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1. Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI

Author

Spaanderman, DJ, Hakkesteegt, SN, Hanff, DF, Schut, ARW, Schiphouwer, LM, Vos, M, Messiou, C, Doran, SJ, Jones, RL, Hayes, AJ, Nardo, L, Abdelhafez, YG, Moawad, AW, Elsayes, KM, Lee, S, Link, TM, Niessen, WJ, van Leenders, GJLH, Visser, JJ, Klein, S, Grünhagen, DJ, Verhoef, C, and Starmans, MPA

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Networking and Information Technology R&D (NITRD), Clinical Research, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Lipomatous tumors, Radiomics, External validation, Prospective validation, Deep learning-based segmentation, Magnetic resonance imaging, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundAs differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility.MethodsThree study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists.FindingsThe validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85).InterpretationThe radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics.FundingHanarth fonds.

Published
2024

2. Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI

Author

Spaanderman, D.J., Hakkesteegt, S.N., Hanff, D.F., Schut, A.R.W., Schiphouwer, L.M., Vos, M., Messiou, C., Doran, S.J., Jones, R.L., Hayes, A.J., Nardo, L., Abdelhafez, Y.G., Moawad, A.W., Elsayes, K.M., Lee, S., Link, T.M., Niessen, W.J., van Leenders, G.J.L.H., Visser, J.J., Klein, S., Grünhagen, D.J., Verhoef, C., and Starmans, M.P.A.

Published
2024
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4. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

Author

Stacchiotti, S., Miah, A.B., Frezza, A.M., Messiou, C., Morosi, C., Caraceni, A., Antonescu, C.R., Bajpai, J., Baldini, E., Bauer, S., Biagini, R., Bielack, S., Blay, J.Y., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Boye, K., Brodowicz, T., Callegaro, D., De Alava, E., Deoras-Sutliff, M., Dufresne, A., Eriksson, M., Errani, C., Fedenko, A., Ferraresi, V., Ferrari, A., Fletcher, C.D.M., Garcia del Muro, X., Gelderblom, H., Gladdy, R.A., Gouin, F., Grignani, G., Gutkovich, J., Haas, R., Hindi, N., Hohenberger, P., Huang, P., Joensuu, H., Jones, R.L., Jungels, C., Kasper, B., Kawai, A., Le Cesne, A., Le Grange, F., Leithner, A., Leonard, H., Lopez Pousa, A., Martin Broto, J., Merimsky, O., Merriam, P., Miceli, R., Mir, O., Molinari, M., Montemurro, M., Oldani, G., Palmerini, E., Pantaleo, M.A., Patel, S., Piperno-Neumann, S., Raut, C.P., Ravi, V., Razak, A.R.A., Reichardt, P., Rubin, B.P., Rutkowski, P., Safwat, A.A., Sangalli, C., Sapisochin, G., Sbaraglia, M., Scheipl, S., Schöffski, P., Strauss, D., Strauss, S.J., Sundby Hall, K., Tap, W.D., Trama, A., Tweddle, A., van der Graaf, W.T.A., Van De Sande, M.A.J., Van Houdt, W., van Oortmerssen, G., Wagner, A.J., Wartenberg, M., Wood, J., Zaffaroni, N., Zimmermann, C., Casali, P.G., Dei Tos, A.P., and Gronchi, A.

Published
2021
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5. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up

Author

Casali, P.G., Blay, J.Y., Abecassis, N., Bajpai, J., Bauer, S., Biagini, R., Bielack, S., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Boye, K., Brodowicz, T., Buonadonna, A., De Álava, E., Dei Tos, A.P., Del Muro, X.G., Dufresne, A., Eriksson, M., Fedenko, A., Ferraresi, V., Ferrari, A., Frezza, A.M., Gasperoni, S., Gelderblom, H., Gouin, F., Grignani, G., Haas, R., Hassan, A.B., Hindi, N., Hohenberger, P., Joensuu, H., Jones, R.L., Jungels, C., Jutte, P., Kasper, B., Kawai, A., Kopeckova, K., Krákorová, D.A., Le Cesne, A., Le Grange, F., Legius, E., Leithner, A., Lopez-Pousa, A., Martin-Broto, J., Merimsky, O., Messiou, C., Miah, A.B., Mir, O., Montemurro, M., Morosi, C., Palmerini, E., Pantaleo, M.A., Piana, R., Piperno-Neumann, S., Reichardt, P., Rutkowski, P., Safwat, A.A., Sangalli, C., Sbaraglia, M., Scheipl, S., Schöffski, P., Sleijfer, S., Strauss, D., Strauss, S.J., Hall, K Sundby, Trama, A., Unk, M., van de Sande, M.A.J., van der Graaf, W.T.A., van Houdt, W.J., Frebourg, T., Gronchi, A., and Stacchiotti, S.

Published
2021
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8. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author

Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., Kassiotis G., Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., and Kassiotis G.

Abstract

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.

Published
2023

9. Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Author

Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., Attard G., Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., and Attard G.

Abstract

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10−8 and 6.4 × 10−4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories.

Published
2023

11. An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG)

Author

Bauer, S., Blay, J.Y., van Coevorden, F., Dileo, P., Dürr, H.R., Fiore, M., Grünwald, V., Jones, R., Judson, I., Kettelhack, C., Kopeckova, K., Lazar, A., Lindner, L.H., Martin-Broto, J., Rutkowski, P., Stacchiotti, S., Stoeckle, E., Valverde, C., Verhoef, K., Wardelmann, E., Wartenberg, M., Kasper, B., Baumgarten, C., Garcia, J., Bonvalot, S., Haas, R., Haller, F., Hohenberger, P., Penel, N., Messiou, C., van der Graaf, W.T., and Gronchi, A.

Published
2017
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12. Gastrointestinal stromal tumours

Author

Casali, P.G., Blay, J.Y., Abecassis, N., Bajpai, J., Bauer, S., Biagini, R., Bielack, S., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Boye, K., Brodowicz, T., Buonadonna, A., Alava, E. de, Tos, A.P. dei, Muro, X.G. del, Dufresne, A., Eriksson, M., Fedenko, A., Ferraresi, V., Ferrari, A., Frezza, A.M., Gasperoni, S., Gelderblom, H., Gouin, F., Grignani, G., Haas, R., Hassan, A.B., Hindi, N., Hohenberger, P., Joensuu, H., Jones, R.L., Jungels, C., Jutte, P., Kasper, B., Kawai, A., Kopeckova, K., Krakorova, D.A., Cesne, A. le, Grange, F. le, Legius, E., Leithner, A., Lopez-Pousa, A., Martin-Broto, J., Merimsky, O., Messiou, C., Miah, A.B., Mir, O., Montemurro, M., Morosi, C., Palmerini, E., Pantaleo, M.A., Piana, R., Piperno-Neumann, S., Reichardt, P., Rutkowski, P., Safwat, A.A., Sangalli, C., Sbaraglia, M., Scheipl, S., Schoffski, P., Sleijfer, S., Strauss, D., Strauss, S.J., Hall, K.S., Trama, A., Unk, M., Sande, M.A.J. van de, Graaf, W.T.A. van der, Houdt, W.J. van, Frebourg, T., Gronchi, A., Stacchiotti, S., ESMO Guidelines Comm, EURACAN, GENTURIS, Casali P.G., Blay J.Y., Abecassis N., Bajpai J., Bauer S., Biagini R., Bielack S., Bonvalot S., Boukovinas I., Bovee J.V.M.G., Boye K., Brodowicz T., Buonadonna A., De Alava E., Dei Tos A.P., Del Muro X.G., Dufresne A., Eriksson M., Fedenko A., Ferraresi V., Ferrari A., Frezza A.M., Gasperoni S., Gelderblom H., Gouin F., Grignani G., Haas R., Hassan A.B., Hindi N., Hohenberger P., Joensuu H., Jones R.L., Jungels C., Jutte P., Kasper B., Kawai A., Kopeckova K., Krakorova D.A., Le Cesne A., Le Grange F., Legius E., Leithner A., Lopez-Pousa A., Martin-Broto J., Merimsky O., Messiou C., Miah A.B., Mir O., Montemurro M., Morosi C., Palmerini E., Pantaleo M.A., Piana R., Piperno-Neumann S., Reichardt P., Rutkowski P., Safwat A.A., Sangalli C., Sbaraglia M., Scheipl S., Schoffski P., Sleijfer S., Strauss D., Strauss S.J., Hall K.S., Trama A., Unk M., van de Sande M.A.J., van der Graaf W.T.A., van Houdt W.J., Frebourg T., Gronchi A., Stacchiotti S., Medical Oncology, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Public Health Research (PHR), and Man, Biomaterials and Microbes (MBM)

Subjects
GIST, clinical practice guidelines, gastrointestinal stromal tumour, surgery, tyrosine kinase inhibitor, Oncology, Medizin, Hematology, clinical practice guideline
Abstract

Gastrointestinal stromal tumours (GISTs) are malignant mesenchymal tumours with a variable clinical behaviour, marked by differentiation towards the interstitial cells of Cajal.1 GISTs belong to the family of soft tissue sarcomas (STSs) but are treated separately due to their peculiar histogenesis, clinical behaviour and specific therapy. This European Society for Medical Oncology (ESMO)–European Reference Network for Rare Adult Solid Cancers (EURACAN)–European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS) Clinical Practice Guideline (CPG) will cover GISTs while other STSs are covered in the ESMO–EURACAN–European Reference Network for Paediatric Oncology (ERN PaedCan)–GENTURIS STS CPG.

Published
2022

13. Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Author

Strauss, S.J., Frezza, A.M., Abecassis, N., Bajpai, J., Bauer, S., Biagini, R., Bielack, S., Blay, J.Y., Bolle, S., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Boye, K., Brennan, B., Brodowicz, T., Buonadonna, A., Alava, E. de, Tos, A.P. dei, Muro, X.G. del, Dufresne, A., Eriksson, M., Fagioli, F., Fedenko, A., Ferraresi, V., Ferrari, A., Gaspar, N., Gasperoni, S., Gelderblom, H., Gouin, F., Grignani, G., Gronchi, A., Haas, R., Hassan, A.B., Hecker-Nolting, S., Hindi, N., Hohenberger, P., Joensuu, H., Jones, R.L., Jungels, C., Jutte, P., Kager, L., Kasper, B., Kawai, A., Kopeckova, K., Krakorova, D.A., Cesne, A. le, Grange, F. le, Legius, E., Leithner, A., Pousa, A.L., Martin-Broto, J., Merimsky, O., Messiou, C., Miah, A.B., Mir, O., Montemurro, M., Morland, B., Morosi, C., Palmerini, E., Pantaleo, M.A., Piana, R., Piperno-Neumann, S., Reichardt, P., Rutkowski, P., Safwat, A.A., Sangalli, C., Sbaraglia, M., Scheipl, S., Schoffski, P., Sleijfer, S., Strauss, D., Hall, K.S., Trama, A., Unk, M., Sande, M.A.J. van de, Graaf, W.T.A. van der, Houdt, W.J. van, Frebourg, T., Ladenstein, R., Casali, P.G., Stacchiotti, S., ESMO Guidelines Comm, EURACAN, GENTURIS, ERN PaedCan, European Society for Medical Oncology, Strauss S.J., Frezza A.M., Abecassis N., Bajpai J., Bauer S., Biagini R., Bielack S., Blay J.Y., Bolle S., Bonvalot S., Boukovinas I., Bovee J.V.M.G., Boye K., Brennan B., Brodowicz T., Buonadonna A., de Alava E., Dei Tos A.P., Garcia del Muro X., Dufresne A., Eriksson M., Fagioli F., Fedenko A., Ferraresi V., Ferrari A., Gaspar N., Gasperoni S., Gelderblom H., Gouin F., Grignani G., Gronchi A., Haas R., Hassan A.B., Hecker-Nolting S., Hindi N., Hohenberger P., Joensuu H., Jones R.L., Jungels C., Jutte P., Kager L., Kasper B., Kawai A., Kopeckova K., Krakorova D.A., Le Cesne A., Le Grange F., Legius E., Leithner A., Lopez Pousa A., Martin-Broto J., Merimsky O., Messiou C., Miah A.B., Mir O., Montemurro M., Morland B., Morosi C., Palmerini E., Pantaleo M.A., Piana R., Piperno-Neumann S., Reichardt P., Rutkowski P., Safwat A.A., Sangalli C., Sbaraglia M., Scheipl S., Schoffski P., Sleijfer S., Strauss D., Sundby Hall K., Trama A., Unk M., van de Sande M.A.J., van der Graaf W.T.A., van Houdt W.J., Frebourg T., Ladenstein R., Casali P.G., Stacchiotti S., ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Public Health Research (PHR), and Man, Biomaterials and Microbes (MBM)

Subjects
medicine.medical_specialty, diagnosis, Medizin, bone sarcoma, Bone Neoplasm, Bone Sarcoma, Follow-Up Studie, 03 medical and health sciences, 0302 clinical medicine, follow-up, medicine, 030304 developmental biology, Osteosarcoma, 0303 health sciences, treatment, business.industry, Sarcoma, Hematology, Guideline, clinical practice guideline, management, 3. Good health, Clinical Practice, diagnosi, Oncology, Diagnosis treatment, 030220 oncology & carcinogenesis, Radiology, business, Human
Abstract

A. Kawai43, K. Kopeckova44, D. A. Krakorova45, A. Le Cesne46, F. Le Grange1, E. Legius47, A. Leithner48, A. Lopez Pousa49, J. Martin-Broto36, O. Merimsky50, C. Messiou51, A. B. Miah52, O. Mir53, M. Montemurro54, B. Morland55, C. Morosi56, E. Palmerini57, M. A. Pantaleo58, R. Piana59, S. Piperno-Neumann60, P. Reichardt61, P. Rutkowski62, A. A. Safwat63, C. Sangalli64, M. Sbaraglia19, S. Scheipl48, P. Schoffski65, S. Sleijfer66, D. Strauss67, K. Sundby Hall13, A. Trama68, M. Unk69, M. A. J. van de Sande70, W. T. A. van der Graaf66,71, W. J. van Houdt72, T. Frebourg73x, R. Ladenstein41z, P. G. Casali2,74z &

Published
2021

14. Modelling Neck Postural Stabilization Using Optimal Control Techniques for Dynamic Driving

Author

Messiou, C. (author), Papaioannou, G. (author), Happee, R. (author), Messiou, C. (author), Papaioannou, G. (author), and Happee, R. (author)

Abstract

The goal of this paper is to contribute to the accurate prediction of human body motion by proposing a novel head-neck model for dynamic driving scenarios with complex vehicle motions. While automated vehicles are considered a potential solution to several transportation issues, there are still significant challenges that need to be addressed, including fundamental questions regarding motion comfort and postural stability. Existing standards fail to accurately describe motion comfort, and current head-neck models have limitations, such as their inability to accurately capture human head responses to dynamic perturbations and lack of adaptability to different perturbations, amplitudes, and individual characteristics. To address these challenges, the authors propose a 3D double inverted pendulum model (DIPM) with a total of 6 degrees of freedom (DoF) as an approximation of head-neck system. The proposed model uses Model Predictive Control (MPC) to derive optimal control inputs for head-neck stabilization. The study validates the proposed model against experimental data of anterior-posterior seat translation and rotation from the literature. The results indicate that the model fitted the experimental data with a variance accounted for 82.80 % in translation and 73.15 % in rotation (pitch). The proposed model paves the path for the accurate assessment of occupants’ postural stability in automated vehicles., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Intelligent Vehicles

Published
2023
Full Text
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21. Soft tissue and visceral sarcomas

Author

Gronchi, A., Miah, A.B., DeiTos, A.P., Abecassis, N., Bajpai, J., Bauer, S., Biagini, R., Bielack, S., Blay, J.Y., Bolle, S., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Boye, K., Brennan, B., Brodowicz, T., Buonadonna, A., DeAlava, E., Muro, X.G. del, Dufresne, A., Eriksson, M., Fagioli, F., Fedenko, A., Ferraresi, V., Ferrari, A., Frezza, A.M., Gasperoni, S., Gelderblom, H., Gouin, F., Grignani, G., Haas, R., Hassan, A.B., Hecker-Nolting, S., Hindi, N., Hohenberger, P., Joensuu, H., Jones, R.L., Jungels, C., Jutte, P., Kager, L., Kasper, B., Kawai, A., Kopeckova, K., Krakorova, D.A., Cesne, A. le, LeGrange, F., Legius, E., Leithner, A., Lopez-Pousa, A., Martin-Broto, J., Merimsky, O., Messiou, C., Mir, O., Montemurro, M., Morland, B., Morosi, C., Palmerini, E., Pantaleo, M.A., Piana, R., Piperno-Neumann, S., Reichardt, P., Rutkowski, P., Safwat, A.A., Sangalli, C., Sbaraglia, M., Scheipl, S., Schoffski, P., Sleijfer, S., Strauss, D., Strauss, S., SundbyHall, K., Trama, A., Unk, M., VandeSande, M.A.J., VanderGraaf, W.T.A., Houdt, W.J. van, Frebourg, T., Casali, P.G., Stacchiotti, S., ESMO Guidelines Comm, EURACAN, GENTURIS, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Public Health Research (PHR), Man, Biomaterials and Microbes (MBM), Gronchi A., Miah A.B., Dei Tos A.P., Abecassis N., Bajpai J., Bauer S., Biagini R., Bielack S., Blay J.Y., Bolle S., Bonvalot S., Boukovinas I., Bovee J.V.M.G., Boye K., Brennan B., Brodowicz T., Buonadonna A., De Alava E., Del Muro X.G., Dufresne A., Eriksson M., Fagioli F., Fedenko A., Ferraresi V., Ferrari A., Frezza A.M., Gasperoni S., Gelderblom H., Gouin F., Grignani G., Haas R., Hassan A.B., Hecker-Nolting S., Hindi N., Hohenberger P., Joensuu H., Jones R.L., Jungels C., Jutte P., Kager L., Kasper B., Kawai A., Kopeckova K., Krakorova D.A., Le Cesne A., Le Grange F., Legius E., Leithner A., Lopez-Pousa A., Martin-Broto J., Merimsky O., Messiou C., Mir O., Montemurro M., Morland B., Morosi C., Palmerini E., Pantaleo M.A., Piana R., Piperno-Neumann S., Reichardt P., Rutkowski P., Safwat A.A., Sangalli C., Sbaraglia M., Scheipl S., Schoffski P., Sleijfer S., Strauss D., Strauss S., Sundby Hall K., Trama A., Unk M., van de Sande M.A.J., van der Graaf W.T.A., van Houdt W.J., Frebourg T., Casali P.G., and Stacchiotti S.

Subjects
sarcoma, uterine sarcoma, treatment, diagnosis, desmoid, Medizin, Sarcoma, Soft Tissue Neoplasms, Hematology, Clinical Practice Guideline, Soft tissue sarcomas, retroperitoneal sarcoma, Retroperitoneal Sarcoma, soft tissue sarcomas, Follow-Up Studie, Desmoid, Uterine Sarcoma, follow-up, management, Oncology, soft tissue sarcoma, Human
Abstract

ispartof: ANNALS OF ONCOLOGY vol:32 issue:11 pages:1348-1365 ispartof: location:England status: published

Published
2021

22. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up

Author

Casali, Paolo G., Blay, Jean-Yves, Abecassis, N., Bajpai, J., Bauer, Sebastian, Biagini, R., Bielack, S., Bonvalot, Sylvie, Boukovinas, I., Bovee, J. V. M. G., Boye, K., Brodowicz, T., Buonadonna, A., Álava, Enrique de, Tos, A. P. dei, García del Muro, Xavier, Dufresne, Armelle, Eriksson, Mikael, Fedenko, Alexander, Ferraresi, Virginia, Ferrari, A., Frezza, Anna M., Gasperoni, Silvia, Gelderblom, Hans, Gouin, Francois, Grignani, Giovanni, Haas, R. L., Hassan, A. B., Hindi, Nadia, Hohenberger, Peter, Joensuu, Heikki, Jones, Robin L., Jungels, C., Jutte, P., Kasper, Bernd, Kawai, Akira, Kopeckova, K., Krákorová, D. A., Le Cesne, A, Le Grange, F, Legius, E., Leithner, Andreas, López-Pousa, Antonio, Martín-Broto, Javier, Merimsky, O., Messiou, C., Miah, A. B., Mir, Olivier, Montemurro, M., Morosi, Carlo, Palmerini, Emanuela, Pantaleo, M. A., Piana, R., Piperno-Neumann, S., Reichardt, Peter, Rutkowski, Piotr, Safwat, A. A., Sangalli, C., Sbaraglia, Marta, Scheipl, S., Schöffski, P., Sleijfer, S., Strauss, D., Strauss, S. J., Sundby-Hall, Kirsten, Trama, A., Unk, M., Sande, M. A. J. van de, Graaf, W.T.A. van der, Houdt, W. J. van, Frebourg, T., Gronchi, Alesandro, Stacchiotti, Silvia, ESMO Guidelines Committee, EURACAN, GENTURIS, Casali, Paolo G., Blay, Jean-Yves, Abecassis, N., Bajpai, J., Bauer, Sebastian, Biagini, R., Bielack, S., Bonvalot, Sylvie, Boukovinas, I., Bovee, J. V. M. G., Boye, K., Brodowicz, T., Buonadonna, A., Álava, Enrique de, Tos, A. P. dei, García del Muro, Xavier, Dufresne, Armelle, Eriksson, Mikael, Fedenko, Alexander, Ferraresi, Virginia, Ferrari, A., Frezza, Anna M., Gasperoni, Silvia, Gelderblom, Hans, Gouin, Francois, Grignani, Giovanni, Haas, R. L., Hassan, A. B., Hindi, Nadia, Hohenberger, Peter, Joensuu, Heikki, Jones, Robin L., Jungels, C., Jutte, P., Kasper, Bernd, Kawai, Akira, Kopeckova, K., Krákorová, D. A., Le Cesne, A, Le Grange, F, Legius, E., Leithner, Andreas, López-Pousa, Antonio, Martín-Broto, Javier, Merimsky, O., Messiou, C., Miah, A. B., Mir, Olivier, Montemurro, M., Morosi, Carlo, Palmerini, Emanuela, Pantaleo, M. A., Piana, R., Piperno-Neumann, S., Reichardt, Peter, Rutkowski, Piotr, Safwat, A. A., Sangalli, C., Sbaraglia, Marta, Scheipl, S., Schöffski, P., Sleijfer, S., Strauss, D., Strauss, S. J., Sundby-Hall, Kirsten, Trama, A., Unk, M., Sande, M. A. J. van de, Graaf, W.T.A. van der, Houdt, W. J. van, Frebourg, T., Gronchi, Alesandro, Stacchiotti, Silvia, ESMO Guidelines Committee, EURACAN, and GENTURIS

Abstract

Gastrointestinal stromal tumours (GISTs) are malignant mesenchymal tumours with a variable clinical behaviour, marked by differentiation towards the interstitial cells of Cajal.1 GISTs belong to the family of soft tissue sarcomas (STSs) but are treated separately due to their peculiar histogenesis, clinical behaviour and specific therapy. This European Society for Medical Oncology (ESMO)–European Reference Network for Rare Adult Solid Cancers (EURACAN)–European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS) Clinical Practice Guideline (CPG) will cover GISTs while other STSs are covered in the ESMO–EURACAN–European Reference Network for Paediatric Oncology (ERN PaedCan)–GENTURIS STS CPG.

Published
2022

24. Lack of clinically meaningful anatomical variations in bone marrow apparent diffusion coefficient in diffuse pattern myeloma allows untargeted sampling to confirm disease burden

Author

Blackledge M, Kaiser M, O’Connor S, Koh Dm, Keeling A, Boyd K, and Messiou C

Subjects
medicine.medical_specialty, Diffuse Pattern, medicine.anatomical_structure, business.industry, medicine, Sampling (statistics), Effective diffusion coefficient, Radiology, Bone marrow, business, Disease burden
Published
2020

25. Gastrointestinal stromal tumours: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up

Author

Casali, P.G., primary, Blay, J.Y., additional, Abecassis, N., additional, Bajpai, J., additional, Bauer, S., additional, Biagini, R., additional, Bielack, S., additional, Bonvalot, S., additional, Boukovinas, I., additional, Bovee, J.V.M.G., additional, Boye, K., additional, Brodowicz, T., additional, Buonadonna, A., additional, De Álava, E., additional, Dei Tos, A.P., additional, Del Muro, X.G., additional, Dufresne, A., additional, Eriksson, M., additional, Fedenko, A., additional, Ferraresi, V., additional, Ferrari, A., additional, Frezza, A.M., additional, Gasperoni, S., additional, Gelderblom, H., additional, Gouin, F., additional, Grignani, G., additional, Haas, R., additional, Hassan, A.B., additional, Hindi, N., additional, Hohenberger, P., additional, Joensuu, H., additional, Jones, R.L., additional, Jungels, C., additional, Jutte, P., additional, Kasper, B., additional, Kawai, A., additional, Kopeckova, K., additional, Krákorová, D.A., additional, Le Cesne, A., additional, Le Grange, F., additional, Legius, E., additional, Leithner, A., additional, Lopez-Pousa, A., additional, Martin-Broto, J., additional, Merimsky, O., additional, Messiou, C., additional, Miah, A.B., additional, Mir, O., additional, Montemurro, M., additional, Morosi, C., additional, Palmerini, E., additional, Pantaleo, M.A., additional, Piana, R., additional, Piperno-Neumann, S., additional, Reichardt, P., additional, Rutkowski, P., additional, Safwat, A.A., additional, Sangalli, C., additional, Sbaraglia, M., additional, Scheipl, S., additional, Schöffski, P., additional, Sleijfer, S., additional, Strauss, D., additional, Strauss, S.J., additional, Hall, K Sundby, additional, Trama, A., additional, Unk, M., additional, van de Sande, M.A.J., additional, van der Graaf, W.T.A., additional, van Houdt, W.J., additional, Frebourg, T., additional, Gronchi, A., additional, and Stacchiotti, S., additional

Published
2022
Full Text
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32. The patient perspective in the era of personalized medicine: What about scanxiety?

Author

Custers, J.A.E., Davis, L., Messiou, C., Prins, J.B., Graaf, W.T.A. van der, Custers, J.A.E., Davis, L., Messiou, C., Prins, J.B., and Graaf, W.T.A. van der

Abstract

Contains fulltext : 245518.pdf (Publisher’s version ) (Open Access), Frequency of scanning has accelerated in the era of personalized medicine and is related, but not restricted, to the exploding number of clinical trials for new cancer treatments. Particularly in drug trials, but also in clinical practice, patients are followed up by scans frequently, which may vary from every 6 to 12 weeks until progression. The authors aimed to raise awareness for this underreported but widely present "Sword of Damocles" scan-related issue also referred to as 'scanxiety.'

Published
2021

33. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

Author

Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica, Stacchiotti, S., Miah, A. B., Frezza, A. M., Messiou, C., Morosi, C., Caraceni, A., Álava Casado, Enrique de, Gronchi, A., Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica, Stacchiotti, S., Miah, A. B., Frezza, A. M., Messiou, C., Morosi, C., Caraceni, A., Álava Casado, Enrique de, and Gronchi, A.

Abstract

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

Published
2021

34. Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Author

European Society for Medical Oncology, Strauss, S. J., Frezza, Anna M., Abecassis, N., Bajpai, J., Bauer, Sebastian, Biagini, R., Bielack, S., Blay, Jean-Yves, Bolle, S., Bonvalot, Sylvie, Boukovinas, I., Bovee, J. V. M. G., Boye, K., Brennan, Bernadette, Brodowicz, T., Buonadonna, A., Álava, Enrique de, Dei Tos, Angelo Paolo, García del Muro, Xavier, Dufresne, Armelle, Eriksson, Mikael, Fagioli, F., Fedenko, Alexander, Ferraresi, Virginia, Ferrari, A., Gaspar, Nathalie, Gasperoni, Silvia, Gelderblom, Hans, Gouin, Francois, Grignani, Giovanni, Gronchi, Alesandro, Haas, R. L., Hassan, A. B., Hecker-Nolting, S., Hindi, Nadia, Hohenberger, Peter, Joensuu, Heikki, Jones, Robin L., Jungels, C., Jutte, P., Kager, L., Kasper, Bernd, Kawai, Akira, Kopeckova, K., Krákorová, D. A., Le Cesne, Axel, Le Grange, F., Legius, E., Leithner, Andreas, López-Pousa, Antonio, Martín-Broto, Javier, Merimsky, O., Messiou, C., Miah, A. B., Mir, Olivier, Montemurro, M., Morland, B., Morosi, Carlo, Palmerini, Emanuela, Pantaleo, M. A., Piana, R., Piperno-Neumann, S., Reichardt, Peter, Rutkowski, Piotr, Safwat, A. A., Sangalli, C., Sbaraglia, Marta, Scheipl, S., Schöffski, P., Sleijfer, S., Strauss, D., Sundby Hall, K., Trama, A., Unk, M., van de Sande, Michiel, van der Graaf, W. T., van Houdt, W. J., Frebourg, T., Ladenstein, Rudolf, Casali, Paolo G., Stacchiotti, Silvia, European Society for Medical Oncology, Strauss, S. J., Frezza, Anna M., Abecassis, N., Bajpai, J., Bauer, Sebastian, Biagini, R., Bielack, S., Blay, Jean-Yves, Bolle, S., Bonvalot, Sylvie, Boukovinas, I., Bovee, J. V. M. G., Boye, K., Brennan, Bernadette, Brodowicz, T., Buonadonna, A., Álava, Enrique de, Dei Tos, Angelo Paolo, García del Muro, Xavier, Dufresne, Armelle, Eriksson, Mikael, Fagioli, F., Fedenko, Alexander, Ferraresi, Virginia, Ferrari, A., Gaspar, Nathalie, Gasperoni, Silvia, Gelderblom, Hans, Gouin, Francois, Grignani, Giovanni, Gronchi, Alesandro, Haas, R. L., Hassan, A. B., Hecker-Nolting, S., Hindi, Nadia, Hohenberger, Peter, Joensuu, Heikki, Jones, Robin L., Jungels, C., Jutte, P., Kager, L., Kasper, Bernd, Kawai, Akira, Kopeckova, K., Krákorová, D. A., Le Cesne, Axel, Le Grange, F., Legius, E., Leithner, Andreas, López-Pousa, Antonio, Martín-Broto, Javier, Merimsky, O., Messiou, C., Miah, A. B., Mir, Olivier, Montemurro, M., Morland, B., Morosi, Carlo, Palmerini, Emanuela, Pantaleo, M. A., Piana, R., Piperno-Neumann, S., Reichardt, Peter, Rutkowski, Piotr, Safwat, A. A., Sangalli, C., Sbaraglia, Marta, Scheipl, S., Schöffski, P., Sleijfer, S., Strauss, D., Sundby Hall, K., Trama, A., Unk, M., van de Sande, Michiel, van der Graaf, W. T., van Houdt, W. J., Frebourg, T., Ladenstein, Rudolf, Casali, Paolo G., and Stacchiotti, Silvia

Published
2021

38. Detection and Characterization of Musculoskeletal Cancer Using Whole-Body Magnetic Resonance Imaging

Author

Isaac, A. Lecouvet, F. Dalili, D. Fayad, L. Pasoglou, V. Papakonstantinou, O. Ahlawat, S. Messiou, C. Weber, M.-A. Padhani, A.R.

Abstract

Whole-body magnetic resonance imaging (WB-MRI) is gradually being integrated into clinical pathways for the detection, characterization, and staging of malignant tumors including those arising in the musculoskeletal (MSK) system. Although further developments and research are needed, it is now recognized that WB-MRI enables reliable, sensitive, and specific detection and quantification of disease burden, with clinical applications for a variety of disease types and a particular application for skeletal involvement. Advances in imaging techniques now allow the reliable incorporation of WB-MRI into clinical pathways, and guidelines recommending its use are emerging. This review assesses the benefits, clinical applications, limitations, and future capabilities of WB-MRI in the context of other next-generation imaging modalities, as a qualitative and quantitative tool for the detection and characterization of skeletal and soft tissue MSK malignancies. © 2020 BMJ Publishing Group. All rights reserved.

Published
2020

39. The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients

Author

Alman, B., Attia, S., Baumgarten, C., Benson, C., Blay, J.Y., Bonvalot, S., Breuing, J., Cardona, K., Casali, P.G., Coevorden, F. van, Colombo, C., Dei Tos, A.P., Dileo, P., Ferrari, A., Fiore, M., Frezza, A.M., Garcia, J., Gladdy, R., Gounder, M., Gronchi, A., Haas, R, Hackett, S., Haller, F., Hohenberger, P., Husson, O., Jones, R.L., Judson, I., Kasper, B., Kawai, A., Kogosov, V., Lazar, A., Maki, R., Mathes, T., Messiou, C., Navid, F., Nishida, Y., Palassini, E., Penel, N., Pollock, R., Pieper, D., Portnoy, M., Raut, C.P., Roets, E., Sandrucci, S., Sbaraglia, M., Stacchiotti, S., Thornton, K.A., Graaf, W.T.A. van der, Zande, K. van der, Houdt, W.J. van, Villalobos, V., Wagner, A.J., Wardelmann, E., Wartenberg, M., Watson, S., Weiss, A., Zafiropoulos, N., Alman, B., Attia, S., Baumgarten, C., Benson, C., Blay, J.Y., Bonvalot, S., Breuing, J., Cardona, K., Casali, P.G., Coevorden, F. van, Colombo, C., Dei Tos, A.P., Dileo, P., Ferrari, A., Fiore, M., Frezza, A.M., Garcia, J., Gladdy, R., Gounder, M., Gronchi, A., Haas, R, Hackett, S., Haller, F., Hohenberger, P., Husson, O., Jones, R.L., Judson, I., Kasper, B., Kawai, A., Kogosov, V., Lazar, A., Maki, R., Mathes, T., Messiou, C., Navid, F., Nishida, Y., Palassini, E., Penel, N., Pollock, R., Pieper, D., Portnoy, M., Raut, C.P., Roets, E., Sandrucci, S., Sbaraglia, M., Stacchiotti, S., Thornton, K.A., Graaf, W.T.A. van der, Zande, K. van der, Houdt, W.J. van, Villalobos, V., Wagner, A.J., Wardelmann, E., Wartenberg, M., Watson, S., Weiss, A., and Zafiropoulos, N.

Abstract

Contains fulltext : 217698.pdf (Publisher’s version ) (Open Access)

Published
2020

43. The National Institute for Health Research: making an impact in imaging research

Author

Smye, S.W., Allen, L., Ashcroft, J., Cooper, M., Gilbert, F.J., Goh, V., Graham, R., Keevil, S., Matthews, J., Mould, A., Nall, S., Papadopoulou, A., Snaith, B., Wadsley, J., Wilson, P., Arthurs, O.J., Baxter, G.M., Beale, A., Bidaut, L., Booth, T., Callaway, M., Denison, A., Hall-Craggs, M., Harden, S.P., Hoggard, N., Jethwa, K.D., Messiou, C., Mistry, M., Ramsden, W.H., Robinson, P., Rubin, C.M.E., Strickland, N.H., and Teh, J.

Published
2019
Full Text
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44. Guidelines for acquisition, interpretation, and reporting of whole-body MRI in myeloma: Myeloma response assessment and diagnosis system (MY-RADS)

Author

Messiou, C. Hillengass, J. Delorme, S. Lecouvet, F.E. Moulopoulos, L.A. Collins, D.J. Blackledge, M.D. Abildgaard, N. Østergaard, B. Schlemmer, H.-P. Landgren, O. Asmussen, J.T. Kaiser, M.F. Padhani, A.

Abstract

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. © 2019 Radiological Society of North America Inc.. All rights reserved.

Published
2019

45. Gemcitabine Re-challenge in Metastatic Soft Tissue Sarcomas: A Therapeutic Option for Selected Patients

Author

Sebio, A., Constantinidou, A., Benson, C., Antoniou, G., Messiou, C., Miah, A., Zaidi, S., Petruckevitch, A., Al-Muderis, O., Thway, K., Graaf, W.T.A. van der, Jones, R.L., Sebio, A., Constantinidou, A., Benson, C., Antoniou, G., Messiou, C., Miah, A., Zaidi, S., Petruckevitch, A., Al-Muderis, O., Thway, K., Graaf, W.T.A. van der, and Jones, R.L.

Abstract

Contains fulltext : 203015.pdf (publisher's version ) (Open Access), BACKGROUND/AIM: Treatment options for patients with metastatic soft tissue sarcomas are limited. Re-challenge with a previously successful gemcitabine-based regimen is common. There are no published data to support this practice. PATIENTS AND METHODS: We conducted a retrospective search to identify patients re-challenged with gemcitabine-based chemotherapy (GBC) from 2003 to 2015. RESULTS: Twenty-nine patients re-challenged with gemcitabine were identified. The response rate for initial GBC was 55% (n=15) and for re-challenge GBC 26% (n=6). The median progression-free survival was 11.1 months (95%CI=7.2-11.9) for initial GBC and 5.3 months (95%CI=2.0-7.5) for re-challenge GBC. Overall survival following gemcitabine re-challenge was 12.2 months (95%CI=7.0-18.2). Twelve out of 26 evaluable patients (46%) treated with re-challenge GBC experienced grade 3-4 adverse events (CTCAE 4.03) with 31% (n=8) of patients requiring dose reduction. CONCLUSION: In selected patients, gemcitabine re-challenge can be considered in advanced sarcomas, however, this approach is associated with toxicity.

Published
2019

46. Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance

Author

Houdt, W.J. van, Husson, O., Patel, Alisha, Jones, R.L., Smith, M.J., Miah, A.B., Messiou, C., Moskovic, E., Al-Muderis, O., Benson, C., Zaidi, S., Dunlop, A., Strauss, D.C., Hayes, A.J., Graaf, W.T.A. van der, Houdt, W.J. van, Husson, O., Patel, Alisha, Jones, R.L., Smith, M.J., Miah, A.B., Messiou, C., Moskovic, E., Al-Muderis, O., Benson, C., Zaidi, S., Dunlop, A., Strauss, D.C., Hayes, A.J., and Graaf, W.T.A. van der

Abstract

Item does not contain fulltext, BACKGROUND: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. METHODS: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. RESULTS: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). CONCLUSIONS: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

Published
2019

47. The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma

Author

Tong, D., Constantinidou, A., Engelmann, B., Chamberlain, F., Thway, K., Fisher, C., Hayes, A., Fotiadis, N., Messiou, C., Miah, A.B., Zaidi, S.H., Benson, C., Graaf, W.T.A. van der, Jones, R.L., Tong, D., Constantinidou, A., Engelmann, B., Chamberlain, F., Thway, K., Fisher, C., Hayes, A., Fotiadis, N., Messiou, C., Miah, A.B., Zaidi, S.H., Benson, C., Graaf, W.T.A. van der, and Jones, R.L.

Abstract

Contains fulltext : 208930.pdf (publisher's version ) (Open Access), BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease.

Published
2019

48. Validating a robust double‐quantum‐filtered 1H MRS lactate measurement method in high‐grade brain tumours

Author

Payne, G.S., Harris, L.M., Cairns, G.S., Messiou, C., deSouza, N.M., Macdonald, A., Saran, F., and Leach, M.O.

Subjects
lactate, MRS, Brain Neoplasms, brain, Proton Magnetic Resonance Spectroscopy, glioblastoma, Reproducibility of Results, Signal Processing, Computer-Assisted, double‐quantum filter, Magnetic Resonance Imaging, Sensitivity and Specificity, Molecular Imaging, single voxel, Biomarkers, Tumor, Humans, Lactic Acid, Neoplasm Grading, Research Articles, Algorithms, Research Article
Abstract

(1) H MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered (1) H MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 × 2 × 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramér-Rao lower bounds ≤ 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 ± 0.03 ppm vs 1.22 ± 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 ± 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 ± 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion.

Published
2016

49. Evaluation of response after pre-operative radiotherapy in soft tissue sarcomas; the European Organisation for Research and Treatment of Cancer – Soft Tissue and Bone Sarcoma Group (EORTC – STBSG) and Imaging Group recommendations for radiological examination and reporting with an emphasis on magnetic resonance imaging

Author

Messiou, C., Bonvalot, S., Gronchi, A., Vanel, D., Meyer, M., Robinson, P., Morosi, C., Bloem, J.L., Terrier, P.H., Lazar, A., Le Péchoux, C., Wardelman, E., Winfield, J.M., Boulet, B., Bovée, J., and Haas, R.L.

Subjects
Cancer Research, Radiotherapy, Oncology, Sarcoma, MRI
Abstract

At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer – Soft Tissue and Bone Sarcoma Group (EORTC – STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials.

Published
2016
Full Text
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50. Prognostic factors for soft tissue sarcoma patients with lung metastases only who are receiving first-line chemotherapy An exploratory, retrospective analysis of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG)

Author

Lindner, L.H., Litiere, S., Sleijfer, S., Benson, C., Italiano, A., Kasper, B., Messiou, C., Gelderblom, H., Wardelmann, E., Cesne, A. le, Blay, J.Y., Marreaud, S., Hindi, N., Desar, I.M.E., Gronchi, A., Graaf, W.T.A. van der, and Medical Oncology

Subjects
Adult, Male, Lung Neoplasms, Datasets as Topic, prognostic factors, Sarcoma, Soft Tissue Neoplasms, lung metastases, Kaplan-Meier Estimate, Middle Aged, Prognosis, Progression-Free Survival, EORTC, SDG 3 - Good Health and Well-being, soft tissue sarcoma, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Neoplasm Metastasis, Aged, Proportional Hazards Models, Retrospective Studies
Abstract

The prognosis of adult soft tissue sarcoma (STS) patients with metastases is generally poor. As little is known about the impact of the involvement of different metastatic sites and the extent of pulmonary lesions on the outcome for patients receiving first-line chemotherapy, we aimed to establish prognostic factors for STS patients with lung metastases only. A retrospective, exploratory analysis was performed on 2,913 metastatic STS patients who received first-line chemotherapy. Detailed information from 580 patients who had lung metastases only, was used for prognostic factor analysis. Patients with lung metastases only were more often asymptomatic and had undergone complete primary tumor resection more frequently compared to patients with additional metastases outside the lung or without lung metastases. For extremity STS, the incidence of lung metastases only was much higher compared to non-extremity STS. Lung involvement only was an independent favorable prognostic factor for overall survival (OS) with regard to metastatic site. Within this subgroup, in a multivariate model, other factors associated with improved OS included: good performance status (PS), no progression at primary site, low histological grade, younger age, long interval between initial diagnosis and trial registration, and smaller diameter of the largest lung lesion. This unique analysis on prognostic factors in STS patients with lung metastases confirms well-known patient factors (such as age and PS), and tumor characteristics (including tumor grade, interval between primary diagnosis, and metastases), but also identifies diameter of the largest lung lesion as a new prognostic factor. Knowledge about these factors may support decision-making within multidisciplinary tumor boards.

Published
2018

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