16 results on '"Maria Coakley"'
Search Results
2. Abstract GS3-06: Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer
- Author
-
Nicholas Turner, Claire Swift, Ben Jenkins, Lucy Kilburn, Maria Coakley, Matthew Beaney, Lisa Fox, Katie Goddard, Isaac Garcia-Murillas, Peter Hall, Catherine Harper-Wynne, Tamas Hickish, Sarah Kernaghan, Iain Macpherson, Alicia Okines, Carlo Palmieri, Sophie Perry, Katrina Randle, Claire Snowdon, Hilary Stobart, Andrew Wardley, Duncan Wheatley, Simon Waters, Matthew Winter, and Judith Bliss
- Subjects
Cancer Research ,Oncology - Abstract
Background Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage triple negative breast cancer (TNBC) is associated with a very high risk of future relapse. Identifiying those at high risk of subsequent relapse may allow tailoring of further therapy to delay or prevent recurrence. The c-TRAK TN trial assessed the utility of prospective ctDNA surveillance in pts treated for TNBC and the activity of pembrolizumab (P) in pts with ctDNA detected.. Methods c-TRAK TN, a multi-centre phase II trial with integrated prospective screening component, enrolled pts with early-stage TNBC and either residual disease following neoadjuvant chemotherapy, or tumour size >20mm and/or axillary lymph node involvement if adjuvant chemotherapy was given. Tumour tissue was sequenced to identify somatic mutations suitable for tracking using personalised digital PCR ctDNA assays (BioRad QX200). Pts had “active” ctDNA surveillance via blood sample testing every 3 months to 12 months (potential up to 18 months if samples missed due to COVID) during which time if ctDNA was detected (ctDNA+) pts could be randomised 2:1 to P (200mg i.v. q 3 weeks for 1 year) or observation (Obs). Pts and clinicians were blinded to ctDNA+ results unless they were allocated P, when staging scans were done and those free of clinical recurrence started treatment. Following advice from the Independent Data Monitoring Committee, the Obs arm closed on 16/06/2020 with all subsequent ctDNA+ pts allocated P. Following the completion of active ctDNA surveillance, 3-monthly visits continued to 24 months to be analysed retrospectively. The aim was to recruit 150 pts to ctDNA surveillance, assuming 30% would be ctDNA+ within 12 months, allowing ctDNA+ rate to be estimated with a 2-sided 95%CI of +/- 7.3%. Co-primary endpoints are i) rates of ctDNA detection by 12 and 24 months from start of ctDNA surveillance; ii) rates of sustained ctDNA clearance on P defined as absence of detectable ctDNA, or disease recurrence 6 months after starting P.. Results 208 pts were registered between 30/01/18 and 06/12/19, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. The rate of ctDNA detection by 12 months after start of surveillance was 27.3% (44/161, 95% CI 20.6-34.9). ctDNA+ rates from baseline, 3, 6, 9 and 12 month ctDNA samples were 23/161 (14.3%), 6/115 (5.2%), 6/99 (5.1%), 7/84 (8.3%), and 2/84 (2.4%) respectively. An additional 2 pts were ctDNA+ on COVID extended active surveillance at 15 (1/51, 2%) or 18 months (1/11, 9%). 7 pts relapsed without prior ctDNA detection. 45 pts entered the therapeutic component of the trial (initially 31 to P and 14 to Obs). 1 Obs pt was re-allocated to P. Of pts allocated to P, 72% (23/32) had metastatic disease at time of ctDNA detection on staging scans (75% (12/16) who were ctDNA+ at baseline and 69% (11/16) at other timepoints). 4 pts declined to start P, largely due to COVID concerns. Of the 5 pts who commenced P, at the time of analysis none achieved sustained ctDNA clearance and 4 had recurred. In pts allocated to Obs, median time to recurrence was 4.1 months (95% CI: 3.2-not-defined).. Conclusion The c-TRAK TN trial is to our knowledge the first study to assess the proof-of-principle of whether ctDNA assays have clinical utility in guiding further therapy in TNBC. Relatively few pts commenced P treatment precluding assessment of potential activity. At enrollment, patients had a relatively high of rate of undiagnosed metastatic disease when imaged. Our findings have implications for future trial design, emphasizing the importance of early start of ctDNA testing, and more sensitive and/or more frequent ctDNA testing regimes. Citation Format: Nicholas Turner, Claire Swift, Ben Jenkins, Lucy Kilburn, Maria Coakley, Matthew Beaney, Lisa Fox, Katie Goddard, Isaac Garcia-Murillas, Peter Hall, Catherine Harper-Wynne, Tamas Hickish, Sarah Kernaghan, Iain Macpherson, Alicia Okines, Carlo Palmieri, Sophie Perry, Katrina Randle, Claire Snowdon, Hilary Stobart, Andrew Wardley, Duncan Wheatley, Simon Waters, Matthew Winter, Judith Bliss. Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS3-06.
- Published
- 2022
3. Abstract PD5-03: PD5-03 Comparison of a personalized sequencing assay and digital PCR for circulating tumor DNA based Molecular Residual Disease detection in early-stage triple negative breast cancer in the cTRAK-TN trial
- Author
-
Maria Coakley, Prithika Sritharan, Guillermo Villacampa, Claire Swift, Kathryn Dunne, Lucy Kilburn, Katie Goddard, Patricia Rojas, Andy Joad, Warren Emmett, Charlene Knape, Karen Howarth, Peter S. Hall, Catherine Harper-Wynne, Tamas Hickish, Iain Macpherson, Alicia F. Okines, Andrew M. Wardley, Duncan Wheatley, Simon Waters, Rosalind Cutts, Isaac Garcia-Murillas, Judith Bliss, and Nicholas Turner
- Subjects
Cancer Research ,Oncology - Abstract
Background: Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage breast cancer is associated with a high risk of future relapse. Identifying those at high risk of subsequent relapse may allow tailoring of further therapy to delay or prevent recurrence. Previous analysis of this cohort showed that tools capable of detecting ctDNA at lower concentrations are needed to increase sensitivity and lengthen the lead time between ctDNA detection and relapse. We compared ctDNA detection via a personalised sequencing assay to dPCR in patients from the cTRAK TN clinical trial. Methods: The cTRAK-TN trial recruited 161 pts into prospective ctDNA surveillance with dPCR, with ctDNA positive pts randomised to 1) CT staging plus pembrolizumab therapy for patients without relapse or 2) observation. Pts had serial post-treatment surveillance plasma samples collected every 3 months for up to 2 years. Whole exome sequencing (WES) was performed on tumor DNA from FFPE samples to design personalised Residual Disease and Recurrence (RaDaR®) multiplex PCR based NGS assays. Retrospectively, plasma DNA extracted from a minimum of 2mls banked plasma, was sequenced with personalised RaDaR assays, and ctDNA detection identified with a proprietary algorithm. dPCR assays tracked 1-2 mutations, as previously described. Primary endpoint was rate of positive ctDNA detection by 12 months from start of surveillance in both assays. Secondary endpoints were agreement in ctDNA detection between RaDaR and dPCR assays and lead-time between ctDNA detection and disease recurrence. Results: Overall, 147 pts and 241 tissue samples were subject to WES, and RaDaR assays were developed for 142 pts with sufficient plasma for testing. RaDaR assays tracked a median of 47 variants (range 33-56) per patient, and a total of 907 timepoints were analysed (median 6 timepoints per pt, range 1-11). With RaDaR, 39.4% (56/142) patients tested ctDNA positive during follow-up, with a median ctDNA detected level of 0.081% estimated variant allele fraction (eVAF). With dPCR, 35.2% (50/142) pts tested ctDNA positive. The ctDNA detection rate by 12 months from the start of ctDNA surveillance was 36.2% (95% CI; 27.6% – 43.7%) with RaDaR and 29.9% (95%CI; 21.6% – 37.3%) with dPCR. The overall test agreement between RaDaR and dPCR assays was 92.7% (95%CI; 90.7% – 94.4%). From a patient perspective, 58.7% pts were ctDNA negative for both assays, 32.9% ctDNA were positive for both assays and 8.6% presented discrepancies. ctDNA was detected by RaDaR but not by dPCR in 9 pts and it was detected by dPCR but not by RaDaR in 3 pts. Among ctDNA positive pts, 55.2% were first detected positive by RaDaR, 5.2% by dPCR, and 39.6% were detected at the same time-point (test of proportions, p< 0.001). The median lead time from ctDNA detection to relapse was 7.1 months (95% CI 5.9 – 15.9%) with RaDaR and 5.7 months (95% CI 3.2% – 7.4%) with dPCR. Conclusion: The RaDaR personalised multi-mutation sequencing assay detected MRD with a longer median lead time prior to relapse, and with higher sensitivity, than dPCR mutation tracking assays. These findings have implications for the choice of ctDNA assay in clinical trials designed to treat patients at the point of MRD detection. Citation Format: Maria Coakley, Prithika Sritharan, Guillermo Villacampa, Claire Swift, Kathryn Dunne, Lucy Kilburn, Katie Goddard, Patricia Rojas, Andy Joad, Warren Emmett, Charlene Knape, Karen Howarth, Peter S. Hall, Catherine Harper-Wynne, Tamas Hickish, Iain Macpherson, Alicia F. Okines, Andrew M. Wardley, Duncan Wheatley, Simon Waters, Rosalind Cutts, Isaac Garcia-Murillas, Judith Bliss, Nicholas Turner. PD5-03 Comparison of a personalized sequencing assay and digital PCR for circulating tumor DNA based Molecular Residual Disease detection in early-stage triple negative breast cancer in the cTRAK-TN trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD5-03.
- Published
- 2023
4. Management of lung cancer
- Author
-
Maria Coakley and Sanjay Popat
- Subjects
General Medicine - Published
- 2020
5. Molecular Targetable Pathways—ALK
- Author
-
Sanjay Popat and Maria Coakley
- Subjects
biology ,business.industry ,ALK Gene Rearrangement ,ALK Pathway ,Pathophysiology ,Receptor tyrosine kinase ,respiratory tract diseases ,hemic and lymphatic diseases ,biology.protein ,Cancer research ,Medicine ,Anaplastic lymphoma kinase ,Tumor growth ,business ,Adverse effect ,Tyrosine kinase - Abstract
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase which becomes oncogenic and drives tumor growth in multiple tumor types, including non-small cell lung cancer (NSCLC). We discuss the pathophysiology of ALK in NSCLC, which is driven predominantly by ALK gene rearrangements. We review the various methods of molecular testing for ALK gene rearrangements in NSCLC, and their limitations. Oral Tyrosine Kinase Inhibitors (TKIs) targeting the ALK pathway have been rapidly developed in the past 10 years. These drugs are well tolerated and offer prolonged disease control. We highlight the most up-to-date clinical data for each of the agents currently available which target the ALK pathway, and discuss adverse events associated with each agent. We discuss mechanisms of resistance to the ALK-targeted TKIs, and options for treatment at disease progression.
- Published
- 2022
6. Abstract P2-01-10: Detection of ctDNA following surgery predicts relapse in breast cancer patients receiving primary surgery
- Author
-
Isaac Garcia-Murillas, Rosalind J Cutts, Lara Ulrich, Matthew Beaney, Marie Robert, Maria Coakley, Catey Bunce, Giselle WalshCrestani, Sarah Hrebien, Ekaterina Kalashnikova, Hsin-Ta Wu, Scott Dashner, Himanshu Sethi, Alexey Aleshin, Alistair Ring, Alicia Okines, Ian E Smith, Mitch Dowsett, Peter Barry, and Nicholas C Turner
- Subjects
Cancer Research ,Oncology - Abstract
Introduction: Identification of Molecular Residual Disease (MRD) by circulating tumour DNA (ctDNA) analysis has the potential to transform the clinical management of patients with early breast cancer. We present results from a proof-of-principle study to assess ctDNA analysis following primary surgery to identify MRD and anticipate which patients are at risk of relapse. Methods: Early breast cancer patients receiving primary surgery for breast cancer (48 total), enrolled in the PlasmaDNA/ITH sample collection studies were included in the analysis. Tumour DNA from FFPE samples was whole exome sequenced to identify patient specific mutations and design personalized Signatera ctDNA assays. Plasma samples were collected pre-surgery (n=31), 1-14 weeks post-surgery and prior to adjuvant therapy (n=48), and following adjuvant chemotherapy (n=36). Cell free DNA was extracted from a total of 144 plasma samples (median volume 3.6ml, range 1.8-4.7ml) and sequenced with Signatera ctDNA assays. Primary objective was to assess whether relapse free survival (RFS) and distant metastasis free survival (DMFS) are worse in patients with ctDNA detected at the post-surgery timepoint compared to those without ctDNA detected. Results: Median age was 50.5 years, 34 had hormone receptor positive HER2 negative (HR+HER2-), 5 HER2 positive and 9 triple negative breast cancer (TNBC), 32 were stage 1-2 and 16 were stage 3-4. At a median follow-up of 60 months post-surgery, 8 patients had relapsed. ctDNA was detected in the single post-surgery timepoint in 29% (14/48) of patients, and detected in 62.5% (5/8) of patients who relapsed. RFS in patients with ctDNA detected at a single post-surgery timepoint was worse than those with no detected ctDNA although it was not statistically significant (Hazard Ratio (HR): 3.7; 95% CI, 0.9-15.6; P=0.07), while ctDNA detection associated with worse DMFS (HR: 5.6; 95% CI, 1.1-29-3; P=0.04). DMFS at 4 years follow-up in those with MRD ctDNA detection was 0.78 (95% CI 0.47-0.92) and those without MRD detection was 0.97 (95% CI 0.80-0.99). In patients with a pre-surgical timepoint (n=31), 64.5% (20/31) had ctDNA detected. Detection of ctDNA at either pre-surgery or post-surgery was associated with worse outcomes compared to no ctDNA detection at both RFS (HR: 7.9; 95% CI, 0.9-64.7; P=0.05) and DMFS (HR: 6.7; 95% CI, 0.8-55.8; P=0.07). Conclusions: In this proof-of-principle study of early-stage breast cancer patients, ctDNA-detected MRD at a single post-surgical timepoint was associated with distant metastasis free survival. The majority of patients with ctDNA detected MRD did not relapse, during the period of follow-up, possibly suggesting activity of adjuvant therapy in these patients. Further assessment is warranted on the prognostic impact of ctDNA MRD detection, and its possible role in adjuvant chemotherapy selection. Citation Format: Isaac Garcia-Murillas, Rosalind J Cutts, Lara Ulrich, Matthew Beaney, Marie Robert, Maria Coakley, Catey Bunce, Giselle WalshCrestani, Sarah Hrebien, Ekaterina Kalashnikova, Hsin-Ta Wu, Scott Dashner, Himanshu Sethi, Alexey Aleshin, Alistair Ring, Alicia Okines, Ian E Smith, Mitch Dowsett, Peter Barry, Nicholas C Turner. Detection of ctDNA following surgery predicts relapse in breast cancer patients receiving primary surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-01-10.
- Published
- 2022
7. Survival following allogeneic transplant in patients with myelofibrosis
- Author
-
Tamila L. Kindwall-Keller, Uday R. Popat, Melhem Solh, Kierstin Luber, Kwang Woo Ahn, Ulrike Bacher, Wael Saber, Ashley Pariser, Siddhartha Ganguly, Edward A. Copelan, Michael Green, Zhen-Huan Hu, Gabriela S. Hobbs, Ruben A. Mesa, Mary Lynn Savoie, Ryotaro Nakamura, Asad Bashey, Shahinaz M. Gadalla, Andrew T. Kuykendall, Tania Jain, Zachariah DeFilipp, Aaron T. Gerds, Belinda R. Avalos, Haris Ali, Bipin N. Savani, Lucia Masarova, Rami S. Komrokji, Jacob M. Rowe, Vikas Gupta, Vaibhav Agrawal, Amer Beitinjaneh, Rebecca Devlin, Ronald Sobecks, Raajit K. Rampal, Shahrukh K. Hashmi, Miguel Angel Diaz, Roni Tamari, Saurabh Chhabra, Krisstina Gowin, Attaphol Pawarode, Taiga Nishihori, Jan Cerny, Sunita Nathan, Michael R. Grunwald, Mark R. Litzow, Sachiko Seo, Karen K. Ballen, Sarah Patches, Edwin P. Alyea, David I. Marks, Jane L. Liesveld, Laura C. Michaelis, Hillard M. Lazarus, Jean A. Yared, Murat O. Arcasoy, Brady L. Stein, Martha Wadleigh, Nicolaus Kröger, Moshe Talpaz, Bart L. Scott, Srdan Verstovsek, Mohamed A. Kharfan-Dabaja, Leo F. Verdonck, Malathi Kandarpa, Corey Cutler, Maria Coakley, Mahmoud Aljurf, and Richard F. Olsson
- Subjects
Oncology ,Transplantation ,medicine.medical_specialty ,Framingham Risk Score ,business.industry ,Proportional hazards model ,Essential thrombocythemia ,medicine.medical_treatment ,Hazard ratio ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,surgical procedures, operative ,International Prognostic Scoring System ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,business ,610 Medicine & health ,Survival analysis - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
- Published
- 2020
- Full Text
- View/download PDF
8. Abstract 536: Molecular residual disease detection in early stage breast cancer with a personalized sequencing approach
- Author
-
Stephen R. D. Johnston, Ian E. Smith, Alistair Ring, Rosalind J. Cutts, Maria Coakley, Mitch Dowsett, Nicholas C. Turner, Malcolm Perry, Peter M. Ellis, Isaac Garcia-Murillas, Anthony Skene, Abigail Evans, Charlene Knape, Duncan Wheatley, Lara Ulrich, Karen Howarth, S. Russell, and Warren Emmett
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cancer ,medicine.disease ,Log-rank test ,Breast cancer ,Cell-free fetal DNA ,Internal medicine ,Biopsy ,medicine ,Sample collection ,business ,Exome ,Triple-negative breast cancer - Abstract
Introduction: Detection of circulating tumor DNA (ctDNA) presents a strategy to identify Molecular Residual Disease (MRD) in patients with breast cancer. Tools capable of detecting ctDNA at lower concentrations are needed to increase sensitivity and lengthen lead time between ctDNA detection and relapse. We present results from a highly sensitive personalized sequencing approach for ctDNA detection of MRD based on multiple patient specific mutations. Methods: 22 early breast cancer patients (12 hormone receptor positive HER2 negative (HR+HER2-), 7 HER2+ and 3 triple negative breast cancer (TNBC)) enrolled in the ChemoNEAR sample collection study were included. Tumor DNA from FFPE samples was Whole Exome Sequenced to identify patient specific mutations and design personalized Residual Disease and Recurrence (RaDaRTM) multiplex PCR assays. Cell free DNA was extracted from 147 plasma samples (median volume 4ml, range 0.5-5ml) and sequenced with RaDaR assays, with 10-61 variants (median 41) per panel, to 100,000x per locus. A matched single timepoint buffy coat was sequenced to identify confounding CHIP mutations. A proprietary algorithm was used to identify ctDNA. Tumor Sequencing of multiple biopsy timepoints was carried out for 14 patients (mean 2.8 samples per patient) and clonal populations estimated with Pyclone. For clusters of greater than 10 mutations, RaDaR panels were supplemented with additional variants for clonal tracking. Results: At a median follow-up of 24.6 months post-surgery, MRD was identified in 100% (17/17) of relapsed patients, and in none of the 54 time points in the 5 patients that did not relapse (p=0.0002, Log rank test). Detection of ctDNA levels ranged from 7.4 parts per million (ppm), equivalent to Allele Frequency (AF) of 0.0007%, to 13,195ppm (1.3%) (median 625ppm and 0.06% AF). Median lead-time from ctDNA detection to clinical relapse in patients with extracranial disease relapse was 12.89 months (range 3.72-26.04). In three patients with brain only relapse, ctDNA was detected prior to relapse in all patients (3/3, 100%) albeit with a reduced lead time over clinical relapse (3.85, 4.21 and 5.65 months), which was not previously achievable with single mutation dPCR MRD-detection assays. In 8/14 patients with multiple tumor samples sequenced, multiple clones (mean 3.4 clones/patient) were identified, with heterogenous polyclonal relapse in 4/8 patients, and a single clone detectable in 4/8 patients. Conclusions: In a retrospective, multi-center, proof-of-principle study of early stage breast cancer patients with personalized sequencing assays, ctDNA-detected MRD associates with relapse free survival and long lead time over clinical relapse. Sequencing based ctDNA testing can detect patients with brain-only relapses, with increased sensitivity over first generation dPCR-based ctDNA assays. Citation Format: Rosalind J. Cutts, Maria Coakley, Isaac Garcia-Murillas, Lara Ulrich, Karen Howarth, Warren Emmett, Malcolm Perry, Pete Ellis, Charlene Knape, Stephen R. Johnston, Alistair Ring, Simon Russell, Abigail Evans, Anthony Skene, Duncan Wheatley, Mitch Dowsett, Ian E. Smith, Nicholas C. Turner. Molecular residual disease detection in early stage breast cancer with a personalized sequencing approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 536.
- Published
- 2021
9. Molecular Residual Disease and Adjuvant Trial Design in Solid Tumors
- Author
-
Nicholas C. Turner, Maria Coakley, and Isaac Garcia-Murillas
- Subjects
0301 basic medicine ,Oncology ,Research design ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Antineoplastic Agents ,Disease ,Risk Assessment ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Neoplasms ,medicine ,Adjuvant therapy ,Biomarkers, Tumor ,Humans ,Chemotherapy ,Clinical Trials as Topic ,Surrogate endpoint ,business.industry ,Retrospective cohort study ,Prognosis ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,Chemotherapy, Adjuvant ,Research Design ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,business ,Adjuvant - Abstract
Advances in diagnosis and treatment have resulted in a high rate of survival for many patients with early-stage cancers. However, identifying who is at ongoing risk of relapse remains of high priority to direct subsequent adjuvant therapy. Multiple recent retrospective studies have shown that detection of tumor-derived materials in blood, in particular with circulating tumor DNA (ctDNA) analysis, can identify patients with residual disease before clinical or radiological evidence of metastatic disease, anticipating relapse with relatively high sensitivity and high specificity. We discuss how these emerging technologies are defining new subgroups of patients with “Molecular Residual Disease” and “Molecular Relapse.” We outline how novel clinical trials in the adjuvant setting designed for these new subgroups of patients may improve selection for adjuvant therapies, and provide new surrogate endpoints that may allow for early registration of adjuvant therapies and novel clinical trial designs in the adjuvant setting. We discuss the current limitations of these techniques and the routes to clinical implementation.
- Published
- 2019
10. Impact of delayed adjuvant chemotherapy: The Royal Marsden Hospital (RMH) experience
- Author
-
I.E. Smith, T. Irfan, Alicia Okines, Maria Coakley, V. Aggelis, S.R.D. Johnston, Emma Kipps, Nicholas C. Turner, Marina Parton, and B. Asare
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,Adjuvant chemotherapy ,General surgery ,Medicine ,Hematology ,business - Published
- 2019
11. Survival Advantage to Allogeneic Transplant in Patients with Myelofibrosis with Intermediate-1 or Higher DIPSS Score
- Author
-
Haris Ali, Kierstin Kuber, Kwang Woo Ahn, Moshe Talpaz, Ying Liu, Laura C. Michaelis, Ashley Pariser, Uday R. Popat, Rami S. Komrokji, Bart L. Scott, Malathi Kandarpa, Ruben A. Mesa, Maria Coakley, Rebecca Devlin, Aaron T. Gerds, Ronald Sobecks, Sarah Patches, Krisstina Gowin, Murat O. Arcasoy, Karen K. Ballen, Martha Wadleigh, Michael Green, Wael Saber, Raajit K. Rampal, Gabriela S. Hobbs, Lucia Masarova, Tania Jain, Andrew T. Kuykendall, Srdan Verstovsek, Edwin P. Alyea, Zhen-Huan Hu, Vikas Gupta, and Brady L. Stein
- Subjects
medicine.medical_specialty ,Framingham Risk Score ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Transplantation ,surgical procedures, operative ,hemic and lymphatic diseases ,Relative risk ,Internal medicine ,Cohort ,medicine ,Myelofibrosis ,business - Abstract
Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). Consideration of HCT is recommended by international working groups and national guidelines for MF patients (pts) age Methods: Disease characteristics, treatments, and outcome data from MF pts receiving non-transplant therapy at 14 US academic medical centers between 2000-2014 were retrospectively collected. MF pts who underwent HCT were identified from the Center for International Blood and Marrow Transplant Research (CIBMTR). The Cox proportional hazards model was used. The reference time point (time zero) was time of referral for the non-transplant (non-HCT) arm and the time of transplant for the HCT arm. The main effect variable (HCT vs. non-HCT) violated the proportionality assumption where comparing to non-HCT, mortality was higher with HCT in early time period from time zero but then was lower in late time period; therefore, the comparison is presented as early time period and late time period. The Cox model identified 14 months from time zero as the ideal cut point to define early and late time periods. The proportionality assumption is satisfied within each of these two periods. Results: A total of 1377 and 551 pts were included in the non-HCT and HCT arms, respectively (Table 1). In the overall cohort, survival was higher with non-HCT vs. HCT in early time period (relative risk [RR]: 0.34, P< .0001, Figure 1D), but in late time period survival was lower with non-HCT vs. HCT (RR: 2.37, P< 0.001) (Table 2). In the DIPSS low-risk MF group, while survival was higher with non-HCT vs. HCT in the early time period (RR: 0.19, P=0.007, Figure 1A), survival was lower with non-HCT in the late time period, but the latter did not reach statistical significance (RR: 1.45, P=0.39). In the DIPSS intermediate-1 risk group, a survival advantage was present with non-HCT treatments vs. HCT in the early time period (RR: 0.27, P < .0001, Figure 1B), however survival was lower with non-HCT in the late time period (RR: 3.13, P < .0001). Similarly, in those with DIPSS intermediate-2 and high-risk MF, survival advantage was observed with non-HCT in the early time period (RR: 0.41, P< .0001, Figure IC), but survival was lower with non-HCT in the late time period (RR: 2.82, P < .0001). Conclusion: A long-term survival advantage with transplant was observed for pts with intermediate-1 or higher risk MF, but at the cost of potential early mortality. The magnitude of benefit increased as DIPSS risk score increased. Although this retrospective study has limitations, the results have an impact on clinical practice by suggesting that transplantation could be considered earlier in the disease course and supports the recommendation for consideration of HCT in the setting of intermediate-1 risk MF. Disclosures Gowin: Incyte: Consultancy, Other: Scientific Advisory Board, Speakers Bureau. Verstovsek:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy; Italfarmaco: Membership on an entity's Board of Directors or advisory committees. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy.
- Published
- 2018
12. Real world use of palliative systemic therapy (tx) in elderly patients (pts) with metastatic colorectal cancer (mCRC) within a UK specialist cancer centre
- Author
-
Shelize Khakoo, Alistair Ring, Scott Shepherd, Chiara Baratelli, Sheela Rao, Alexandros Georgiou, V. Calamai, Ian Chau, David Cunningham, David Watkins, Naureen Starling, Kyriakos Kouvelakis, Andrea Lanese, R. Kalaitzaki, D. Hughes, and Maria Coakley
- Subjects
medicine.medical_specialty ,Oncology ,Colorectal cancer ,business.industry ,Cancer centre ,medicine ,Hematology ,medicine.disease ,Intensive care medicine ,business ,Systemic therapy - Published
- 2017
13. BRCA1/2 germline testing in non-mucinous epithelial ovarian carcinoma: changing international practice and implications for service provision
- Author
-
Seamus O'Reilly, Maria Coakley, Vicki Cleary, and Nicholas Power
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Letter ,endocrine system diseases ,International Cooperation ,Genetic Counseling ,Carcinoma, Ovarian Epithelial ,030105 genetics & heredity ,Biology ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Internal medicine ,Ovarian carcinoma ,Genetics ,medicine ,Carcinoma ,Humans ,Genetic Testing ,Neoplasms, Glandular and Epithelial ,Family history ,Germ-Line Mutation ,Genetics (clinical) ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,Cancer ,medicine.disease ,female genital diseases and pregnancy complications ,Serous fluid ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Female ,Ovarian cancer ,Ireland - Abstract
Ovarian carcinoma is the fourth most common cancer for women in Republic of Ireland, with an average of 361 cases per year.1 The association with germline mutations in BRCA1/2 genes in non-mucinous ovarian cancer risk is well established.2 Determining the BRCA status of ovarian cancer patients has important prognostic and therapeutic implications for individual patients.3 The frequency of BRCA1/2 germline mutations in non-mucinous ovarian carcinoma is estimated at 14–15%,2 with previous studies finding a higher rate of 16.6% in serous ovarian carcinoma and 17.1% in high-grade serous carcinoma.3 Family history has been shown not to be sufficiently accurate to predict mutation status.2, 3 In Ireland, as in most European countries, and the United States, the current recommendation is that patients with a family history of breast/ovarian cancer should be offered full mutation screening of the BRCA1/2 genes as appropriate following the assessment by a clinical genetics service.4
- Published
- 2016
14. Locoregional treatment of ‘immune escape' metastatic melanoma in the setting of immune checkpoint inhibition for widespread disease
- Author
-
Henry Paul Redmond, Richard Martin Bambury, Maria Coakley, Seamus O'Reilly, David Cormican, Derek G. Power, Cynthia Heffron, and Deirdre O'Mahony
- Subjects
Cancer Research ,Electrochemotherapy ,Metastatic melanoma ,business.industry ,Immune escape ,Widespread Disease ,behavioral disciplines and activities ,Immune checkpoint ,Oncology ,mental disorders ,Cancer research ,Medicine ,Survival advantage ,business ,Advanced melanoma - Abstract
e14544Background: Metastectomy confers a survival advantage in advanced melanoma in appropriately selected patients. Combining local therapies, e.g. surgery and electrochemotherapy (ECT) with immun...
- Published
- 2016
15. Poor Correlation Between DIPSS and Passamonti Prognostic Risk Scores for Post Polycythemia Vera and Essential Thrombocythemia Myelofibrosis
- Author
-
Krisstina L. Gowin, Heidi E. Kosiorek, Maria Coakley, and Ruben A. Mesa
- Subjects
education.field_of_study ,medicine.medical_specialty ,Framingham Risk Score ,Thrombocytosis ,Essential thrombocythemia ,Constitutional symptoms ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Spearman's rank correlation coefficient ,International Prognostic Scoring System ,Internal medicine ,medicine ,Myelofibrosis ,education ,business - Abstract
Background: Post polycythemia vera (PV) and essential thrombocytosis (ET) myelofibrosis (MF), like primary MF (PMF), are heralded by splenomegaly, cytopenias, heavy symptom burden, and decreased overall survival. Risk prognostication tools, including the dynamic international prognostic scoring system (DIPSS) and the Passamonti risk score for post-PV MF (Passamonti et al. Blood 2010, 2008), are helpful to estimate survival and guide therapeutic decision-making. For Post-PV/ET MF, it is unknown if DIPSS correlates with the Passamonti risk score. Here we evaluate the correlation between the two available risk prognostication tools in post-PV/ET MF. Methods: Retrospective chart review conducted for patients with post-PV/ET MF seen between 2000-2012. Descriptive statistics were used to describe patient demographic and clinical variables in post PV/ET patients. DIPSS Score: calculated at time of last follow up: 1 point for age >65, 2 points for hemoglobin 25 x 109, 1 point for circulating blasts 1% and 1 point for constitutional symptoms. Risk group was assigned: low-risk (0 adverse points), intermediate-1 risk (1 adverse point), intermediate-2 risk (2-3 adverse points) and high-risk (4-6 adverse points). Passamonti Risk Scores: calculated at time of last follow up: with 1 point assigned for hemoglobin level less than 100 g/L (10 g/dL), platelet count less than 100 x10 (9)/L, and/or leukocyte count more than 30x10(9)/L. Cross-tabulation of DIPSS score versus Passamonti risk score at time of last follow-up was conducted and the percent agreement was described. Spearman correlation coefficient between DIPSS score at follow-up with Passamonti score was conducted. Results: Patients: Sixty-one (58%) post-ET and 44 (42%) post-PV patients were identified, total N=105. Male to Female ratio was 1:1. Median age was 65 (range 25-87). JAK2 V617Fpresent in 68 (65.4%). Median hemoglobin was 10.9 g/dL (range 5.3-17.0), median platelet count 287 x 109 (range 20-1864), and median WBC was 11.1x 109 (range 1.1-165). Risk prognostication: When DIPSS risk scores were applied 11 patients were low, 48 patients were Intermediate-1, 31 patients were Intermediate-2, and 10 patients were high. When Passamonti risk scores were applied 57 patients received score of 0, 31 patients scored 1, 9 patients scored 2, and 3 patients scored 3. DIPSS and Passamonti risk score agreement: The overall agreement between DIPSS and Passamonti risk scores was low, with 24% of cases in agreement. Spearman correlation: Rho=0.451; p Table 1. DIPSS and Passamonti Agreement Passamonti Risk Score DIPSS 0 1 2 3 Total Low 9 (75%) 3 (25%) 0 0 12 Int-1 31 (77.5%) 8 (20%) 1 (2.5%) 0 40 Int-2 17 (43.6%) 14 (35.9%) 6 (15.4%) 2 (5.1%) 39 High 0 6 (75%) 1 (12.5%) 1 (12.5%) 8 Total 57 (57.6%) 31 (31.3%) 8 (8%) 3 (3%) 100 Conclusion: Post PV/ET MF represents a unique clinical entity and risk prognostication schemes developed for PMF, such as DIPSS, may not represent accurate prognosis estimation in this subgroup of MF. When DIPSS and Passamonti risk scores were applied to same post PV/ET group, agreement was poor at 24%. Additionally, DIPSS was more likely to assign patients to high-risk category than Passamonti. Further studies are needed to evaluate the DIPSS and Passamonti prognostic risk score application to the post PV/ET MF population. Disclosures Mesa: Incyte Corporation: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; CTI Biopharma: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding.
- Published
- 2015
16. Impact of timing of adjuvant chemotherapy for early breast cancer: the Royal Marsden Hospital experience
- Author
-
Alicia Okines, Stephen R. D. Johnston, Vaselios Angelis, T. Irfan, Ian E. Smith, Emma Kipps, Maria Coakley, Kabir Mohammed, Nicholas C. Turner, Alistair Ring, G. Walsh, Bernice Asare, and Marina Parton
- Subjects
Adult ,Bridged-Ring Compounds ,Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Anthracycline ,medicine.medical_treatment ,Population ,Breast Neoplasms ,Article ,Breast Neoplasms, Male ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Anthracyclines ,education ,Retrospective Studies ,education.field_of_study ,Chemotherapy ,Taxane ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,United Kingdom ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Taxoids ,business - Abstract
BACKGROUND: The optimal time to deliver adjuvant chemotherapy has not been defined. METHODS: A retrospective study of consecutive patients receiving adjuvant anthracycline and/or taxane 1993–2010. Primary endpoint included 5-year disease-free survival (DFS) in patients commencing chemotherapy
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.