Publications by authors named "Sanjay Popat"

160 Publications

A pilot of Blood-First diagnostic cell free DNA (cfDNA) next generation sequencing (NGS) in patients with suspected advanced lung cancer.

Lung Cancer 2022 Jan 20;165:34-42. Epub 2022 Jan 20.

Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

Introduction: The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic.

Methods: A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%.

Results: Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001).

Conclusion: Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making.
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http://dx.doi.org/10.1016/j.lungcan.2022.01.009DOI Listing
January 2022

Lung Cancer in the United Kingdom.

J Thorac Oncol 2022 Feb;17(2):186-193

Lung Unit, Royal Marsden Hospital, London, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jtho.2021.11.002DOI Listing
February 2022

Targeting un-MET needs in advanced non-small cell lung cancer.

Lung Cancer 2022 02 29;164:56-68. Epub 2021 Dec 29.

Lung Unit. The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London SW3 6JJ, UK; Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, UK.

Lung cancer classification has been radically transformed in recent years as genomic profiling has identified multiple novel therapeutic targets including MET exon 14 (METex14) alterations and MET amplification. Utilizing targeted therapies in patients with molecularly-defined NSCLC leads to remarkable objective response rates and improved progression-free survival. However, acquired resistance is inevitable. Several recent phase II trials have confirmed that METex14 NSCLC can be treated effectively with MET kinase inhibitors, such as crizotinib, capmatinib, tepotinib, and savolitinib. However, response rates for many MET TKIs are modest relative to the activity of targeted therapy in other oncogene-driven lung cancers, where ORRs are more consistently greater than 60%. In spite of significant gains in the field of MET inhibition in NSCLC, challenges remain: the landscape of resistance mechanisms to MET TKIs is not yet well characterized, and there may be intrinsic and acquired resistance mechanisms that require further characterization to enable increased MET TKI activity. In this review, we overview MET pathway dysregulation in lung cancer, methods of detection in the clinic, recent clinical trial data, and discuss current mechanisms of TKI resistance, exploring emerging strategies to overcome resistance.
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http://dx.doi.org/10.1016/j.lungcan.2021.12.016DOI Listing
February 2022

Durable Response to Vismodegib in PTCH1 F1147fs Mutant Relapsed Malignant Pleural Mesothelioma: Implications for Mesothelioma Drug Treatment.

JCO Precis Oncol 2021 Nov;5:39-43

Leicester Mesothelioma Research Programme, Leicester Cancer Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, Leicestershire, United Kingdom.

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http://dx.doi.org/10.1200/PO.20.00260DOI Listing
November 2021

Assessment of tumour-agnostic therapies in basket trials.

Lancet Oncol 2022 Jan;23(1):e7

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(21)00714-2DOI Listing
January 2022

Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations.

JTO Clin Res Rep 2021 Dec 2;2(12):100253. Epub 2021 Nov 2.

Department of Radiology, Royal Marsden NHS Foundation Trust, London, United Kingdom.

Introduction: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response.

Methods: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival.

Results: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment ( = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment ( = -0.560,  = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival ( = 0.45,  = 0.03).

Conclusions: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626584PMC
December 2021

Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications.

Front Med (Lausanne) 2021 1;8:764563. Epub 2021 Nov 1.

Lung Unit, The Royal Marsden, National Health Service (NHS) Foundation Trust, London, United Kingdom.

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3-2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days-19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.
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http://dx.doi.org/10.3389/fmed.2021.764563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591134PMC
November 2021

Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG).

Lung Cancer 2021 12 21;162:9-15. Epub 2021 Sep 21.

Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. Electronic address:

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance.

Methods: In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR).

Results: At the start of afatinib treatment, median age (range) was 62 years (34-88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0-30.2) and median OS was 36.5 months (95% CI: 32.9-41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups.

Conclusion: Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment.
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http://dx.doi.org/10.1016/j.lungcan.2021.09.009DOI Listing
December 2021

Severe Immune Checkpoint Inhibitor Hepatitis in G12C-Mutant NSCLC Potentially Triggered by Sotorasib: Case Report.

JTO Clin Res Rep 2021 Sep 2;2(9):100213. Epub 2021 Aug 2.

Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.

Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474489PMC
September 2021

Biomarker Testing for People With Advanced Lung Cancer in England.

JTO Clin Res Rep 2021 Jun 27;2(6):100176. Epub 2021 Apr 27.

Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.

Introduction: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England.

Methods: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information.

Results: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy.

Conclusions: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474239PMC
June 2021

Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With -Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study.

JTO Clin Res Rep 2021 Feb 26;2(2):100114. Epub 2020 Oct 26.

Division of Oncology, Department of Medicine, Stanford University, Stanford, California.

Introduction: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets T790M and common -activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs.

Methods: Patients with advanced or metastatic -mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel).

Results: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07,  = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively).

Conclusions: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced -mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point.
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http://dx.doi.org/10.1016/j.jtocrr.2020.100114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474221PMC
February 2021

Integrated genomics point to immune vulnerabilities in pleural mesothelioma.

Sci Rep 2021 09 27;11(1):19138. Epub 2021 Sep 27.

National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW36LY, UK.

Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.
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http://dx.doi.org/10.1038/s41598-021-98414-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476593PMC
September 2021

Grading in Lung Adenocarcinoma: Another New Normal.

J Thorac Oncol 2021 10;16(10):1601-1604

National Heart and Lung Institute, Imperial College, London, United Kingdom; Lung Unit, Royal Marsden Hospital, Fulham Road, London, United Kingdom; The Institute of Cancer Research, Fulham Road, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jtho.2021.06.031DOI Listing
October 2021

Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial.

J Thorac Oncol 2021 12 16;16(12):2091-2108. Epub 2021 Sep 16.

Royal Marsden Hospital, London, United Kingdom.

Introduction: In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.

Methods: Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy.

Results: A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed.

Conclusions: In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
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http://dx.doi.org/10.1016/j.jtho.2021.07.035DOI Listing
December 2021

Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists.

Br J Cancer 2021 10 6;125(9):1210-1216. Epub 2021 Sep 6.

Department of Pathology, Aberdeen University School of Medicine and Aberdeen Royal Infirmary, Aberdeen, UK.

Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
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http://dx.doi.org/10.1038/s41416-021-01407-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548341PMC
October 2021

Brigatinib vs alectinib in crizotinib-resistant advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALTA-3).

Future Oncol 2021 Nov 23;17(32):4237-4247. Epub 2021 Aug 23.

Department of Medical Oncology, National Taiwan University Cancer Center, No. 57, Ln. 155, Sec. 3, Keelung Road, Da'an District, Taipei City, Taiwan.

Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Clinical trial registration number: NCT03596866 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2021-0608DOI Listing
November 2021

Pleural mesothelioma (PM) - The status of systemic therapy.

Cancer Treat Rev 2021 Nov 5;100:102265. Epub 2021 Aug 5.

Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Thoracic Oncology, Institute of Cancer Research, London, United Kingdom. Electronic address:

Pleural mesothelioma (PM) remains a malignancy with poor prognosis. Despite initial disappointing response rates to single-agent chemotherapy, upfront platinum and anti-folate-based combination chemotherapy has remained the backbone of treatment for PM for the last three decades. The role of maintenance chemotherapy remains unclear; switch-maintenance gemcitabine has shown improvements in progression-free but not overall survival. The addition of antiangiogenic agents to chemotherapy yielded modest improvements in survival, both upfront in combination with platinum-pemetrexed, and in the relapsed setting. Immunotherapy, particularly PD-(L)1 inhibitors, has shown important but variable effectiveness in relapsed PM when used as monotherapy, and is an important salvage treatment after first-line chemotherapy. Furthermore, the randomized phase 3 trial of ipilimumab-nivolumab versus platinum-pemetrexed chemotherapy demonstrated improved overall survival favouring ipilimumab-nivolumab (HR 0.74, 96.6% CI 0.60-0.91; p = 0.0020), establishing this regimen as the new standard first-line treatment for PM, particularly in those with non-epithelioid histology. Increased interest in PM genomics has led to development of novel personalized therapeutics, such as those targeting DNA repair and EZH2 pathways, however with variable outcomes in trials. Targeting the membrane glycoprotein mesothelin and arginine deprivation are other important strategies under ongoing investigation. The field of PM is changing and new treatments bring hope to a largely lethal and poor prognostic malignancy. Despite these developments, current challenges include understanding the role of combination and multimodality treatments, drivers of resistance to treatment, and establishing predictive biomarkers to improve patient selection and treatment sequencing.
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http://dx.doi.org/10.1016/j.ctrv.2021.102265DOI Listing
November 2021

Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis.

Lung Cancer 2021 08 6;158:97-106. Epub 2021 Jun 6.

Department of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Debinki Street, 80-211 Gdańsk, Poland. Electronic address:

Background: Immune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2.

Methods: We conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included: Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I. The review is registered on PROSPERO (CRD42020162668).

Findings: Sixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were: for ORR 0.46 (95 %CI: 0.39-0.54, I:0 %); for DCR 0.39 (95 %CI: 0.33-0.48, I:50 %) and for AEs 1.12 (95 %CI: 0.84-1.48, I:39 %). The pooled hazard ratio for PFS was 2.17 (95 %CI: 1.96-2.39, I:65 %) and for OS was 2.76 (95 %CI: 2.43-3.14, I:76 %). The safety profile was comparable regardless of the PS status.

Interpretation: Patients with impaired PS status are, on average, twice less likely to achieve a response when exposed to ICIs when compared with representative PS ≤ 1 population. For lung cancer patients treated with ICIs, the impaired PS is not only prognostic, but also predictive for response, while the safety profile is not affected. Prospective randomized studies are indispensable to determine whether poor PS patients derive benefit from ICIs.
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http://dx.doi.org/10.1016/j.lungcan.2021.06.004DOI Listing
August 2021

Y disruption, autosomal hypomethylation and poor male lung cancer survival.

Sci Rep 2021 06 14;11(1):12453. Epub 2021 Jun 14.

National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK.

Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA-IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40-10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4-2.0, P = 1.2 × 10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
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http://dx.doi.org/10.1038/s41598-021-91907-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203787PMC
June 2021

Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma.

Drugs 2021 Jun 9;81(9):971-984. Epub 2021 Jun 9.

Lung Unit, Department of Medicine, Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK.

Immune checkpoint inhibitors (ICI) have shown important but variable efficacy in mesothelioma despite a lack of strong biological rationale. Initial trials assessed ICI monotherapy in patients with relapsed mesothelioma, with objective response rates (ORR) between 4.5 and 29%, median progression-free survival (PFS) between 2.5-6.2 months, and median overall survival (OS) between 7.7 and 18.0 months. In randomised trials of chemotherapy pre-treated patients, nivolumab was recently shown to improve PFS compared to placebo, but tremelimumab was not superior to placebo, and there was no difference in OS between pembrolizumab and chemotherapy. However, response to combination ICI appear more promising in both pre-treated and treatment-naïve mesothelioma. The randomised Phase 3 trial of upfront ipilimumab-nivolumab versus platinum-pemetrexed chemotherapy demonstrated improved OS favouring ipilimumab-nivolumab (HR 0.74, 96.6% CI 0.60-0.91; p = 0.0020), establishing this regimen as a new standard of care, especially in non-epithelioid histological subtypes. However, initially PFS was poorer in the ipilimumab-nivolumab than chemotherapy treatment arms. A single-arm Phase 2 trial of upfront platinum chemotherapy and durvalumab met its primary endpoint, with a 6-month PFS of 57% (95% CI 44-70) with chemo-immunotherapy under evaluation as an alternative upfront regimen. Several questions remain unanswered. Comparative studies of chemo-immunotherapy versus chemotherapy are underway, but these do not compare chemo-immunotherapy to combination ICI. There is a critical need to establish predictive biomarkers to improve patient selection. As ICI use moves into the front-line setting, patient selection, role for operable patients, and understanding ICI resistance mechanisms alongside role of ICI rechallenge in previous responders need further evaluation.
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http://dx.doi.org/10.1007/s40265-021-01506-0DOI Listing
June 2021

HER3 expression and MEK activation in non-small-cell lung carcinoma.

Lung Cancer Manag 2021 Apr 9;10(2):LMT48. Epub 2021 Apr 9.

Drug Development Unit, Royal Marsden Hospital, Downs Road, Sutton, London, SM2 5PT, UK.

Aim: We explore HER3 expression in lung adenocarcinoma (adeno-NSCLC) and identify potential mechanisms of HER3 expression.

Materials & Methods: Tumor samples from 45 patients with adeno-NSCLC were analyzed. HER3 and HER2 expression were identified using immunohistochemistry and bioinformatic interrogation of The Cancer Genome Atlas (TCGA).

Results: HER3 was highly expressed in 42.2% of cases. copy number did not account for HER3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a surrogate of functional signaling) did not correlate with HER3 ligands. RNA expression levels were significantly correlated with MEK activity after adjusting for expression.

Conclusion: HER3 expression is common and is a potential therapeutic target by virtue of frequent overexpression and functional downstream signaling.
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http://dx.doi.org/10.2217/lmt-2020-0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162178PMC
April 2021

Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer.

Lung Cancer 2021 07 24;157:9-16. Epub 2021 May 24.

Oncology Department, University of Turin, AOU San Luigi, 10043, Orbassano, Turin, Italy. Electronic address:

Background: The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice.

Methods: UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes.

Results: Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34).

Conclusions: These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.017DOI Listing
July 2021

Safety monitoring of two and four-weekly adjuvant durvalumab for patients with stage III NSCLC: implications for the COVID-19 pandemic and beyond.

Lung Cancer 2021 06 30;156:147-150. Epub 2021 Apr 30.

Lung Unit, Department of Medical Oncology, The Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT, UK; The Drug Development Unit, The Royal Marsden Hospital/Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK. Electronic address:

Durvalumab is the first approved adjuvant immunotherapy agent for patients with stage III NSCLC treated with concurrent chemoradiotherapy and is associated with improved overall survival. In order to minimise the number of hospital visits for patients receiving durvalumab during the COVID-19 pandemic we implemented 4-weekly (20 mg/kg) durvalumab in place of 2-weekly infusions at The Royal Marsden Hospital. We assessed the potential impact of the safety of a 4-weekly schedule in patients receiving adjuvant durvalumab. We carried out a retrospective study of 40 patients treated with 2-weekly and 4-weekly infusions of durvalumab prior to and during the COVID-19 pandemic. Clinical documentation was analysed from 216 consultations across 40 patients receiving 2-weekly durvalumab and 66 consultations of 14 patients who switched from 2-weekly to 4-weekly durvalumab during the COVID-19 pandemic. In patients receiving 2-weekly durvalumab, the rate of grade 3 and 4 toxicities was 15 % compared to 7% in patients receiving 4-weekly durvalumab. Pre-existing autoimmune disease was considered a risk factor for the development of grade 3 or 4 toxicities. We did not observe any difference in the rate of grade 1 and 2 toxicities between the two groups. Our findings support the use of 4-weekly durvalumab during the COVID-19 pandemic and beyond, obviating the need for 2-weekly face-to-face consultations and blood tests, relevant given the current pandemic and the need to re-structure cancer services to minimise patient hospital visits and exposure to SARS-CoV-2.
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http://dx.doi.org/10.1016/j.lungcan.2021.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086258PMC
June 2021

Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor-naive ALK + non-small cell lung cancer (ALTA-1L).

Lung Cancer 2021 05 9;155:68-77. Epub 2021 Mar 9.

University of Colorado Cancer Center, 1665 Aurora Court, Aurora, CO, 80045, USA. Electronic address:

Objective: In ALTA-1 L, first-line brigatinib versus crizotinib significantly prolonged progression-free survival in advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQOL) outcomes from ALTA-1 L.

Materials And Methods: HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and lung cancer-specific module (QLQ-LC13). HRQOL time to worsening, change from baseline, and duration of improvement were analyzed.

Results: EORTC QLQ-C30 and QLQ-LC13 compliance was >90 % for both groups (n = 131 each). Brigatinib versus crizotinib significantly delayed time to worsening in the EORTC QLQ-C30 global health status (GHS)/QOL (median: 26.74 vs 8.31 months; hazard ratio [HR]: 0.70; 95 % CI: 0.49, 1.00; log-rank P = 0.0485); emotional functioning, social functioning, fatigue, nausea and vomiting, appetite loss, and constipation scales (log-rank P < 0.05); delays in time to worsening for the physical, role, and cognitive functioning scales were not statistically significant. Mean change from baseline showed greater improvement in GHS/QOL and most EORTC QLQ-C30 functional and symptom scales with brigatinib versus crizotinib. Among patients with GHS/QOL improvement, brigatinib had longer duration of improvement versus crizotinib (median: not reached vs 11.99 months); similar results were seen in the physical, role, emotional, and social functioning; fatigue; nausea and vomiting; and appetite loss scales. Median time to worsening in dyspnea (QLQ-LC13) was 23.98 versus 8.25 months (brigatinib vs crizotinib; HR: 0.64; 95 % CI: 0.39, 1.05).

Conclusion: Brigatinib significantly delayed time to worsening and prolonged duration of improvement in GHS/QOL versus crizotinib, supported by improvement in functional and symptom scores. These preliminary analyses suggest brigatinib is the first ALK inhibitor with better HRQOL versus another ALK inhibitor in ALK inhibitor-naive advanced ALK + NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2021.03.005DOI Listing
May 2021

First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial.

Lancet 2021 01 21;397(10272):375-386. Epub 2021 Jan 21.

Bichat-Claude Bernard University Hospital, AP-HP, Université de Paris, Paris, France.

Background: Approved systemic treatments for malignant pleural mesothelioma (MPM) have been limited to chemotherapy regimens that have moderate survival benefit with poor outcomes. Nivolumab plus ipilimumab has shown clinical benefit in other tumour types, including first-line non-small-cell lung cancer. We hypothesised that this regimen would improve overall survival in MPM.

Methods: This open-label, randomised, phase 3 study (CheckMate 743) was run at 103 hospitals across 21 countries. Eligible individuals were aged 18 years and older, with previously untreated, histologically confirmed unresectable MPM, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to nivolumab (3 mg/kg intravenously once every 2 weeks) plus ipilimumab (1 mg/kg intravenously once every 6 weeks) for up to 2 years, or platinum plus pemetrexed chemotherapy (pemetrexed [500 mg/m intravenously] plus cisplatin [75 mg/m intravenously] or carboplatin [area under the concentration-time curve 5 mg/mL per min intravenously]) once every 3 weeks for up to six cycles. The primary endpoint was overall survival among all participants randomly assigned to treatment, and safety was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02899299, and is closed to accrual.

Findings: Between Nov 29, 2016, and April 28, 2018, 713 patients were enrolled, of whom 605 were randomly assigned to either nivolumab plus ipilimumab (n=303) or chemotherapy (n=302). 467 (77%) of 605 participants were male and median age was 69 years (IQR 64-75). At the prespecified interim analysis (database lock April 3, 2020; median follow-up of 29·7 months [IQR 26·7-32·9]), nivolumab plus ipilimumab significantly extended overall survival versus chemotherapy (median overall survival 18·1 months [95% CI 16·8-21·4] vs 14·1 months [12·4-16·2]; hazard ratio 0·74 [96·6% CI 0·60-0·91]; p=0·0020). 2-year overall survival rates were 41% (95% CI 35·1-46·5) in the nivolumab plus ipilimumab group and 27% (21·9-32·4) in the chemotherapy group. Grade 3-4 treatment-related adverse events were reported in 91 (30%) of 300 patients treated with nivolumab plus ipilimumab and 91 (32%) of 284 treated with chemotherapy. Three (1%) treatment-related deaths occurred in the nivolumab plus ipilimumab group (pneumonitis, encephalitis, and heart failure) and one (<1%) in the chemotherapy group (myelosuppression).

Interpretation: Nivolumab plus ipilimumab provided significant and clinically meaningful improvements in overall survival versus standard-of-care chemotherapy, supporting the use of this first-in-class regimen that has been approved in the USA as of October, 2020, for previously untreated unresectable MPM.

Funding: Bristol Myers Squibb.
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http://dx.doi.org/10.1016/S0140-6736(20)32714-8DOI Listing
January 2021

Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations.

J Thorac Oncol 2021 05 14;16(5):764-773. Epub 2020 Dec 14.

Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI), of which five as follows are predominantly available in practice: gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Most prospective clinical trial data with these agents are limited to patients with the common activating and sensitizing EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, 10% to 20% of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to their molecular structures, afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations in up to 25% of the cases complicate treatment decisions in this patient subgroup. Here, we collate the latest preclinical and clinical data regarding the activity of different TKIs against major uncommon EGFR mutations including compound mutations, but excluding exon 20 insertions which are generally insensitive to TKIs. On the basis of these data, we offer suggestions regarding treatment strategies for uncommon EGFR mutations. Moving forward, it will be important to include uncommon EGFR mutations in the first-line molecular analysis of all patients with adenocarcinoma of the lung, as this will help optimize patient outcomes according to their precise genotype.
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http://dx.doi.org/10.1016/j.jtho.2020.12.002DOI Listing
May 2021

Real-world outcomes in thoracic cancer patients with severe Acute respiratory syndrome Coronavirus 2 (COVID-19): Single UK institution experience.

Cancer Treat Res Commun 2020 2;25:100261. Epub 2020 Dec 2.

Lung Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Thoracic Oncology, Institute of Cancer Research, London, United Kingdom. Electronic address:

Background: UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19.

Methods: Patients undergoing care for thoracic cancer diagnosed with COVID-19 (RT-PCR/radiology/clinically) between March-June 2020 were included. Data were extracted from patient records.

Results: Thirty-two patients were included: 14 (43%) diagnosed by RT-PCR, 18 (57%) by radiology and/or convincing symptoms. 88% had advanced thoracic malignancies. Eleven of 14 (79%) patients diagnosed by RT-PCR and 12 of 18 (56%) patients diagnosed by radiology/clinically were hospitalised, of which four (29%) and 2 (11%) patients required high-dependency/intensive care respectively. Three (21%) patients diagnosed by RT-PCR and 2 (11%) patients diagnosed by radiology/clinically required non-invasive ventilation; none were intubated. Complications included pneumonia and sepsis (43% and 14% respectively in patients diagnosed by RT-PCR; 17% and 11% respectively in patients diagnosed by radiology/clinically). In patients receiving active cancer treatment, therapy was delayed/ceased in 10/12 (83%) and 7/11 (64%) patients diagnosed by RT-PCR and radiology/clinically respectively. Nine (28%) patients died; all were smokers. Median time from symptom onset to death was 7 days (range 3-37).

Conclusions: The immediate morbidity from COVID-19 is high in thoracic cancer patients. Hospitalisation and treatment interruption rates were high. Improved risk-stratification models for UK cancer patients are urgently needed to guide safe cancer-care delivery without compromising efficacy.
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http://dx.doi.org/10.1016/j.ctarc.2020.100261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709731PMC
January 2021

Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease.

BMC Cancer 2020 Dec 9;20(1):1210. Epub 2020 Dec 9.

Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Down Rd, Sutton, SM2 5PT, UK.

Background: Malignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking.

Methods: In this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, aiming to describe identified metastatic sites, and correlate with clinical outcomes.

Results: 67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p = 0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without.

Conclusions: This report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.
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http://dx.doi.org/10.1186/s12885-020-07662-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724793PMC
December 2020

Navigating Diagnostic and Treatment Decisions in Non-Small Cell Lung Cancer: Expert Commentary on the Multidisciplinary Team Approach.

Oncologist 2021 02 21;26(2):e306-e315. Epub 2020 Nov 21.

Lung Unit, Royal Marsden Hospital, London, United Kingdom.

Non-small cell lung cancer (NSCLC) accounts for approximately one in five cancer-related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence-based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national-level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC. IMPLICATIONS FOR PRACTICE: This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non-small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per-patient decision making as treatment options become ever more specialized in the era of biomarker-driven therapeutic strategies.
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http://dx.doi.org/10.1002/onco.13586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873339PMC
February 2021
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