My research has been published in leading peer reviewed journals and is regularly presented at international meetings.
Recent publications
Gene expression patterns in adenoid cystic carcinoma with and without diffuse NOTCH1 intracellular domain (NICD1) immunohistochemistry staining Karan Patel, Massimiliano Manzo, Brindley Hapuarachi, Samuel Rack, Philip Jermann, Laura Feeney, Emily Heathcote, Guy Betts, Jon C Aster, Maximilien Murone, Maria Bobadilla, Rajwinder Lehal, Florian D Vogl, Kevin Harrington , Robert Metcalf Oral Oncol. 2023 Aug 22;146:106542 10.1016/ j.oraloncology 2023.106542. Online ahead of print.
In this study, we investigated adenoid cystic carcinoma (ACC) and its association with the intracellular domain of NOTCH1 (NICD1) staining patterns. We saw that ACC tumours displaying diffuse NICD1 staining through immunohistochemistry were linked to adverse clinical outcomes, indicating a potential prognostic marker. Using multi-dimensional scaling analysis of RNA data, we observed distinct clustering patterns between ACC tumors with and without diffuse NICD1 staining, underscoring genetic differences between these groups. Interestingly, some ACC tumours lacking diffuse NICD1 staining but with SPEN or TP53 mutations clustered more closely with NICD1-positive ACC. Additionally, we applied the gene expression data to classify ACC into ACC-I and ACC-II subclasses in a separate dataset, although the correlation with NICD1 status was only partially evident. This research reinforces the importance of the molecular heterogeneity of ACC and its potential implications for clinical management.
Clinical and genomic characterisation of adenoid cystic carcinoma of the head and neck, lung, and breast. Emily Heathcote, Karan Patel, Samuel Rack, Clare Hodgson, Hitesh Mistry, Guy Betts, Paul Bishop, Rachel Hall, Anne C. Armstrong, Kevin Joseph Harrington, Robert Metcalf. Presented at ASCO Annual Meeting, Chicago, June 2023. J Clin Oncol 41, 2023 (suppl 16; abstr 6094)
In this presentation we reported a study on 450 ACC patients in the UK to understand the disease better. We collected clinical and genomic data from the patients and analyzed their outcomes. The majority of ACC cases (44.7%) originated from the major salivary glands, followed by other sites like sinonasal (22.0%), upper aerodigestive (15.3%), and tracheobronchial (10.2%). Recurrent or metastatic disease was confirmed in 69.8% of patients. The median time to first confirmed recurrence (TTFR) was 4.5 years, and the median overall survival from recurrence (OS-rec) was 4.8 years. Major salivary ACC had the longest TTFR (5.8 years), while tracheobronchial and sinonasal ACC had significantly shorter TTFR. Breast ACC had a similar overall survival from diagnosis (OS-diag) compared to major salivary ACC but showed increased TTFR and shorter OS-rec. This study suggests the need for different follow-up protocols and systemic therapy strategies may be needed for ACC of different primary sites.
Tumour mutational burden as a predictive and prognostic biomarker in locally advanced and recurrent/metastatic adenoid cystic carcinoma. Karan Patel, Samuel Rack, Hitesh Mistry, Emily Heathcote, Guy Betts, Kevin Joseph Harrington, and Robert Metcalf. Journal of Clinical Oncology 202341 (suppl 16, abstr e18086)
In this study we analysed the distribution of tumor mutational burden (TMB) and its relationship with NOTCH pathway activation in two independent cohorts of ACC patients. We found that ACC had a low TMB profile, with only one tumor classified as TMB-high. Tumors with NOTCH activation had higher TMB levels. Higher TMB correlated with reduced survival in ACC tumors with NOTCH activation.
Addressing the unmet need for salivary gland cancers in the UK and beyond. E Kinloch, R Metcalf. Presented at ESMO Rare Cancers Conference, Lugano, Switzerland. ESMO Open, volume 8 issue 1 supplement 3, 101062, March 2023. https://doi.org/10.1016/j.esmoop.2023.101062
In this presentation we describe the impact of Salivary Gland Cancer UK (SGC-UK), a unique charity we launched in April 2019 to address the unmet need for patients, carers, and healthcare professionals treating and researching salivary cancers. The charity focuses on building an active patient and research community, advancing understanding of SGC biology, developing new treatments, and supporting patients and carers. Patients with all SGC types are supported through a specialist hub at The Christie NHS Foundation Trust, Manchester, UK, and a biobank of tumor and blood samples has been established to support national and international research. SGC-UK also co-produces reliable patient information and support materials, including real-life stories and videos from their network, empowering patients and advocates. The collaboration and co-production efforts are aimed at driving forward research and advancing outcomes for patients with SGC.
Targeting MYB/MYBL1 gene rearrangements as diagnostic biomarkers in salivary cancers. Emily Heathcote, Samuel Rack, Laura Feeney, Karan Patel, Guy Betts, Clare Hodgson, Kate Garcez, Kevin Harrington, Robert Metcalf. Presented at European Congress on Head and Neck Oncology, Lisbon, March 2023. Abstract PO-097
In this study we validated MYB/MYBL1 detection using fluorescent in situ hybridization (FISH) probes for diagnosis of salivary adenoid cystic carcinoma (sACC). The study evaluated 62 patients with salivary cancer, where 49 had sACC, and 13 had non-ACC salivary cancer. FISH was used to detect MYB/MYBL1 rearrangement in patients with sACC, and DNA-based next-generation sequencing was used to confirm MYB gene rearrangement in a subgroup of 28 patients. Results showed that MYB/MYBL1 alterations were detected in 90% of sACC patients, making FISH probes a highly specific diagnostic biomarker for sACC. The study concludes that FISH probes have higher sensitivity than DNA-based NGS for detecting MYB gene fusions, making them useful for sACC diagnosis.
Clinical parameters associated with immunotherapy outcomes in metastatic cutaneous squamous cell carcinoma. Sam Rack, Sherin Babu, Sradha Bhagani, Olly Donnelly, Guy Faust, Patrick Isola, Harriet Walter, Robert Metcalf. Presented at European Congress on Head and Neck Oncology, Lisbon, March 2023. Abstract PO-143
We want to understand which subgroups of patients we treat respond well to immunotherapies. The use of anti-programmed death 1 (PD1) therapy cemiplimab has shown significant clinical benefit in patients with recurrent/ metastatic cutaneous squamous cell carcinoma (R/M-cSCC), with durable responses seen in most patients. However, around 30% of patients do not benefit from the treatment, and there is a need to develop predictors of response and resistance to therapy. In this study we aimed to identify clinical parameters that predict response/resistance to therapy in a cohort of 88 R/M-cSCC patients treated with cemiplimab at three UK cancer centers. The results showed that patients with R/M-cSCC with a head and neck primary site had a significantly improved overall survival (OS) and progression-free survival (PFS) compared with other primary sites when treated with cemiplimab. The median OS and PFS were not reached for the entire cohort, and the 2-year OS rate was 60%. The overall response rate (ORR) was 60%, and 40% of patients developed immune-related toxicities of any CTCAE grade, while 13% developed grade 3 or above. The study concludes that cemiplimab treatment demonstrated significant clinical benefit with a manageable side effect profile, and future work should investigate the observed difference in survival outcomes based on primary site further.
Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation. Feeney L, Hapuarachi B, Adderley H, Rack S, Morgan D, Walker R, Rauch R, Herz E, Kaye J, Harrington K, Metcalf R. Oral Oncology. 2022 Aug 8;133:106028.
In this study we retrospectively assessed 120 patients with recurrent or metastatic ACC, identifying NOTCH pathway activation in 11% of patients. Patients with NOTCH pathway activation had significantly reduced median overall survival from diagnosis (4.0 vs 16.3 years) and from time of disease recurrence/metastasis (1.9 vs 9.6 years) compared to patients without NOTCH pathway activation. This study supports the need for developing new drugs targeting the NOTCH pathway for this sub-group of patients, for whom effective treatments are lacking.
Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer. Rack S., Feeney L., Hapuarachi B., Adderley H., Woodhouse L., Betts G., Burghel G., Harrington K., Metcalf R. Cancers 2022 Feb 23 14(5), 1133
In this study we evaluated the clinical utility of genomic profiling to match patients with recurrent or metastatic salivary gland cancer to clinical trial therapies. 209 patients were profiled with 24-gene and >325 gene DNA-based next-generation sequencing panels, and the frequency of available matched drug therapies within clinical trials based on the results was identified. DNA-based NGS analysis was successful in 84% of patients with salivary gland cancer, and actionable alterations were identified in 27% of patients. TP53 was the most frequently altered gene across all subtypes, but there were no trials recruiting based on TP53 status. Genomic profiling using focused NGS panels has potential utility in matching to trial therapies for most patients with non-ACC salivary gland cancer, and broader genomic profiling has added clinical utility for patients with ACC.
The prevalence and prognostic impact of mutations promoting chromatin remodelling dysregulation in non-resectable or recurrent/metastatic adenoid cystic carcinoma. Samuel Rack, Laura Feeney, Hitesh Mistry, Guy Betts, Kevin Joseph Harrington, and Robert Metcalf. ASCO Annual Meeting June 2022. Journal of Clinical Oncology 2022 40:16_suppl, 6087-6087
In almost 50% of ACC patients, mutations in genes that regulate chromatin remodeling are observed. In this study we classified mutations in chromatin remodeling genes in ACC based on their predicted pathogenicity and to evaluate the impact of chromatin remodeling dysregulation (CRD) on clinical outcomes. The research analyzed data from 269 ACC patients, and mutations that promoted CRD were detected in 35% of patients. CRD mutations were associated with decreased survival from recurrence. The association was significant for mutations in KDM6A, CREBBP, and SETD2. The study identified a novel prognostic group of ACC patients characterized by CRD mutations, which may provide potential therapeutic options. Alterations in EP300/CREBBP/ARID1A may provide a rationale for treatment with CREBBP/EP300 inhibitors currently in clinical development. The co-occurrence of CRD mutations with NOTCH gain-of-function may provide a rationale for future combination studies.
Results of ACCURACY: A phase 2 trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut). Renata Ferrarotto, Robert Metcalf, Cristina P. Rodriguez, Jameel Muzaffar, Caroline Even, Cesar Augusto Perez, Carla M.L.- Van Herpen, Marc Oliva, Bing Xia, Daniel W. Bowles, Aharon Popovtzer, Eric Winquist, Lori J. Wirth, Desiree Hao, Hyunseok Kang, Sebastien J. Hotte, Salomon M. Stemmer, Ranee Mehra, Francis P. Worden, and Alan Loh Ho ASCO Annual Meeting June 2022. Journal of Clinical Oncology 2022 40:16_suppl, 6046-6046
We reported the results of an international multi-centre phase 2 study called ACCURACY, in which AL101 was administered to 82 patients with relapsed or metastatic ACC with Notch1-4 mutation. The primary endpoint of the study was overall response rate (ORR) by RECIST v1.1, as assessed by investigators, while the secondary endpoints were ORR by central review, duration of response, and safety. The study provided ≥80% power to detect an increase of the ORR from 8% to 25% using a type I error of 5%. Most common treatment-related adverse events were diarrhea, fatigue, and nausea. Of the 77 evaluable subjects, there were 9 partial responses and 44 stable diseases, resulting in a disease control rate of 69%.
Appraising the Costs of Genomic Testing for Histology-Independent Technologies: An Illustrative Example for NTRK Fusions. Beresford L, Murphy P, Dias S, Claxton L, Walton M, Metcalf R, Schlecht H, Ottensmeier C, Pereira M, Hodgson R. Value in Health. 2022 Jul; 25(7):1133-1140.
Histology-independent (HI) technologies require genomic testing to identify eligible patients with advanced or metastatic cancer expressing a particular biomarker, irrespective of the tumor's location in the body. However, the cost of genomic testing poses a challenge to the cost-effectiveness of HI therapies. In this article we discuss the key issues affecting the cost of genomic testing for HI technologies and provide illustrative analyses of the cost of testing for NTRK fusions in England. The prevalence of the mutation, testing strategy adopted, and current testing provision impact the cost of identifying eligible patients. The estimated cost of RNA-based next-generation sequencing to identify one individual with an NTRK fusion ranges between £377 and £282,258. The cost-effectiveness of HI technologies may be improved by sharing testing costs across multiple agents.
LEAP-009: Phase 2 study of lenvatinib with or without pembrolizumab vs chemotherapy for the treatment of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) upon progression after platinum and immunotherapy (PD-1/PD-L1 inhibition). Kevin J. Harrington, Hye Ryun Kim, Sebastien Salas, Marc Oliva, Robert Metcalf, Mogens Bernsdorf, Ji-Won Kim, Ezra E. W. Cohen, Lillian Siu, Danny Rischin, Lisa Licitra, Jan Vermorken, Quynh Le, Makoto Tahara, Jean-Pascal Machiels, Karen O'Hara, Kumudu Pathiraja, Burak Gumuscu, Behzad Bidadi, Barbara Burtness, Elani Bowers Presented at Clinical Oncology Society of Australia Annual Scientific Meeting 2022. Asia Pacific Journal of Clinical Oncology https://doi.org/10.1111/ajco.13869
TACTI-003: A randomized Phase IIb study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab as first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma. Irene Brana, Valerii Cheshuk, Claus Andrup Kristensen, Maria Eugenia Ortega, Brieuc Sautois, Antonio López-Pousa, Judith Christian, Willem Lybaert, Julio Peguero, John Park, Robert Metcalf, Lisle Nabell, Bernard Doger de Spéville, Jordi Rubió Casadevall, Ainara Soria Rivas, Martin Forster, Frederic Triebel Presented at SITC Annual Meeting 2022. Journal for ImmunoTherapy of Cancer Nov 2022, 10 (Suppl 2) 1537-1592
Durable complete response rates following radiotherapy and immunotherapy combination in recurrent and metastatic head and neck squamous cell carcinoma: A retrospective single-centre cohort study. Khera R, Feeney L, Swinton M, Rack S, Sykes A, Metcalf R. ClinicalOtolaryngology. 2022 Sep;47(5):606-610.
We want to understand which subgroups of patients we treat respond well to immunotherapies. In this study we report that a sub-set of patients receiving radiotherapy–immunotherapy combination in platinum-resistant HNSCC-derived durable complete response associated with significant clinical benefit. This study highlights the need for a personalised approach in treatment decision making for patients who develop oligoprogression on nivolumab and provides a rationale for prospective clinical studies or registry studies to further address the role for multi-modality therapy in the recurrent or metastatic setting.
ACCURACY: A phase II trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut): Results of 6-mg cohort. R. Ferrarotto, L.J. Wirth, J. Muzaffar, C.P. Rodriguez, B. Xia, C.A. Perez, D.W. Bowles, E. Winquist, S.J. Hotte, R. Metcalf, C. Even, G.B. Gordon, G. Gordon, A. Ho. Presented at ESMO Congress, 2021 Annals of Oncology (2021) 32 (suppl_5): S786-S817.
In this presentation we report a phase II study of an investigational drug, AL101, for the treatment of recurrent/metastatic adenoid cystic carcinoma (ACC). The study focuses on ACC tumors with Notch mutations, which are found in approximately 20% of ACC cases. AL101 is a γ-secretase inhibitor that blocks Notch signaling and inhibits tumor growth in ACC patient-derived xenograft models. The study is an open-label, multicenter trial that included 37 subjects treated with 6 mg of AL101 once a week. The primary endpoint is overall response rate, and the secondary endpoints are duration of response and safety. The study results show that AL101 6 mg QW had diarrhea, fatigue, and nausea as the most common side effects. The efficacy and pharmacokinetic data will be presented, and the study will continue to accrue and follow up with the 6-mg cohort.
Evaluation of the frequency of durable complete responses following radiotherapy-immunotherapy combination in platinum-resistant head and neck squamous carcinoma. Khera R, Feeney L, Swinton M, Rack S, Sykes A, Metcalf R. Presented at the NCRI Cancer Conference, Birmingham, 2021.
Evaluating serum biochemistry to predict time to cessation of immune checkpoint blockade and clinical outcome in patients with platinum-resistant recurrent/metastatic head and neck squamous carcinoma. Becky Bola, Laura Feeney, John Baron, Kathleen Mais, Claire McVey, Andrew Sykes, Robert Metcalf. Presented at the NCRI Cancer Conference, Birmingham, 2021.
In this study we aimed to determine the association between baseline serum biochemical parameters and patient survival in a homogenous cohort of 91 patients with platinum-resistant recurrent or metastatic head and neck squamous carcinoma (R/M-HNSCC) treated with nivolumab. The study found that elevated lactate dehydrogenase (LDH) at treatment initiation was associated with significantly shorter time to treatment discontinuation of any cause. Additionally, elevated corrected calcium predicted shorter overall survival. On the other hand, hyponatraemia did not have a significant effect on patient survival. The study highlights the potential additional value of using baseline serum biochemical parameters alongside biomarkers like PD-L1 expression to select patients for immunotherapy. Overall, these findings suggest that monitoring serum biochemical parameters can help identify patients who are less likely to benefit from immunotherapy and guide treatment decisions.
The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma. Adderley H., Rack S., HapuarachiB., Feeney F., Morgan D., Hussell T., WallaceA., Betts G., Hodgson C, Harrington K., Metcalf R., Oral Oncology. 2021 Feb;113:105095
We aimed to find biomarkers that can help identify patients at the highest risk of recurrence and analysed DNA samples from 145 ACC patients to identify mutations in two genes, TP53 and PIK3CA, and evaluated their impact on disease recurrence and overall survival. TP53 mutations were identified in 8% of the cases, and these patients had a significantly shorter median overall survival from diagnosis (5.3 years vs. 16.3 years) and lower 10-year survival (48% vs. 81%) compared to TP53 wild-type ACC. However, there were too few PIK3CA mutations in the cohort to draw any conclusions. Solid-pattern histopathology was more frequent in TP53-mutated ACC. TP53 mutation status, combined with other established clinical, pathological, and genomic biomarkers, may be useful in informing follow-up strategies for SACC patients
Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma. Feeney L., Jain Y., Beasley M.,Donnelly O., Kong A., Moleron R., NallathambiC., Rolles M., Sanghera P., Tin A., UlahannanD., Walter H, Webster R., Metcalf R., Cancers 2021 Aug 27 13(17):4336
In this study we evaluated real-world experience with lenvatinib monotherapy in recurrent or metastatic (R/M) ACC patients within the UK National Health Service (NHS) to determine response rates and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centers were included, and RECIST 1.1 complete or partial response was not observed in any patients. The median time on treatment was 4 months, and the median survival from discontinuation was 1 month. The median progression-free survival (PFS) and overall survival (OS) from treatment initiation were 4.5 months and 12 months, respectively. Multicenter collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.
Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma (ACC) with NOTCH signaling pathway activation. Brindley Sonal Hapuarachi, Laura Feeney, Sam Rack, Helen Adderley, David Morgan, Guy Betts, Russell Walker, Rami Rauch, Elad Herz, Kevin Joseph Harrington, and Robert Metcalf. ASCO Annual Meeting June 2021 Journal of Clinical Oncology2021 39:15 suppl, 6072-6072
A study to determine the utility of TP53 mutations as a prognostic biomarker in adenoid cystic carcinoma. Robert Metcalf, Khaireah Mubarak, Becky Bola, Samuel Rack, David Morgan, Tracy Hussell, Andrew Wallace, Guy Betts, and Kevin Joseph Harrington. Presented at ASCO Annual Meeting June 2020. Journal of Clinical Oncology 2020 38:15 suppl, 6585-6585
Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer. Hanna GJ, Guenette JP, Chau NG, Sayehli CM, Wilhelm C,Metcalf R, Wong DJ, Brose M, Razaq M, Pérez-Ruiz E, Cohen EEW, Aggarwal R, Scholz C, Gualberto A, Ho AL. Cancer. 2020 Sep 1;126(17):3972-3981
In this study we evaluated the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M salivary gland cancer. A total of 13 patients were enrolled, all of whom had received prior systemic therapy, and one objective response was observed. Seven of 12 evaluable patients had stable disease as their best response, with a median duration of 9 months. The most frequent activating HRAS mutation noted was Q61R. The median progression-free survival was 7 months, and the median overall survival was 18 months, with approximately 58.6% of patients alive at 1 year. No participant discontinued treatment because of toxicity. The study suggests that tipifarnib may have modest clinical activity with a promising disease control rate among patients with HRAS-mutant, R/M SGC who developed disease progression within the last 6 months.
Primary epithelial-myoepithelial carcinoma of the pituitary gland. Lavin V, Callipo F, Donofrio CA, Ellwood-Thompson R, Metcalf R, Djoukhadar I, Higham CE, Kearney T, Colaco R, Gnanalingham K, Roncaroli F.Neuropathology. 2020 Jun;40(3):261-267.
Salivary gland-like tumors of the sella are uncommon and challenging to diagnose. They are believed to originate from glandular tissue that is trapped in the infundibulum during fetal development. In this report we describe the care of a 68-year-old man who presented with visual loss in the left eye, headache, weight loss, and reduced muscle bulk. Imaging showed a cystic and solid, avidly enhancing lesion expanding the pituitary fossa and extending to the left cavernous sinus. Craniotomy revealed an epithelial-myoepithelial carcinoma with no primary tumor found outside the sella. The tumor exhibited a novel TP53 in-frame deletion (Gly154del). Despite adjuvant radio-chemotherapy, the lesion was progressive, and the patient died 22 months after onset. The report highlights the importance of expert review of rare, non-neuroendocrine tumors of the pituitary and sella regions.
Looking a Gift Horse in the Mouth: Observations on NHS England's Interim Guidance on Pembrolizumab in Head and Neck Squamous Cell Cancer. Harrington KJ, Bhide SA, Forster MD, Good JS, Gunn L, Kong A, Melcher AA, Metcalf R, Nenclares P, Newbold KL, Nutting CM, Prestwich R, Sacco JJ, Soliman H, Wong KH. Clin Oncol (R Coll Radiol). 2020 Aug;32(8):490-492.
Setting up a charity for an “orphan” cancer. Emma Kinloch and Robert Metcalf. BMJ Opinion, 18 Oct 2019. https://blogs.bmj.com/bmj/2019/10/18/setting-up-a-charity-for-an-orphan-cancer/
In this BMJ opinion piece, we describe how we used patient-advocate/clinician collaboration to set up Salivary Gland Cancer UK, a new charity to promote partnership in research and drive better care and support for patients with rare salivary cancers.
In this study we describe the use of next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) in the context of phase I clinical trials. The TARGET program is a molecular profiling program designed to match patients with advanced cancer to early phase clinical trials based on the analysis of somatic mutations and copy number alterations (CNA) in a 641 cancer-associated-gene panel using a single ctDNA assay. The ctDNA data for the first 100 TARGET patients showed good concordance with matched tumor and were processed within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. Applying a 2.5% variant allele frequency (VAF) threshold, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. The results support the use of ctDNA in early phase clinical trials, where broad genomic profiling of contemporaneous tumor material improves patient stratification to novel therapies and provides a practical model for implementing routine blood-based analyses in the clinic.
In this article we highlight the recent advancements in molecular sub-classification of cancers and personalized treatments based on molecular aberrations. In particular, androgen receptor (AR) positive salivary gland cancer has shown a 42% response rate with androgen deprivation therapy, while NTRK3 rearranged mammary analogue secretory carcinoma has shown a 75% response rate in a non-randomized trial of pan-trk inhibition with larotrectinib, irrespective of the primary tumor site. We further review ongoing clinical trials recruiting patients with salivary gland cancer and the potential for tumor profiling to stratify patients for trials targeting molecular sub-groups. We discuss the future application of next-generation sequencing in salivary gland cancer to inform clinical decision-making. Overall, these findings demonstrate the promise of personalized treatments based on molecular sub-classification in cancer, particularly in rare and difficult-to-treat cases like salivary gland cancer.
Molecular phenotyping of mucoepidermoid carcinoma of the major and minor salivary gland using a MAML2 break apart FISH assay. European Journal of Surgical Oncology, Vol. 43, Issue 11, p2223 November 2017
Molecular profiling of recurrent and metastatic salivary gland cancer to personalise cancer therapy. Annals of Oncology, Volume 28, Issue suppl_7, 1 October 2017, mdx508.016
The application of liquid biopsies in metastatic salivary gland cancer to identify candidate therapeutic targets. Annals of Oncology, Volume 28, Issue suppl_7, 1 October 2017, mdx508.016
Small cell lung cancer (SCLC) is known for early metastasis, poor prognosis, and prevalent circulating tumor cells (CTCs). Through my PhD studies we found that SCLC patients have rare CTC subpopulations that express vascular endothelial-cadherin (VE-cadherin) and cytokeratins, indicative of vasculogenic mimicry (VM) – the formation of "endothelial-like" vessels by tumor cells. Genomic analysis revealed characteristic SCLC genomic changes in both VE-cadherin-positive and negative CTCs. Higher levels of VM were associated with worse overall survival in limited-stage patient biopsies. VE-cadherin was found to be required for VM in NCI-H446 SCLC xenografts, where VM decreased tumor latency and decreased cisplatin efficacy. The findings suggest that VM regulation could be a new target for therapeutic intervention in SCLC, highlighting the significance of VM in SCLC and the need for further research.
Natural history of venous thromboembolism in gastrointestinal cancers. Robert Metcalf , Nicholas Hopley, Thomas Henry, Jurjees Hasan. Presented at ASCO GI cancers symposium, San Francisco, 2014. Journal of Clinical Oncology, Vol 32, Issue 3, suppl abstract 593
The incidence of venous thromboembolism (VTE) in cancer patients is high, with VTE being a leading cause of mortality in patients with cancer. We performed a retrospective analysis of 910 upper gastrointestinal (UGI) cancer patients and 1,299 colorectal cancer (CRC) patients to identify the incidence of VTE and its relationship to chemotherapy and impact on survival. This study found that 9.7% of UGI cancer patients and 8.9% of CRC patients had VTE. The peak incidence of VTE was in the first 6 months following diagnosis. No adverse impact on survival was seen for patients with VTE compared to stage-matched controls, implying that VTE is not a prognosticator of poor outcomes in gastrointestinal cancers. Chemotherapy was received by more than half of the patients who developed VTE, suggesting that prophylactic anticoagulation may benefit high-risk populations.
Thrombotic events are common in ovarian cancer patients, and in this study we aimed to determine their incidence, risk factors, and impact on patient outcomes. The retrospective cohort included 417 patients with ovarian cancer treated between 2006 and 2009. Ninety thrombotic events occurred in 90 patients (21.6%), peaking in the 4 months following diagnosis. Patients with thrombosis were older, had a worse performance status, and had more advanced FIGO stages than those without thrombosis. Patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis had a shorter overall survival than those without thrombosis. However, when the control group was matched for prognostic factors, no survival difference was seen, indicating that thrombosis did not impact upon prognosis. Therefore, this study highlights the importance of early recognition and management of thrombotic events in ovarian cancer patients, as prompt treatment can improve patient outcomes.
Clinical utility of circulating tumour cell detection in non-small-cell lung cancer. Curr Treat Options Oncol. 2013 Dec;14(4):610-22. doi: 10.1007/s11864-013-0253-5. PMID: 23996475.No
Biology and clinical relevance of circulating tumour cells. J Thorac Dis. 2012 Oct;4(5):453-5. doi: 10.3978/j.issn.2072-1439.2012.09.02. PMID: 23050105