37 results on '"Sebag-Montefiore D"'
Search Results
2. The Long and the Short of it: the Role of Short-course Radiotherapy in the Neoadjuvant Management of Rectal Cancer
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Slevin, F., Hanna, C.R., Appelt, A., Cunningham, C., Marijnen, C.A.M., Sebag-Montefiore, D., and Muirhead, R.
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- 2022
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3. Multicentre Investigation of Prognostic Factors Incorporating p16 and Tumour Infiltrating Lymphocytes for Anal Cancer After Chemoradiotherapy
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Wakeham, K., Murray, L., Muirhead, R., Hawkins, M.A., Sebag-Montefiore, D., Brown, S., Murphy, L., Thomas, G., Bell, S., Whibley, M., Morgan, C., Sleigh, K., and Gilbert, D.C.
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- 2021
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4. Hitting the Target: Developing High-quality Evidence for Proton Beam Therapy Through Randomised Controlled Trials
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Hudson, E.M., primary, Slevin, F., additional, Biscombe, K., additional, Brown, S.R., additional, Haviland, J.S., additional, Murray, L., additional, Kirby, A.M., additional, Thomson, D.J., additional, Sebag-Montefiore, D., additional, and Hall, E., additional
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- 2023
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5. Modeling Acute Chemoradiotherapy (CRT) Diarrhea Severity Using Automatically Contoured Small Bowel
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Shen, Z., primary, Brand, D., additional, Zhang, Y., additional, Simard, M., additional, Lopes, A., additional, Miles, E., additional, Gilbert, A., additional, West, N., additional, Blake, A., additional, Royle, G., additional, Appelt, A., additional, Maughan, T.S., additional, Sebag-Montefiore, D., additional, Collins-Fekete, C.A., additional, and Hawkins, M.A., additional
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- 2023
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6. OC-0831 Standard vs dose reduced chemoradiotherapy in anal cancer: short-term results of the PLATO-ACT4 RCT
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Gilbert, A., primary, Webster, J., additional, Brown, S., additional, Copeland, J., additional, Ruddock, S., additional, Gilbert, D., additional, Hawkins, M., additional, Muirhead, R., additional, Renehan, A., additional, Adams, R., additional, Harrison, M., additional, and Sebag-Montefiore, D., additional
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- 2023
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7. OC-0909 COVID RT – a national study of radiotherapy decisions and their impact on patient outcomes.
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Evans, M., primary, Shelton, J., additional, Hinchliffe, R., additional, Wills, L., additional, Spencer, K., additional, Lewis, P., additional, Johnson, S., additional, Huddart, R., additional, Chan, C., additional, Burnett, A., additional, Morris, E., additional, and Sebag-Montefiore, D., additional
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- 2023
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8. OC-0272 Organ preservation in rectal cancer: the randomised STAR-TREC phase II trial
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Marijnen, C., primary, de Wilt, J., additional, Bach, S., additional, Peters, F., additional, Spindler, K., additional, Appelt, A., additional, Teo, M., additional, Homer, V., additional, Abbott, N., additional, Geh, I., additional, Korsgen, S., additional, Al-Najami, I., additional, Rombouts, A., additional, Christensen, P., additional, Gilbert, A., additional, Navarro-Nunez, L., additional, Quirke, P., additional, West, N., additional, and Sebag-Montefiore, D., additional
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- 2023
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9. EP05.01-007 CONCORDE - A Phase Ib Platform Study of Novel Agents in COmbinatioN with COnventional RaDiothErapy in Non-small Cell Lung Cancer (NSCLC)
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Horne, A., primary, Brown, S., additional, Butterworth, K., additional, Chalmers, A., additional, Collinson, F., additional, Dive, C., additional, Faivre-Finn, C., additional, Forster, M., additional, Franks, K., additional, Gilbert, A., additional, Hallam, M., additional, Hanna, G., additional, Harrow, S., additional, Hartley, J., additional, Hiley, C., additional, Jones, R., additional, Katona, E., additional, Kendall, J., additional, Krebs, M., additional, Mallison, G., additional, Oughton, J.B., additional, Phillip, R., additional, Rothwell, D., additional, Sebag-Montefiore, D., additional, Shaw, P., additional, Walls, G., additional, Walker, F., additional, Young, R., additional, and Greystoke, A., additional
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- 2022
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10. OC-0269 Standard vs dose escalated chemoradiotherapy in anal cancer: Phase II results of the PLATO-ACT5 RCT
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Gilbert, A., primary, Webster, J., additional, Brown, S., additional, Copeland, J., additional, Ruddock, S., additional, Adams, R., additional, Harrison, M., additional, Muirhead, R., additional, Renehan, A., additional, Sebag-Montefiore, D., additional, and Hawkins, M., additional
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- 2022
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11. PO-1321 Prognostic factors for anal cancer treated with conformal radiotherapy – a systematic review
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Theophanous, S., primary, Samuel, R., additional, Lilley, J., additional, Henry, A., additional, Sebag-Montefiore, D., additional, Gilbert, A., additional, and Appelt, A., additional
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- 2022
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12. OC-0103 SCALOP2:A multicenter randomized trial of RT dose escalation and nelfinavir in pancreatic cancer
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Mukherjee, S., primary, Qi, C., additional, Shaw, R., additional, Bridgewater, J., additional, Radhakrishna, G., additional, Patel, N., additional, Tranter, B., additional, Parsons, P., additional, Falk, S., additional, Wasan, H., additional, Holyoake, D., additional, Roy, R., additional, Scott-Brown, M., additional, Hurt, C., additional, Sebag-Montefiore, D., additional, Maughan, T., additional, Hawkins, M., additional, and Corrie, P., additional
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- 2022
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13. Bayesian network structure for predicting local tumor recurrence in rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery.
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Osong, B, Masciocchi, C, Damiani, A, Bermejo, I, Meldolesi, E, Chiloiro, G, Berbee, M, Lee, SH, Dekker, A, Valentini, V, Gerard, J-P, Rödel, C, Bujko, K, van de Velde, C, Folkesson, J, Sainato, A, Glynne-Jones, R, Ngan, S, Brændengen, M, Sebag-Montefiore, D, van Soest, J, Osong, B, Masciocchi, C, Damiani, A, Bermejo, I, Meldolesi, E, Chiloiro, G, Berbee, M, Lee, SH, Dekker, A, Valentini, V, Gerard, J-P, Rödel, C, Bujko, K, van de Velde, C, Folkesson, J, Sainato, A, Glynne-Jones, R, Ngan, S, Brændengen, M, Sebag-Montefiore, D, and van Soest, J
- Abstract
BACKGROUND AND PURPOSE: Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques. PATIENTS AND METHODS: A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values. RESULTS: The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest. CONCLUSION: We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5 years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert-based structures.
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- 2022
14. 'Global Multidisciplinary Team Meetings': Challenging Cases Virtual Forums from the International Multidisciplinary Anal Cancer Conference (IMACC)
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Segelov, E, Guren, MG, Sebag-Montefiore, D, Rao, S, Johnsson, A, Franco, P, Deutsch, E, Arnold, D, and Spindler, KLG
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Patient Care Team ,Oncology ,Clinical Decision-Making ,Gastroenterology ,Anal Canal ,Humans ,Anus Neoplasms - Published
- 2022
15. Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study
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Theophanous, S, Lønne, P-I, Choudhury, A, Berbee, M, Dekker, A, Dennis, K, Dewdney, A, Gambacorta, MA, Gilbert, A, Guren, MG, Holloway, L, Jadon, R, Kochhar, R, Mohamed, AA, Muirhead, R, Parés, O, Raszewski, L, Roy, R, Scarsbrook, A, Sebag-Montefiore, D, Spezi, E, Spindler, K-LG, van Triest, B, Vassiliou, V, Malinen, E, Wee, L, Appelt, AL, on behalf of the atomCAT consortium, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Radiotherapie OC (9), RS: GROW - R2 - Basic and Translational Cancer Biology, RS: FSE BISS, Adams, Richard, Amin, Muhammad, Capocchiano, Nikola Dino, Colley, Peter, Damiani, Andrea, De Luca, Viola, Deijen, Charlotte, Demetriou, Antri, Eble, Michael J., Field, Matthew, Georgiou, Loukia, Henry, Ann, Lau, Joanna, Lee, Mark, Lilley, John, Lopes, Patricia, Lutz, Christina Maria, Manfrida, Stefania, Marsden, Jenny, Masciocchi, Carlotta, Mercer, Joseph, Nyvang, Lars, Papageorgiou, Elisavet, Price, Gareth, Rackley, Thomas, Savino, Mariachiara, Stroom, Joep, Stylianou, Ioannis, Tambe, Nilesh, Thwaites, David, Trojanowski, Maciej, Valentini, Vincenzo, and Vieira, Sandra
- Subjects
Distributed learning ,Locoregional control ,Freedom from distant metastasis ,Squamous cell carcinoma ,Federated learning ,outcome modelling ,Overall survival ,Chemoradiotherapy ,Anal cancer ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA - Abstract
Diagnostic and prognostic research 6, 14 (2022). doi:10.1186/s41512-022-00128-8, Published by BioMed Central, [London]
- Published
- 2022
16. The Long and the Short of it: the Role of Short-course Radiotherapy in the Neoadjuvant Management of Rectal Cancer
- Author
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Slevin, F., primary, Hanna, C.R., additional, Appelt, A., additional, Cunningham, C., additional, Marijnen, C.A.M., additional, Sebag-Montefiore, D., additional, and Muirhead, R., additional
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- 2021
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17. A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer (APHRODITE): protocol for a multicentre, open-label randomised controlled trial
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Hudson, EM, Noutch, S, Brown, S, Adapala, R, Bach, SP, Burnett, C, Burrage, A, Gilbert, A, Hawkins, M, Howard, D, Jefford, M, Kochhar, R, Saunders, M, Seligmann, J, Smith, A, Teo, M, Webb, EJ, Webster, A, West, N, Sebag-Montefiore, D, Gollins, S, and Appelt, AL
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Clinical Trials, Phase II as Topic ,Postoperative Complications ,Rectal Neoplasms ,Quality of Life ,Humans ,Multicenter Studies as Topic ,Chemoradiotherapy ,Syndrome ,General Medicine ,Randomized Controlled Trials as Topic - Abstract
IntroductionThe standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR). This non-surgical management can be attractive, particularly for patients at high risk of surgical complications. Modern radiotherapy techniques allow increased treatment conformality, enabling increased radiation dose to the tumour while reducing dose to normal tissue. The objective of this trial is to assess if radiotherapy dose escalation increases the cCR rate, with acceptable toxicity, for treatment of patients with early rectal cancer unsuitable for radical surgery.Methods and analysisAPHRODITE (A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer) is a multicentre, open-label randomised controlled phase II trial aiming to recruit 104 participants from 10 to 12 UK sites. Participants will be allocated with a 2:1 ratio of intervention:control. The intervention is escalated dose radiotherapy (62 Gy to primary tumour, 50.4 Gy to surrounding mesorectum in 28 fractions) using simultaneous integrated boost. The control arm will receive 50.4 Gy to the primary tumour and surrounding mesorectum. Both arms will use intensity-modulated radiotherapy and daily image guidance, combined with concurrent chemotherapy (capecitabine, 5-fluorouracil/leucovorin or omitted). The primary endpoint is the proportion of participants with cCR at 6 months after start of treatment. Secondary outcomes include early and late toxicities, time to stoma formation, overall survival and patient-reported outcomes (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30 and QLQ-CR29, low anterior resection syndrome (LARS) questionnaire).Ethics and disseminationThe trial obtained ethical approval from North West Greater Manchester East Research Ethics Committee (reference number 19/NW/0565) and is funded by Yorkshire Cancer Research. The final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines.Trial registration numberISRCTN16158514.
- Published
- 2022
18. OC-0420 Assessing plan quality in the ‘PLATO anal cancer trial 5’ pilot phase with automated planning
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Barrell, M., Abbott, N., Adams, R., Hawkins, M., Sebag-Montefiore, D., Millin, A., and Wheeler, P.
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- 2023
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19. The Impact of National Radiotherapy Guidelines: The UK Anal Cancer Story.
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Adams, R., Drinkwater, K., Gilbert, D.C., Hawkins, M.A., Sebag-Montefiore, D., Thorpe, N., and Muirhead, R.
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MEDICAL protocols , *RADIOTHERAPY , *ANAL tumors - Published
- 2024
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20. Pre-treatment magnetic resonance imaging in anal cancer: large-scale evaluation of mrT, mrN and novel staging parameters.
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Sekhar H, Kochhar R, Carrington B, Kaye T, Tolan D, Malcomson L, Saunders MP, Sperrin M, Sebag-Montefiore D, van Herk M, and Renehan AG
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- Humans, Male, Female, Middle Aged, Aged, Chemoradiotherapy, Adult, Aged, 80 and over, Prognosis, Anus Neoplasms therapy, Anus Neoplasms pathology, Anus Neoplasms diagnostic imaging, Anus Neoplasms mortality, Magnetic Resonance Imaging methods, Neoplasm Staging, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell pathology
- Abstract
Background: In patients with squamous cell carcinoma of the anus (SCCA), magnetic resonance (MR) imaging is recommended for pre-treatment staging prior to chemo-radiotherapy (CRT), but large-scale evaluation of its staging performance is lacking., Methods: We re-characterised pre-treatment MRs from 228 patients with non-metastatic SCCA treated consecutively by CRT (2006-2015) at one UK cancer centre. We derived TN staging from tumour size (mrTr) and nodal involvement (mrN), and additionally characterised novel beyond TN features such as extramural vascular invasion (mrEMVI) and tumour signal heterogeneity (mrTSH). Primary outcomes were 5-year overall survival (OS) and 3-year loco-regional failure (LRF). Time-to-event analyses used Kaplan-Meier estimates; Hazard Ratios (HRs) with confidence intervals (CIs) were derived from Cox models., Results: With a median follow up of 60.9 months, 5-year OS was 74%. Poor OS was associated with increasing mrT (HR: 1.12 per cm [95% CI: 1.07-1.33]), nodal positivity (HR 2.08 [95% CI 1.23-3.52]) and mrEMVI (HR 3.66 [95% CI: 1.88-7.41]). 3-year LRF rate was 16.5%. Increased LRF was associated with increasing mrT (HR: 1.43 per cm [95% CI: 1.26-1.63]), nodal positivity (HR 2.70 [95% CI 1.39-5.24]) and mrTSH (HR 2.66 [95% CI 1.29-5.48])., Conclusions: In SCCA, the study demonstrates that mrT and mrN stages are prognostic, while mrEMVI and mrTSH may be novel prognostic factors., (© 2024. The Author(s).)
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- 2024
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21. Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.
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Mukherjee S, Qi C, Shaw R, Jones CM, Bridgewater JA, Radhakrishna G, Patel N, Holmes J, Virdee PS, Tranter B, Parsons P, Falk S, Wasan HS, Ajithkumar TV, Holyoake D, Roy R, Scott-Brown M, Hurt CN, O'Neill E, Sebag-Montefiore D, Maughan TS, Hawkins MA, and Corrie P
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- Humans, Male, Female, Middle Aged, Aged, Adult, Paclitaxel administration & dosage, Paclitaxel adverse effects, Maximum Tolerated Dose, Deoxycytidine analogs & derivatives, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine therapeutic use, Gemcitabine, Aged, 80 and over, Quality of Life, Albumins administration & dosage, Albumins therapeutic use, Albumins adverse effects, Progression-Free Survival, Protease Inhibitors adverse effects, Protease Inhibitors therapeutic use, Protease Inhibitors administration & dosage, Nelfinavir therapeutic use, Nelfinavir administration & dosage, Nelfinavir adverse effects, Pancreatic Neoplasms therapy, Pancreatic Neoplasms pathology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms mortality, Chemoradiotherapy adverse effects, Chemoradiotherapy methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects
- Abstract
Background: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel., Methods: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL)., Results: High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment., Conclusions: Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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22. Identification and validation of a machine learning model of complete response to radiation in rectal cancer reveals immune infiltrate and TGFβ as key predictors.
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Domingo E, Rathee S, Blake A, Samuel L, Murray G, Sebag-Montefiore D, Gollins S, West N, Begum R, Richman S, Quirke P, Redmond K, Chatzipli A, Barberis A, Hassanieh S, Mahmood U, Youdell M, McDermott U, Koelzer V, Leedham S, Tomlinson I, Dunne P, Buffa FM, and Maughan TS
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Biomarkers, Tumor genetics, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Prognosis, Transcriptome, Treatment Outcome, Machine Learning, Rectal Neoplasms genetics, Rectal Neoplasms radiotherapy, Rectal Neoplasms pathology, Rectal Neoplasms therapy, Rectal Neoplasms metabolism, Rectal Neoplasms immunology, Transforming Growth Factor beta metabolism, Transforming Growth Factor beta genetics
- Abstract
Background: It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications., Methods: We identified two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211)., Findings: Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC., Interpretation: RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFβ signalling. These tumours may be identified with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFβ signalling inhibition., Funding: The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1)., Competing Interests: Declaration of interests TSM is now employed by the University of Liverpool and acknowledges consultancy payments from Astrazeneca, Ground Truth Laboratories and Nordic Pharma. V.H.K. has served as an invited speaker on behalf of Indica Labs. U.M is now employed by and holds stocks in Astrazeneca. Other authors declare no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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23. The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review.
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Gilbert A, Samuel R, Cagney D, Sebag-Montefiore D, Brown J, and Brown SR
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- Humans, Clinical Trials as Topic, Radiotherapy methods, Radiotherapy economics, Clinical Trial Protocols as Topic, Radiation Oncology standards, Neoplasms radiotherapy, Research Design
- Abstract
The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex setup pathways (including quality assurance, user training, and integrating multiple modalities of treatment) may hinder clinical advances. We carried out a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, reviewing the findings using a landscape analysis. Results were summarized descriptively, reporting on trial characteristics highlighting the benefits, limitations, and challenges of developing and implementing radiotherapy master protocols, with three case studies selected to explore these issues in more detail. Twelve studies were suitable for inclusion (4 platform trials, 3 umbrella trials, and 5 basket trials), evaluating a mix of solid tumor sites in both curative and palliative settings. The interventions were categorized into 1) novel agent and radiotherapy combinations; 2) radiotherapy dose personalization; and 3) device evaluation, with a case study provided for each intervention. Benefits of master protocol trials for radiotherapy intervention include protocol efficiency for implementation of novel radiotherapy techniques; accelerating the evaluation of novel agent drug and radiotherapy combinations; and more efficient translational research opportunities, leading to cost savings and research efficiency to improve patient outcomes. Master protocols offer an innovative platform under which multiple clinical questions can be addressed within a single trial. Due to the complexity of radiotherapy trial setup, cost and research efficiency savings may be more apparent than in systemic treatment trials. Use of this research approach may be the change needed to push forward oncological innovation within radiation oncology., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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24. Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures.
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Mahmood U, Blake A, Rathee S, Samuel L, Murray G, Sebag-Montefiore D, Gollins S, West NP, Begum R, Bach SP, Richman SD, Quirke P, Redmond KL, Salto-Tellez M, Koelzer VH, Leedham SJ, Tomlinson I, Dunne PD, Buffa FM, Maughan TS, and Domingo E
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Capecitabine therapeutic use, Capecitabine administration & dosage, Fluorouracil therapeutic use, Fluorouracil administration & dosage, Fluorouracil pharmacology, Gene Expression Profiling, Oxaliplatin therapeutic use, Oxaliplatin administration & dosage, Oxaliplatin pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Gene Expression Regulation, Neoplastic drug effects, Rectal Neoplasms pathology, Rectal Neoplasms genetics, Rectal Neoplasms therapy, Rectal Neoplasms radiotherapy, Rectal Neoplasms mortality, Neoadjuvant Therapy, Transcriptome
- Abstract
Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU., Significance: Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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25. Image-based consensus molecular subtyping in rectal cancer biopsies and response to neoadjuvant chemoradiotherapy.
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Lafarge MW, Domingo E, Sirinukunwattana K, Wood R, Samuel L, Murray G, Richman SD, Blake A, Sebag-Montefiore D, Gollins S, Klieser E, Neureiter D, Huemer F, Greil R, Dunne P, Quirke P, Weiss L, Rittscher J, Maughan T, and Koelzer VH
- Abstract
The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n = 114 and SALZBURG, n = 55 patients). DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR = 2.69, 95% CI 1.01-7.17, p = 0.048). Conversely, imCMS4 was associated with lack of pCR (OR = 0.25, 95% CI 0.07-0.88, p = 0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3. imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment., (© 2024. The Author(s).)
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- 2024
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26. Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) - protocol for a multi-centre open-label randomised trial.
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Hudson EM, Noutch S, Webster J, Brown SR, Boele FW, Al-Salihi O, Baines H, Bulbeck H, Currie S, Fernandez S, Hughes J, Lilley J, Smith A, Parbutt C, Slevin F, Short S, Sebag-Montefiore D, and Murray L
- Subjects
- Adult, Humans, Quality of Life, Neoplasm Recurrence, Local drug therapy, Brain, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Clinical Trials, Phase II as Topic, Glioblastoma drug therapy, Glioblastoma radiotherapy, Re-Irradiation
- Abstract
Introduction: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM., Methods and Analysis: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival., Ethics and Dissemination: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines., Trial Registration Number: ISRCTN60524., Competing Interests: Competing interests: FS reports grants from Cancer Research UK, during the conduct of the study. DS-M reports grants from Jon Moulton Charitable Foundation, grants from Yorkshire Cancer Research, during the conduct of the study. LM reports grants from Jon Moulton Charity Trust, grants from Cancer Research UK, during the conduct of the study; grants from Yorkshire Cancer Research, outside the submitted work. SRB reports grants from Jon Moulton Charitable Foundation, grants from Yorkshire Cancer Research, during the conduct of the study. SS reports advisory board activity for Bayer, CeCaVa Laboratory Research project support, Apollomics., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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27. Preoperative Treatment of Locally Advanced Rectal Cancer.
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Sebag-Montefiore D, Cervantes A, and Rodel C
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- Humans, Treatment Outcome, Rectum, Rectal Neoplasms surgery
- Published
- 2023
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28. Patient-reported outcomes in PROSPECT trial (Alliance N1048) - FOLFOX is not a panacea.
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O'Cathail SM, Adams R, Hawkins MA, Sebag-Montefiore D, Marijnen CAM, and Fokas E
- Abstract
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2023
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29. Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision.
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Gilbert A, Homer V, Brock K, Korsgen S, Geh I, Hill J, Gill T, Hainsworth P, Tutton M, Khan J, Robinson J, Steward M, Cunningham C, Kaur M, Magill L, Russell A, Quirke P, West NP, Sebag-Montefiore D, and Bach SP
- Subjects
- Humans, Aged, Quality of Life, Rectal Neoplasms radiotherapy, Colorectal Neoplasms
- Abstract
Background: Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1-2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84-99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group., Methods: Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed., Findings: Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67-80] vs 65 years [61-71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6-12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups., Interpretation: The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery., Funding: Cancer Research UK., Competing Interests: Declaration of interests AG is funded by a Cancer Research UK clinical trial fellowship (CRUK/28301). PQ and NPW were funded by a programme grant from Yorkshire Cancer Research. PQ is a National Institute for Health and Care Research senior investigator. NPW reports personal fees from Eisai. KB reports stock ownership in GlaxoSmithKline and UCB. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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30. Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units.
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Love SB, Cafferty F, Snowdon C, Carty K, Savage J, Pallmann P, McParland L, Brown L, Masters L, Schiavone F, Hague D, Townsend S, Amos C, South A, Sturgeon K, Langley R, Maughan T, James N, Hall E, Kernaghan S, Bliss J, Turner N, Tutt A, Yap C, Firth C, Kong A, Mehanna H, Watts C, Hills R, Thomas I, Copland M, Bell S, Sebag-Montefiore D, Jones R, Parmar MKB, and Sydes MR
- Subjects
- Humans, United Kingdom, Data Management, Research Design
- Abstract
Background: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations., Methods: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols., Results: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement., Discussion: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently., (© 2022. The Author(s).)
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- 2022
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31. Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study.
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Theophanous S, Lønne PI, Choudhury A, Berbee M, Dekker A, Dennis K, Dewdney A, Gambacorta MA, Gilbert A, Guren MG, Holloway L, Jadon R, Kochhar R, Mohamed AA, Muirhead R, Parés O, Raszewski L, Roy R, Scarsbrook A, Sebag-Montefiore D, Spezi E, Spindler KG, van Triest B, Vassiliou V, Malinen E, Wee L, and Appelt AL
- Abstract
Background: Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy., Methods: This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients., Discussion: The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification., (© 2022. The Author(s).)
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- 2022
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32. Prognostic factors for patients with anal cancer treated with conformal radiotherapy-a systematic review.
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Theophanous S, Samuel R, Lilley J, Henry A, Sebag-Montefiore D, Gilbert A, and Appelt AL
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- Chemoradiotherapy methods, Humans, Prognosis, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Retrospective Studies, Anus Neoplasms radiotherapy, Radiotherapy, Conformal adverse effects, Radiotherapy, Intensity-Modulated methods
- Abstract
Aims: Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques., Materials and Methods: A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results., Results: The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study - pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors., Conclusion: Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach., (© 2022. The Author(s).)
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- 2022
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33. Bayesian network structure for predicting local tumor recurrence in rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery.
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Osong B, Masciocchi C, Damiani A, Bermejo I, Meldolesi E, Chiloiro G, Berbee M, Lee SH, Dekker A, Valentini V, Gerard JP, Rödel C, Bujko K, van de Velde C, Folkesson J, Sainato A, Glynne-Jones R, Ngan S, Brændengen M, Sebag-Montefiore D, and van Soest J
- Abstract
Background and Purpose: Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques., Patients and Methods: A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values., Results: The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest., Conclusion: We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5 years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert-based structures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)
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- 2022
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34. A Machine-Learning-Based Bibliometric Analysis of the Scientific Literature on Anal Cancer.
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Franco P, Segelov E, Johnsson A, Riechelmann R, Guren MG, Das P, Rao S, Arnold D, Spindler KG, Deutsch E, Krengli M, Tombolini V, Sebag-Montefiore D, and De Felice F
- Abstract
Squamous-cell carcinoma of the anus (ASCC) is a rare disease. Barriers have been encountered to conduct clinical and translational research in this setting. Despite this, ASCC has been a prime example of collaboration amongst researchers. We performed a bibliometric analysis of ASCC-related literature of the last 20 years, exploring common patterns in research, tracking collaboration and identifying gaps. The electronic Scopus database was searched using the keywords "anal cancer", to include manuscripts published in English, between 2000 and 2020. Data analysis was performed using R-Studio 0.98.1091 software. A machine-learning bibliometric method was applied. The bibliometrix R package was used. A total of 2322 scientific documents was found. The average annual growth rate in publication was around 40% during 2000-2020. The five most productive countries were United States of America (USA), United Kingdom (UK), France, Italy and Australia. The USA and UK had the greatest link strength of international collaboration (22.6% and 19.0%). Two main clusters of keywords for published research were identified: (a) prevention and screening and (b) overall management. Emerging topics included imaging, biomarkers and patient-reported outcomes. Further efforts are required to increase collaboration and funding to sustain future research in the setting of ASCC.
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- 2022
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35. Treatment of Squamous Cell Carcinoma of the Anus, Unresolved Areas and Future Perspectives for Research: Perspectives of Research Needs in Anal Cancer.
- Author
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Guren MG, Sebag-Montefiore D, Franco P, Johnsson A, Segelov E, Deutsch E, Rao S, Spindler KG, and Arnold D
- Subjects
- Anal Canal, Chemoradiotherapy, Humans, Prognosis, Anus Neoplasms drug therapy, Carcinoma, Squamous Cell drug therapy
- Abstract
Anal cancer is a relatively rare, mostly HPV-related cancer. The curative treatment consists of concurrent chemoradiation delivered with modern radiotherapy techniques. The prognosis for most patients with early localized disease is very favourable; however patients with locally advanced disease and/or HPV negative tumours are at higher risk of locoregional and distant treatment failure. Tailored approaches are presently being investigated to determine the most suitable regimen in terms of radiotherapy dose prescription, target volume selection, normal tissue avoidance, and combination therapy. Metastatic anal cancer is treated with chemotherapy aiming at prolonged survival. The role of immune therapy in the clinical setting is being investigated. There is little knowledge on the biology of anal cancer, and an urgent need for more clinical and translational research dedicated to this disease. In this article, the evidence-base for the current treatment is briefly reviewed, and perspectives on future research needs are high-lighted., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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36. International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer.
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Fokas E, Appelt A, Glynne-Jones R, Beets G, Perez R, Garcia-Aguilar J, Rullier E, Smith JJ, Marijnen C, Peters FP, van der Valk M, Beets-Tan R, Myint AS, Gerard JP, Bach SP, Ghadimi M, Hofheinz RD, Bujko K, Gani C, Haustermans K, Minsky BD, Ludmir E, West NP, Gambacorta MA, Valentini V, Buyse M, Renehan AG, Gilbert A, Sebag-Montefiore D, and Rödel C
- Subjects
- Chemoradiotherapy adverse effects, Consensus, Delphi Technique, Humans, Organ Preservation standards, Rectal Neoplasms therapy
- Abstract
Multimodal treatment strategies for patients with rectal cancer are increasingly including the possibility of organ preservation, through nonoperative management or local excision. Organ preservation strategies can enable patients with a complete response or near-complete clinical responses after radiotherapy with or without concomitant chemotherapy to safely avoid the morbidities associated with radical surgery, and thus to maintain anorectal function and quality of life. However, standardization of the key outcome measures of organ preservation strategies is currently lacking; this includes a lack of consensus of the optimal definitions and selection of primary end points according to the trial phase and design; the optimal time points for response assessment; response-based decision-making; follow-up schedules; use of specific anorectal function tests; and quality of life and patient-reported outcomes. Thus, a consensus statement on outcome measures is necessary to ensure consistency and facilitate more accurate comparisons of data from ongoing and future trials. Here, we have convened an international group of experts with extensive experience in the management of patients with rectal cancer, including organ preservation approaches, and used a Delphi process to establish the first international consensus recommendations for key outcome measures of organ preservation, in an attempt to standardize the reporting of data from both trials and routine practice in this emerging area., (© 2021. Springer Nature Limited.)
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- 2021
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37. The benefit of MR-only radiotherapy treatment planning for anal and rectal cancers: A planning study.
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Bird D, Nix MG, McCallum H, Teo M, Gilbert A, Casanova N, Cooper R, Buckley DL, Sebag-Montefiore D, Speight R, Al-Qaisieh B, and Henry AM
- Subjects
- Anal Canal diagnostic imaging, Female, Humans, Magnetic Resonance Spectroscopy, Organs at Risk, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Rectum diagnostic imaging, Radiotherapy, Intensity-Modulated, Rectal Neoplasms diagnostic imaging, Rectal Neoplasms radiotherapy
- Abstract
Introduction: Limited evidence exists showing the benefit of magnetic resonance (MR)-only radiotherapy treatment planning for anal and rectal cancers. This study aims to assess the impact of MR-only planning on target volumes (TVs) and treatment plan doses to organs at risks (OARs) for anal and rectal cancers versus a computed tomography (CT)-only pathway., Materials and Methods: Forty-six patients (29 rectum and 17 anus) undergoing preoperative or radical external beam radiotherapy received CT and T2 MR simulation. TV and OARs were delineated on CT and MR, and volumetric arc therapy treatment plans were optimized independently (53.2 Gy/28 fractions for anus, 45 Gy/25 fractions for rectum). Further treatment plans assessed gross tumor volume (GTV) dose escalation. Differences in TV volumes and OAR doses, in terms of Vx Gy (organ volume (%) receiving x dose (Gy)), were assessed., Results: MR GTV and primary planning TV (PTV) volumes systematically reduced by 13 cc and 98 cc (anus) and 44 cc and 109 cc (rectum) respectively compared to CT volumes. Statistically significant OAR dose reductions versus CT were found for bladder and uterus (rectum) and bladder, penile bulb, and genitalia (anus). With GTV boosting, statistically significant dose reductions were found for sigmoid, small bowel, vagina, and penile bulb (rectum) and vagina (anus)., Conclusion: Our findings provide evidence that the introduction of MR (whether through MR-only or CT-MR pathways) to radiotherapy treatment planning for anal and rectal cancers has the potential to improve treatments. MR-related OAR dose reductions may translate into less treatment-related toxicity for patients or greater ability to dose escalate., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)
- Published
- 2021
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