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2. Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus

Author

Fitzgerald, R.C., Noorani, A., Edwards, P.A.W., Grehan, N., Nutzinger, B., Hughes, C., Fidziukiewicz, E., MacRae, S., Northrop, A., Contino, G., Li, X., de la Rue, R., Katz-Summercorn, A., Abbas, S., Loureda, D., O'Donovan, M., Miremadi, A., Malhotra, S., Tripathi, M., Tavaré, S., Lynch, A.G., Eldridge, M., Secrier, M., Devonshire, G., Perner, J., Jammula, S., Davies, J., Crichton, C., Carroll, N., Safranek, P., Hindmarsh, A., Sujendran, V., Hayes, S.J., Ang, Y., Sharrocks, A., Preston, S.R., Oakes, S., Bagwan, I., Save, V., Skipworth, R.J.E., Hupp, T.R., O'Neill, J.R., Tucker, O., Beggs, A., Taniere, P., Puig, S., Underwood, T.J., Walker, R.C., Grace, B.L., Barr, H., Shepherd, N., Old, O., Lagergren, J., Davies, A., Chang, F., Goh, V., Ciccarelli, F.D., Sanders, G., Berrisford, R., Harden, C., Lewis, M., Cheong, E., Kumar, B., Parsons, S.L., Soomro, I., Kaye, P., Saunders, J., Lovat, L., Haidry, R., Igali, L., Scott, M., Sothi, S., Suortamo, S., Lishman, S., Hanna, G.B., Moorthy, K., Peters, C.J., Grabowska, A., Turkington, R., McManus, D., Coleman, H., Khoo, D., Fickling, W., Knight, William R.C., McEwen, Ricardo, Byrne, Ben E., Habib, Wais, Bott, Rebecca, Zylstra, Janine, Mahadeva, Ula, and Gossage, James A.

Published
2020
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4. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Author

Noorani, Ayesha, Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Hughes, Caitriona, Fidziukiewicz, Elwira, Bornschein, Jan, MacRae, Shona, Crawte, Jason, Contino, Gianmarco, Li, Xiaodun, Rue, Rachel de la, O’Donovan, Maria, Miremad, Ahmad, Malhotra, Shalini, Tripathi, Monika, Tavaré, Simon, Lynch, Andy G., Eldridge, Matthew, Secrier, Maria, Bower, Lawrence, Devonshire, Ginny, Perner, Juliane, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O’Neill, J. Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Underwood, Timothy J., Noble, Fergus, Owsley, Jack, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Igali, Laszlo, Scott, Michael, Sothi, Sharmila, Suortamo, Sari, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Grabowska, Anna, Turkington, Richard, Sawas, Tarek, Killcoyne, Sarah, Iyer, Prasad G., Wang, Kenneth K., Smyrk, Thomas C., Kisiel, John B., Qin, Yi, Ahlquist, David A., Rustgi, Anil K., Costa, Rui J., Gerstung, Moritz, Fitzgerald, Rebecca C., and Katzka, David A.

Published
2018
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5. Prehabilitation exercise before oesophagectomy: long-term follow-up of patients declining/withdrawing from the program

Author

Knight, William, primary, Moore, Jonathan L, additional, Whyte, Greg P, additional, Zylstra, Janine, additional, Lane, Andrew M, additional, Pate, James, additional, Gervais-Andre, Louise, additional, Maisey, Nick, additional, Hill, Mark, additional, Tham, Gemma, additional, Lagergren, Jesper, additional, Kelly, Mark, additional, Baker, Cara, additional, Van Hemelrijck, Mieke, additional, Goh, Vicky, additional, Gossage, James, additional, Browning, Mike, additional, and Davies, Andrew R, additional

Published
2023
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10. The Impact of COVID-19 on Clinical Nurse Specialists and Patients With Cancer:A Pan-Specialty Cross-sectional Survey

Author

Forster, Alice S, Zylstra, Janine, von Wagner, Christian, Hirst, Yasemin, Forster, Martin, Walshe, Rebecca, Kazzaz, Zainab, Steptoe, Andrew, Birchall, Martin, Patani, Neill, Forster, Alice S, Zylstra, Janine, von Wagner, Christian, Hirst, Yasemin, Forster, Martin, Walshe, Rebecca, Kazzaz, Zainab, Steptoe, Andrew, Birchall, Martin, and Patani, Neill

Abstract

PURPOSE/AIMS: Uptake and delivery of cancer services across the United Kingdom have been significantly impacted by the COVID-19 pandemic. This study aimed to understand the impact of the pandemic on the working practices of clinical nurse specialists and their patient interactions across different cancer specialties. DESIGN: We performed a cross-sectional survey exploring nurses' experiences of delivering care during the pandemic, as well as their perceptions of the concerns that cancer patients were experiencing. METHODS: Clinical nurse specialists working in London cancer services were invited to complete an online questionnaire. Nurses' experiences and their perceptions of patients' concerns were analyzed descriptively. RESULTS: Fifty-four nurses participated. Almost half had been redeployed to other clinical areas during the pandemic (n = 19). COVID-19 discussions added 5 to 10 minutes on average to most consultations, with nurses either working longer/unpaid hours (34%) or spending less time talking to patients about cancer (39%) to deal with this. Approximately 50% of nurses would have liked additional information and support from their hospital. CONCLUSIONS: Clinical nurse specialist time and resources have been stretched during the COVID-19 pandemic. Hospitals need to work with nursing staff to ensure the specific information needs of cancer patients are being met.

Published
2022

11. Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial

Author

Zylstra, Janine, primary, Whyte, Greg P, additional, Beckmann, Kerri, additional, Pate, James, additional, Santaolalla, Aida, additional, Gervais-Andre, Louise, additional, Russell, Beth, additional, Maisey, Nick, additional, Waters, Justin, additional, Tham, Gemma, additional, Lagergren, Jesper, additional, Green, Michael, additional, Kelly, Mark, additional, Baker, Cara, additional, Van Hemelrijck, Mieke, additional, Goh, Vicky, additional, Gossage, James, additional, Browning, Mike, additional, and Davies, Andrew, additional

Published
2022
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13. Predicting response to neoadjuvant chemotherapy in patients with oesophageal adenocarcinoma

Author

Bott, Rebecca K., primary, George, Gincy, additional, McEwen, Ricardo, additional, Zylstra, Janine, additional, Knight, William R. C., additional, Baker, Cara R., additional, Kelly, Mark, additional, Griffin, Nyree, additional, McAddy, Naami, additional, Maisey, Nick, additional, Van Hemelrijck, Mieke, additional, Gossage, James A., additional, Lagergren, Jesper, additional, and Davies, Andrew R., additional

Published
2021
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14. 646 PREDICTING RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH OESOPHAGEAL ADENOCARCINOMA

Author

Bott, Rebecca, primary, George, Gincy, additional, McEwen, Ricardo, additional, Zylstra, Janine, additional, Knight, William, additional, Baker, Cara, additional, Kelly, Mark, additional, Griffin, Nyree, additional, Mcaddy, Naami, additional, Maisey, Nick, additional, Van Hemelrijck, Mieke, additional, Gossage, James, additional, Lagergren, Jesper, additional, and Davies, Andrew, additional

Published
2021
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15. 674 TRANSITION FROM ESOPHAGECTOMY TO ENDOSCOPIC THERAPY FOR EARLY ESOPHAGEAL CANCER

Author

Reyhani, Arasteh, primary, Dunn, Jason M, additional, Santaolalla, Aida, additional, Zylstra, Janine, additional, Gimson, Eliza, additional, Pennington, Mark, additional, Baker, Cara R, additional, Kelly, Mark, additional, Van Hemelrijck, Mieke, additional, Lagergren, Jesper, additional, Zeki, Sebastian S, additional, Gossage, James A, additional, and Davies, Andrew R, additional

Published
2021
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16. Transition from esophagectomy to endoscopic therapy for early esophageal cancer

Author

Dunn, Jason M, primary, Reyhani, Arasteh, additional, Santaolalla, Aida, additional, Zylstra, Janine, additional, Gimson, Eliza, additional, Pennington, Mark, additional, Baker, Cara, additional, Kelly, Mark, additional, Van Hemelrijck, Mieke, additional, Lagergren, Jesper, additional, Zeki, Sebastian S, additional, Gossage, James A, additional, and Davies, Andrew R, additional

Published
2021
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17. Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins

Author

Bott, Rebecca K., primary, Beckmann, Kerri, additional, Zylstra, Janine, additional, Wilkinson, Michelle J., additional, Knight, William R. C., additional, Baker, Cara R., additional, Kelly, Mark, additional, Maisey, Nick, additional, Waters, Justin, additional, Van Hemelrijck, Mieke, additional, Smyth, Elizabeth C., additional, Allum, William H., additional, Lagergren, Jesper, additional, Gossage, James A., additional, Cunningham, David, additional, and Davies, Andrew R., additional

Published
2021
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19. P107 PREDICTION OF A POSITIVE CIRCUMFERENTIAL RESECTION MARGIN IN ADENOCARCINOMA OF THE ESOPHAGUS

Author

Goh Vicky, Jacques Audrey, Yip Connie, Griffin Nyree, Landau David, Kelly Mark, Van Hemelrijck Mieke, R C Knight William, R Davies Andrew, Zylstra Janine, R Baker Cara, Wulaningsih Wahyu, Largergren Jesper, Gaya DrAndrew, Maisey Nick, and A Gossage James

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Gastroenterology, medicine, Adenocarcinoma, Circumferential resection margin, General Medicine, Radiology, Esophagus, medicine.disease, business
Abstract

Aim To determine if a positive circumferential resection margin (CRM) can be predicted in patients with esophageal adenocarcinoma undergoing neo-adjuvant chemotherapy prior to surgery Methods 223 patients were included in this study. Multivariable analyses of clinico-pathological and computed tomography (CT) imaging predictors were performed to evaluate the likelihood of a positive CRM at initial staging and following neoadjuvant chemotherapy, with prediction models constructed. Area under curve (AUC) with 95% confidence interval (CI) from 1000 bootstrapping was assessed. Results Advanced clinical T-stage (T3-4) (odds ratio, OR 2.93 95%CI 1.03-9.48) and poor tumor differentiation (OR 2.84, 95%CI 1.39-6.01) were independently associated with an increased risk of a positive CRM. Non response to chemotherapy as estimated by CT independently corresponded with an increased risk of CRM positivity (OR 3.38 95% CI 1.43-8.50). Additional CT evidence of local invasion/pleural thickening and higher CT tumor volume (14cm3) improved the performance of a prediction model, including all above parameters; with AUC (c-index) of 0.76 (0.68-0.83). Conclusion Combining advanced clinical T-stage, poor tumor differentiation, CT non-response to chemotherapy, higher CT tumor volume and local invasion may be helpful in selecting patients for intensification of neo-adjuvant treatment prior to resection.

Published
2019

20. Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus

Author

Knight, William R.C., primary, McEwen, Ricardo, additional, Byrne, Ben E., additional, Habib, Wais, additional, Bott, Rebecca, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Gossage, James A., additional, Fitzgerald, R.C., additional, Noorani, A., additional, Edwards, P.A.W., additional, Grehan, N., additional, Nutzinger, B., additional, Hughes, C., additional, Fidziukiewicz, E., additional, MacRae, S., additional, Northrop, A., additional, Contino, G., additional, Li, X., additional, de la Rue, R., additional, Katz-Summercorn, A., additional, Abbas, S., additional, Loureda, D., additional, O'Donovan, M., additional, Miremadi, A., additional, Malhotra, S., additional, Tripathi, M., additional, Tavaré, S., additional, Lynch, A.G., additional, Eldridge, M., additional, Secrier, M., additional, Devonshire, G., additional, Perner, J., additional, Jammula, S., additional, Davies, J., additional, Crichton, C., additional, Carroll, N., additional, Safranek, P., additional, Hindmarsh, A., additional, Sujendran, V., additional, Hayes, S.J., additional, Ang, Y., additional, Sharrocks, A., additional, Preston, S.R., additional, Oakes, S., additional, Bagwan, I., additional, Save, V., additional, Skipworth, R.J.E., additional, Hupp, T.R., additional, O'Neill, J.R., additional, Tucker, O., additional, Beggs, A., additional, Taniere, P., additional, Puig, S., additional, Underwood, T.J., additional, Walker, R.C., additional, Grace, B.L., additional, Barr, H., additional, Shepherd, N., additional, Old, O., additional, Lagergren, J., additional, Davies, A., additional, Chang, F., additional, Goh, V., additional, Ciccarelli, F.D., additional, Sanders, G., additional, Berrisford, R., additional, Harden, C., additional, Lewis, M., additional, Cheong, E., additional, Kumar, B., additional, Parsons, S.L., additional, Soomro, I., additional, Kaye, P., additional, Saunders, J., additional, Lovat, L., additional, Haidry, R., additional, Igali, L., additional, Scott, M., additional, Sothi, S., additional, Suortamo, S., additional, Lishman, S., additional, Hanna, G.B., additional, Moorthy, K., additional, Peters, C.J., additional, Grabowska, A., additional, Turkington, R., additional, McManus, D., additional, Coleman, H., additional, Khoo, D., additional, and Fickling, W., additional

Published
2020
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21. Identification of Subtypes of Barrett’s Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data

Author

Jammula, SriGanesh, primary, Katz-Summercorn, Annalise C., additional, Li, Xiaodun, additional, Linossi, Constanza, additional, Smyth, Elizabeth, additional, Killcoyne, Sarah, additional, Biasci, Daniele, additional, Subash, Vinod V., additional, Abbas, Sujath, additional, Blasko, Adrienn, additional, Devonshire, Ginny, additional, Grantham, Amber, additional, Wronowski, Filip, additional, O’Donovan, Maria, additional, Grehan, Nicola, additional, Eldridge, Matthew D., additional, Tavaré, Simon, additional, Fitzgerald, Rebecca C., additional, Noorani, Ayesha, additional, Edwards, Paul A.W., additional, Nutzinger, Barbara, additional, Hughes, Caitriona, additional, Fidziukiewicz, Elwira, additional, Bornschein, Jan, additional, MacRae, Shona, additional, Crawte, Jason, additional, Northrop, Alex, additional, Contino, Gianmarco, additional, de la Rue, Rachel, additional, Miremadi, Ahmad, additional, Malhotra, Shalini, additional, Tripathi, Monika, additional, Lynch, Andy G., additional, Eldridge, Matthew, additional, Secrier, Maria, additional, Bower, Lawrence, additional, Perner, Juliane, additional, Jammula, Sriganesh, additional, Davies, Jim, additional, Crichton, Charles, additional, Carroll, Nick, additional, Safranek, Peter, additional, Hindmarsh, Andrew, additional, Sujendran, Vijayendran, additional, Hayes, Stephen J., additional, Ang, Yeng, additional, Preston, Shaun R., additional, Oakes, Sarah, additional, Bagwan, Izhar, additional, Save, Vicki, additional, Skipworth, Richard J.E., additional, Hupp, Ted R., additional, O’Neill, J. Robert, additional, Tucker, Olga, additional, Beggs, Andrew, additional, Taniere, Philippe, additional, Puig, Sonia, additional, Underwood, Timothy J., additional, Noble, Fergus, additional, Owsley, Jack, additional, Barr, Hugh, additional, Shepherd, Neil, additional, Old, Oliver, additional, Lagergren, Jesper, additional, Gossage, James, additional, Davies, Andrew, additional, Chang, Fuju, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Goh, Vicky, additional, Ciccarelli, Francesca D., additional, Sanders, Grant, additional, Berrisford, Richard, additional, Harden, Catherine, additional, Lewis, Mike, additional, Cheong, Ed, additional, Kumar, Bhaskar, additional, Parsons, Simon L., additional, Soomro, Irshad, additional, Kaye, Philip, additional, Saunders, John, additional, Lovat, Laurence, additional, Haidry, Rehan, additional, Igali, Laszlo, additional, Scott, Michael, additional, Sothi, Sharmila, additional, Suortamo, Sari, additional, Lishman, Suzy, additional, Hanna, George B., additional, Moorthy, Krishna, additional, Peters, Christopher J., additional, Grabowska, Anna, additional, and Turkington, Richard, additional

Published
2020
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22. Machine learning to predict early recurrence after oesophageal cancer surgery

Author

Rahman, S A, primary, Walker, R C, additional, Lloyd, M A, additional, Grace, B L, additional, van Boxel, G I, additional, Kingma, B F, additional, Ruurda, J P, additional, van Hillegersberg, R, additional, Harris, S, additional, Parsons, S, additional, Mercer, S, additional, Griffiths, E A, additional, O'Neill, J R, additional, Turkington, R, additional, Fitzgerald, R C, additional, Underwood, T J, additional, Noorani, Ayesha, additional, Elliott, Rachael Fels, additional, Edwards, Paul A W, additional, Grehan, Nicola, additional, Nutzinger, Barbara, additional, Crawte, Jason, additional, Chettouh, Hamza, additional, Contino, Gianmarco, additional, Li, Xiaodun, additional, Gregson, Eleanor, additional, Zeki, Sebastian, additional, de la Rue, Rachel, additional, Malhotra, Shalini, additional, Tavaré, Simon, additional, Lynch, Andy G, additional, Smith, Mike L, additional, Davies, Jim, additional, Crichton, Charles, additional, Carroll, Nick, additional, Safranek, Peter, additional, Hindmarsh, Andrew, additional, Sujendran, Vijayendran, additional, Hayes, Stephen J, additional, Ang, Yeng, additional, Preston, Shaun R, additional, Oakes, Sarah, additional, Bagwan, Izhar, additional, Save, Vicki, additional, Skipworth, Richard J E, additional, Hupp, Ted R, additional, O'Neill, J Robert, additional, Tucker, Olga, additional, Beggs, Andrew, additional, Taniere, Philippe, additional, Puig, Sonia, additional, Underwood, Timothy J, additional, Noble, Fergus, additional, Byrne, James P, additional, Kelly, Jamie J, additional, Owsley, Jack, additional, Barr, Hugh, additional, Shepherd, Neil, additional, Old, Oliver, additional, Lagergren, Jesper, additional, Gossage, James, additional, Chang, Andrew Davies Fuju, additional, Zylstra, Janine, additional, Goh, Vicky, additional, Ciccarelli, Francesca D, additional, Sanders, Grant, additional, Berrisford, Richard, additional, Harden, Catherine, additional, Bunting, David, additional, Lewis, Mike, additional, Cheong, Ed, additional, Kumar, Bhaskar, additional, Parsons, Simon L, additional, Soomro, Irshad, additional, Kaye, Philip, additional, Saunders, John, additional, Lovat, Laurence, additional, Haidry, Rehan, additional, Eneh, Victor, additional, Igali, Laszlo, additional, Scott, Michael, additional, Sothi, Shamila, additional, Suortamo, Sari, additional, Lishman, Suzy, additional, Hanna, George B, additional, Peters, Christopher J, additional, and Grabowska, Anna, additional

Published
2020
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26. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Author

Sawas, Tarek, primary, Killcoyne, Sarah, additional, Iyer, Prasad G., additional, Wang, Kenneth K., additional, Smyrk, Thomas C., additional, Kisiel, John B., additional, Qin, Yi, additional, Ahlquist, David A., additional, Rustgi, Anil K., additional, Costa, Rui J., additional, Gerstung, Moritz, additional, Fitzgerald, Rebecca C., additional, Katzka, David A., additional, Noorani, Ayesha, additional, Edwards, Paul A.W., additional, Grehan, Nicola, additional, Nutzinger, Barbara, additional, Hughes, Caitriona, additional, Fidziukiewicz, Elwira, additional, Bornschein, Jan, additional, MacRae, Shona, additional, Crawte, Jason, additional, Contino, Gianmarco, additional, Li, Xiaodun, additional, Rue, Rachel de la, additional, O’Donovan, Maria, additional, Miremad, Ahmad, additional, Malhotra, Shalini, additional, Tripathi, Monika, additional, Tavaré, Simon, additional, Lynch, Andy G., additional, Eldridge, Matthew, additional, Secrier, Maria, additional, Bower, Lawrence, additional, Devonshire, Ginny, additional, Perner, Juliane, additional, Jammula, Sriganesh, additional, Davies, Jim, additional, Crichton, Charles, additional, Carroll, Nick, additional, Safranek, Peter, additional, Hindmarsh, Andrew, additional, Sujendran, Vijayendran, additional, Hayes, Stephen J., additional, Ang, Yeng, additional, Preston, Shaun R., additional, Oakes, Sarah, additional, Bagwan, Izhar, additional, Save, Vicki, additional, Skipworth, Richard J.E., additional, Hupp, Ted R., additional, O’Neill, J. Robert, additional, Tucker, Olga, additional, Beggs, Andrew, additional, Taniere, Philippe, additional, Puig, Sonia, additional, Underwood, Timothy J., additional, Noble, Fergus, additional, Owsley, Jack, additional, Barr, Hugh, additional, Shepherd, Neil, additional, Old, Oliver, additional, Lagergren, Jesper, additional, Gossage, James, additional, Davies, Andrew, additional, Chang, Fuju, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Goh, Vicky, additional, Ciccarelli, Francesca D., additional, Sanders, Grant, additional, Berrisford, Richard, additional, Harden, Catherine, additional, Bunting, David, additional, Lewis, Mike, additional, Cheong, Ed, additional, Kumar, Bhaskar, additional, Parsons, Simon L., additional, Soomro, Irshad, additional, Kaye, Philip, additional, Saunders, John, additional, Lovat, Laurence, additional, Haidry, Rehan, additional, Eneh, Victor, additional, Igali, Laszlo, additional, Scott, Michael, additional, Sothi, Sharmila, additional, Suortamo, Sari, additional, Lishman, Suzy, additional, Hanna, George B., additional, Peters, Christopher J., additional, Grabowska, Anna, additional, and Turkington, Richard, additional

Published
2018
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28. A longitudinal assessment of psychological distress after oesophageal cancer surgery

Author

Hellstadius, Ylva, Lagergren, Jesper, Zylstra, Janine, Gossage, James, Davis, Andrew, M Hultman, Christina, Lagergren, Pernilla, Wikman, Anna, Hellstadius, Ylva, Lagergren, Jesper, Zylstra, Janine, Gossage, James, Davis, Andrew, M Hultman, Christina, Lagergren, Pernilla, and Wikman, Anna

Abstract

Background: Psychological distress is common among patients with oesophageal cancer. However, little is known about the course and predictors of psychological distress among patients treated with curative intent. Therefore, the aim of this study was to explore the prevalence, course and predictors of anxiety and depression in patients operated for oesophageal cancer, from prior to surgery to 12 months post-operatively. Methods: A prospective cohort of patients with oesophageal cancer (n ¼ 218) were recruited from one high-volume specialist oesophago-gastric treatment centre (St Thomas’ Hospital, London, UK). Anxiety and depression were assessed prior to surgery, 6 and 12 months post-operatively. Mixed-effects modelling was performed to investigate changes over time and to estimate the association between clinical and socio-demographic predictor variables and anxiety and depression symptoms. Results: The proportion of patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12 months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12-month follow-up. Anxiety symptoms remained stable over time whereas depression symptoms appeared to increase from pre-surgery to 6 months, levelling off between 6 and 12 months. Younger age, female sex, living alone and more severe self-reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety symptoms. In-hospital complications, greater limitations in activity status and more severe selfreported dysphagia were predictive of higher depression. Conclusions: Many patients report psychological distress during the first year following oesophageal cancer surgery. Whether improving the experience of swallowing difficulties may also reduce distress among these patients warrants further study.

Published
2017
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29. Extent of lymphadenectomy and prognosis after esophageal cancer surgery

Author

Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, Davies, Andrew, Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, and Davies, Andrew

Abstract

IMPORTANCE: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95%CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95%CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95%CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mort

Published
2017

30. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Achilleos, Achilleas [0000-0001-7157-8991], Apollo - University of Cambridge Repository, and Davies, J

Subjects
0301 basic medicine, Male, Esophageal Neoplasms, Sequence analysis, medicine.medical_treatment, CD8 Antigens, Antineoplastic Agents, Adenocarcinoma, Poly(ADP-ribose) Polymerase Inhibitors, medicine.disease_cause, Receptor tyrosine kinase, DNA sequencing, Targeted therapy, Cohort Studies, 03 medical and health sciences, Genetic Heterogeneity, 0302 clinical medicine, Cell Line, Tumor, Genetics, medicine, Humans, Aged, Mutation, biology, Genetic heterogeneity, Genome, Human, Cancer, Receptor Protein-Tyrosine Kinases, DNA, Neoplasm, Sequence Analysis, DNA, medicine.disease, 3. Good health, Homologous Recombination Pathway, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, DNA Damage
Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

Published
2016

32. Extent of lymphadenectomy and prognosis after esophageal cancer surgery

Author

Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, Davies, Andrew, Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, and Davies, Andrew

Abstract

Importance: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. Objective: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. Design, Setting, and Participants: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. Exposures: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. Main Outcomes and Measures: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. Results: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased m

Published
2015

33. Reply to R.C. Turkington et al

Author

Davies, Andrew R., primary, Gossage, James A., additional, Zylstra, Janine L., additional, Mattsson, Fredrik, additional, Lagergren, Jesper, additional, Maisey, Nick, additional, Smyth, Elizabeth C., additional, Cunningham, David, additional, Allum, William H., additional, and Mason, Robert C., additional

Published
2015
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34. Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

Author

Davies, Andrew R., primary, Gossage, James A., additional, Zylstra, Janine, additional, Mattsson, Fredrik, additional, Lagergren, Jesper, additional, Maisey, Nick, additional, Smyth, Elizabeth C., additional, Cunningham, David, additional, Allum, William H., additional, and Mason, Robert C., additional

Published
2014
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35. Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Author

Mourikis, Thanos P., Benedetti, Lorena, Foxall, Elizabeth, Temelkovski, Damjan, Nulsen, Joel, Perner, Juliane, Cereda, Matteo, Lagergren, Jesper, Howell, Michael, Yau, Christopher, Fitzgerald, Rebecca C., Scaffidi, Paola, Ciccarelli, Francesca D., Noorani, Ayesha, Edwards, Paul A. W., Elliott, Rachael Fels, Grehan, Nicola, Nutzinger, Barbara, Hughes, Caitriona, Fidziukiewicz, Elwira, Bornschein, Jan, MacRae, Shona, Crawte, Jason, Northrop, Alex, Contino, Gianmarco, Li, Xiaodun, De La Rue, Rachel, Katz-Summercorn, Annalise, Abbas, Sujath, Loureda, Daniel, O’Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Tavaré, Simon, Lynch, Andy G., Eldridge, Matthew, Secrier, Maria, Bower, Lawrence, Devonshire, Ginny, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J. E., Hupp, Ted R., Robert O’Neill, J., Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Barr, Hugh, Shepherd, Neil, Old, Oliver, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Mahadeva, Ula, Goh, Vicky, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Igali, Laszlo, Scott, Michael, Sothi, Sharmila, Suortamo, Sari, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Khoo, David, and Fickling, Will

Subjects
631/67, 13/31, 13/44, 631/67/1504/1477, 38/23, 38/22, 38/77, 38/88, article, 38/90, 631/67/69, 13/109, 3. Good health
Abstract

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.

36. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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37. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

Full Text
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38. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

Full Text
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39. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, and Grimmond, Sean M.

Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

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41. Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins

Author

William R. C. Knight, Justin S. Waters, William H. Allum, R Bott, J Zylstra, David Cunningham, Nick Maisey, Michelle J. Wilkinson, Jesper Lagergren, James A. Gossage, Mark Kelly, Kerri Beckmann, Cara R. Baker, Elizabeth C Smyth, Andrew Davies, Mieke Van Hemelrijck, Bott, Rebecca K, Beckmann, K, Zylstra, Janine, Wilkinson, Michelle J, Knight, William RC, Baker, Cara R, Kelly, Mark, Maisey, Nick, Waters, Justin, Van Hemelrijck, Mieke, Smyth, Elizabeth C, Allum, William H, Lagergren, Jesper, Gossage, James A, Cunningham, David, and Davies, Andrew R

Subjects
Surgical resection, medicine.medical_specialty, medicine.medical_treatment, Oesophageal adenocarcinoma, Adenocarcinoma, 030218 nuclear medicine & medical imaging, Resection, Cohort Studies, surgery, 03 medical and health sciences, 0302 clinical medicine, medicine, Adjuvant therapy, Humans, Radiology, Nuclear Medicine and imaging, In patient, Retrospective Studies, Chemotherapy, business.industry, Margins of Excision, adjuvant therapy, Chemoradiotherapy, Adjuvant, Hematology, General Medicine, Margin status, medicine.disease, Neoadjuvant Therapy, Surgery, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, business, neoadjuvant chemotherapy
Abstract

Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. Methods: This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. Results: Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40–1.06; p.0.087). Responders to NAC (Mandard 1–3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15–1.11; p.1.081). Conclusions: Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours. Refereed/Peer-reviewed

Published
2021

42. Transition from esophagectomy to endoscopic therapy for early esophageal cancer.

Author

Dunn JM, Reyhani A, Santaolalla A, Zylstra J, Gimson E, Pennington M, Baker C, Kelly M, Van Hemelrijck M, Lagergren J, Zeki SS, Gossage JA, and Davies AR

Subjects
Esophagoscopy adverse effects, Humans, Retrospective Studies, Treatment Outcome, Esophageal Neoplasms pathology, Esophagectomy adverse effects
Abstract

Background: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET)., Methods: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs., Results: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient)., Conclusion: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
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