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2. Association of dynamic contrast-enhanced MRI and 18F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer

Author

Baker, C.R., Bell, J., Chang, F., Chicklore, S., Cominos, M., Coombes, A., Dunn, J.N., George, S., Gill-Barman, B., Gossage, J.A., Gourtsoyianni, S., Green, A., Griffin, N., Hill, M., Hynes, O., Iezzi, C., Jacques, A., Kelly, M., Mahadeva, U., McEwan, R., Meenan, J., Neji, R., Ngan, S., Padormo, F., Qureshi, A., Reyhani, A., Sharkey, A.R., Spence, J., Subesinghe, M., Tham, G., Waters, J., Zeki, S.S., Withey, Samuel J., Owczarczyk, Kasia, Grzeda, Mariusz T., Yip, Connie, Deere, Harriet, Green, Mike, Maisey, Nick, Davies, Andrew R., Cook, Gary J., and Goh, Vicky

Published
2023
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4. Association of dynamic contrast-enhanced MRI and 18F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer

Author

Withey, Samuel J., primary, Owczarczyk, Kasia, additional, Grzeda, Mariusz T., additional, Yip, Connie, additional, Deere, Harriet, additional, Green, Mike, additional, Maisey, Nick, additional, Davies, Andrew R., additional, Cook, Gary J., additional, Goh, Vicky, additional, Baker, C.R., additional, Bell, J., additional, Chang, F., additional, Chicklore, S., additional, Cominos, M., additional, Coombes, A., additional, Dunn, J.N., additional, George, S., additional, Gill-Barman, B., additional, Gossage, J.A., additional, Gourtsoyianni, S., additional, Green, A., additional, Griffin, N., additional, Hill, M., additional, Hynes, O., additional, Iezzi, C., additional, Jacques, A., additional, Kelly, M., additional, Mahadeva, U., additional, McEwan, R., additional, Meenan, J., additional, Neji, R., additional, Ngan, S., additional, Padormo, F., additional, Qureshi, A., additional, Reyhani, A., additional, Sharkey, A.R., additional, Spence, J., additional, Subesinghe, M., additional, Tham, G., additional, Waters, J., additional, and Zeki, S.S., additional

Published
2023
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7. 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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8. Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

Author

Moore, Jonathan L., Green, Michael, Santaolalla, Aida, Deere, Harriet, Evans, Richard P.T., Elshafie, Mona, Lavery, Anita, McManus, Damian T., McGuigan, Andrew, Douglas, Rosalie, Horne, Joanne, Walker, Robert, Mir, Hira, Terlizzo, Monica, Kamarajah, Sivesh K., Van Hemelrijck, Mieke, Maisey, Nick, Sita-Lumsden, Ailsa, Ngan, Sarah, and Kelly, Mark

Published
2023
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10. OGC P20 Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients undergoing surgical resection for locally advanced oesophageal adenocarcinoma

Author

Moore, Jonathan, primary, Subesinghe, Manil, additional, Santaolalla, Aida, additional, Green, Michael, additional, Deere, Harriet, additional, Van Hemelrijck, Mieke, additional, Lagergren, Jesper, additional, Chicklore, Sugama, additional, Maisey, Nick, additional, Gossage, James, additional, Kelly, Mark, additional, Baker, Cara, additional, and Davies, Andrew, additional

Published
2022
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11. OGC O02 The prognostic effect of pathological lymph node regression after neoadjuvant chemotherapy for oesophageal adenocarcinoma – a multicentre study

Author

Moore, Jonathan, primary, Green, Michael, additional, Deere, Harriet, additional, Santaolalla, Aida, additional, Evans, Richard, additional, Elshafie, Mona, additional, Lavery, Anita, additional, McGuigan, Andrew, additional, McManus, Damian, additional, Horne, Joanne, additional, Walker, Robert, additional, Mir, Hira, additional, Terlizzo, Monica, additional, Kamarajah, Sivesh, additional, Van Hemelrijck, Mieke, additional, Maisey, Nick, additional, Lumsden, Ailsa, additional, Ngan, Sarah, additional, Kelly, Mark, additional, Baker, Cara, additional, Kumar, Sacheen, additional, Lagergren, Jesper, additional, Allum, William, additional, Gossage, James, additional, Griffiths, Ewan, additional, Grabsch, Heike, additional, Turkington, Richard, additional, Underwood, Tim, additional, Smyth, Elizabeth, additional, Fitzgerald, Rebecca, additional, Cunningham, David, additional, and Davies, Andrew, additional

Published
2022
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12. 568. THE PROGNOSTIC EFFECT OF PATHOLOGICAL LYMPH NODE REGRESSION AFTER NEOADJUVANT CHEMOTHERAPY FOR OESOPHAGEAL ADENOCARCINOMA – A MULTICENTRE STUDY

Author

Moore, Jonathan, primary, Green, Michael, additional, Van Hemelrijck, Mieke, additional, Deere, Harriet, additional, Evans, Richard PT, additional, Elshafie, Mona, additional, Lavery, Anita, additional, McGuigan, Andrew, additional, Douglas, Rosalie, additional, Mcmanus, Damian, additional, Horne, Joanne, additional, Walker, Robert, additional, Mir, Hira, additional, Terlizzo, Monica, additional, Kamarajah, Sivesh K, additional, Santaolalla, Aida, additional, Maisey, Nick, additional, Lumsden, Ailsa, additional, Ngan, Sarah, additional, Kelly, Mark, additional, Baker, Cara R, additional, Kumar, Sacheen, additional, Lagergren, Jesper, additional, Allum, William H, additional, Gossage, James A, additional, Griffiths, Ewan, additional, Grabsch, Heike I, additional, Turkington, Richard C, additional, Underwood, Tim, additional, Smyth, Elizabeth, additional, Fitzgerald, Rebecca, additional, Cunningham, David, additional, and Davies, Andrew R, additional

Published
2022
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13. 354. THE PARADIGM OF INACCURACIES IN STAGING EARLY OESOPHAGEAL ADENOCARCINOMA

Author

Reyhani, Arasteh, primary, Gimson, Eliza, additional, Baker, Cara, additional, Kelly, Mark, additional, Maisey, Nick, additional, Meenan, John, additional, Subesinghe, Manil, additional, Hill, Mark, additional, Lagergren, Jesper, additional, Gossage, James, additional, Zeki, Sebastian, additional, Dunn, Jason, additional, and Davies, Andrew, additional

Published
2022
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14. 577. FDG PT-CT METABOLIC TUMOUR AND NODAL RESPONSE AS A PREDICTOR OF PATHOLOGICAL RESPONSE AND SURVIVAL IN PATIENTS WITH OESOPHAGEAL ADENOCARCINOMA

Author

Moore, Jonathan, primary, Subesinghe, Manil, additional, Santaolalla, Aida, additional, Green, Michael, additional, Deere, Harriet, additional, Van Hemelrijck, Mieke, additional, Lagergren, Jesper, additional, Chicklore, Sugama, additional, Maisey, Nick, additional, Kelly, Mark, additional, Gossage, James A, additional, Baker, Cara R, additional, and Davies, Andrew R, additional

Published
2022
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15. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial

Author

Seymour, Matthew T, Brown, Sarah R, Middleton, Gary, Maughan, Timothy, Richman, Susan, Gwyther, Stephen, Lowe, Catherine, Seligmann, Jennifer F, Wadsley, Jonathan, Maisey, Nick, Chau, Ian, Hill, Mark, Dawson, Lesley, Falk, Stephen, O'Callaghan, Ann, Benstead, Kim, Chambers, Philip, Oliver, Alfred, Marshall, Helen, Napp, Vicky, and Quirke, Phil

Published
2013
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16. Effect of peri-operative chemotherapy regimen on survival in the treatment of locally advanced oesophago-gastric adenocarcinoma – A comparison of the FLOT and ‘MAGIC’ regimens

Author

Moore, Jonathan L., primary, Kumar, Sacheen, additional, Santaolalla, Aida, additional, Patel, Pranav H., additional, Kapiris, Matthaios, additional, Van Hemelrijck, Mieke, additional, Maisey, Nick, additional, Hill, Mark, additional, Lagergren, Jesper, additional, Gossage, James A., additional, Kelly, Mark, additional, Chaudry, Asif, additional, Allum, William H., additional, Baker, Cara R., additional, Cunningham, David, additional, Davies, Andrew R., additional, Jacques, A., additional, Griffin, N., additional, Goh, V., additional, Ngan, S., additional, Owczarczyk, K., additional, Lumsden, A., additional, Qureshi, A., additional, Deere, H., additional, Green, M., additional, Chang, F., additional, Mahadeva, U., additional, Gill-Barman, B., additional, George, S., additional, Ong, M., additional, Waters, J., additional, Cominos, M., additional, Sevitt, T., additional, Hynes, O., additional, Tham, G., additional, Bott, R.K., additional, Dunn, J.M., additional, and Zeki, S.S., additional

Published
2022
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17. 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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19. 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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22. Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer

Author

Hall, Peter S., Swinson, Daniel, Cairns, David A., Waters, Justin S., Petty, Russell, Allmark, Christine, Ruddock, Sharon, Falk, Stephen, Wadsley, Jonathan, Roy, Rajarshi, Tillett, Tania, Nicoll, Jonathan, Cummins, Sebastian, Mano, Joseph, Grumett, Simon, Stokes, Zuzana, Konstantinos-Velios, Kamposioras, Chatterjee, Anirban, Garcia, Angel, Waddell, Tom, Guptal, Kamalnayan, Maisey, Nick, Khan, Mohammed, Dent, Jo, Lord, Simon, Crossley, Ann, Katona, Eszter, Marshall, Helen, Grabsch, Heike I., Velikova, Galina, Ow, Pei Loo, Handforth, Catherine, Howard, Helen, and Seymour, Matthew T.

Subjects
Research, Online First, Comments, Original Investigation
Abstract

Key Points Question Do older and/or frail patients with advanced gastroesophageal cancer benefit from less intensive palliative chemotherapy, and can a formal geriatric assessment assist treatment decision-making? Findings This phase 3 randomized clinical trial including 559 patients with advanced gastroesophageal cancer found that reducing the intensity of chemotherapy provided an improved patient experience with no significant detriment in cancer control. Baseline frailty, quality of life, and neutrophil/lymphocyte ratio (an inflammation marker) were predictive of outcome and may contribute to treatment decisions. Meaning Decision-making for older and/or frail patients with advanced cancer can be enhanced using geriatric assessment; such patients generally benefit from reducing the intensity of chemotherapy., This randomized clinical trial assesses the efficacy of reduced-intensity chemotherapy for patient quality of life and cancer control in the treatment of older and/or frail patients, Importance Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration isrctn.org Identifier: ISRCTN44687907

Published
2021

23. 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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25. 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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26. Impact of primary tumour location in patients with RAS/RAF wild- type metastatic colorectal cancer treated with first-line chemotherapy & anti-EGFR antibodies: A retrospective study at Guy's Cancer Centre

Author

Gousis, Charalampos, Tsotra, Eirini, Dolly, Saoirse, Kiruthikah Thillai, Maisey, Nick, Qureshi, Asad, Harris, Victoria, Owczarczyk, Kasia, Ferreira, Miguel Reis, Russell, Beth, Moss, Charlotte, Hemelrijck, Mieke Van, Denaurois, Julien, Ross, Paul, and Roca, Jose

Published
2020
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27. 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

28. Optimising Chemotherapy for Frail and Older Patients With Advanced Gastroesophageal Cancer: The GO2 Phase III Trial

Author

Hall, Peter, primary, Swinson, Daniel, additional, Cairns, David A., additional, Waters, Justin, additional, Petty, Russell, additional, Allmark, Christine, additional, Ruddock, Sharon, additional, Falk, Stephen, additional, Wadsley, Jonathan, additional, Roy, Rajarshi, additional, Tillett, Tania, additional, Nicoll, Jonathan, additional, Cummins, Sebastian, additional, Mano, Joseph, additional, Grumett, Simon, additional, Stokes, Zuzana, additional, Kostantinos-Vellios, Kamposioras, additional, Chatterjee, Anirban, additional, Garcia, Angel, additional, Waddell, Tom, additional, Kamalnayan, Guptal, additional, Maisey, Nick, additional, Khan, Mohammed, additional, Dent, Jo, additional, Lord, Simon, additional, Crossley, Anne, additional, Katona, Eszter, additional, Marshall, Helen, additional, Grabsch, Heike I., additional, Velikova, Galina, additional, Ow, Pei Loo, additional, Handforth, Catherine, additional, Howard, Helen, additional, and Seymour, Matthew T., additional

Published
2020
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34. 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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35. 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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36. A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: Results of the Panitumumab, Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO)

Author

Middleton, Gary, primary, Brown, Sarah, additional, Lowe, Catherine, additional, Maughan, Timothy, additional, Gwyther, Stephen, additional, Oliver, Alfred, additional, Richman, Susan, additional, Blake, Denise, additional, Napp, Vicky, additional, Marshall, Helen, additional, Wadsley, Jonathan, additional, Maisey, Nick, additional, Chau, Ian, additional, Hill, Mark, additional, Gollins, Simon, additional, Myint, Sun, additional, Slater, Sarah, additional, Wagstaff, John, additional, Bridgewater, John, additional, and Seymour, Matthew, additional

Published
2013
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41. Tumor Necrosis Factor α As a New Target for Renal Cell Carcinoma: Two Sequential Phase II Trials of Infliximab at Standard and High Dose

Author

Harrison, Michelle L., primary, Obermueller, Eva, additional, Maisey, Nick R., additional, Hoare, Susan, additional, Edmonds, Kim, additional, Li, Ningfeng F., additional, Chao, David, additional, Hall, Kate, additional, Lee, Chooi, additional, Timotheadou, Eleni, additional, Charles, Kellie, additional, Ahern, Roger, additional, King, D. Mike, additional, Eisen, Tim, additional, Corringham, Robert, additional, DeWitte, Mark, additional, Balkwill, Frances, additional, and Gore, Martin, additional

Published
2007
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45. 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

46. Association of dynamic contrast-enhanced MRI and 18 F-Fluorodeoxyglucose PET/CT parameters with neoadjuvant therapy response and survival in esophagogastric cancer.

Author

Withey SJ, Owczarczyk K, Grzeda MT, Yip C, Deere H, Green M, Maisey N, Davies AR, Cook GJ, and Goh V

Subjects
Male, Humans, Aged, Fluorodeoxyglucose F18 therapeutic use, Positron Emission Tomography Computed Tomography methods, Neoadjuvant Therapy methods, Radiopharmaceuticals, Prospective Studies, Magnetic Resonance Imaging, Esophageal Neoplasms diagnostic imaging, Esophageal Neoplasms therapy, Esophageal Neoplasms metabolism, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms therapy
Abstract

Introduction: Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome., Materials and Methods: Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18 F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18 F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables., Results: 39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUV max ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18 F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified., Conclusion: Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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47. Tumor necrosis factor alpha as a new target for renal cell carcinoma: two sequential phase II trials of infliximab at standard and high dose.

Author

Harrison ML, Obermueller E, Maisey NR, Hoare S, Edmonds K, Li NF, Chao D, Hall K, Lee C, Timotheadou E, Charles K, Ahern R, King DM, Eisen T, Corringham R, DeWitte M, Balkwill F, and Gore M

Subjects
Adult, Aged, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents pharmacology, Antibodies, Monoclonal administration & dosage, Antineoplastic Agents administration & dosage, Chemokine CCL2 blood, Female, Humans, Infliximab, Interleukin-6 metabolism, Male, Middle Aged, Treatment Outcome, Tumor Necrosis Factor-alpha blood, Antibodies, Monoclonal pharmacology, Antineoplastic Agents pharmacology, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell metabolism, Kidney Neoplasms drug therapy, Kidney Neoplasms metabolism, Tumor Necrosis Factor-alpha metabolism
Abstract

Purpose: Tumor necrosis factor alpha (TNF-alpha) may play a role in renal cell carcinoma (RCC). We performed two sequential phase II studies of infliximab, an anti-TNF-alpha monoclonal antibody, in patients with immunotherapy-resistant or refractory RCC., Patients and Methods: Patients progressing after cytokine therapy were treated with intravenous infliximab as follows: study 1 (19 patients), 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks; study 2 (18 patients), 10 mg/kg at weeks 0, 2, and 6, and then every 4 weeks. Treatment continued until disease progression (PD). Response was assessed according to Response Evaluation Criteria in Solid Tumors. Plasma levels of TNF-alpha, CCL2, and interleukin-6 (IL-6) were measured before and during treatment., Results: TNF-alpha and its receptors were detected in malignant cells in RCC biopsies. In study 1, three patients (16%) achieved partial response (PR) and three patients (16%) achieved stable disease (SD). Median duration of response (PR + SD) was 7.7 months (range, 5.0 to 40.5+ months). In study 2, 11 patients (61%) achieved SD. Median duration of response was 6.2 months (range, 3.5 to 24+ months). One patient developed grade 3 hypersensitivity and another died as a result of pulmonary infection/sepsis. Enzyme-linked immunosorbent assay analysis of plasma revealed that higher levels of TNF-alpha at baseline and higher levels of CCL2 during treatment were associated with PD. There were also correlations between higher levels of TNF-alpha, IL-6, and CCL2 and poor survival (< 12 months)., Conclusion: This is the first direct clinical evidence suggesting that TNF-alpha may be a therapeutic target in RCC. Plasma levels of TNF-alpha, IL-6, and CCL2 may have predictive and prognostic significance.

Published
2007
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