86 results on '"Leila Khoja"'
Search Results
2. Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
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Roy Rabbie, Naser Ansari-Pour, Oliver Cast, Doreen Lau, Francis Scott, Sarah J. Welsh, Christine Parkinson, Leila Khoja, Luiza Moore, Mark Tullett, Kim Wong, Ingrid Ferreira, Julia M. Martínez Gómez, Mitchell Levesque, Ferdia A. Gallagher, Alejandro Jiménez-Sánchez, Laura Riva, Martin L. Miller, Kieren Allinson, Peter J. Campbell, Pippa Corrie, David C. Wedge, and David J. Adams
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Science - Abstract
Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
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- 2020
- Full Text
- View/download PDF
3. Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS).
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Bethany Pitcher, Leila Khoja, Robert J Hamilton, Kald Abdallah, Melania Pintilie, and Anthony M Joshua
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Medicine ,Science - Abstract
BACKGROUND:Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. METHODS:We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment. RESULTS:Despite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53-4.91, p < .0001). CONCLUSION:Despite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in outcome analyses, as well as the effect of PSA response on survival and toxicity prediction.
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- 2017
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4. Characteristics and outcomes in patients with KRAS mutated lung adenocarcinomas: a retrospective data analysis
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Jingyao Zhang, Xuelian Liu, Brendan O’Sullivan, Philippe Taniere, Shobhit Baijal, Leila Khoja, and Oliver Pickles
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
5. Evaluating the Histopathological Effects of Short-term and Long-term Doses of Ketamine Injection on Heart Tissue of Male and Female Rats
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Behrooz Yahyaei, Faeze Gholipour, Leila Khojasteh, Mohammadbagher Gilak Hakimabadi, Fatemeh Bahoosh Feyzabadi, Fatemeh Dankoub, and Melika Nasehi
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ketamine ,histopathology ,heart ,male rats ,female rats ,short-term doses ,long-term doses. ,Medicine (General) ,R5-920 - Abstract
Introduction: Ketamine is a general anesthetic drug that acts by inhibiting the NMDA receptoran important component of excitatory neurotransmission. Existing of NMDA receptors all over the central nervous system and the special type of anesthesia induced by ketamine, called dissociative anesthesia has led to its use as an analgesic and also paved the way for abuse. Ketamine affects the cardiovascular system by increasing indices such as heart rate, blood pressure, and cardiac output. Methods: For further evaluation of ketamine effects on heart tissue, we used 15 male and 15 female Wistar rats and divided them into 6 groups, including male and female control groups (MC and FC), male and female short-term exposure (MS and FS), and male and female long-term exposure (ML and FL) to ketamine. Each group included 5 Wistar rats. The ML and FL groups received 75mg of ketamine once a week for 4 weeks in the posterior muscle of the thigh and the MS and FS groups received 25mg of ketamine 3 times a week for 4 weeks at the same site. Results: After preparation of histopathological slides, it was observed that only in the group of female mice receiving long-term ketamine, empty spaces and intercellular distances increased, and in the group of male mice receiving long-term ketamine, in addition to the increase of intercellular spaces, tissue accumulations were also observed in the heart tissue. Conclusion: This study showed that long-term ketamine injection in both sexes can cause some qualitative changes in heart tissue. Expanding the duration of long-term exposure to ketamine and more studies based on sexes can lead to more findings.
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- 2024
6. CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset
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William Buller, Lalit Pallan, Teresa Chu, and Leila Khoja
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Oncology ,Pharmacology (medical) - Abstract
Introduction CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy. Methods A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021. Toxicity was evaluated along with variability in full blood counts and liver function over the first 12 weeks of therapy. Results Two hundred and seventeen patients were treated (palbociclib 59%, abemaciclib 25% and ribociclib 16%). 86% received the agent as 1st line therapy. Most patients were white women with a median age of 61 years (32–95) and ECOG 0/1. Twelve patients were switched to an alternative CDK4/6 inhibitor due to toxicity and two did not tolerate this. Toxicity profiles of agents were consistent with published trials. However, there was greater overlap in hepatitis, diarrhoea and bone marrow suppression. Blood results indicated a minimum of four weeks treatment before development of neutropenia. Forty percent of patients went onto have subsequent lines of therapy. The progression-free survival per agent was palbociclib 27.9 months (95% CI 23–32.5), ribociclib 29 months (95% CI 21.5–37.0) and abemaciclib 20.6 months (95% CI 15.0–26.0). The overall survival was palbociclib 38.0 months (95% CI 33.5–42.5), ribociclib 33.9 months (95% CI 26.7–41.1) and abemaciclib 27.3 months (95% CI 22.5–32.1). Conclusions Toxicity across CDK4/6 inhibitors overlaps. The optimal sequence of therapies post CDK4/6 inhibitors remains unknown but rechallenge with an alternative agent is possible.
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- 2023
7. Extracellular vesicles from biological fluids as potential biomarkers for prostate cancer
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Wendy Y. Choi, Catherine Sánchez, Jiao Jiao Li, Mojdeh Dinarvand, Hans Adomat, Mazyar Ghaffari, Leila Khoja, Fatemeh Vafaee, Anthony M. Joshua, Kim N. Chi, Emma S. Tomlinson Guns, and Elham Hosseini-Beheshti
- Abstract
Purpose Despite the high incidence of false positives, prostate specific antigen (PSA) screening remains a widely used diagnostic test for prostate cancer, driving an urgent need for the discovery of better biomarkers for early prostate cancer detection. Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as a source of biomarkers. Methods EV from serum and urine of healthy men and prostate cancer patients were isolated, and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC-MS) analyses were conducted. Results There was a successful enrichment of exosomes isolated from serum and urine. EV derived from biological fluids of prostate cancer patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient. Conclusion Some of the EV proteins identified from our analyses have potential to be used as prostate cancer biomarkers, either to depict cancer progression or for disease diagnosis through non-invasive testing.
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- 2022
8. Correlation of immune-related adverse events and response from immune checkpoint inhibitors in patients with advanced non-small cell lung cancer
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Leila Khoja, Preet Walia, Alona Zer, Geoffrey Liu, Mike Sung, Catherine Labbé, Penelope A. Bradbury, Frances A. Shepherd, Manjula Maganti, and Natasha B. Leighl
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Brief Report ,Immune checkpoint inhibitors ,MEDLINE ,medicine.disease ,Immune system ,Internal medicine ,Medicine ,In patient ,Non small cell ,Adverse effect ,business ,Lung cancer - Published
- 2020
9. Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis
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Mabel Teng, Neil M. Stevens, Yi Pan, Douglas G. Ward, Eshetu G. Atenafu, Lara Gracie, Leila Khoja, and Lallit Pallan
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Oncology ,Cancer Research ,medicine.medical_specialty ,Metastatic melanoma ,business.industry ,Melanoma ,Hazard ratio ,Cochrane Library ,medicine.disease ,Pharmacodynamics ,Meta-analysis ,Internal medicine ,Medicine ,Biomarker (medicine) ,Digital polymerase chain reaction ,business - Abstract
Introduction : Circulating tumour DNA (ctDNA) is an emerging biomarker in melanoma. We performed a systematic review and meta-analysis to explore its clinical utility as a prognostic, pharmacodynamic (PD) and predictive biomarker. Methods A systematic search was conducted from Jan 2015 to April 2021, of the electronic databases PubMed, Cochrane Library and Ovid MEDLINE to identify studies. Studies were restricted to those published in English within the last 5 years, evaluating ctDNA in humans in ≥10 patients. Survival data were extracted for meta-analysis using pooled treatment effect (TE), i.e. log hazard ratios (HRs) and corresponding standard error of TE for progression-free survival or overall survival differences in patients who were ctDNA positive or negative. PRISMA statement guidelines were followed. Results A meta-analysis of 19 studies grouped according to methodology of ctDNA detection, revealed a combined estimate for HR of progression-free survival (13 studies using droplet digital Polymerase Chain Reaction (ddPCR) methodology (N = 1002) of 2.10 (95% CI: 1.71–2.59) revealing a poorer prognosis when ctDNA was detected. This result was confirmed in the smaller analysis of (non-ddPCR, N = 347) five studies: HR = 2.45 (95% CI: 1.29–4.63). Similar findings were found in the overall survival analysis of nine studies (ddPCR methodology, N = 841) where the combined HR was 2.78 (95% CI: 2.21–3.49) and of the five studies (non-ddPCR methodology, N = 326) where the combined HR was 2.58 (95% CI: 1.74–3.84). Serial ctDNA levels on treatment showed a pharmacodynamic role reflecting response or resistance earlier than radiological assessment. Conclusions : Circulating tumour DNA is a predictive, prognostic and PD biomarker in melanoma. Technical standardisation of assays is required before clinical adoption.
- Published
- 2021
10. Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2
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Anthony M. Joshua, Wey Leong, Habeeb Majeed, Ayman Al-Habeeb, Michael Reedijk, Pamela S. Ohashi, Michael Fyrsta, Diana Gray, Charlotte Lo, Stephanie Effendi, Pei Hua Yen, Samuel Saibil, Jennifer Y. Yam, Danny Ghazarian, Alexandra M. Easson, Aaron R. Hansen, Sarah Boross-Harmer, Michael X. Le, Jessica Nie, Kazuhiro Yasufuku, Ragitha Ellenchery, Leila Khoja, Megan E. Nelles, Linh T. Nguyen, Anna Spreafico, Elizabeth Scheid, Luisa Bonilla, Bianzheng Zhang, David P. Goldstein, Michael Crump, Marcus O. Butler, David Hogg, Thomas K. Waddell, Stephanie DeLuca, Jane Cipollone, Alisha R. Elford, Valentin Sotov, Lisa Wang, Naoto Hirano, Marcelo Cypel, Vinicius Motta, Andrew Pierre, David R. McCready, and Norman Franke
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Adult ,Male ,Oncology ,Interleukin 2 ,Cancer Research ,medicine.medical_specialty ,Adoptive cell transfer ,Skin Neoplasms ,medicine.medical_treatment ,Immunology ,Population ,chemical and pharmacologic phenomena ,Immunotherapy, Adoptive ,Cell therapy ,Lymphocytes, Tumor-Infiltrating ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Immunology and Allergy ,Neoplasm Metastasis ,education ,Melanoma ,Cells, Cultured ,Cell Proliferation ,Interleukin-15 ,Chemotherapy ,education.field_of_study ,Tumor-infiltrating lymphocytes ,business.industry ,Middle Aged ,Clinical trial ,Treatment Outcome ,Interleukin-2 ,Female ,business ,medicine.drug - Abstract
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vβ chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.).
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- 2019
11. Management of immune-related hepatitis in patients being treated with checkpoint inhibitors for metastatic melanoma, a review and case series
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Alice Tew, Leila Khoja, Lalit Pallan, and Neil Steven
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Oncology ,Pharmacology (medical) - Abstract
Introduction Immune-related hepatitis is an adverse effect following treatment with immune-checkpoint inhibitors, such as ipilimumab, nivolumab and pembrolizumab. International guidelines advise on the use of corticosteroids as first-line treatment, although guidance on how to treat cases resistant to corticosteroids is limited. We aimed to evaluate the presentation and management of patients with grade 3-4 immune-related hepatitis, following treatment with immune-checkpoint inhibitors for stage 4 or unresectable or stage 3 melanoma, with a particular focus on steroid-refractory cases. Methods A retrospective observational review of patients developing immune-related hepatitis whilst undergoing treatment with immune checkpoint inhibitors for advanced melanoma from July 2014 to February 2020 at a tertiary oncology centre. Results Forty-one patients developed immune-related hepatitis, of which 83% had been treated with the combination of ipilimumab and nivolumab. The median time to onset of IR-hepatitis was 47 days (range: 4–476), and the median time to peak alanine aminotransferase was 71 days (range: 4–478). Four patients had resolution of grade 3 immune-related hepatitis without the introduction of corticosteroids. A total of 37 patients were treated with corticosteroids. A total of 12 required oral treatment only and 13 were successfully managed as outpatients. Six patients had steroid-refractory immune-related hepatitis; and all received tacrolimus, with one also receiving mycophenolate mofetil and infliximab. Conclusions This study describes the largest UK series of immune-related hepatitis patients in the literature. We present two important deviations from current guidelines. Firstly, there is some evidence that withholding steroids is possible in grade 3-4 immune-related hepatitis. Secondly, tacrolimus can be used successfully to manage patients resistant to corticosteroids, with the early introduction most beneficial to reduce time on steroids.
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- 2022
12. Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases
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Luiza Moore, David J. Adams, Alejandro Jiménez-Sánchez, Mark Tullett, Laura Riva, Kim Wong, David C. Wedge, Martin L. Miller, Sarah J. Welsh, Doreen Lau, Christine Parkinson, Julia M. Martínez Gómez, Kieren Allinson, Pippa Corrie, Ingrid Ferreira, Francis Scott, Leila Khoja, Roy Rabbie, Naser Ansari-Pour, Peter J. Campbell, Mitchell P. Levesque, Ferdia A. Gallagher, Oliver Cast, Rabbie, Roy [0000-0002-9195-5659], Cast, Oliver [0000-0002-5880-7726], Lau, Doreen [0000-0002-7623-2401], Moore, Luiza [0000-0001-5315-516X], Wong, Kim [0000-0002-0984-1477], Ferreira, Ingrid [0000-0002-4321-5250], Gallagher, Ferdia A. [0000-0003-4784-5230], Miller, Martin L. [0000-0003-3161-8690], Campbell, Peter J. [0000-0002-3921-0510], Wedge, David C. [0000-0002-7572-3196], Adams, David J. [0000-0001-9490-0306], Apollo - University of Cambridge Repository, Gallagher, Ferdia A [0000-0003-4784-5230], Miller, Martin L [0000-0003-3161-8690], Campbell, Peter J [0000-0002-3921-0510], Wedge, David C [0000-0002-7572-3196], and Adams, David J [0000-0001-9490-0306]
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Male ,0301 basic medicine ,Oncology ,Skin Neoplasms ,Microarrays ,Biopsy ,DNA Mutational Analysis ,General Physics and Astronomy ,02 engineering and technology ,Disease ,Somatic evolution in cancer ,Metastasis ,631/114/2397 ,Computational models ,Prospective Studies ,lcsh:Science ,Melanoma ,Skin ,45/90 ,Multidisciplinary ,Phylogenetic tree ,medicine.diagnostic_test ,article ,49/39 ,021001 nanoscience & nanotechnology ,631/67/322 ,0210 nano-technology ,medicine.medical_specialty ,Génétique moléculaire ,Lineage (genetic) ,Tumour heterogeneity ,Science ,45/22 ,45/23 ,Biology ,631/67/1813/1634 ,631/67/2329 ,631/114/2407 ,General Biochemistry, Genetics and Molecular Biology ,Clonal Evolution ,Genetic Heterogeneity ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Whole Genome Sequencing ,Genetic heterogeneity ,General Chemistry ,medicine.disease ,Sciences humaines ,030104 developmental biology ,lcsh:Q - Abstract
Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy., Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
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- 2020
13. Multi-site clonality analyses uncovers pervasive subclonal heterogeneity and branching evolution across melanoma metastases
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Mitchell P. Levesque, Martin L. Miller, Ferdia A. Gallagher, Leila Khoja, Ingrid Ferreira, David C. Wedge, Peter J. Campbell, David J. Adams, Sarah J. Welsh, Kim Wong, Julia M. Martínez Gómez, Kieren Allinson, Doreen Lau, Roy Rabbie, Oliver Cast, Pippa Corrie, Luiza Moore, Laura Riva, Alejandro Jiménez-Sánchez, Christine Parkinson, Francis Scott, Mark Tullett, and Naser Ansari-Pour
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0303 health sciences ,Phylogenetic tree ,medicine.diagnostic_test ,Melanoma ,Multi site ,Single sample ,Disease ,Biology ,medicine.disease ,3. Good health ,Patient management ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Evolutionary biology ,030220 oncology & carcinogenesis ,Biopsy ,medicine ,030304 developmental biology - Abstract
Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal that metastatic cells may depart the primary tumour very early in the disease course and follow a branched pattern of evolution. Truncal UV-induced mutations that often swamp downstream analyses of heterogeneity, were found to be replaced by APOBEC-associated mutations in the branches of the evolutionary tree. Multi-sample analyses from a further 7 patients confirmed that branched evolution was pervasive, representing an important mode of melanoma dissemination. Our analyses illustrate that combining cancer cell fraction estimates across multiple metastases provides higher resolution phylogenetic reconstructions relative to single sample analyses and highlights the limitations of accurately inferring inter-tumoural heterogeneity from a single biopsy.
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- 2019
14. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review
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Leila Khoja, T. Wei-Wu Chen, Aaron R. Hansen, Daphne Day, and Lillian L. Siu
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Internal medicine ,medicine ,Lung cancer ,Adverse effect ,Pneumonitis ,biology ,business.industry ,Hematology ,Odds ratio ,medicine.disease ,Rash ,030104 developmental biology ,CTLA-4 ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Antibody ,medicine.symptom ,business - Abstract
Background Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class. Methods Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR),χ2 tests and multivariable regression models were used to analyse for effect size and associations. Results We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8–12.9), hypophysitis (OR 6.5, 95% CI 3.0–14.3) and rash (OR 2.0, 95% CI 1.8–2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2–12.7), hypothyroidism (OR 4.3, 95% CI 2.9–6.3), arthralgia (OR 3.5, 95% CI 2.6–4.8) and vitiligo (OR 3.5, 95% CI 2.3–5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials [melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis. Discussion CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
- Published
- 2017
15. An open-label, multicenter phase I/IIa study evaluating the safety and clinical activity of clonal neoantigen reactive T cells in patients with advanced non-small cell lung cancer (CHIRON)
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Martin Forster, Jane Robertson, Mariam Jamal-Hanjani, Karl S. Peggs, Michael M. Grant, Shreenal Patel, Alastair Greystoke, Jennifer Allison, Gary Middleton, Kim Orchard, Leila Khoja, Judith Cave, Christian H. Ottensmeier, Yvonne Summers, and Fiona C Thistlethwaite
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,In patient ,Non small cell ,Open label ,business ,Lung cancer ,medicine.disease - Abstract
TPS9138 Background: Lung cancer is the most common cause of cancer-related death worldwide with over 1.6 million deaths per year. Non-small cell lung cancer (NSCLC) accounts for 80% of cases, the majority of which are adenocarcinomas. 75% of patients present with inoperable tumours and/or with distant metastatic spread, with 5-year survival for stage IV disease as low as 5%. Treatment options include chemotherapy, targeted therapies for specific mutations, and - increasingly - immune checkpoint inhibitors (CPI). Adoptive cell therapies (ACT) can produce durable responses in pre-treated NSCLC. Evidence also suggests potential benefit of combining ACT with CPIs, even after acquired resistance. Efforts to improve efficacy include the expansion of T cells able to recognise patient-specific clonal tumour neoantigens. Clonal tumour neoantigens arise early in cancer evolution and represent a subset of patient-specific mutations present in all cancer cells. Developing ACTs that target clonal neoantigens represents a personalised approach to treating all cancer cells concurrently, minimising the risk of tumour escape and reducing potential for off-target toxicities. Insights gained from applying the PELEUS bioinformatic platform (developed using UK TRACERx study data) to matched tumour and blood samples from NSCLC patients – as part of a tissue acquisition study (NCT03517917) – has enabled the manufacture of a personalized clonal neoantigen-reactive T cell (cNeT) product (ATL001), which is now in clinical development. Methods: The CHIRON Study (NCT04032847), is a first-in-human, open-label, multi-centre, phase I/IIa study to characterise the safety and clinical activity of ATL001 administered intravenously in up to 40 adults with advanced unresectable or metastatic NSCLC. Following consent and screening, patients enter the study for procurement of tumor tissue and blood to manufacture ATL001. Tissue may be procured during treatment with standard systemic therapies. Patients in Cohort A receive cyclophosphamide/fludarabine on days -6 to -4, followed by a single dose of ATL001 and 10 daily doses of subcutaneous IL-2; Patients in Cohort B will additionally receive one dose of pembrolizumab between days -13 and -6 before receiving ATL001, then restart pembrolizumab 2 weeks after receiving ATL001 and continue for up to 12 months. Key eligibility criteria include treatment with at least one prior systemic therapy (including a PD-1 inhibitor). Primary endpoints are the safety and tolerability of ATL001 as a monotherapy and in combination with pembrolizumab. Secondary endpoints include change in tumor size and response rate by RECIST 1.1 and imRECIST. Correlative studies will investigate the effects of cNeT dose and engraftment kinetics on clinical activity. The study began enrolling patients in Cohort A in August 2019. Clinical trial information: NCT04032847.
- Published
- 2021
16. Significance of baseline FDG-PET/CT scan as a method of staging regional lymph nodes in patients with operable distal oesophageal or gastroesophageal junction adenocarcinoma
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Leila Khoja, Theodora Germetaki, Ana Patrao, Zoe Kordatou, Alia Alchawaf, George Papaxoinis, Sofia Stamatopoulou, Jamie M J Weaver, Vikki Owen-Holt, and Wasat Mansoor
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Adult ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,Adenocarcinoma ,030230 surgery ,Gastroesophageal Junction Adenocarcinoma ,Multimodal Imaging ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,medicine ,Overall survival ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Cancer ,Retrospective cohort study ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,Fdg pet ct ,Esophagogastric Junction ,Lymph Nodes ,Radiology ,Lymph ,Neoplasm Recurrence, Local ,Radiopharmaceuticals ,business - Abstract
The new American Joint Committee on Cancer eighth edition (AJCC8) staging is the first to describe separate clinical and pathology staging systems, but still has low performance to predict prognosis in patients with oesophageal/gastroesophageal junction (O/GOJ) adenocarcinoma, who are candidates for surgery. Recent studies have demonstrated that O/GOJ cancer patients with 18F-fluorodeoxyglucose (FDG) avid regional lymph nodes (RLNs) may have poor prognosis. The aim of our study was to examine whether the baseline assessment of the FDG uptake of RLN improves the prognostic accuracy of the new AJCC8 staging.This single-centre retrospective study included patients with operable FDG avid O/GOJ adenocarcinoma treated with perioperative chemotherapy. All patients were reclassified according to the new AJCC8 clinical staging. Prognostic factors for time-to-progression (TTP) and overall survival (OS) were explored.Of 430 patients included in the study, 180 (41.9%) had FDG avid RLN at baseline PET/CT scan before starting perioperative chemotherapy. The presence of FDG avid RLN was significantly and independently associated with shorter TTP and OS, especially in clinical stage III patients (p .001 in both cases). Stage III patients with FDG avid RLN had similar TTP and OS to those with stage IVA. Classifying stage III patients with FDG avid RLN into stage IVA led to a significant improvement of the prognostic accuracy of the new AJCC8 clinical staging system (Harrell's concordance index improved from 0.555 to 0.588, p .001). Of 430 patients starting perioperative chemotherapy, 332 underwent radical tumour resection. The presence of FDG avid RLN before starting perioperative chemotherapy could additionally predict a significantly shorter postoperative time-to-relapse and OS (p .001 in both cases).We propose that the incorporation of RLN status (by FDG PET/CT scan) into the AJCC8 staging system of O/GOJ adenocarcinoma improves its prognostic accuracy and may also improve treatment stratification.
- Published
- 2017
17. Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients
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Ur Metser, Marcus O. Butler, Craig Gedye, David Hogg, Leila Khoja, Eshetu G. Atenafu, Anthony M. Joshua, and Minnie Kibiro
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Antineoplastic Agents ,Pembrolizumab ,immune-related response criteria ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,melanoma ,medicine ,Humans ,Response Evaluation Criteria in Solid Tumors ,Aged ,Retrospective Studies ,Aged, 80 and over ,Lung ,business.industry ,checkpoint immunotherapy ,Melanoma ,biomarkers ,Retrospective cohort study ,Immunotherapy ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,RECIST ,Oncology ,030220 oncology & carcinogenesis ,Monoclonal ,Clinical Study ,Female ,medicine.symptom ,business - Abstract
Background: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS). Methods: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined. Results: Response varied according to site; lung lesions had the highest rate of complete response (69 out of 163 (42%) vs other sites 71 out of 404 (18%), P
- Published
- 2016
18. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study
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Anthony M. Joshua, Eshetu G. Atenafu, Poulam M. Patel, L. de Vries, Sophie Piperno-Neumann, Serge Leyvraz, Nicolas Penel, Stefan Suciu, Leila Khoja, Sandip Pravin Patel, P. Huppert, G. Fiorentini, Ulrich Keilholz, Ernie Marshall, L. B. J. Van Iersel, Claudia Pfoehler, Lisa Zimmer, Takami Sato, Ahmad A. Tarhini, T. Vogl, Shailender Bhatia, Richard D. Carvajal, Tina Cheng, Tero Kivelä, Josep M. Piulats, Frédéric Mouriaux, Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Institut Curie [Paris], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Princess Margaret Hospital, University of Toronto, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), HUS Head and Neck Center, Department of Ophthalmology and Otorhinolaryngology, Silmäklinikka, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Medische Oncologie (9)
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Male ,Uveal Neoplasms ,0301 basic medicine ,Oncology ,Time Factors ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Medizin ,Datasets as Topic ,Phases of clinical research ,CHOROIDAL MELANOMA ,Kaplan-Meier Estimate ,Metastasis ,0302 clinical medicine ,STAGE-IV MELANOMA ,Prospective Studies ,Prospective cohort study ,Melanoma ,Aged, 80 and over ,Clinical Trials as Topic ,survival benchmarks ,Liver Neoplasms ,TEMOZOLOMIDE ,Hematology ,Middle Aged ,Prognosis ,Progression-Free Survival ,3. Good health ,Benchmarking ,Research Design ,030220 oncology & carcinogenesis ,CHEMOEMBOLIZATION TACE ,Female ,medicine.symptom ,uveal melanoma ,PHASE-II TRIAL ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,3122 Cancers ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,LIVER METASTASES ,Young Adult ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Sex Factors ,Metàstasi ,Internal medicine ,medicine ,Humans ,3125 Otorhinolaryngology, ophthalmology ,Progression-free survival ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,COMBINATION ,Aged ,Temozolomide ,L-Lactate Dehydrogenase ,business.industry ,Cancer ,Alkaline Phosphatase ,medicine.disease ,Elevated alkaline phosphatase ,meta-analysis ,1ST-LINE TREATMENT ,030104 developmental biology ,trial design ,INTRAARTERIAL ,business ,GEMCITABINE PLUS TREOSULFAN - Abstract
International audience; BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus
- Published
- 2019
19. 1143P Nivolumab and ipilimumab (N+I) is active in patients (pts) with metastatic uveal melanoma (mUM) with extra-hepatic only involvement: Pooled analysis from 2 phase II trials
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Srujal Patel, M.S. Pelster, E. Espinosa, Anthony M. Joshua, C. Tebe, J.M. Piulats Rodriguez, L. de la Cruz Merino, Leila Khoja, and Alfonso Berrocal
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Ipilimumab ,Hematology ,medicine.disease ,Pooled analysis ,Internal medicine ,medicine ,In patient ,Nivolumab ,business ,medicine.drug - Published
- 2020
20. Prognostic factors for first-line therapy and overall survival of metastatic uveal melanoma: The Princess Margaret Cancer Centre experience
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Eshetu G. Atenafu, David Hogg, Leila Khoja, Marcus O. Butler, Mathew N Nicholas, Anthony M. Joshua, and Ian Quirt
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Oncology ,Adult ,Male ,Uveal Neoplasms ,Cancer Research ,medicine.medical_specialty ,Canada ,Skin Neoplasms ,Adolescent ,medicine.medical_treatment ,Lymphocyte ,Dermatology ,Metastasis ,Targeted therapy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Young adult ,Child ,Melanoma ,Survival analysis ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,030221 ophthalmology & optometry ,Absolute neutrophil count ,Female ,business - Abstract
Metastatic uveal melanoma (MUM) has a poor prognosis, with no established standard of care. Delineation of prognostic factors in MUM patients may enable stratified treatment algorithms of stage-specific survival. Overall, 132 MUM patients who presented to a single tertiary institution in Toronto, Canada, over 12 years were identified and data (demographics, clinical status, radiographic images, and laboratory values) were extracted. Associations with systemic first-line treatment outcome 12 weeks after first-line treatment, time to progression (TTP), and overall survival (OS) were explored by univariate and multivariable analysis. Age, presence of liver metastases, and time from primary presentation to metastatic presentation were significant variables affecting first-line treatment outcomes. Age, Eastern Cooperative Oncology Group (ECOG) score, presence of liver metastases, liver metastasis size, neutrophil lymphocyte ratio, absolute neutrophil count, lactate dehydrogenase (LDH), alkaline phosphatase, time from primary presentation to metastatic presentation, and patients receiving surgery as the first-line treatment were significant variables affecting TTP. Age, ECOG score, presence of liver metastases, liver metastasis size, neutrophil lymphocyte ratio, absolute neutrophil count, LDH, and alkaline phosphatase were significant variables affecting OS. Patients who underwent surgery, chemotherapy, immunotherapy, liver-directed therapy, or targeted therapy had better OS compared with patients not receiving treatment with surgery, associated with a significantly better OS compared with all other therapies. Multivariable analysis showed increased age, absence of liver metastases, and absence of bone metastases to be associated with positive treatment outcomes. ECOG score of at least 1, increased LDH, and decreased time from primary to metastatic presentation would predict decreased TTP. Increased LDH, older age, and ECOG score of at least 1 were associated with decreased OS. These results identified prognostic markers and models thereof of treatment benefit and survival. Further validation in larger cohorts is required.
- Published
- 2018
21. Association between Condylar Bone Changes and Eichner Index in Patients with Temporomandibular Dysfunction: A Cone Beam Computed Tomography Study
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Maryam Paknahad, Leila Khojastepour, Salma Tabatabaei, and Mohammad Mahjoori-Ghasrodashti
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cone beam computed tomography ,eichner index ,temporomandibular joint ,temporomandibular joint disorders ,Medicine ,Dentistry ,RK1-715 - Abstract
Statement of the Problem: Eichner index is a dental index, which is based on the occlusal contacts between naturally existing teeth in premolar and molar regions. One controversial topic is the association between occlusal status and temporomandibular joint dysfunction (TMD) and its associated degenerative bony changes.Purpose: Through the use of cone-beam computer tomography (CBCT), the current study sought to ascertain the relationship between the Eichner index and condylar bone alterations in TMD patientsMaterials and Method: In this retrospective study, the CBCT images of bilateral temporomandibular joints (TMJs) of 107 patients with TMD were evaluated. The patients’ dentition was classified into three groups of A (71%), B (18.7%), and C (10.3%), according to the Eichner index. Radiographic indicators of condylar bone alterations, including as flattening, erosion, osteophytes, marginal sclerosis, subchondral sclerosis, and joint mice, were either present or absent and registered as 1 or 0, respectively. Chi-square test was used to evaluate the link between the condylar bony changes and the Eichner groupsResults: According to the Eichner index, the most prevalent group was group “A”. The most prevalent radiographic finding was “flattening of the condyles” (58%). Condylar bony changes were found to be statistically related to age (p= 0.00). However, no significant relationship was found between sex and condylar bony changes (p= 0.80). There was a significant relationship between the Eichner index and condylar bony changes (p= 0.05).Conclusion: Patients with greater loss of tooth supporting zones have more condylar bony changes.
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- 2023
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22. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance
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Ulrich Keilholz, Paul Lorigan, Leila Khoja, Caroline Dive, and Alberto Fusi
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Oncology ,medicine.medical_specialty ,Skin Neoplasms ,business.industry ,Eye Neoplasms ,Melanoma ,Ocular Melanoma ,Cancer ,Mucous membrane ,Hematology ,Disease ,Neoplastic Cells, Circulating ,medicine.disease ,Malignancy ,Circulating tumor cell ,medicine.anatomical_structure ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Clinical significance ,business ,neoplasms - Abstract
Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.
- Published
- 2015
23. AR Signaling and the PI3K Pathway in Prostate Cancer
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Leila Khoja, Megan Crumbaker, and Anthony M. Joshua
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,AR signaling ,medicine.drug_class ,Disease ,Review ,PI3K ,Pathogenesis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Treatment resistance ,PI3K/AKT/mTOR pathway ,business.industry ,Mechanism (biology) ,Androgen ,medicine.disease ,prostate cancer ,Androgen receptor ,030104 developmental biology ,030220 oncology & carcinogenesis ,castrate resistant prostate cancer ,business - Abstract
Prostate cancer is a leading cause of cancer-related death in men worldwide. Aberrant signaling in the androgen pathway is critical in the development and progression of prostate cancer. Despite ongoing reliance on androgen receptor (AR) signaling in castrate resistant disease, in addition to the development of potent androgen targeting drugs, patients invariably develop treatment resistance. Interactions between the AR and PI3K pathways may be a mechanism of treatment resistance and inhibitors of this pathway have been developed with variable success. Herein we outline the role of the PI3K pathway in prostate cancer and, in particular, its association with androgen receptor signaling in the pathogenesis and evolution of prostate cancer, as well as a review of the clinical utility of PI3K targeting.
- Published
- 2017
24. Malignant bowel obstruction in advanced ovarian cancer
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Andrew R Clamp, Jurjees Hasan, Gordon C Jayson, Leila Khoja, D Goonetilleke, Alicia M Conway, and Emma Dean
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Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Kaplan-Meier Estimate ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Overall survival ,Humans ,In patient ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,Ovarian Neoplasms ,Chemotherapy ,Advanced ovarian cancer ,030219 obstetrics & reproductive medicine ,business.industry ,Disease Management ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Bowel obstruction ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Ovarian cancer ,business ,Intestinal Obstruction - Abstract
Aim: Malignant bowel obstruction (MBO) in ovarian cancer is poorly understood. Methods: This retrospective cohort study analyzed 129 patients with ovarian cancer and MBO. Results: At presentation, 69 (53%) had platinum-resistant, 37 (29%) platinum-sensitive and 23 (18%) chemotherapy-naive disease. In patients receiving chemotherapy following the MBO episode, median overall survival (OS) was 107 days for chemotherapy-naive patients compared with 83 and 86 for platinum-sensitive or platinum-resistant patients (p = 0.98). OS was inferior for best supportive care (45 days) compared with chemotherapy (152 days) or surgery (124 days; p < 0.001). The Manchester Bowel Obstruction Score using Eastern Cooperative Oncology Group and obstruction level discriminated patients by median OS of 181 days (neither) versus 98 days (one) versus 42 days (both; p < 0.01). Conclusion: The Manchester Bowel Obstruction Score may aide treatment stratification.
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- 2017
25. Circulating biomarkers in hepatocellular carcinoma
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Juan W. Valle, Karen Morris, Atsuhiko Katoh, Caroline Dive, Jonathan Tugwood, Clare Hodgson, Matthew Lancashire, Debbie Burt, Robert Sloane, Cong Zhou, Leila Khoja, Takahiro Ishiguro, Patrick Shenjere, and Toshihiko Ohtomo
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cell Separation ,Biology ,Toxicology ,Keratin 18 ,Immunoenzyme Techniques ,Cytokeratin ,Glypicans ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Pharmacology (medical) ,Stage (cooking) ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Pharmacology ,Univariate analysis ,Keratin-18 ,Liver Neoplasms ,Cancer ,Middle Aged ,Neoplastic Cells, Circulating ,Prognosis ,medicine.disease ,Circulating biomarkers ,Hepatocellular carcinoma ,Immunohistochemistry ,Female ,Follow-Up Studies - Abstract
Our aims are to determine levels of circulating cellular and protein biomarkers in hepatocellular carcinoma (HCC) patients and to analyse any relationships with clinical parameters. Fifty-four consenting patients were recruited. Circulating tumour cells (CTCs) were enumerated (by CellSearch) and characterised via filtration [by isolation by size of epithelial tumour cells (ISET)] with downstream immunohistochemistry (IHC). Glypican-3 (GPC3) expression in tumour biopsies and CTCs (by IHC) was compared, and levels of circulating caspase-cleaved and full-length cytokeratin 18 (CK18, measured using M30 and M65 ELISAs) were examined as a putative prognostic factor and marker of tumour burden. CTCs were identified in 14 out of 50 (28 %) patients by CellSearch and in 19 out of 19 (100 %) patients by ISET. The presence of GPC3-positive CTCs by ISET was 100 % concordant with the presence of GPC3-positive cells in the original tumour (n = 5). No statistically significant correlations were observed between CTC number and clinical characteristics, although trends were noted between CTC subtypes, Child–Pugh score and tumour node metastasis stage. Serum M30 and M65 levels (as continuous variables) significantly correlated with overall survival (OS) in a univariate analysis (p = 0.003 and p
- Published
- 2014
26. Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma
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Paul Lorigan, Andrew Hughes, Patrick Shenjere, Caroline Dive, Clare Hodgson, Glen Clack, Jackie Hodgetts, and Leila Khoja
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Metastatic Cutaneous Melanoma ,Tumour heterogeneity ,Dermatology ,Biology ,Immunophenotyping ,Genetic Heterogeneity ,Circulating tumor cell ,Antigen ,Biomarkers, Tumor ,Prevalence ,medicine ,Humans ,Melanoma ,Aged ,Aged, 80 and over ,Genetic heterogeneity ,Middle Aged ,Neoplastic Cells, Circulating ,Oncology ,Biological significance ,Immunohistochemistry ,Female - Abstract
We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients' blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1-44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100- CTCs, 11 patients' CTCs were S100+ and 33 patients had S100+ and S100- CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity.
- Published
- 2014
27. Assessing the efficacy of a modified crushing technique for the management of concha bullosa: a cone beam computer tomography study
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Alireza Mesbahi, Najmeh Movahhedian, Fatemeh Akbarizadeh, Amir A. Hakimi, and Leila Khojastepour
- Subjects
Concha bullosa ,Crushing ,Technique ,Cone beam computed tomography ,Otorhinolaryngology ,RF1-547 - Abstract
Introduction: Although many surgical techniques exist to manage obstructive concha bullosa, there continues to be a drive to find the least invasive technique with the fewest complications and best results. Objectives: The purpose of this study is to describe and assess the short- and long-term efficacy of a modified crushing technique for concha bullosa management. Methods: Patients who met inclusion criteria underwent a detailed nasal examination and cone beam computed tomography imaging prior to and after septoplasty with crushing surgery for obstructive concha bullosa. Patients were divided into short- and long-term groups based on their followup period such that the short-term group had a mean followup of 15.14 months (range 6–22 months) and the long-term group had a mean followup of 56.66 (range 29–80) months. Results: Twenty-four cases of obstructive concha bullosa were included in this study with 13 short-term and 11 long-term follow-ups. All patients showed a significantly decreased postoperative CB size (p
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- 2022
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28. Phase I clinical and translational evaluation of AZD6738 in combination with durvalumab in patients (pts) with lung or head and neck carcinoma
- Author
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Sophie Postel-Vinay, Christine Stephens, Juanita Lopez, Emma Dean, Amy Cheung, Paul Frewer, Andrew J. Pierce, Nathan Standifer, Simon J. Hollingsworth, S.-A. Im, Gemma N Jones, Y.-J. Bang, Leila Khoja, Alienor Berges, Brunella Felicetti, Anthony B. El-Khoueiry, Paola Marco-Casanova, W. Abidah, and Matthew G Krebs
- Subjects
0301 basic medicine ,Brachial Plexus Neuritis ,medicine.medical_specialty ,Lung ,Durvalumab ,business.industry ,Hematology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,medicine ,Carcinoma ,In patient ,Radiology ,business ,Head and neck ,Head and neck carcinoma - Published
- 2018
29. P3.04-20 Correlation of Immune-Related Adverse Events and Response from Immune Checkpoint Inhibitors in Patients with Advanced NSCLC
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G. Liu, Natasha B. Leighl, Catherine Labbé, Frances A. Shepherd, P. Walia, P. A. Bradbury, Leila Khoja, Alona Zer, Manjula Maganti, and Mike Sung
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,business.industry ,Immune checkpoint inhibitors ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Medicine ,In patient ,business ,Adverse effect - Published
- 2018
30. Determining the existence of the foramen of Huschke in patients with temporomandibular joint disorders using cone beam computed tomography: retrospective cohort study
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Mahvash Hasani, Abdolaziz Haghnegahdar, Leila Khojastepour, and Mohammad Javad Golbahar Haghighi
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Foramen of Huschke ,External auditory canal ,Temporomandibular disorders ,Cone beam computed tomography ,Medical technology ,R855-855.5 - Abstract
Abstract Background Foramen of Huschke has been presented as an unusual developmental defect in anteroinferior aspect of external auditory canal. It can be associated with significant otologic complications. The purpose of this study was to determine the association between existence of foramen of Huschke and temporomandibular joint disorders in Cone Beam Computed Tomography (CBCT) images. Methods Of an initial sample of 465 patients, we retrospectively evaluated the CBCT images of 118 individuals with clinical signs and symptoms of temporomandibular joint disorders as case group and 256 individuals as control group. The presence, size and localization of foramen of Huschke were assessed in the axial and corrected sagittal images. The sex and age distribution were determined. Fisher’s exact test, T-test and Pearson’s Chi-square were applied to assess the relationship between foramen of Huschke and temporomandibular joint disorders in the case and control groups considering age and sex. Results The foramen of Huschke prevalence was slightly higher in patients with temporomandibular joint disorders (3.4%) than patients without temporomandibular joint disorders (0.8%). However, the difference was not statistically significant (P = 0.082). foramen of Huschke was found in five females and one male. There was no significant difference between case and control groups considering the age of patients with foramen of Huschke (P = 0.683). There was no significant difference between the case and control groups, considering the right and left ears in distribution of foramen of Huschke (P = 0.099) (P = 0.183). Conclusions Higher prevalence of foramen of Huschke in patients with temporomandibular joint disorders may suggest possible mechanism for temporomandibular joint disorders development that can be affected by presence of foramen of Huschke.
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- 2022
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31. Biomarker Utility of Circulating Tumor Cells in Metastatic Cutaneous Melanoma
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Jeffrey Cummings, Raffaele Califano, Andrew Hughes, Caroline Dive, Jessica Booth, Glen Clack, Leila Khoja, Paul Lorigan, Matthew Lancashire, and Cong Zhou
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Pathology ,Skin Neoplasms ,Dermatology ,Biochemistry ,Circulating tumor cell ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,Prevalence ,medicine ,Humans ,Melanoma ,neoplasms ,Molecular Biology ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Univariate analysis ,business.industry ,Proportional hazards model ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,Cell Biology ,Middle Aged ,Neoplastic Cells, Circulating ,Prognosis ,medicine.disease ,Predictive value of tests ,Multivariate Analysis ,Biomarker (medicine) ,Female ,Reagent Kits, Diagnostic ,Drug Monitoring ,business - Abstract
The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P
- Published
- 2013
32. Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial
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A. Douglas Laird, Arun Azad, Raanan Berger, Anthony M. Joshua, Raya Leibowitz-Amit, Dana T. Aftab, Melania Pintilie, Leila Khoja, and Kim N. Chi
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,C-Met ,Cabozantinib ,Pyridines ,Statistics, Nonparametric ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Post-hoc analysis ,Biomarkers, Tumor ,medicine ,Humans ,Anilides ,Neoplasm Metastasis ,c-MET ,Medicine(all) ,Clusterin ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Research ,Reproducibility of Results ,Biomarker ,General Medicine ,Middle Aged ,Hypoxia (medical) ,medicine.disease ,VEGF ,Clinical trial ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Biomarker (medicine) ,medicine.symptom ,business ,VEFR - Abstract
Background Cabozantinib is an orally available inhibitor of tyrosine kinases including VEGFR2 and c-MET. We performed a post hoc analysis to find associations between select plasma biomarkers and treatment response in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) who received cabozantinib 100 mg daily as part of a phase 2 non-randomized expansion cohort (NCT00940225). Methods Plasma samples were collected at baseline, 6 weeks and at time of maximal response from 81 mCRPC pts with bone metastases, of which 33 also had measurable soft-tissue disease. Levels of 27 biomarkers were measured in duplicate using enzyme-linked immunosorbent assay. Spearman correlation coefficients were calculated for the association between biomarker levels or their change on treatment and either bone scan response (BSR) or soft tissue response according to RECIST. Results A BSR and RECIST response were seen in 66/81 pts (81 %) and 6/33 pts (18 %) respectively. No significant associations were found between any biomarker at any time point and either type of response. Plasma concentrations of VEGFA, FLT3L, c-MET, AXL, Gas6A, bone-specific alkaline phosphatase, interleukin-8 and the hypoxia markers CA9 and clusterin significantly increased during treatment with cabozantinib irrespective of response. The plasma concentrations of VEGFR2, Trap5b, Angiopoietin-2, TIMP-2 and TIE-2 significantly decreased during treatment with caboznatinib. Conclusions Our data did not reveal plasma biomarkers associated with response to cabozantinib. The observed alterations in several biomarkers during treatment with cabozantinib may provide insights on the effects of cabozantinib on tumor cells and on tumor micro-environment and may help point to potential co-targeting approaches.
- Published
- 2016
33. Does clinical trial participation improve outcomes in patients with ovarian cancer?
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J D Machin, Laura Horsley, Andrew R Clamp, Jurjees Hasan, Claire Mitchell, A Heesters, Gordon C Jayson, and Leila Khoja
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Cancer Research ,medicine.medical_specialty ,Performance status ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,trial effect ,Cancer ,Retrospective cohort study ,medicine.disease ,Health outcomes ,Clinical trial ,ovarian cancer ,Oncology ,Internal medicine ,outcome ,medicine ,Physical therapy ,In patient ,Stage (cooking) ,Ovarian cancer ,business ,Original Research - Abstract
Introduction: Treatment on a clinical trial isconsidered to be beneficial to oncology patients.However, supportive evidence for this is scarce. Trialeffect describes the phenomenon of improved healthoutcomes in patients treated with standard of care(SOC) on trial compared to those receiving SOCoutside of a clinical trial. We evaluated trial effect inpatients with ovarian cancer treated at our tertiarycancer centre.Methods: We performed a retrospective cohort studyof patients with ovarian cancer treated at The ChristieNational Health Service Foundation Trust. Patientstreated on one of three first-line clinical trials:(SCOTROC-4, ICON-5, ICON-7) were matched (for age,International Federation of Gynaecology and Obstetricsstage, surgical status and performance status) withindividuals receiving the same SOC off trial. Survivalwas calculated using Kaplan-Meier methodology.Results: 60 patients were evaluated; 30 on trial and30 on SOC off trial. The median progression-freesurvival (PFS) was 21.8 months (control group) and25.9 months (trial group), median overall survival (OS)was 64.3 months (control group) and 68.9 months(trial group). There was no difference in PFS (log-ranktest: HR 0.87 (95% CI 0.48 to 1.54), p=0.6) or OS(log-rank test: HR 0.87 (95% CI 0.46 to 1.64), p=0.7)between groups.Conclusions: Patient survival was similar regardless iftreated on trial or as SOC. Our findings do not supporttrial effect, at least in a tertiary cancer centre. Clinicaltrial participation in specialised cancer centrespromotes best practice to the benefit of all patients.These findings may impact discussions round consentof patients to trials and organisation of oncologyservices.
- Published
- 2016
34. Improved survival from ovarian cancer in patients treated in Phase III trial active cancer centres in the UK
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Nerissa Mescallado, Henry C Kitchener, Brett Winter-Roach, Jonathan A. Ledermann, Gordon C Jayson, Leila Khoja, Jurjees Hasan, A Milani, Timothy J. Perren, T Mould, K Nolan, Richard Hutson, R Mekki, Geoffrey Hall, Richard J. Edmondson, Linda Ashcroft, and Andrew R Clamp
- Subjects
medicine.medical_specialty ,survival outcomes ,Improved survival ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,030212 general & internal medicine ,UK ,Aged ,Ovarian Neoplasms ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Cancer ,clinical trial ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,Clinical trial ,ovarian cancer ,Oncology ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Cancer centre ,Female ,prognosis ,Ovarian cancer ,business ,Developed country ,Median survival - Abstract
AimsOvarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally.Materials and methodsData from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres.ResultsThe analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9–73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres.ConclusionThe data suggest that international survival statistics are achieved in UK regional cancer centres.
- Published
- 2016
35. P3.02c-076 Correlation of Neutrophil to Lymphocyte Ratio (NLR) with Clinical Benefit from Checkpoint Inhibitors in Advanced Lung Cancer
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Leila Khoja, Ronald Feld, Frances A. Shepherd, Alona Zer, Manjula Maganti, Dianne Zawisza, Catherine Labbé, Natasha B. Leighl, Penelope A. Bradbury, Kanwalpreet Walia, Nazanin Nouriany, Melissa Iazzi, Mike Sung, and Geoffrey Liu
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,business.industry ,Immune checkpoint inhibitors ,Immunology ,medicine ,Cancer research ,Neutrophil to lymphocyte ratio ,Lung cancer ,medicine.disease ,business - Published
- 2017
36. A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker
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Robert Sloane, Ruth E Board, Fiona H Blackhall, Glen Clack, Leila Khoja, Lia P Menasce, W David J Ryder, Alison Backen, Andrew Hughes, Caroline Dive, Matthew G Krebs, and Juan W. Valle
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,Pathology ,medicine.medical_specialty ,circulating tumour cells ,pancreatic cancer ,Pilot Projects ,Vimentin ,Adenocarcinoma ,chemistry.chemical_compound ,Predictive Value of Tests ,tumour biopsy ,Pancreatic cancer ,Internal medicine ,ISET ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Molecular Diagnostics ,Survival analysis ,Aged ,Aged, 80 and over ,CellSearch ,biology ,circulating tumour microemboli ,Mesenchymal stem cell ,Epithelial cell adhesion molecule ,Middle Aged ,Neoplastic Cells, Circulating ,medicine.disease ,Survival Analysis ,Pancreatic Neoplasms ,England ,chemistry ,biology.protein ,Biomarker (medicine) ,Female - Abstract
Background: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. Patients and methods: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. Results: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0–240) vs 0 (range 0–144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. Conclusion: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.
- Published
- 2011
37. Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer
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Catherine Labbé, Penelope A. Bradbury, Ronald Feld, Nazanin Nouriany, Manjula Maganti, Preet Walia, Geoffrey Liu, Melissa Iazzi, Natasha B. Leighl, Leila Khoja, Alona Zer, Frances A. Shepherd, Dianne Zawisza, and Mike R. Sung
- Subjects
Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Neutrophils ,medicine.medical_treatment ,Lymphocyte ,Adenocarcinoma ,Gastroenterology ,B7-H1 Antigen ,Correlation ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Platelet ,Lymphocytes ,Prospective Studies ,Neutrophil to lymphocyte ratio ,Lung cancer ,Aged ,Aged, 80 and over ,business.industry ,Cancer ,Immunotherapy ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Absolute neutrophil count ,Carcinoma, Large Cell ,Female ,business ,Follow-Up Studies - Abstract
Introduction Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non–small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. Materials and Methods The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD-1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. Results Of 88 patients treated with PD-1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD-L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. Conclusion Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies.
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- 2018
38. Changes in the pharyngeal airway after different orthognathic procedures for correction of class III dysplasia
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Mohammad Saleh Khaghaninejad, Leila Khojastehpour, Hossein Danesteh, Mehdi Changizi, and Farzaneh Ahrari
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Orthognathic surgery ,Pharyngeal airway ,Class III malocclusion ,Oropharynx ,Airway obstruction ,Maxillary advancement ,Dentistry ,RK1-715 ,Surgery ,RD1-811 - Abstract
Abstract Objective This study was conducted to compare changes in pharyngeal airway after different orthognathic procedures in subjects with class III deformity. Methods The study included CBCT scans of 48 skeletal class III patients (29 females and 19 males, mean age 23.50 years) who underwent orthognathic surgery in conjunction with orthodontic treatment. The participants were divided into three groups of 16, as follows: Group 1, mandibular setback surgery; group 2, combined mandibular setback and maxillary advancement surgery; and group 3, maxillary advancement surgery. CBCT images were taken 1 day before surgery (T0), 1 day (T1), and 6 months (T2) later. The dimensions of the velopharynx, oropharynx, and hypopharynx were measured in CBCT images. Results In all groups, there was a significant decrease in airway variables immediately after surgery, with a significant reversal 6 months later (P
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- 2022
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39. An open-label, multidrug, biomarker-directed, multicentre phase II umbrella study in patients with non-small cell lung cancer, who progressed on an anti-PD-1/PD-L1 containing therapy (HUDSON)
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Leila Khoja, Sabina Patel, Peter G. Mortimer, Helen Ambrose, Benjamin Besse, Michael Thomas, Philip J. Jewsbury, Mark M. Awad, Naiyer A. Rizvi, John V. Heymach, Glenwood D. Goss, Kris Sachsenmeier, Si-Houy Lao-Sirieix, Wolfram Brugger, Patrick M. Forde, and Keunchil Park
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Anti pd 1 ,Improved survival ,medicine.disease ,respiratory tract diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,PD-L1 ,Internal medicine ,medicine ,biology.protein ,Biomarker (medicine) ,In patient ,Non small cell ,Open label ,Lung cancer ,business - Abstract
TPS3120Background: Immune checkpoint inhibitor (ICI) containing regimens have significantly improved survival outcomes in first- and second-line non-small cell lung cancer (NSCLC). However, the maj...
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- 2018
40. Increased treatment-related toxicity subsequent to an anti-PD-1 agent
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Marcus O. Butler, Anthony M. Joshua, David Hogg, Mary Anne Chappell, and Leila Khoja
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Trametinib ,medicine.medical_specialty ,business.industry ,Dabrafenib ,Ipilimumab ,Pembrolizumab ,Rash ,Gastroenterology ,Surgery ,Internal medicine ,medicine ,Maculopapular rash ,medicine.symptom ,Nivolumab ,Vemurafenib ,business ,Letter to the Editor ,medicine.drug - Abstract
The Editor Current Oncology 6 May 2015 The approval of ipilimumab1 and, subsequently, the braf inhibitors vemurafenib2 and dabrafenib3 for the treatment of metastatic melanoma has improved survival in this hitherto often fatal disease. However, resistance to those agents limits efficacy. The keynote-001 phase i study evaluated the use of pembrolizumab, an anti–PD-1 antibody in metastatic melanoma, in treatment-naive and refractory disease. A range of doses and schedules were evaluated: 2 mg/kg 3 weekly, 10 mg/kg 3 weekly, and 10 mg/kg 2 weekly4–6. Efficacy and safety with all doses were similar and favourable. Pembrolizumab (2 mg/kg every 3 weeks) is now approved by the U.S. Food and Drug Administration for treatment-refractory metastatic melanoma, providing a further line of therapy in a difficult-to-treat population. Recently, preliminary results from the first-line keynote-006 phase iii trial (comparing pembrolizumab at 10 mg/kg on 2 weekly and 3 weekly schedules with ipilimumab as the standard arm) showed superior survival in pembrolizumab-treated patients7. Given the significant activity of first-line pembrolizumab, it is likely that this drug will be used earlier in a patient’s treatment trajectory. The optimum sequencing of immunotherapy and targeted therapy is yet to be determined8. Decisions about the sequencing of the anti–PD-1 antibodies—either off-trial or after trial enrolment once disease progression occurs—currently remain unclear. We treated 8 patients on the phase i trial with pembrolizumab, a high-affinity human immunoglobulin G4 monoclonal antibody against PD-1, with a half-life of 2–3 weeks. All 8 patients were later switched to other agents on disease progression: 3 patients were BRAF-mutant and received vemurafenib; 5 were BRAF-negative and received ipilimumab (Table i details patient characteristics and treatment toxicities). Of the 3 BRAF-mutant patients, all 3 had a grade 3 maculopapular rash that occurred within 4 weeks of stopping pembrolizumab and starting vemurafenib. Vemurafenib was discontinued, and all 3 were treated with high-dose steroids (1 patient also had concurrent grade 2 pyrexia requiring inpatient care). The rash completely resolved over 2 weeks, and treatment with dabrafenib was started thereafter in 2 patients. One patient had no recurrence of toxicity, but another developed possible Guillain–Barre syndrome (and remains under investigative workup) 2 months later (3 months after stopping pembrolizumab). The third patient restarted vemurafenib at a reduced dose of 720 mg twice daily, which was well tolerated. In the patients that went on to receive ipilimumab, 4 of 5 had immune-related side effects of fevers, diarrhea (with 1 case of colitis requiring infliximab treatment), and hepatitis. Additionally, 1 patient had a 24-hour episode of unexplained encephalopathy that spontaneously resolved within 48 hours in hospital. Those toxicities all occurred within 7 weeks of treatment—that is, within the 1st or 2nd cycle of treatment with ipilimumab. Of the 8 patients described, 3 had an immune-related side effect with pembrolizumab: thyroiditis that progressed to hypothyroidism requiring treatment by week 8 of pembrolizumab therapy. Autoantibody profiling (for thyroid and antinuclear antibodies during treatment with pembrolizumab) did not correlate with development of toxicity either on pembrolizumab or on subsequent agents (data not shown). Of our patients reported here, 2 received 2 mg/kg every 3 weeks, the dose going forward for the treatment of metastatic melanoma. TABLE I Patient characteristics, treatment, and subsequent toxicities Grade 3 rash is not uncommon with single-agent vemurafenib. The incidence of grade 3 rash in the brim 3 trial was 8%2. Skin toxicities are reported to be lower with dabrafenib than they are with vemurafenib, and maculopapular rashes were not reported in the break-3 trial3. As in our experience, the increased incidence of rash was seen in patients sequentially treated with ipilimumab and then vemurafenib, where patients were successfully re-challenged with vemurafenib at lower doses9. Increased toxicity with vemurafenib has also been reported post nivolumab, another PD-1 inhibitor, and skin biopsies in those patients showed a dermal hypersensitivity reaction10. Now that dabrafenib is also a standard of care, the choice of a braf-targeted therapeutic could be dictated by its toxicity profile. Although immune-related toxicities are well documented with ipilimumab, the incidence of several toxicities in the same patient is more unusual. Neurologic toxicities—most commonly neuropathies and case reports of aseptic meningitis or encephalopathy—secondary to ipilimumab alone have been reported11. The mechanisms dictating increased toxicity with vemurafenib post anti–PD-1 treatment are unclear. There is evidence to show increased tumour infiltration after braf inhibition12. An activated immune response by PD-1 inhibition before either vemurafenib or ipilimumab might well result in increased immunomodulation and toxicity thereof. Trials are ongoing with respect to combinations of checkpoint inhibitors either alone (https://clinicaltrials.gov/ct2/show/NCT01844505) or in combination with targeted agents such as dabrafenib and trametinib (https://clinicaltrials.gov/ct2/show/NCT01767454), and in sequencing (https://clinicaltrials.gov/ct2/show/NCT01673854). Although our patient numbers are small and the findings here observational, our experience suggests that toxicity might be increased with subsequent treatments after an anti-PD-1 antibody.
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- 2015
41. Pembrolizumab
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S. Peter Kang, Anthony M. Joshua, Leila Khoja, Marcus O. Butler, and Scot Ebbinghaus
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Ipilimumab ,Pembrolizumab ,Review ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Immunology and Allergy ,Medicine ,Cytotoxic T cell ,Programmed death receptor 1 ,Lung cancer ,Melanoma ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Chemotherapy ,biology ,business.industry ,medicine.disease ,3. Good health ,Programmed death receptor ligand 1 ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Non small cell ,Antibody ,business ,Immune checkpoint blockade ,medicine.drug - Abstract
The development of the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab and its approval in 2011 for the treatment of metastatic melanoma has heralded a new era in immuno-oncology. Subsequently, novel agents against the programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis have shown significant activity in melanoma and a variety of other tumor types. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma with disease progression following ipilimumab, and if BRAF (V600) mutation positive, a BRAF inhibitor. Pembrolizumab has also received breakthrough status for the treatment of EGFR mutation-negative, ALK rearrangement-negative non-small cell lung cancer (NSCLC) that has progressed on or following platinum-based chemotherapy. There remain a number of pivotal trials in progress to further evaluate the optimal use of pembrolizumab alone and in combination for melanoma, NSCLC, and other tumor types. In this article, we review the efficacy and toxicity profile of pembrolizumab and evaluate its future development.
- Published
- 2015
42. Dabrafenib in the treatment of metastatic or unresectable melanoma
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David Hogg and Leila Khoja
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Oncology ,medicine.medical_specialty ,Skin Neoplasms ,Metastatic melanoma ,medicine.medical_treatment ,Antineoplastic Agents ,Disease-Free Survival ,Internal medicine ,Oximes ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Stage (cooking) ,Neoplasm Metastasis ,Melanoma ,Protein Kinase Inhibitors ,Neoplasm Staging ,Trametinib ,business.industry ,Imidazoles ,Dabrafenib ,Immunotherapy ,medicine.disease ,Clinical trial ,Survival Rate ,Toxicity ,business ,medicine.drug - Abstract
Dabrafenib is a potent inhibitor of mutant BRAF. Trials to date have shown it to be well tolerated, with significant activity in unresectable stage III or IV metastatic melanoma. Overall response rates of approximately 50% were seen in addition to improved progression-free and overall survival of 6 and 18 months, respectively. Preclinical studies suggested that combining BRAF and MEK inhibition would increase response rates and decrease toxicity. Clinical trials with the combination of dabrafenib and trametinib have improved progression-free and overall survival in interim analyses. Future improvements in responses and outcomes will depend on additional combination strategies, possibly employing immunotherapy.
- Published
- 2015
43. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma
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Leila Khoja, Anthony M. Joshua, Joshua S. Manusow, Nataly Pesin, and Efrem D. Mandelcorn
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Cancer Research ,Pathology ,medicine.medical_specialty ,Melanoma-associated Retinopathy (MAR) ,Immunology ,Case Report ,Pembrolizumab ,Metastasis ,Retinal vasculitis ,medicine ,Immunology and Allergy ,Melanoma ,Pharmacology ,biology ,business.industry ,medicine.disease ,Extravasation ,eye diseases ,PD-1 inhibitor ,Oncology ,Vitreous hemorrhage ,Optic nerve ,biology.protein ,Molecular Medicine ,Vitreous metastasis ,sense organs ,Antibody ,business - Abstract
We report on a 36-year-old woman treated with the anti PD-1 antibody Pembrolizumab for metastatic cutaneous melanoma in the first line setting. She achieved a complete response and then relapsed with metastases to the vitreous cavity with an associated angiographically determined retinal vasculitis. Vitreous metastasis without choroidal involvement is unusual and may be due to individual cell extravasation, vitreous hemorrhage containing malignant cells, or direct spread through the optic nerve. This finding highlights the need for immune sanctuary sites to be monitored in the presence of PD-1 inhibition and we hypothesize that the use of PD-1 inhibitor potentiated the patient’s angiographically determined retinal vasculitis.
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- 2014
44. Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma
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Maryanne Chappell, Qian Ye, Marcus O. Butler, Anthony M. Joshua, Eshetu G. Atenafu, Leila Khoja, David Hogg, and Craig Gedye
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Oncology ,Cancer Research ,medicine.medical_specialty ,Metastatic Cutaneous Melanoma ,Metastatic melanoma ,business.industry ,Immune checkpoint inhibitors ,Melanoma ,Ipilimumab ,Pembrolizumab ,Articles ,medicine.disease ,3. Good health ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Second line ,030220 oncology & carcinogenesis ,Internal medicine ,Toxicity ,medicine ,business ,030215 immunology ,medicine.drug - Abstract
Approved by the Food and Drug Administration in 2011, the anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of ≥3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in "real world" settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression-free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune-related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre-treatment factor independently predicted toxicity. The number of infusions (4 vs. ≤3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long-term vigilance.
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- 2014
45. Mortality within 30 days following systemic anti-cancer therapy, a review of all cases over a 4 year period in a tertiary cancer centre
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Shien Chow, Antony McGurk, Leila Khoja, Catherine O'Hara, and Jurjees Hasan
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Adolescent ,Cancer therapy ,Antineoplastic Agents ,Audit ,Audit process ,Young Adult ,Risk Factors ,Cause of Death ,Neoplasms ,Cancer centre ,Outcome Assessment, Health Care ,Medicine ,Humans ,Intensive care medicine ,Aged ,Quality of Health Care ,Retrospective Studies ,Clinical governance ,Performance status ,business.industry ,Treatment Setting ,Middle Aged ,Survival Analysis ,Survival Rate ,Increased risk ,Logistic Models ,Oncology ,Emergency medicine ,Multivariate Analysis ,Female ,Immunotherapy ,business - Abstract
Background The national confidential enquiry into patient outcomes and death (NCEPOD) set important benchmarks in assessing the quality of care received by patients dying within 30 days of systemic anticancer therapy (SACT). Monthly morbidity and mortality audits conducted to recommendations in the NCEPOD were commenced at the Christie NHS Foundation Trust in 2009, specifically to assess and improve patient outcomes. Methods We evaluated the outcomes of patients who died within 30 days of SACT over a 4 year period 2009–2013. We collated audit findings to determine the number of treatment related deaths, clinical characteristics of patients, causes of death and quality of care received. We examined the benefit of the audit in decreasing 30 day mortality during the 4 years and considered factors that may be associated with an increased risk of SACT related death. Results A total of 31,183 patients were treated at the Christie from 2009 to 2013. Of these 4% died within 30 days of SACT. Death was treatment related in 11%. The decision to treat with SACT was appropriate in 87% of but there was room for improvement in care in 24%. Mortality decreased over the 4 years. Possible factors associated with 30 day mortality post SACT included performance status ⩾2, presence of comorbidities, treatment type and treatment setting. Conclusions We demonstrated that our audit process is feasible and robust. Further areas of research to determine predictive scores for patient treatment selection and improve outcomes were highlighted and are ongoing.
- Published
- 2014
46. A cone-beam computed tomography study to assess anterior loop and other anatomic variations in mental foramen area in an Iranian population
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Leila Khojastepour, Sahar Assar, Najmeh Movahhedian, Mohammad Mahjoori-ghasrodashti, and Farzaneh Ahrari
- Subjects
cone-beam computed tomography ,dental implants ,mental foramen ,mandibular nerve ,mandible ,prevalence ,Dentistry ,RK1-715 - Abstract
Purpose: This study aimed to determine the prevalence and length of the anterior loop (AL) of the inferior alveolar nerve, and evaluate the emergence direction of the mental nerve and the location of mental foramen in a group of Iranian patients. Material and Methods: This study was carried out on CBCT scans of 150 patients (57 males and 93 females; mean age 40.8 ±14.33 years). The presence and extent of the AL was determined in reconstructed images. The emergence path of the mental nerve was classified into three groups: anteriorly directed emergence, right-angled pattern of emergence, and posteriorly directed emergence. The location of mental foramen relative to adjacent premolars was determined. Results: AL was identified in 14.7% of the cases with a mean length of 1.39± 0.91 mm (range 0.25 to 3.50 mm). No significant differences were observed in the prevalence and extent of the AL between genders (p>0.05). The right-angled pattern of emergence was more dominant (43.7%). The most prevalent location of mental foramen was between the first and second premolars (68.3%). There was no significant association between the presence of AL with the path of emergence of the mental nerve (p=0.627) or the location of the mental foramen (p=0.100). Conclusion: The prevalence of anterior loop was relatively low in the present sample (14.7%) with a length range of 0.25 to 3.5 mm. Due to the importance of this anatomic variation in implant surgery, it is suggested to carefully assess CBCT images before the surgical procedure to avoid neurosensory complications.
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- 2022
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47. Are Osteomeatal Complex Variations Related to Nasolacrimal Canal Morphometry?
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Leila Khojastepour, Sonia Dokohaki, and Maryam Paknahad
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cone-beam computed tomography ,morphometry ,nasolacrimal canal ,osteomeatal complex variation ,Otorhinolaryngology ,RF1-547 - Abstract
Introduction:Due to the close anatomic relationship between paranasal structures and NLC, the morphometric measure of the nasolacrimal canal (NLC) could be affected by the osteomeatal complex (OMC) anatomical variations. The present study aimed to assess the effect of OMC variations on the NLC morphometric features using cone-beam computed tomography (CBCT). Materials and Methods: This cross-sectional study consisted of CBCT images of 150 subjects in the case group with at least one OMC variation and 40 cases in the control group without any OMC variation within the age range of 18-50 years. The presence of the OMC variations, including agger nasi, nasal septum deviation, concha bullosa, Haller cells, paradoxical middle turbinate, and pneumatization of the uncinate process, was evaluated in each patient. The NLC morphometric measurements were performed and compared between the case and control groups. Results:The middle anteroposterior diameter and middle sectional area of NCL were significantly higher in patients with OMC variations, as compared to that in the control group. The NLC volume was significantly higher in patients with agger nasi, nasal septum deviation, concha bullosa, and pneumatization of the uncinate process, as compared to that in the control group. Nonetheless, no significant difference in NLC angulation with the nasal floor or Frankfurt horizontal plane was observed in the presence of each OMC variation.Conclusions:As evidenced by the obtained results, a higher volume of the canal was revealed in the presence of some of the OMC variations. Therefore, it can be suggested that OMC variations cannot be a predisposing factor in cases with primary acquired nasolacrimal duct obstruction.
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- 2022
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48. Evaluation of hypertension and proteinuria as markers of efficacy in antiangiogenic therapy for metastatic colorectal cancer
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Andrew R Clamp, Gordon C Jayson, Leila Khoja, Ric Swindell, Jurjees Hasan, Gireesh C Kumaran, Nishanth Murukesh, Gregory Wilson, Ying-Kiat Zee, Mark P Saunders, and Juan W. Valle
- Subjects
Oncology ,Adult ,Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Bevacizumab ,Colorectal cancer ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Survival rate ,Protein Kinase Inhibitors ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Proteinuria ,Neovascularization, Pathologic ,business.industry ,Surrogate endpoint ,Gastroenterology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Vascular endothelial growth factor ,Survival Rate ,Treatment Outcome ,chemistry ,Hypertension ,Female ,medicine.symptom ,business ,Colorectal Neoplasms ,medicine.drug - Abstract
BACKGROUND:: The vascular endothelial growth factor pathway is strongly implicated in cancer-related angiogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome. STUDY:: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009. RESULTS:: Of 90 patients evaluated, 50 were eligible. Seventeen (34%), 4 (8%), and 3 (6%) patients developed Common Toxicity Criteria (v 3.0) grades 1, 2, and 3 HTN, respectively. Response rates were 42% for patients with grades 0 to 1 HTN compared with 86% for patients with ?grade 2 HTN (P=0.043). Median overall survival was 21.6 months for patients with grades 0 to 1 HTN and 25.2 months for patients with ?grade 2 HTN (P=0.270). Twelve patients (24%) developed grade 1 PTN and 4 patients (8%) developed ?grade 2 PTN. Median overall survival was 23.9 months for patients with grades 0 to 1 PTN and 4.2 months for those with ?grade 2 PTN (P=0.028). CONCLUSIONS:: To our knowledge, this is the first study to demonstrate the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for metastatic colorectal cancer. Although HTN is predictive of a significantly higher response rate, the development of PTN during treatment with bevacizumab or tyrosine kinase inhibitor portends poorer survival and should be evaluated prospectively.
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- 2013
49. Choosing a better end point for trials of bone-protective agents
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Ian F. Tannock, Leila Khoja, Anthony M. Joshua, and Raya Leibowitz-Amit
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Oncology ,medicine.medical_specialty ,Prostate cancer ,End point ,business.industry ,Protective Agents ,Internal medicine ,Medicine ,Hematology ,business ,medicine.disease - Abstract
There is ongoing debate about the appropriate choice, timing and length of administration of bone protective agents in prostate cancer. In this letter, Leibowitz-Amit et al make the case that more clinical relevant endpoints are warranted and present sub analysis of existing datasets.
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- 2015
50. Assessment of the relationship between the maxillary sinus and the canine root tip using cone beam computed tomography
- Author
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Leila Khojastepour, Najmeh Movahhedian, Mohadeseh Zolghadrpour, and Mohammad Mahjoori-Ghasrodashti
- Subjects
Maxillary sinus ,Anterior extension ,Canine apex ,Incisor ,Cone beam computed tomography ,Dentistry ,RK1-715 - Abstract
Abstract Background The purpose of the present study is to investigate the relationship between the maxillary sinus and the canine root apices in cone beam computed tomographic images (CBCT) and to assess the amount of extension of the maxillary sinus to the anterior region of the jaw in different sexes and age groups. Methods CBCT of 300 individuals (154 males and 146 females) over 20 years (with a mean age of 35.12 ± 8.40 years) were evaluated. The subjects were categorized into three age groups (20–30, 30–40, and 40–50 years). When the maxillary sinus extended to the canine area, the vertical distance between them was measured, and their relationship was classified into three types: I (more than 2 mm distance), II (less than 2 mm distance or in-contact), and III (interlock). Results 413 out of 600 maxillary sinuses (68.8%) were extended into the canine area or beyond. Among them, 15 maxillary sinuses pneumatized into the incisor area (2.5%). The prevalence of the maxillary sinuses extended to the anterior region of the jaw was not significantly different between genders. However, it was significantly less frequent in the older age group and more frequent on the left side. In addition, the mean amount of anterior extension of the maxillary sinus (mm) was significantly lower in the older age group. Type I was the most frequent vertical relationship between the maxillary sinuses and canine apices with no significant difference in gender, side, and age groups. Conclusions In most cases, the maxillary sinus extended to the canine area and sometimes reached the incisor region. This necessitates paying more attention to the maxillary anterior sextant during surgical procedures.
- Published
- 2021
- Full Text
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