N. George Mikhaeel

Dr. N. George Mikhaeel

Department of Clinical Oncology, Guy's & St Thomas' NHS Foundation Trust, London, UK

Research Focus & Metrics

Academic Career Length

22Years (2005-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 September 2005 in Annals of Oncology
Verified
Journal Article
Open access
PDF file
N. George MikhaeelN. George Mikhaeel
N. George Mikhaeel
MHM. Hutchings
M. Hutchings
PFP. A. Fields
P. A. Fields
MOM. J. O'Doherty
M. J. O'Doherty
ATA. R. Timothy
A. R. Timothy
Background: Less than 50% of all high-grade non-Hodgkin lymphoma (NHL) patients experience lasting disease-free survival. Risk-adapted treatment strategies require better tools for prediction of outcome. This investigation aimed to assess the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two to three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). Patients and methods: One hundred and twenty-one patients with high-grade NHL underwent FDG-PET. The therapy response on FDG-PET was correlated to PFS and OS using Kaplan–Meier survival analysis. Cox regression analyses were employed to test for independence of known pretreatment prognostic factors. Results: Fifty FDG-PET scans were negative, 19 scans showed minimal residual uptake (MRU), and 52 scans were positive. The estimated 5 year PFS was 88.8% for the PET-negative group, 59.3% for the MRU group, and 16.2% for the PET-positive group. Kaplan–Meier analyses showed strong associations between FDG-PET results and PFS (P <0.0001) and OS (P <0.01). Early interim FDG-PET was independent of the other prognostic factors. Conclusions: Early interim FDG-PET is an accurate and independent predictor of PFS and OS. An early assessment of chemotherapy response with FDG-PET could provide the basis for selection of patients for alternative therapeutic strategies.

6 June 2005 in Annals of Oncology
Verified
Journal Article
Open access
PDF file
MHM. Hutchings
M. Hutchings
N. George MikhaeelN. George Mikhaeel
N. George Mikhaeel
PFP. A. Fields
P. A. Fields
TNT. Nunan
T. Nunan
ATA. R. Timothy
A. R. Timothy
Background: Long-term survival from Hodgkin lymphoma (HL) is 80–90%, but the treatment has serious late adverse effects. Modern risk-adapted treatment requires accurate assessment of the patient's prognosis. This investigation assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-d-glucose (FDG-PET) after two or three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). Patients and methods: A total of 85 patients with HL underwent FDG-PET after two or three cycles of chemotherapy. Median follow-up was 3.3 years. FDG-PET results were related to PFS and OS using Kaplan–Meier analysis. Regression analyses were employed to test for independence of established pretreatment prognostic factors. Results: After two or three cycles of chemotherapy, 63 patients had negative FDG-PET scans, nine patients had minimal residual uptake (MRU) and 13 patients had positive scans. Three PET-negative patients and one patient from the MRU group relapsed. In the PET-positive group, nine patients progressed and two died. Survival analyses showed highly significant associations between early interim FDG-PET and PFS (P <0.0001) and OS (P <0.03). All advanced-stage patients with positive interim FDG-PET relapsed within 2 years. Conclusion: Early interim FDG-PET is an accurate and independent predictor of PFS and OS in HL. A positive interim FDG-PET is highly predictive of relapse in advanced-stage disease.

23 February 2016 in European Journal of Nuclear Medicine and Molecular Imaging
Verified
Journal Article
Open access
PDF file
N. George MikhaeelN. George Mikhaeel
N. George Mikhaeel
DSDaniel Smith
Daniel Smith
JDJoel T. Dunn
Joel T. Dunn
MPMichael Phillips
Michael Phillips
HMHenrik Møller
Henrik Møller
SBSally F. Barrington
Sally F. Barrington
Background The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. Methods A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan–Meier survival analysis was performed. Results The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm3. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) Conclusions MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur.

31 March 2022 in Journal of Clinical Oncology
Verified
Journal Article
Open access
N. George MikhaeelN. George Mikhaeel
N. George Mikhaeel
MHMartijn W. Heymans
Martijn W. Heymans
JEJakoba J. Eertink
Jakoba J. Eertink
HVHenrica C.W. de Vet
Henrica C.W. de Vet
RBRonald Boellaard
Ronald Boellaard
SBSally F. Barrington
Sally F. Barrington
PURPOSE: Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model. METHODS: PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times. RESULTS: The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm3. MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3% v 58.0% and 3-year OS 51.5% v 66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities. CONCLUSION: A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.

21 May 2020 in Blood
Verified
Journal Article
Open access
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JYJoachim Yahalom
Joachim Yahalom
BDBouthaina Shbib Dabaja
Bouthaina Shbib Dabaja
URUmberto Ricardi
Umberto Ricardi
ANAndrea Ng
Andrea Ng
N. George MikhaeelN. George Mikhaeel
N. George Mikhaeel
LSLena Specht
Lena Specht
The International Lymphoma Radiation Oncology Group (ILROG) guidelines for using radiation therapy (RT) in hematological malignancies are widely used in many countries. The emergency situation created by the COVID-19 pandemic may result in limitations of treatment resources. Furthermore, in recognition of the need to also reduce the exposure of patients and staff to potential infection with COVID-19, the ILROG task force has made recommendations for alternative radiation treatment schemes. The emphasis is on maintaining clinical efficacy and safety by increasing the dose per fraction while reducing the number of daily treatments. The guidance is informed by adhering to acceptable radiobiological parameters and clinical tolerability. The options for delaying or omitting RT in some hematological categories are also discussed.

4 May 2021 in Blood Advances
Verified
Journal Article
Open access
PDF file
JEJ. J. Eertink
J. J. Eertink
CBC. N. Burggraaff
C. N. Burggraaff
MHM. W. Heymans
M. W. Heymans
UDU. Dührsen
U. Dührsen
AHA. Hüttmann
A. Hüttmann
HVH. C. W. de Vet
H. C. W. de Vet
Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.