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330 results on '"Roxburgh, Campbell S."'

3. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors

Author

Pennel, Kathryn A. F., Hatthakarnkul, Phimmada, Wood, Colin S., Lian, Guang-Yu, Al-Badran, Sara S. F., Quinn, Jean A., Legrini, Assya, Inthagard, Jitwadee, Alexander, Peter G., van Wyk, Hester, Kurniawan, Ahmad, Hashmi, Umar, Gillespie, Michael A., Mills, Megan, Ammar, Aula, Hay, Jennifer, Andersen, Ditte, Nixon, Colin, Rebus, Selma, Chang, David K., Kelly, Caroline, Harkin, Andrea, Graham, Janet, Church, David, Tomlinson, Ian, Saunders, Mark, Iveson, Tim, Lannagan, Tamsin R. M., Jackstadt, Rene, Maka, Noori, Horgan, Paul G., Roxburgh, Campbell S. D., Sansom, Owen J., McMillan, Donald C., Steele, Colin W., Jamieson, Nigel B., Park, James H., Roseweir, Antonia K., and Edwards, Joanne

Published
2024
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5. Corrigendum

Author

Beach, Callum, MacLean, David, Majorova, Dominika, Melemenidis, Stavros, Nambiar, Dhanya K., Kim, Ryan K., Valbuena, Gabriel N., Guglietta, Silvia, Krieg, Carsten, Darvish-Damavandi, Mahnaz, Suwa, Tatsuya, Easton, Alistair, Hillson, Lily V.S., McCulloch, Ashley K., McMahon, Ross K., Pennel, Kathryn, Edwards, Joanne, O'Cathail, Sean M., Roxburgh, Campbell S., Domingo, Enric, Moon, Eui Jung, Jiang, Dadi, Jiang, Yanyan, Zhang, Qingyang, Koong, Albert C., Woodruff, Trent M., Graves, Edward E., Maughan, Tim, Buczacki, Simon J.A., Stucki, Manuel, Le, Quynh-Thu, Leedham, Simon J., Giaccia, Amato J., and Olcina, Monica M.

Abstract

Original citation: J Clin Invest. 2023;133(23):e168277. https://doi.org/10.n72/JCI168277. During the preparation of this manuscript, the dose for PMX205 used for in vitro experiments was stated incorrectly in the legend for Figure [...]

Published
2024
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8. Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1

Author

Beach, Callum, MacLean, David, Majorova, Dominika, Melemenidis, Stavros, Nambiar, Dhanya K., Kim, Ryan K., Valbuena, Gabriel N., Guglietta, Silvia, Krieg, Carsten, Darvish-Damavandi, Mahnaz, Suwa, Tatsuya, Easton, Alistair, Hillson, Lily V.S., McCulloch, Ashley K., McMahon, Ross K., Pennel, Kathryn, Edwards, Joanne, O'Cathail, Sean M., Roxburgh, Campbell S., Domingo, Enric, Moon, Eui Jung, Jiang, Dadi, Jiang, Yanyan, Zhang, Qingyang, Koong, Albert C., Woodruff, Trent M., Graves, Edward E., Maughan, Tim, Buczacki, Simon J.A., Stucki, Manuel, Le, Quynh-Thu, Leedham, Simon J., Giaccia, Amato J., and Olcina, Monica M.

Subjects
Thermo Fisher Scientific Inc., Scientific equipment and supplies industry, Gene expression, T cells, Tumors, Genes, Cancer -- Diagnosis, Colorectal cancer, Ethylenediaminetetraacetic acid, B cells, Radiotherapy, Health care industry, Wellcome Trust
Abstract

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor [CD8.sup.+] T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased NF-[kappa]B-dependent apoptosis specifically in tumors and not normal tissues, indicating that, in malignant cells, C5aR1 primarily regulated cell fate. Collectively, these data revealed that increased complement gene expression is part of the stress response mounted by irradiated tumors and that targeting C5aR1 could improve radiotherapy, even in tumors displaying immunosuppressive features., Introduction The composition of the tumor microenvironment (TME) affects treatment responses in cancer (1-3). Immunosuppressive TME features, which act as a barrier to extensive [CD8.sup.+] T cell infiltration typically characterize [...]

Published
2023
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12. Relationship between CT-derived cervical muscle mass and quality, systemic inflammation, and survival in symptomatic patients undergoing carotid endarterectomy.

Author

Bradley, Nicholas A, Dosanj, Karamonique, Chan, Sharon Yen Ming, Wilson, Alasdair, Siddiqui, Tamim, Forsythe, Rachel, Roxburgh, Campbell S D, McMillan, Donlad C, and Guthrie, Graeme J K

Abstract

Background Sarcopenia appears to be associated with inferior outcomes in surgical conditions. Chronic systemic inflammation confers an inferior long-term prognosis in cardiovascular disease and is associated with the development of sarcopenia. The aim of this study was to describe the prognostic role of sarcopenia assessed using computed tomography (CT)-derived body composition analysis and systemic inflammation in patients undergoing carotid endarterectomy for symptomatic carotid stenosis. Methods In this retrospective cohort study, patients undergoing carotid endarterectomy for symptomatic carotid stenosis between 1 January 2011 and 1 October 2021 at four referral centres were included. The C3 skeletal muscle index and C3 skeletal muscle density were recorded from preoperative CT images. Systemic inflammation was assessed using the preoperative systemic inflammatory grade (SIG). The primary outcome was overall mortality during the study interval. Results A total of 618 patients were included, with a median follow-up of 69 (interquartile range 34–85) months. On univariable analysis, age greater than or equal to 75 years (P < 0.001), American Society of Anesthesiologists (ASA) grade greater than II (P < 0.001), low C3 skeletal muscle index (P = 0.002), low C3 skeletal muscle density (P < 0.001), SIG greater than or equal to 2 (P < 0.001), and low L3 derived skeletal muscle index (P < 0.001) were associated with increased mortality, whereas body mass index greater than or equal to 25 kg/m2 was associated with decreased mortality (P = 0.023). On multivariable analysis, age 75 years or older (HR 2.17 (95% c.i. 1.58 to 2.97), P < 0.001), ASA grade greater than II (HR 2.06 (95% c.i. 1.35 to 3.12), P < 0.001), low C3 skeletal muscle density (HR 1.84 (95% c.i. 1.33 to 2.54), P < 0.001), and SIG greater than or equal to 2 (HR 1.63 (95% c.i. 1.33 to 1.99), P < 0.001) were independently associated with increased mortality. Conclusion Cervical CT-derived muscle mass and density, and markers of systemic inflammation, such as systemic inflammatory grade, may be associated with an inferior long-term prognosis after carotid endarterectomy. [ABSTRACT FROM AUTHOR]

Published
2024
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18. The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Author

Alexander, Peter G., Roseweir, Antonia K., Pennel, Kathryn A. F., van Wyk, Hester C., Powell, Arfon G. M. T., McMillan, Donald C., Horgan, Paul G., Kelly, Caroline, Hay, Jennifer, Sansom, Owen, Harkin, Andrea, Roxburgh, Campbell S. D., Graham, Janet, Church, David N., Tomlinson, Ian, Saunders, Mark, Iveson, Tim J., Edwards, Joanne, and Park, James H.

Published
2021
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19. Correction to: Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer: a study protocol of a randomised phase II trial (PRIME-RT)

Author

Hanna, Catherine R., O’Cathail, Sean M., Graham, Janet S., Saunders, Mark, Samuel, Leslie, Harrison, Mark, Devlin, Lynsey, Edwards, Joanne, Gaya, Daniel R., Kelly, Caroline A., Lewsley, Liz-Anne, Maka, Noori, Morrison, Paula, Dinnett, Louise, Dillon, Susan, Gourlay, Jacqueline, Platt, Jonathan J., Thomson, Fiona, Adams, Richard A., and Roxburgh, Campbell S. D.

Published
2021
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20. Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer: a study protocol of a randomised phase II trial (PRIME-RT)

Author

Hanna, Catherine R., O’Cathail, Sean M., Graham, Janet S., Saunders, Mark, Samuel, Leslie, Harrison, Mark, Devlin, Lynsey, Edwards, Joanne, Gaya, Daniel R., Kelly, Caroline A., Lewsley, Liz-Anne, Maka, Noori, Morrison, Paula, Dinnett, Louise, Dillon, Susan, Gourlay, Jacqueline, Platt, Jonathan J., Thomson, Fiona, Adams, Richard A., and Roxburgh, Campbell S. D.

Published
2021
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23. CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

Author

Bradley, Nicholas A., McGovern, Josh, Dolan, Ross D., Golder, Allan M., Roxburgh, Campbell S. D., Guthrie, Graeme J. K., and McMillan, Donald C.

Subjects
ABDOMINAL aortic aneurysms, SKELETAL muscle, COHORT analysis, BODY composition, COLORECTAL cancer, MUSCLE mass, PROGNOSIS
Abstract

Background: Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. Methods: Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). Results: 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38–1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09–1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66–2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55–7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08–1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03–1.37, p = 0.02) were independently associated with increased odds of low SMD. Conclusions: Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Effect of differing flap reconstruction strategies in perineal closure following advanced pelvic oncological resection: a retrospective cohort study

Author

Galbraith, Norman J., primary, McCollum, Catherine, additional, Di Mascio, Lucia, additional, Lowrie, Joanna, additional, Hinckley, Matthew, additional, Lo, Steven, additional, Watson, Stuart, additional, Telfer, John R.C., additional, Roxburgh, Campbell S., additional, Horgan, Paul G., additional, Chong, Peter S., additional, Quinn, Martha, additional, and Steele, Colin. W., additional

Published
2023
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27. An investigation into the relationships between host and tumour related factors and their influence on survival in patients with colorectal cancer

Author

Roxburgh, Campbell S. D.

Subjects
616.99, RB Pathology, RD Surgery
Abstract

Colorectal cancer is the second commonest cause of cancer death in the western world. In addition to tumour factors such as depth of invasion, lymph node involvement and venous invasion it is increasingly recognised that host factors, are important determinants of survival. In particular the host local and systemic inflammatory responses are stage independent predictors of survival in operable disease. The present thesis further examines the prognostic importance of host and tumour factors in colorectal cancer, specifically: 1. An examination of the prognostic importance of venous invasion (detected using elastica stains) in colorectal cancer. 2. Detailed analysis of the determinants (including age, comorbidity and deprivation) of the systemic inflammatory response and their relationship with survival. 3. The application and validation of a prognostic score providing a measure of the local inflammatory response in colorectal cancer. 4. Detailed analysis of the determinants (including all white cells, lymphocytes and macrophages) of the local inflammatory response and their relationship with survival. 5. The inter-relationships between the local and systemic inflammatory responses in colorectal cancer specifically: early stage disease (node negative) and in patients receiving adjuvant chemotherapy. 6. Mediators (including immunological parameters and vitamin antioxidants) of the local and systemic inflammatory responses and their relationship with survival.

Published
2011

38. Abstract 1080: JAK inhibition as a therapeutic approach to enhance radiation response in rectal cancer

Author

Pennel, Kathryn A., primary, Hathakarnkul, Phimmada, additional, Al-Badran, Sara S., additional, Hashmi, Umar, additional, Hillson, Lily, additional, Quinn, Jean A., additional, Jones, Leia, additional, Steele, Colin W., additional, McMillan, Donald C., additional, Park, James H., additional, Sansom, Owen J., additional, Birch, Joanna, additional, and Roxburgh, Campbell S., additional

Published
2023
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39. Abstract 3231: Temporal changes in intratumoral and systemic lymphocytes in response to short and long course radiotherapy regimens in locally advanced rectal cancer

Author

Hillson, Lily V., primary, McMahon, Ross K., additional, Pennel, Kathryn A., additional, Quinn, Jean A., additional, Jones, Leia, additional, Amirkhah, Raheleh, additional, Ammar, Aula, additional, Hatthakarnkul, Phimmada, additional, Ferguson, Annabelle, additional, Milling, Simon W., additional, McDonald, Alec, additional, Dunne, Philip D., additional, Edwards, Joanne, additional, O'Cathail, Sean M., additional, and Roxburgh, Campbell S., additional

Published
2023
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42. Impact of microsatellite status in early-onset colonic cancer

Author

Zaborowski, Alexandra M., Adamina, Ahmed Abdile. Michel, Aigner, Felix, D'Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Bach, Sam Atallah Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Berdinskikh, Anton, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Brouwer, Nelleke, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D., Buchwald, Pamela, Burger, Jacobus W. A., Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Collinson, Rowan, Cologne, Kyle G., Contreras, Tomas, Croner, Roland, Daniels, Ian R., Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D'Hoore, Andre, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, el-Hussuna, Alaa, Elliot, Brodie, Emile, Sameh, Espin, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Figueiredo, Nuno, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Goran, Barisic, Greenwood, Emma, Guren, Marianne G., Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah D., Salido, Andrea Jimenez, Jimenez-Toscano, Marta, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A., Keller, Deborah S., Kelly, Justin, Kennelly, Rory, Khrykov, Gleb, Kocian, Peter, Koh, Cherry, Kok, Neils, Knight, Katrina A., Knol, Joep, Kontovounisios, Christos, Korner, Hartwig, Krivokapic, Zoran, Kronberger, Irmgard, Kroon, Hidde Maarten, Kryzauskas, Marius, Kural, Said, Kusters, Miranda, Lakkis, Zaher, Lankov, Timur, Larson, David, Lázár, György, Lee, Kai-Yin, Lee, Suk Hwan, Lefèvre, Jeremie H., Lepisto, Anna, Lieu, Christopher, Loi, Lynette, Lynch, Craig, Maillou-Martinaud, Helene, Maroli, Annalisa, Martin, Sean, Martling, Anna, Matzel, Klaus E., Mayol, Julio, McDermott, Frank, Meurette, Guillaume, Millan, Monica, Mitteregger, Martin, Moiseenko, Andrei, Monson, John Rt., Morarasu, Stefan, Moritani, Konosuke, Möslein, Gabriela, Munini, Martino, Nahas, Caio, Nahas, Sergio, Negoi, Ionut, Novikova, Anastasia, Ocares, Misael, Okabayashi, Koji, Olkina, Alexandra, Oñate-Ocaña, Luis, Otero, Jaime, Ozen, Cihan, Pace, Ugo, Julião, Guilherme Pagin S. o, Panaiotti, Lidiia, Panis, Yves, Papamichael, Demetris, Patel, Swati, Uriburu, Juan Carlos Patrón, Peng, Sze-Lin, Pera, Miguel, Perez, Rodrigo O., Petrov, Alexei, Pfeffer, Frank, Phang, Terry P., Poskus, Tomas, Pringle, Heather, Proud, David, Raguz, Ivana, Rama, Nuno, Rasheed, Shahnawaz, Raval, Manoj J., Rega, Daniela, Reissfelder, Christoph, Meneses, Juan Carlos Reyes, Ris, Frederic, Riss, Stefan, Rodriguez-Zentner, Homero, Roxburgh, Campbell S., Saklani, Avanish, Sammour, Tarik, Saraste, Deborah, Schneider, Martin, Seishima, Ryo, Sekulic, Aleksandar, Seppala, Toni, Sheahan, Kieran, Shlomina, Alexandra, Sigismondo, Guiseppe, Singnomklao, Tongplaew, Siragusa, Leandro, Smart, Neil, Solis-Peña, Alejandro, Spinelli, Antonino, Staiger, Roxane D., Stamos, Michael J., Steele, Scott, Tan, Ker-Kan, Tanis, Pieter J., Tekkis, Paris, Teklay, Biniam, Tengku, Sabrina, Tsarkov, Petr, Turina, Matthias, Ulrich, Alexis, Vailati, Bruna B., van Harten, Meike, Verhoef, Cornelis, Warrier, Satish, Wexner, Steven, de Wilt, Hans, Weinberg, Benjamin A., Wells, Cameron, Wolthuis, Albert, Xynos, Evangelos, You, Nancy, Zakharenko, Alexander, Zeballos, Justino, Zhou, Jonathan, Winter, Des C., CCA - Cancer Treatment and Quality of Life, Surgery, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and nuclear medicine, and CCA - Cancer Treatment and quality of life

Subjects
Proto-Oncogene Proteins B-raf, Microsatellite Repeats/genetics, Colonic Neoplasms/genetics, Prognosis, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins p21(ras)/genetics, SDG 3 - Good Health and Well-being, Colonic Neoplasms, Mutation, Proto-Oncogene Proteins B-raf/genetics, Humans, Microsatellite Instability, Surgery, 03.02. Klinikai orvostan, Colorectal Neoplasms, Microsatellite Repeats
Abstract

Background The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Methods Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I–III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. Results A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Conclusion Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.

Published
2022

43. Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response

Author

Williams, Christopher J. M., Peddle, Allyson M., Kasi, Pashtoon M., Seligmann, Jenny F., Roxburgh, Campbell S., Middleton, Gary M., and Tejpar, Sabine

Abstract

Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant ‘window-of-opportunity’ trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance.

Published
2024
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44. The neoadjuvant rectal score and a novel magnetic resonance imaging based neoadjuvant rectal score are stage independent predictors of long‐term outcome in locally advanced rectal cancer.

Author

McMahon, Ross K., O'Cathail, Sean M., Nair, Harikrishnan, Steele, Colin W., Platt, Jonathan J., Digby, Michael, McDonald, Alec C., Horgan, Paul G., and Roxburgh, Campbell S. D.

Subjects
RECTAL cancer, MAGNETIC resonance imaging, PRESERVATION of organs, tissues, etc., PROGNOSIS, NEOADJUVANT chemotherapy, RECTAL surgery, CANCER radiotherapy
Abstract

Aim: Neoadjuvant rectal (NAR) score is an early surrogate for longer‐term outcomes in rectal cancer undergoing radiotherapy and resection. In an era of increasing organ preservation, resection specimens are not always available to calculate the NAR score. Post‐treatment magnetic resonance imaging (MRI) re‐staging of regression is subjective, limiting reproducibility. We explored the potential for a novel MRI‐based NAR score (mrNAR) adapted from the NAR formula. Methods: Locally advanced rectal cancer patients undergoing neoadjuvant therapy (nCRT) and surgery were retrospectively identified between 2008 and 2020 in a single cancer network. mrNAR was calculated by adapting the NAR formula, replacing pathological (p) stages with post‐nCRT MR stages (ymr). Cox regression assessed relationships between clinicopathological characteristics, NAR and mrNAR with overall survival (OS) and recurrence‐free survival (RFS). Results: In total, 381 NAR and 177 mrNAR scores were calculated. On univariate analysis NAR related to OS (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.33–3.14, p = 0.001) and RFS (HR 2.52, 95% CI 1.77–3.59, p = 0.001). NAR 3‐year OS <8 was 95.3%, 8–16 was 88.6% and >16 was 80%. mrNAR related to OS (HR 2.96, 95% CI 1.38–6.34, p = 0.005) and RFS (HR 2.99, 95% CI 1.49–6.00, p = 0.002). 3‐year OS for mrNAR <8 was 96.2%, 8–16 was 92.4% and >16 was 78%. On multivariate analysis, mrNAR was a stage‐independent predictor of OS and RFS. mrNAR corresponded to NAR score category in only 15% (positive predictive value 0.23) and 47.5% (positive predictive value 0.48) of cases for categories <8 and >16, respectively. Conclusions: Neoadjuvant rectal score is validated as a surrogate end‐point for long‐term outcomes. mrNAR categories do not correlate with NAR but have stage‐independent prognostic value. mrNAR may represent a novel surrogate end‐point for future neoadjuvant treatments that focus on organ preservation. [ABSTRACT FROM AUTHOR]

Published
2023
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