53 status.
Minchom A, Popat S, 2023, Sitravatinib and Acquired Immune Checkpoint Inhibitor Resistance: A Gem for the Future?, J Thorac Oncol, Vol: 18, Pages: 830-833
Girard N, Ponce Aix S, Cedres S, et al., 2023, Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial., ESMO Open, Vol: 8
BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primar
Wu MY, Shepherd STC, Fendler A, et al., 2023, Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer., Cancer Cell, Vol: 41, Pages: 821-823
Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants.
Reck M, Popat S, Grohé C, et al., 2023, Anti-angiogenic agents for NSCLC following first-line immunotherapy: Rationale, recent updates, and future perspectives., Lung Cancer, Vol: 179
The implementation of immune checkpoint inhibitors (ICIs), with or without chemotherapy, as first-line treatment for patients who do not have actionable mutations has proved to be a major paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). However, the transition of ICIs, such as pembrolizumab and nivolumab, to a first-line setting has left an unmet need for effective second-line treatment options, which is an area of intense research. In 2020, we reviewed the biological and mechanistic rationale for anti-angiogenic agents in combination with, or following, immunotherapy with the aim of eliciting a so called 'angio-immunogenic' switch in the tumor microenvironment. Here, we review the latest clinical evidence of the benefits of incorporating anti-angiogenic agents into treatment regimens. While there is a paucity of prospective data, several recent observational studies indicate that the marketed anti-angiogenic drugs, nintedanib or ramucirumab, are effective in combination with docetaxel following immuno-chemotherapy. Addition of anti-angiogenics, like bevacizumab, have also demonstrated clinical benefit when combined with first-line immuno-chemotherapy regimens. Ongoing clinical trials are assessing these agents in combination with ICIs, with encouraging early results (e.g., ramucirumab plus pembrolizumab in LUNG-MAP S1800A). Also, several emerging anti-angiogenic agents combined with ICIs are currently being assessed in phase III trials following immunotherapy, including lenvatinib (LEAP-008), and sitravatinib (SAPPHIRE) It is hoped that these trials will help expand second-line treatment options in patients with NSCLC. Areas of focus in the future will include further molecular dissection of the mechanisms of resistance to immunotherapy and the various response-progression profiles to immunotherapy observed in the clinic and the monitoring of the dynamics of immunomodulation over the course of treatment. Improved understanding of the
Ng KW, Boumelha J, Enfield KSS, et al., 2023, Antibodies against endogenous retroviruses promote lung cancer immunotherapy., Nature, Vol: 616, Pages: 563-573
B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
Mulla K, Farag S, Moore B, et al., 2023, Hyperglycaemia following immune checkpoint inhibitor therapy-Incidence, aetiology and assessment, Diabetic Medicine, Vol: 40, Pages: 1-10, ISSN: 0742-3071
AimsWe systematically studied the presence of hyperglycaemia during treatment with Immune Checkpoint Inhibitors (ICPI) for cancer, in those with and without diabetes at baseline, and determined the cause of new-onset hyperglycaemia,MethodsRetrospective review of electronic records of those receiving an ICPI for melanoma, lung or renal cancer.ResultsOverall, 959 participants were included. In this study, 103 had diabetes at baseline (10.7%). Those with lung cancer had the highest frequency of diabetes; 131 people had hyperglycaemia (defined as at least one glucose ≥11.1 mmol/L) in the year after starting an ICPI. The incidence was 55% in those with diabetes at baseline, and 8.6% in those without baseline diabetes. Among 74 with new-onset hyperglycaemia (without pre-existing diabetes) 76% was attributable to steroid induced diabetes, with 9.5% due to ICPI Induced diabetes resembling type 1 diabetes.ConclusionsHyperglycaemia is common in persons receiving an ICPI for cancer, including 8.6% of those without known diabetes. While much of this is due to glucocorticoid use, care is needed to avoid missing those with ICPI-induced diabetes who are at risk of diabetic ketoacidosis, which is a medical emergency.
Kroeze SGC, Pavic M, Stellamans K, et al., 2023, Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium., Lancet Oncol, Vol: 24, Pages: e121-e132
Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.
Popat S, Ahn M-J, Ekman S, et al., 2023, Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies (Jan, 10.1007/s11523-022-00941-7, 2023), TARGETED ONCOLOGY, ISSN: 1776-2596
Cerone MA, Mills TC, Sharpe R, et al., 2023, The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care (JAN, 10.1038/s41416-023-02160-x, 2023), BRITISH JOURNAL OF CANCER, ISSN: 0007-0920
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Popat S, Ahn M-J, Ekman S, et al., 2023, Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies, TARGETED ONCOLOGY, ISSN: 1776-2596
Cerone MA, Mills TC, Sharpe R, et al., 2023, The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care, BRITISH JOURNAL OF CANCER, ISSN: 0007-0920
Garcia Campelo MR, Zhou C, Ramalingam SS, et al., 2023, Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort, JOURNAL OF CLINICAL MEDICINE, Vol: 12
O'Sullivan HM, Feber A, Popat S, 2023, Minimal Residual Disease Monitoring in Radically Treated Non-Small Cell Lung Cancer: Challenges and Future Directions., Onco Targets Ther, Vol: 16, Pages: 249-259, ISSN: 1178-6930
Circulating tumor DNA (ctDNA) analysis can identify patients with residual disease before it is clinically or radiologically evident. Minimal residual disease (MRD) is an advancing area in the management of radically treated solid tumors. Which MRD assay is optimum and when it should be used is still not defined. Whilst promising, the clinical utility of this technology to guide patient care is still investigational in non-small cell lung cancer (NSCLC) and has not entered routine care. Once technically and clinically optimized, MRD may be utilized to personalize adjuvant therapy, detect disease relapse earlier and improve cure rates. In this review, we discuss the current status of MRD monitoring in NSCLC by summarizing frequently used MRD assays and their associated evidence in NSCLC. We discuss the potential applications of these technologies and the challenge of demonstrating MRD clinical utility in trials.
Paz-Ares LG, Ciuleanu T-E, Pluzanski A, et al., 2022, Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817, JOURNAL OF THORACIC ONCOLOGY, Vol: 18, Pages: 79-92, ISSN: 1556-0864
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Popat S, Fidyk C, Patel R, 2022, Demographic Analysis of Cancer Patients Who Voluntarily Used a Digital Health Tool to Self-Report Medications, Symptoms and Well-Being, Publisher: ELSEVIER SCIENCE INC, Pages: S396-S396, ISSN: 1098-3015
Ahn MJ, Kim HR, Yang JCH, et al., 2022, Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK plus Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study, CLINICAL LUNG CANCER, Vol: 23, Pages: 720-730, ISSN: 1525-7304
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Chouaid C, Girard N, Kron A, et al., 2022, AMIVANTAMAB VERSUS REAL-WORLD CLINICAL PRACTICE IN EUROPE AND THE US FOR PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER WITH ACTIVATING EPIDERMAL GROWTH FACTOR RECEPTOR EXON 20 INSERTION MUTATIONS, Publisher: ELSEVIER SCIENCE INC, Pages: S32-S32, ISSN: 1098-3015
Stergiopoulos S, King S, Curtis M, et al., 2022, INDIRECT COMPARISON OF EFFICACY AND SAFETY FOR AUMOLERTINIB VS OSIMERTINIB IN PATIENTS WITH EGFR-MUTANT NON-SMALL CELL LUNG CANCER (NSCLC), Publisher: ELSEVIER SCIENCE INC, Pages: S42-S42, ISSN: 1098-3015
Meunier A, Longworth L, Popat S, et al., 2022, DISTRIBUTIONAL COST-EFFECTIVENESS ANALYSIS OF LUNG CANCER TREATMENTS FROM AN NHS ENGLAND PERSPECTIVE, Publisher: ELSEVIER SCIENCE INC, Pages: S339-S339, ISSN: 1098-3015
Kent S, Gupta A, Duffield S, et al., 2022, BIAS ADJUSTING FOR UNMEASURED CONFOUNDERS IN SYNTHETIC CONTROL ANALYSIS (SCA) ESTIMATES OF IMMUNOTHERAPY EFFECTIVENESS IN ADVANCED NON-SMALL CELL LUNG CANCER (ANSCLC): AN OUTPUT FROM THE Q-BASEL STUDY, Publisher: ELSEVIER SCIENCE INC, Pages: S374-S374, ISSN: 1098-3015
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