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1. Developing a novel measure of Theory of Mind : 'The Friendship Game'

Author

Smithers, M.

Subjects
616.85
Abstract

Advanced tests of Theory of Mind (ToM) have offered support for the ToM model of ASD with adults with High Functioning Autism Spectrum Disorder (HF ASD). Other support for the ToM model of ASD has arisen from research incorporating video and audio elements to improve the real-life applicability of ToM tests for adults with HF ASD. Building upon this research, the current study develops a new measure of Theory of Mind (ToM) that adopts a game-like design that is both challenging and engaging for adults with HF ASD: The Friendship Game (TFG). The thesis documents the initial development of TFG, followed by an exploratory quantitative and qualitative validation of TFG. Eight participants with HF ASD were recruited to the study. Their individual performances on TFG were compared to their performances on Cognitive and Social Cognitive Assessments and self-report measures, relative to UK norms. The participants’ verbal responses in TFG were explored to assess perceived evidence of ToM application and accuracy. The participants also provided feedback on the testing experience to further assess TFG’s validity and relevance to the adult HF ASD population. The results provided initial support for TFG’s validation as a new measure of ToM for adults with HF ASD. Exploration of the participants’ verbal responses suggest that there was no evidence of floor or ceiling effects in TFG. Participant feedback also indicated that the TFG is both an engaging and challenging test of ToM. Whilst they reflected that social interaction is more complex in everyday life, TFG helped to identify and prompt a discussion around these difficulties. Ideas for how TFG could be developed into an intervention to support adults with HF ASD were also discussed. The findings of the study were discussed in relation to previous research and ideas for future directions. The study’s methodological and theoretical limitations were also explored. For example, the impact of the small participant size on the conclusions that can be draw from of the study. Also, the contextual challenges involved in the validation of a new measure of ToM.

Published
2020
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4. 1239P Radiomics biomarkers are associated with survival in patients with oesophageal adenocarcinoma

Author

Aoude, L.G., primary, Bonazzi, V.F., additional, Brosda, S., additional, Wong, B., additional, Moradi, H., additional, Lonie, J., additional, Bradford, J., additional, Bloxham, C., additional, Atkinson, V.G., additional, Law, P., additional, Lampe, G., additional, Smithers, M., additional, Waddell, N., additional, Vegh, V., additional, Miles, K., additional, and Barbour, A.P., additional

Published
2022
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5. Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial

Author

Nilsson, M, Olafsdottir, H, Alexandersson von Doebeln, G, Villegas, F, Gagliardi, G, Hellstroem, M, Wang, Q-L, Johansson, H, Gebski, V, Hedberg, J, Klevebro, F, Markar, S, Smyth, E, Lagergren, P, Al-Haidari, G, Rekstad, LC, Aahlin, EK, Wallner, B, Edholm, D, Johansson, J, Szabo, E, Reynolds, JV, Pramesh, CS, Mummudi, N, Joshi, A, Ferri, L, Wong, RKS, O'Callaghan, C, Lukovic, J, Chan, KKW, Leong, T, Barbour, A, Smithers, M, Li, Y, Kang, X, Kong, F-M, Chao, Y-K, Crosby, T, Bruns, C, van Laarhoven, H, van Berge Henegouwen, M, van Hillegersberg, R, Rosati, R, Piessen, G, de Manzoni, G, Lordick, F, Nilsson, M, Olafsdottir, H, Alexandersson von Doebeln, G, Villegas, F, Gagliardi, G, Hellstroem, M, Wang, Q-L, Johansson, H, Gebski, V, Hedberg, J, Klevebro, F, Markar, S, Smyth, E, Lagergren, P, Al-Haidari, G, Rekstad, LC, Aahlin, EK, Wallner, B, Edholm, D, Johansson, J, Szabo, E, Reynolds, JV, Pramesh, CS, Mummudi, N, Joshi, A, Ferri, L, Wong, RKS, O'Callaghan, C, Lukovic, J, Chan, KKW, Leong, T, Barbour, A, Smithers, M, Li, Y, Kang, X, Kong, F-M, Chao, Y-K, Crosby, T, Bruns, C, van Laarhoven, H, van Berge Henegouwen, M, van Hillegersberg, R, Rosati, R, Piessen, G, de Manzoni, G, and Lordick, F

Abstract

BACKGROUND: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. METHODS: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier: NCT04460352.

Published
2022

6. Additional file 1 of Patient-reported outcome (PRO) results from the AGITG DOCTOR trial: a randomised phase 2 trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma

Author

Mercieca-Bebber, R., Barnes, E. H., Wilson, K., Samoon, Z., Walpole, E., Mai, T., Ackland, S., Burge, M., Dickie, G., Watson, D., Leung, J., Wang, T., Bohmer, R., Cameron, D., Simes, J., Gebski, V., Smithers, M., Thomas, J., Zalcberg, J., and Barbour, A. P.

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2022
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7. Additional file 3 of Patient-reported outcome (PRO) results from the AGITG DOCTOR trial: a randomised phase 2 trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma

Author

Mercieca-Bebber, R., Barnes, E. H., Wilson, K., Samoon, Z., Walpole, E., Mai, T., Ackland, S., Burge, M., Dickie, G., Watson, D., Leung, J., Wang, T., Bohmer, R., Cameron, D., Simes, J., Gebski, V., Smithers, M., Thomas, J., Zalcberg, J., and Barbour, A. P.

Subjects
Data_FILES
Abstract

Additional file 3.

Published
2022
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15. 1430P Patient-reported outcome (PRO) results from AGITG DOCTOR: A randomised phase II trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma

Author

Mercieca-Bebber, R., primary, Barnes, E.H., additional, Wilson, K., additional, Samoon, Z., additional, Walpole, E.T., additional, Mai, T., additional, Ackland, S., additional, Burge, M., additional, Dickie, G., additional, Watson, D., additional, Leung, J., additional, Wang, T., additional, Bohmer, R., additional, Cameron, D., additional, Simes, R., additional, Gebski, V., additional, Smithers, M., additional, Thomas, J., additional, Zalcberg, J.R., additional, and Barbour, A., additional

Published
2020
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16. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Landi MT, Bishop DT, MacGregor S, Machiela MJ, Stratigos AJ, Ghiorzo P, Brossard M, Calista D, Choi J, Fargnoli MC, Zhang T, Rodolfo M, Trower AJ, Menin C, Martinez J, Hadjisavvas A, Song L, Stefanaki I, Scolyer R, Yang R, Goldstein AM, Potrony M, Kypreou KP, Pastorino L, Queirolo P, Pellegrini C, Cattaneo L, Zawistowski M, Gimenez-Xavier P, Rodriguez A, Elefanti L, Manoukian S, Rivoltini L, Smith BH, Loizidou MA, Del Regno L, Massi D, Mandala M, Khosrotehrani K, Akslen LA, Amos CI, Andresen PA, Avril MF, Azizi E, Soyer HP, Bataille V, Dalmasso B, Bowdler LM, Burdon KP, Chen WV, Codd V, Craig JE, Debniak T, Falchi M, Fang S, Friedman E, Simi S, Galan P, Garcia-Casado Z, Gillanders EM, Gordon S, Green A, Gruis NA, Hansson J, Harland M, Harris J, Helsing P, Henders A, Hocevar M, Höiom V, Hunter D, Ingvar C, Kumar R, Lang J, Lathrop GM, Lee JE, Li X, Lubinski J, Mackie RM, Malt M, Malvehy J, McAloney K, Mohamdi H, Molven A, Moses EK, Neale RE, Novakovic S, Nyholt DR, Olsson H, Orr N, Fritsche LG, Puig-Butille JA, Qureshi AA, Radford-Smith GL, Randerson-Moor J, Requena C, Rowe C, Samani NJ, Sanna M, Schadendorf D, Schulze HJ, Simms LA, Smithers M, Song F, Swerdlow AJ, van der Stoep N, Kukutsch NA, Visconti A, Wallace L, Ward SV, Wheeler L, Sturm RA, Hutchinson A, Jones K, Malasky M, Vogt A, Zhou W, Pooley KA, Elder DE, Han J, Hicks B, Hayward NK, Kanetsky PA, Brummett C, Montgomery GW, Olsen CM, Hayward C, Dunning AM, Martin NG, Evangelou E, Mann GJ, Long G, Pharoah PDP, Easton DF, Barrett JH, Cust AE, Abecasis G, Duffy DL, Whiteman DC, Gogas H, De Nicolo A, Tucker MA, Newton-Bishop JA, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, SDH Study Group, IBD Investigators, Essen-Heidelberg Investigators, AMFS Investigators, MelaNostrum Consortium, Peris K, Chanock SJ, Demenais F, Brown KM, Puig S, Nagore E, Shi J, Iles MM, and Law MH

Abstract

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma. Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.

Published
2020

17. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Landi, M.T. Bishop, D.T. MacGregor, S. Machiela, M.J. Stratigos, A.J. Ghiorzo, P. Brossard, M. Calista, D. Choi, J. Fargnoli, M.C. Zhang, T. Rodolfo, M. Trower, A.J. Menin, C. Martinez, J. Hadjisavvas, A. Song, L. Stefanaki, I. Scolyer, R. Yang, R. Goldstein, A.M. Potrony, M. Kypreou, K.P. Pastorino, L. Queirolo, P. Pellegrini, C. Cattaneo, L. Zawistowski, M. Gimenez-Xavier, P. Rodriguez, A. Elefanti, L. Manoukian, S. Rivoltini, L. Smith, B.H. Loizidou, M.A. Del Regno, L. Massi, D. Mandala, M. Khosrotehrani, K. Akslen, L.A. Amos, C.I. Andresen, P.A. Avril, M.-F. Azizi, E. Soyer, H.P. Bataille, V. Dalmasso, B. Bowdler, L.M. Burdon, K.P. Chen, W.V. Codd, V. Craig, J.E. Dębniak, T. Falchi, M. Fang, S. Friedman, E. Simi, S. Galan, P. Garcia-Casado, Z. Gillanders, E.M. Gordon, S. Green, A. Gruis, N.A. Hansson, J. Harland, M. Harris, J. Helsing, P. Henders, A. Hočevar, M. Höiom, V. Hunter, D. Ingvar, C. Kumar, R. Lang, J. Lathrop, G.M. Lee, J.E. Li, X. Lubiński, J. Mackie, R.M. Malt, M. Malvehy, J. McAloney, K. Mohamdi, H. Molven, A. Moses, E.K. Neale, R.E. Novaković, S. Nyholt, D.R. Olsson, H. Orr, N. Fritsche, L.G. Puig-Butille, J.A. Qureshi, A.A. Radford-Smith, G.L. Randerson-Moor, J. Requena, C. Rowe, C. Samani, N.J. Sanna, M. Schadendorf, D. Schulze, H.-J. Simms, L.A. Smithers, M. Song, F. Swerdlow, A.J. van der Stoep, N. Kukutsch, N.A. Visconti, A. Wallace, L. Ward, S.V. Wheeler, L. Sturm, R.A. Hutchinson, A. Jones, K. Malasky, M. Vogt, A. Zhou, W. Pooley, K.A. Elder, D.E. Han, J. Hicks, B. Hayward, N.K. Kanetsky, P.A. Brummett, C. Montgomery, G.W. Olsen, C.M. Hayward, C. Dunning, A.M. Martin, N.G. Evangelou, E. Mann, G.J. Long, G. Pharoah, P.D.P. Easton, D.F. Barrett, J.H. Cust, A.E. Abecasis, G. Duffy, D.L. Whiteman, D.C. Gogas, H. De Nicolo, A. Tucker, M.A. Newton-Bishop, J.A. Peris, K. Chanock, S.J. Demenais, F. Brown, K.M. Puig, S. Nagore, E. Shi, J. Iles, M.M. Law, M.H. GenoMEL Consortium Q-MEGA QTWIN Investigators ATHENS Melanoma Study Group 23andMe The SDH Study Group IBD Investigators Essen-Heidelberg Investigators AMFS Investigators MelaNostrum Consortium

Abstract

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2020

21. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Landi, M.T. Bishop, D.T. MacGregor, S. Machiela, M.J. Stratigos, A.J. Ghiorzo, P. Brossard, M. Calista, D. Choi, J. Fargnoli, M.C. Zhang, T. Rodolfo, M. Trower, A.J. Menin, C. Martinez, J. Hadjisavvas, A. Song, L. Stefanaki, I. Scolyer, R. Yang, R. Goldstein, A.M. Potrony, M. Kypreou, K.P. Pastorino, L. Queirolo, P. Pellegrini, C. Cattaneo, L. Zawistowski, M. Gimenez-Xavier, P. Rodriguez, A. Elefanti, L. Manoukian, S. Rivoltini, L. Smith, B.H. Loizidou, M.A. Del Regno, L. Massi, D. Mandala, M. Khosrotehrani, K. Akslen, L.A. Amos, C.I. Andresen, P.A. Avril, M.-F. Azizi, E. Soyer, H.P. Bataille, V. Dalmasso, B. Bowdler, L.M. Burdon, K.P. Chen, W.V. Codd, V. Craig, J.E. Dębniak, T. Falchi, M. Fang, S. Friedman, E. Simi, S. Galan, P. Garcia-Casado, Z. Gillanders, E.M. Gordon, S. Green, A. Gruis, N.A. Hansson, J. Harland, M. Harris, J. Helsing, P. Henders, A. Hočevar, M. Höiom, V. Hunter, D. Ingvar, C. Kumar, R. Lang, J. Lathrop, G.M. Lee, J.E. Li, X. Lubiński, J. Mackie, R.M. Malt, M. Malvehy, J. McAloney, K. Mohamdi, H. Molven, A. Moses, E.K. Neale, R.E. Novaković, S. Nyholt, D.R. Olsson, H. Orr, N. Fritsche, L.G. Puig-Butille, J.A. Qureshi, A.A. Radford-Smith, G.L. Randerson-Moor, J. Requena, C. Rowe, C. Samani, N.J. Sanna, M. Schadendorf, D. Schulze, H.-J. Simms, L.A. Smithers, M. Song, F. Swerdlow, A.J. van der Stoep, N. Kukutsch, N.A. Visconti, A. Wallace, L. Ward, S.V. Wheeler, L. Sturm, R.A. Hutchinson, A. Jones, K. Malasky, M. Vogt, A. Zhou, W. Pooley, K.A. Elder, D.E. Han, J. Hicks, B. Hayward, N.K. Kanetsky, P.A. Brummett, C. Montgomery, G.W. Olsen, C.M. Hayward, C. Dunning, A.M. Martin, N.G. Evangelou, E. Mann, G.J. Long, G. Pharoah, P.D.P. Easton, D.F. Barrett, J.H. Cust, A.E. Abecasis, G. Duffy, D.L. Whiteman, D.C. Gogas, H. De Nicolo, A. Tucker, M.A. Newton-Bishop, J.A. Peris, K. Chanock, S.J. Demenais, F. Brown, K.M. Puig, S. Nagore, E. Shi, J. Iles, M.M. Law, M.H. GenoMEL Consortium Q-MEGA QTWIN Investigators ATHENS Melanoma Study Group 23andMe The SDH S and Landi, M.T. Bishop, D.T. MacGregor, S. Machiela, M.J. Stratigos, A.J. Ghiorzo, P. Brossard, M. Calista, D. Choi, J. Fargnoli, M.C. Zhang, T. Rodolfo, M. Trower, A.J. Menin, C. Martinez, J. Hadjisavvas, A. Song, L. Stefanaki, I. Scolyer, R. Yang, R. Goldstein, A.M. Potrony, M. Kypreou, K.P. Pastorino, L. Queirolo, P. Pellegrini, C. Cattaneo, L. Zawistowski, M. Gimenez-Xavier, P. Rodriguez, A. Elefanti, L. Manoukian, S. Rivoltini, L. Smith, B.H. Loizidou, M.A. Del Regno, L. Massi, D. Mandala, M. Khosrotehrani, K. Akslen, L.A. Amos, C.I. Andresen, P.A. Avril, M.-F. Azizi, E. Soyer, H.P. Bataille, V. Dalmasso, B. Bowdler, L.M. Burdon, K.P. Chen, W.V. Codd, V. Craig, J.E. Dębniak, T. Falchi, M. Fang, S. Friedman, E. Simi, S. Galan, P. Garcia-Casado, Z. Gillanders, E.M. Gordon, S. Green, A. Gruis, N.A. Hansson, J. Harland, M. Harris, J. Helsing, P. Henders, A. Hočevar, M. Höiom, V. Hunter, D. Ingvar, C. Kumar, R. Lang, J. Lathrop, G.M. Lee, J.E. Li, X. Lubiński, J. Mackie, R.M. Malt, M. Malvehy, J. McAloney, K. Mohamdi, H. Molven, A. Moses, E.K. Neale, R.E. Novaković, S. Nyholt, D.R. Olsson, H. Orr, N. Fritsche, L.G. Puig-Butille, J.A. Qureshi, A.A. Radford-Smith, G.L. Randerson-Moor, J. Requena, C. Rowe, C. Samani, N.J. Sanna, M. Schadendorf, D. Schulze, H.-J. Simms, L.A. Smithers, M. Song, F. Swerdlow, A.J. van der Stoep, N. Kukutsch, N.A. Visconti, A. Wallace, L. Ward, S.V. Wheeler, L. Sturm, R.A. Hutchinson, A. Jones, K. Malasky, M. Vogt, A. Zhou, W. Pooley, K.A. Elder, D.E. Han, J. Hicks, B. Hayward, N.K. Kanetsky, P.A. Brummett, C. Montgomery, G.W. Olsen, C.M. Hayward, C. Dunning, A.M. Martin, N.G. Evangelou, E. Mann, G.J. Long, G. Pharoah, P.D.P. Easton, D.F. Barrett, J.H. Cust, A.E. Abecasis, G. Duffy, D.L. Whiteman, D.C. Gogas, H. De Nicolo, A. Tucker, M.A. Newton-Bishop, J.A. Peris, K. Chanock, S.J. Demenais, F. Brown, K.M. Puig, S. Nagore, E. Shi, J. Iles, M.M. Law, M.H. GenoMEL Consortium Q-MEGA QTWIN Investigators ATHENS Melanoma Study Group 23andMe The SDH S

Abstract

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2020

22. Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma

Author

Cebon, JS, Gore, M, Thompson, JF, Davis, ID, McArthur, GA, Walpole, E, Smithers, M, Cerundolo, V, Dunbar, PR, MacGregor, D, Fisher, C, Millward, M, Nathan, P, Findlay, MPN, Hersey, P, Evans, TRJ, Ottensmeier, CH, Marsden, J, Dalgleish, AG, Corrie, PG, Maria, M, Brimble, M, Williams, G, Winkler, S, Jackson, HM, Endo-Munoz, L, Tutuka, CSA, Venhaus, R, Old, LJ, Haack, D, Maraskovsky, E, Behren, A, Chen, W, Cebon, JS, Gore, M, Thompson, JF, Davis, ID, McArthur, GA, Walpole, E, Smithers, M, Cerundolo, V, Dunbar, PR, MacGregor, D, Fisher, C, Millward, M, Nathan, P, Findlay, MPN, Hersey, P, Evans, TRJ, Ottensmeier, CH, Marsden, J, Dalgleish, AG, Corrie, PG, Maria, M, Brimble, M, Williams, G, Winkler, S, Jackson, HM, Endo-Munoz, L, Tutuka, CSA, Venhaus, R, Old, LJ, Haack, D, Maraskovsky, E, Behren, A, and Chen, W

Abstract

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

Published
2020

24. Efficacy of immune checkpoint inhibitors for in-transit melanoma

Author

Nan Tie, E, Lai-Kwon, J, Rtshiladze, MA, Na, L, Bozzi, J, Read, T, Atkinson, V, Au-Yeung, G, Long, G, McArthur, GA, Sandhu, S, Saw, R, Walpole, E, Menzies, A, Smithers, M, Gyorki, DE, Nan Tie, E, Lai-Kwon, J, Rtshiladze, MA, Na, L, Bozzi, J, Read, T, Atkinson, V, Au-Yeung, G, Long, G, McArthur, GA, Sandhu, S, Saw, R, Walpole, E, Menzies, A, Smithers, M, and Gyorki, DE

Abstract

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM. METHODS: A retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments. RESULTS: Fifty-four patients were included: 27 (50%) female; median age 75 (range 26-94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2-46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR. CONCLUSIONS AND RELEVANCE: ICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.

Published
2020

27. Progression-free survival and recurrence results for AGITG DOCTOR: Pre-op cisplatin, 5FU & DOCetaxel +/-radiotherapy after poor early response to cisplatin & 5FU for resectable oesophageal adenocarcinoma

Author

Barbour, A.P., primary, Walpole, E.T., additional, Mai, G.T., additional, Barnes, L., additional, Watson, D.I., additional, Ackland, S.P., additional, Wills, V., additional, Martin, J., additional, Burge, M., additional, Karapetis, C.S., additional, Shannon, J., additional, Nott, L.M., additional, Gebski, V., additional, Oostendorp, M., additional, Wilson, K., additional, Thomas, J., additional, Lampe, G., additional, Zalcberg, J.R., additional, Simes, J., additional, and Smithers, M., additional

Published
2018
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28. Neoadjuvant therapy for esophageal adenocarcinoma: A propensity score-matched comparison of paclitaxel and carboplatin chemoradiotherapy with cisplatin and 5-fluoruracil-based chemo- or chemoradiotherapy

Author

Barbour, A.P., primary, Brosda, S., additional, Wijnhoven, B., additional, van Hootgem, S., additional, Lanschot, J.J.B., additional, Barbour, S., additional, Lagarde, S., additional, Krause, L., additional, Pryor, D., additional, Thomas, J., additional, Walpole, E.T., additional, van der Gaast, A., additional, and Smithers, M., additional

Published
2018
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29. Neoadjuvant therapy for esophageal adenocarcinoma: A propensity score-matched comparison of paclitaxel and carboplatin chemoradiotherapy with cisplatin and 5-fluoruracil-based chemo- or chemoradiotherapy

Author

Barbour, A.P. (A. P.), Brosda, S. (S.), Wijnhoven, B.P.L. (Bas), van Hootgem, S. (S.), Lanschot, J.J.B. (J. J.B.), Barbour, S. (S.), Lagarde, S.M. (Sjoerd), Krause, L. (L.), Pryor, D. (D.), Thomas, J. (J.), Walpole, E.T. (E. T.), Gaast, A. (Ate) van der, Smithers, M. (M.), Barbour, A.P. (A. P.), Brosda, S. (S.), Wijnhoven, B.P.L. (Bas), van Hootgem, S. (S.), Lanschot, J.J.B. (J. J.B.), Barbour, S. (S.), Lagarde, S.M. (Sjoerd), Krause, L. (L.), Pryor, D. (D.), Thomas, J. (J.), Walpole, E.T. (E. T.), Gaast, A. (Ate) van der, and Smithers, M. (M.)

Published
2018
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31. An AGITG trial –A randomised phase II study of pre-operative cisplatin, fluorouracil and DOCetaxel +/-radioTherapy based on poOR early response to cisplatin and fluorouracil for resectable esophageal adenocarcinoma

Author

Barbour, A., primary, Walpole, E., additional, Mai, G.T., additional, Chan, H., additional, Barnes, E., additional, Watson, D., additional, Ackland, S., additional, Wills, V., additional, Martin, J., additional, Burge, M., additional, Karapetis, C., additional, Shannon, J., additional, Nott, L., additional, Gebski, V., additional, Wilson, K., additional, Thomas, J., additional, Lampe, G., additional, Zalcberg, J., additional, Simes, J., additional, and Smithers, M., additional

Published
2016
Full Text
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35. 618PD - Progression-free survival and recurrence results for AGITG DOCTOR: Pre-op cisplatin, 5FU & DOCetaxel +/-radiotherapy after poor early response to cisplatin & 5FU for resectable oesophageal adenocarcinoma

Author

Barbour, A.P., Walpole, E.T., Mai, G.T., Barnes, L., Watson, D.I., Ackland, S.P., Wills, V., Martin, J., Burge, M., Karapetis, C.S., Shannon, J., Nott, L.M., Gebski, V., Oostendorp, M., Wilson, K., Thomas, J., Lampe, G., Zalcberg, J.R., Simes, J., and Smithers, M.

Published
2018
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38. 610O - An AGITG trial –A randomised phase II study of pre-operative cisplatin, fluorouracil and DOCetaxel +/-radioTherapy based on poOR early response to cisplatin and fluorouracil for resectable esophageal adenocarcinoma

Author

Barbour, A., Walpole, E., Mai, G.T., Chan, H., Barnes, E., Watson, D., Ackland, S., Wills, V., Martin, J., Burge, M., Karapetis, C., Shannon, J., Nott, L., Gebski, V., Wilson, K., Thomas, J., Lampe, G., Zalcberg, J., Simes, J., and Smithers, M.

Published
2016
Full Text
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