21 results on '"Pipinikas C"'
Search Results
2. EP07.02-15 Longitudinal ctDNA Testing in Resected, Early Stage Non-small Cell Lung Cancers
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Feng, J., primary, Waddell, T., additional, Yasufuku, K., additional, Kelly, D., additional, Meti, N., additional, Pierre, A., additional, Keshavjee, S., additional, Yeung, J., additional, Cypel, M., additional, Donahoe, L., additional, Wakeam, E., additional, de Perrot, M., additional, Law, J., additional, Salvarrey, A., additional, Le, L.W., additional, Lister, J., additional, Cabanero, M., additional, Tsao, M.S., additional, Pipinikas, C., additional, Howarth, K., additional, and Leighl, N.B., additional
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- 2023
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3. P1.22-04 Plasma-First to Accelerate Time to Treatment and Improve Target Detection in Advanced Lung Cancer: A Prospective Study
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Garcia Pardo, M., primary, Czarnecka, K., additional, Law, J.H., additional, Fan, Z.J., additional, Waddell, T.K., additional, Yasufuku, K., additional, Liu, G., additional, Donahoe, L.L., additional, Pierre, A., additional, Le, L.W., additional, Gunasegaran, T., additional, Ghumman, N., additional, Bradbury, P.A., additional, Shepherd, F., additional, Sacher, A., additional, Corke, L., additional, Feng, J., additional, Stockley, T., additional, Pal, P., additional, Rogalla, P., additional, Pipinikas, C., additional, Howarth, K.D., additional, Tsao, M., additional, and Leighl, N.B., additional
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- 2023
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4. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial.
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Dorp, J. van, Pipinikas, C., Suelmann, B.B.M., Mehra, N., Dijk, N. van, Marsico, G., Montfoort, M.L. van, Hackinger, S., Braaf, L.M., Amarante, T., Steenis, C. van, McLay, K., Daletzakis, A., Broek, D. van den, Kamp, M.W. van de, Hendricksen, K., Feijter, J.M. de, Boellaard, T.N., Meijer, R.P., Heijden, Toine G. van der, Rosenfeld, N., Rhijn, B.W. van, Jones, G., Heijden, M.S. van der, Dorp, J. van, Pipinikas, C., Suelmann, B.B.M., Mehra, N., Dijk, N. van, Marsico, G., Montfoort, M.L. van, Hackinger, S., Braaf, L.M., Amarante, T., Steenis, C. van, McLay, K., Daletzakis, A., Broek, D. van den, Kamp, M.W. van de, Hendricksen, K., Feijter, J.M. de, Boellaard, T.N., Meijer, R.P., Heijden, Toine G. van der, Rosenfeld, N., Rhijn, B.W. van, Jones, G., and Heijden, M.S. van der
- Abstract
Item does not contain fulltext, Cohort 1 of the phase 1B NABUCCO trial showed high pathological complete response (pCR) rates with preoperative ipilimumab plus nivolumab in stage III urothelial cancer (UC). In cohort 2, the aim was dose adjustment to optimize responses. Additionally, we report secondary endpoints, including efficacy and tolerability, in cohort 2 and the association of presurgical absence of circulating tumor DNA (ctDNA) in urine and plasma with clinical outcome in both cohorts. Thirty patients received two cycles of either ipilimumab 3 mg kg(-1) plus nivolumab 1 mg kg(-1) (cohort 2A) or ipilimumab 1 mg kg(-1) plus nivolumab 3 mg kg(-1) (cohort 2B), both followed by nivolumab 3 mg kg(-1). We observed a pCR in six (43%) patients in cohort 2A and a pCR in one (7%) patient in cohort 2B. Absence of urinary ctDNA correlated with pCR in the bladder (ypT0Nx) but not with progression-free survival (PFS). Absence of plasma ctDNA correlated with pCR (odds ratio: 45.0; 95% confidence interval (CI): 4.9-416.5) and PFS (hazard ratio: 10.4; 95% CI: 2.9-37.5). Our data suggest that high-dose ipilimumab plus nivolumab is required in stage III UC and that absence of ctDNA in plasma can predict PFS. ClinicalTrials.gov registration: NCT03387761 .
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- 2023
5. Longitudinal Plasma ctDNA Testing in Resected Early-Stage NSCLC
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Feng, J., Waddell, T., Yasufuku, K., Pierre, A., Salvarrey, A., Le, L., Tsao, M., Pipinikas, C., Carter, A., and Leighl, N.
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- 2023
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6. 1770P Updated follow-up data and biomarker analysis of pre-operative ipilimumab and nivolumab in locoregional advanced urothelial cancer (NABUCCO)
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Stockem, C.F., primary, Gil Jimenez, A., additional, van Dorp, J., additional, van Dijk, N., additional, Alkemade, M., additional, Seignette, I., additional, Pipinikas, C., additional, Jones, G., additional, Rosenfeld, N., additional, van Montfoort, M.L., additional, Hendricksen, K., additional, de Feijter, J., additional, Meijer, R., additional, van der Heijden, A., additional, Mehra, N., additional, Suelmann, B.B., additional, van Rhijn, B.W.G., additional, and van der Heijden, M.S., additional
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- 2022
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7. 684P Liquid biopsy for detection of molecular residual disease and recurrence in head and neck squamous cell carcinoma
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Flach, S., primary, Howarth, K., additional, Hackinger, S., additional, Pipinikas, C., additional, Ellis, P., additional, McLay, K., additional, Marsico, G., additional, Walz, C., additional, Käsmann, L., additional, Reichel, C.A., additional, Gires, O., additional, Canis, M., additional, and Baumeister, P., additional
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- 2022
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8. P1.16-02 Clinical Utility of ctDNA in Advanced NSCLC at Diagnosis or Where Insufficient Tissue Was Available, Based on the ESMO ESCAT Scale
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Mezquita, L., primary, Riudavets, M., additional, Garcia de Herreros, M., additional, Auclin, E., additional, Dorta, M., additional, Albarran, V., additional, Aldea, M., additional, Naltet, C., additional, Grecea, M., additional, Martin-Romano, P., additional, Lacroix, L.L., additional, Nicotra, C., additional, Arcocha, A., additional, Gazzah, A., additional, Pipinikas, C., additional, Morris, C., additional, Howarth, K., additional, Teixidó, C., additional, Reyes, R., additional, Viñolas, N., additional, Massard, C., additional, Barlesi, F., additional, Planchard, D., additional, and Besse, B., additional
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- 2022
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9. 884P Personalised circulating cell-free tumour DNA analysis for detection of minimal residual disease and recurrence in patients with head and neck squamous cell carcinoma
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Flach, S., primary, Howarth, K., additional, Hackinger, S., additional, Pipinikas, C., additional, McLay, K., additional, Marsico, G., additional, Walz, C., additional, Reichel, C.A., additional, Gires, O., additional, Canis, M., additional, and Baumeister, P., additional
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- 2021
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10. 144P A personalised sequencing approach for liquid biopsy-based detection of recurrent disease in early-stage breast cancer
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Janni, W., primary, Huober, J., additional, Huesmann, S., additional, Pipinikas, C., additional, Braun, T., additional, Müller, V., additional, Marsico, G., additional, Fink, A., additional, Freire-Pritchett, P., additional, Koretz, K., additional, Knape, C., additional, de Gregorio, A., additional, Rack, B., additional, Friedl, T.W.P., additional, Wiesmueller, L., additional, Möller, P., additional, Howarth, K., additional, Pantel, K., additional, and Rosenfeld, N., additional
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- 2021
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11. 1268P Real-time clinical utility of ctDNA genomic alterations in untreated patients with advanced NSCLC
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De Herreros, M. Garcia, primary, Muñoz, S., additional, Teixido, C., additional, Díez-Guardia, V., additional, Arcocha, A., additional, Pipinikas, C., additional, Martínez, D., additional, Castillo, S., additional, Reyes, R., additional, Melia, M. Riudavets, additional, Auclin, E., additional, Marin, E., additional, Howarth, K., additional, Martinez, D., additional, Puig, J.A., additional, Prat, A., additional, Aransay, N. Reguart, additional, Viñolas, N., additional, and Mezquita, L., additional
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- 2021
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12. Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes
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Tubio, J. M., Li, Y., Ju, Y. S., Martincorena, I., Cooke, S. L., Tojo Castro, Marta, Gundem, G., Pipinikas, C. P., Zamora, J., Raine, K., Menzies, A., Roman-Garcia, P., Fullam, A., Gerstung, M., Shlien, A., Tarpey, P. S., Papaemmanuil, E., Knappskog, S., Van Loo, P., Ramakrishna, M., Davies, H. R., Marshall, J., Wedge, D. C., Teague, J. W., Butler, A. P., Nik-Zainal, S., Alexandrov, L., Behjati, S., Yates, L. R., Bolli, N., Mudie, L., Hardy, C., Martin, S., McLaren, S., O'Meara, S., Anderson, E., Maddison, M., Gamble, S., Foster, C., Warren, A. Y., Whitaker, H., Brewer, D., Eeles, R., Cooper, C., Neal, D., Lynch, A. G., Visakorpi, T., Isaacs, W. B., van't Veer, L., Caldas, C., Desmedt, C., Sotiriou, C., Aparicio, S., Foekens, J. A., Eyfjörd, J. E., Lakhani, S. R., Thomas, G., Myklebost, O., Span, P. N., Børresen-Dale, A. L., Richardson, A. L., Van de Vijver, M., Vincent-Salomon, A., Van den Eynden, G. G., Flanagan, A. M., Futreal, P. A., Janes, S. M., Bova, G. S., Stratton, M. R., McDermott, U., Campbell, P. J., Group, ICGC Breast Cancer, Group, ICGC Bone Cancer, and Group, ICGC Prostate Cancer
- Subjects
Mutagenesis, Insertional ,Long Interspersed Nucleotide Elements ,Carcinogenesis ,Genome, Human ,Transduction, Genetic ,Neoplasms ,DNA Transposable Elements ,food and beverages ,Humans ,Exons ,Chromatin ,Translocation, Genetic - Abstract
Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.
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- 2014
13. Molecular Profiling of Small Intestinal Neuroendocrine Tumours
- Author
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Karpathakis, A., primary, Feber, A., additional, Morris, T., additional, Dibra, H., additional, Pipinikas, C., additional, Oukrife, D., additional, Francis, J., additional, Mandair, D., additional, Toumpanakis, C., additional, Meyer, T., additional, Luong, T.V., additional, Caplin, M., additional, Meyerson, M., additional, Beck, S., additional, and Thirlwell, C., additional
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- 2014
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14. 1133O - Molecular Profiling of Small Intestinal Neuroendocrine Tumours
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Karpathakis, A., Feber, A., Morris, T., Dibra, H., Pipinikas, C., Oukrife, D., Francis, J., Mandair, D., Toumpanakis, C., Meyer, T., Luong, T.V., Caplin, M., Meyerson, M., Beck, S., and Thirlwell, C.
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- 2014
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15. 2024 Canadian Surgery Forum: Sept. 25-28, 2024.
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Li C, Guo M, Karimuddin A, Guo M, Li C, Karimuddin A, Sutherland J, Huo B, McKechnie T, Ortenzi M, Lee Y, Antoniou S, Mayol J, Ahmed H, Boudreau V, Ramji K, Eskicioglu C, de Jager P, Urbach D, Poole M, Abbad A, Al-Shamali H, Al-Faraj Z, Wen C, Pescarus R, Bechara R, Hong D, Park LJ, Marcucci M, Ofori S, Bogach J, Serrano PE, Simunovic M, Yang I, Cadeddu M, Marcaccio MJ, Borges FK, Nenshi R, Devereaux PJ, Urbanellis P, Douglas J, Nemeth E, Ellsmere J, Spence R, Cunningham J, Falk R, Skinner T, Ebert N, Galbraith L, Prins M, Joharifard S, Joos E, Orovec A, Lethbridge L, Spence R, Hoogerboord M, Stuart H, Bergeron AM, Yang I, Bogach J, Nguyen L, Reade C, Eiriksson L, Morais M, Hanley G, Mah S, Brar K, Seymour KA, Eckhouse SR, Sudan R, Greenberg JA, Portenier D, Jung JJ, Light A, Dingley B, Delisle M, Apte S, Mallick R, Hamilton T, Stuart H, Talbot M, McKinnon G, Jost E, Thiboutot E, Nessim C, Katote N, Drohan A, Spence R, Neumann K, Shi G, Leung R, Lim C, Van Oirschot M, Grant A, Knowles S, Van Koughnett JA, Brousseau K, Monette L, McIsaac D, Wherrett C, Mallick R, Workneh A, Ramsay T, Tinmouth A, Shaw J, Carrier FM, Fergusson D, Martel G, Cornacchia M, Ivankovic V, Mamalchi SA, Choi D, Glen P, Matar M, Balaa F, Caminsky N, Mashal S, Boulanger N, Watt L, Campbell J, Grushka J, Fata P, Wong E, Guo M, Karimuddin A, Sutherland J, Li C, Lin W, Karimuddin A, Huo B, Calabrese E, Kumar S, Slater B, Walsh DS, Vosburg W, Jogiat U, Turner S, Baracos V, Eurich D, Filafilo H, Bedard E, Khan S, Waddell T, Yasufuku K, Pierre A, Keshavjee S, Wakeam E, Donahoe L, Cypel M, Safieddine N, Ko M, Leighl N, Feng J, Yeung J, De Perrot M, Salvarrey A, Ahmadi N, Simone C, Sayf G, Parente D, Cheung V, Rabey MR, Cabanero M, Le LW, Pipinikas C, Chevalier A, Chaulk R, Sahai D, Malthaner R, Qiabi M, Fortin D, Inculet R, Nayak R, Campbell J, White P, Bograd A, Farivar A, Louie B, Berger G, French D, Houston S, Gallardo F, Macek B, Liu R, Kidane B, Hanna NM, Patel YS, Browne I, Provost E, Farrokhyar F, Haider E, Hanna WC, Johnson G, Okoli G, Askin N, Abou-Setta A, Singh H, Coxon-Meggy A, Cornish J, Group LISM, Sharma S, Khamar J, Petropolous JA, Ghuman A, Lin W, Li C, Brown C, Phang T, Raval M, Ghuman A, Clement E, Karimuddin A, McKechnie T, Khamar J, Chu C, Hatamnejad A, Jessani G, Lee Y, Doumouras A, Hong D, Eskicioglu C, Sticca G, Poirier M, Tremblay JF, Latulippe JF, Bendavid Y, Trépanier JS, Lacaille-Ranger A, Henri M, McKechnie T, Kazi T, Shi V, Grewal S, Aldarraji A, Brennan K, Patel S, Amin N, Doumouras A, Parpia S, Eskicioglu C, Bhandari M, Talwar G, McKechnie T, Khamar J, Heimann L, Anant S, Eskicioglu C, Shi V, McKechnie T, Anant S, Ahmed M, Sharma S, Talwar G, Hong D, Eskicioglu C, Kazi T, McKechnie T, Lee Y, Alsayari R, Talwar G, Doumouras A, Hong D, Eskicioglu C, Park LJ, Moloo H, Ramsay T, Thavorn K, Presseau J, Zwiep T, Martel G, Devereaux PJ, Talarico R, McIsaac DI, Lemke M, Lin W, Brown C, Clement E, Ghuman A, Phang T, Raval M, Karimuddin A, Li C, Lin W, Clement E, Ghuman A, Hague C, Karimuddin A, Phang PT, Raval M, Tiwari P, Vos P, Brown C, Ricci A, Farooq A, Patel S, Brennan K, Wiseman V, McKechnie T, Keeping A, Johnson P, Bentley H, Messak K, Bogach J, Pond G, Forbes S, Grubac V, Tsai S, Van Der Pol C, Simunovic M, Bondzi-Simpson A, Behman R, Ribeiro T, Perera S, Lofters A, Sutradhar R, Snyder R, Clarke C, Coburn N, Hallet J, Caminsky N, Chen A, Moon J, Brassard P, Marinescu D, Dumitra T, Salama E, Vasilevsky CA, Boutros M, Brennan K, McKechnie T, Wiseman V, Ricci A, Farooq A, Patel S, Kazi T, McKechnie T, Jessani G, Shi V, Sne N, Doumouras A, Hong D, Eskicioglu C, Jogendran M, Flemming J, Djerboua M, Korzeniowski M, Wilson B, Merchant S, Bennett S, Hickey K, Gill S, Breen Z, Harding K, Yaremko H, Power P, Mathieson A, Pace D, Neveu J, Bennett S, Wilson B, Chen N, Kong W, Patel S, Booth C, Merchant S, Bennett S, Nelson G, AlMarzooqi N, Jogendran M, Djerboua M, Wilson B, Flemming J, Merchant S, Park LJ, Wang C, Archer V, McKechnie T, Cohen D, Bogach J, Simunovic M, Serrano PE, Breau RH, Karanicolas P, Devereaux PJ, Nelson G, AlMarzooqi N, Merchant S, Bennett S, Charbonneau J, Gervais MK, Brind'Amour A, Singbo N, Soucisse ML, Sidéris L, Leblanc G, Tremblay JF, Dubé P, Kouzmina E, Castelo M, Hong NL, Hallet J, Coburn N, Write F, Nguyen L, Gandhi S, Jerzak K, Eisen A, Roberts A, Vidovic D, Cruickshank B, Helyer L, Giacomantonio C, Mir Z, Faleiro M, Hiebert S, Livingstone S, Walsh M, Gala-Lopez B, Jatana S, Krys D, Jogiat U, Kung J, Verhoeff K, Lenet T, Carrier FM, Brousseau K, Vandenbroucke-Menu F, Collin Y, Gilbert RWD, Segedi M, Khalil JA, Bertens KA, Balaa F, Fergusson DA, Martel G, Wherrett C, Mallette K, Monette L, Workneh A, Ruel M, Sabri E, Maddison H, Tokessym M, Wong PBY, Massicotte L, Chassé M, Perrault MA, Hamel-Perreault É, Park J, Lim S, Maltais V, Leung P, Ramsay T, Tinmouth A, Czarnecka Z, Dadheeech N, Pawlick R, Razavy H, Shapiro J, Pouramin P, Allen S, Gala-Lopez B, Amhis N, Hennessey RL, Yang Y, Guan R, Zhang Y, Meneghetti A, Chiu C, Srikrishnaraj D, Hawel J, Schlachta C, Elnahas A, Yilbas A, Mainprize M, Svendrovski A, Paasch C, Netto FS, Khamar J, McKechnie T, Hatamnejad A, Lee Y, Huo B, Passos E, Sne N, Eskicioglu C, Hong D, Bennett S, Flemming J, Djerboua M, Wiseman V, Moore J, Szasz P, Nanji S, Moore J, Wiseman V, Szasz P, Lunsky I, Nanji S, Flemming JA, Bennett S, McKeown S, Mouhammed O, Gibb C, Verhoeff K, Kim M, Strickland M, Anantha R, Georgescu I, Lee Y, Shin T, Tessier L, Javidan A, Jung J, Hong D, McKechnie T, Strong A, Kroh M, Dang J, Faran M, McKechnie T, O'Callaghan E, Anvari S, Hughes T, Crowther M, Anvari M, Doumouras A, Andalib A, Safar A, Bouchard P, Demyttenaere S, Court O, Parmar S, Brand B, Switzer N, Gil R, Aujla S, Schellenberg M, Owattanapanich N, Emigh B, Van Gent JM, Egodage T, Murphy PB, Ball C, Spencer AL, Vogt KN, Keeley JA, Doris S, Inaba K, Nantais J, Baxter N, Saskin R, Calzavara A, Gomez D, Le A, Dawe P, Hameed M, Hassanpour A, Shlomovitz E, Gomez D, Al-Sukhni E, Wiseman V, Patel S, Bennett S, Mir Z, Roberts S, Hawes H, Merali K, Morris R, de Moya M, Neideen T, Kastenmeier A, Somberg L, Holena D, Murphy P, Nantais J, Baxter N, Saskin R, Calzavara A, Gomez D, Naveed A, Deshpande U, Gomez D, Rezende-Neto J, Ahmed N, and Beckett A
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- 2024
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16. Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial.
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van Dorp J, Pipinikas C, Suelmann BBM, Mehra N, van Dijk N, Marsico G, van Montfoort ML, Hackinger S, Braaf LM, Amarante T, van Steenis C, McLay K, Daletzakis A, van den Broek D, van de Kamp MW, Hendricksen K, de Feijter JM, Boellaard TN, Meijer RP, van der Heijden AG, Rosenfeld N, van Rhijn BWG, Jones G, and van der Heijden MS
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- 2024
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17. Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.
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García-Pardo M, Czarnecka-Kujawa K, Law JH, Salvarrey AM, Fernandes R, Fan ZJ, Waddell TK, Yasufuku K, Liu G, Donahoe LL, Pierre A, Le LW, Gunasegaran T, Ghumman N, Shepherd FA, Bradbury PA, Sacher AG, Schmid S, Corke L, Feng J, Stockley T, Pal P, Rogalla P, Pipinikas C, Howarth K, Ambasager B, Mezquita L, Tsao MS, and Leighl NB
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- Male, Humans, Adult, Middle Aged, Aged, Aged, 80 and over, Time-to-Treatment, Ontario, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Circulating Tumor DNA
- Abstract
Importance: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear., Objective: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment., Design, Setting, and Participants: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis., Interventions: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care., Main Outcome and Measures: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis., Results: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing., Conclusions and Relevance: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing., Trial Registration: ClinicalTrials.gov Identifier: NCT04863924.
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- 2023
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18. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial.
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van Dorp J, Pipinikas C, Suelmann BBM, Mehra N, van Dijk N, Marsico G, van Montfoort ML, Hackinger S, Braaf LM, Amarante T, van Steenis C, McLay K, Daletzakis A, van den Broek D, van de Kamp MW, Hendricksen K, de Feijter JM, Boellaard TN, Meijer RP, van der Heijden AG, Rosenfeld N, van Rhijn BWG, Jones G, and van der Heijden MS
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- Humans, Ipilimumab adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Progression-Free Survival, Nivolumab adverse effects, Neoplasms chemically induced
- Abstract
Cohort 1 of the phase 1B NABUCCO trial showed high pathological complete response (pCR) rates with preoperative ipilimumab plus nivolumab in stage III urothelial cancer (UC). In cohort 2, the aim was dose adjustment to optimize responses. Additionally, we report secondary endpoints, including efficacy and tolerability, in cohort 2 and the association of presurgical absence of circulating tumor DNA (ctDNA) in urine and plasma with clinical outcome in both cohorts. Thirty patients received two cycles of either ipilimumab 3 mg kg
-1 plus nivolumab 1 mg kg-1 (cohort 2A) or ipilimumab 1 mg kg-1 plus nivolumab 3 mg kg-1 (cohort 2B), both followed by nivolumab 3 mg kg-1 . We observed a pCR in six (43%) patients in cohort 2A and a pCR in one (7%) patient in cohort 2B. Absence of urinary ctDNA correlated with pCR in the bladder (ypT0Nx) but not with progression-free survival (PFS). Absence of plasma ctDNA correlated with pCR (odds ratio: 45.0; 95% confidence interval (CI): 4.9-416.5) and PFS (hazard ratio: 10.4; 95% CI: 2.9-37.5). Our data suggest that high-dose ipilimumab plus nivolumab is required in stage III UC and that absence of ctDNA in plasma can predict PFS. ClinicalTrials.gov registration: NCT03387761 ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2023
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19. Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)-a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma.
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Flach S, Howarth K, Hackinger S, Pipinikas C, Ellis P, McLay K, Marsico G, Forshew T, Walz C, Reichel CA, Gires O, Canis M, and Baumeister P
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- Biomarkers, Tumor genetics, Humans, Liquid Biopsy, Neoplasm, Residual genetics, Prospective Studies, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck surgery, Circulating Tumor DNA genetics, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms genetics, Head and Neck Neoplasms surgery
- Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC., Methods: We conducted a single-centre prospective cohort study to investigate ctDNA in patients with p16-negative HNSCC who received curative-intent primary surgical treatment. Whole-exome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tumour tissue. We utilised RaDaR
TM , a highly sensitive personalised assay using deep sequencing for tumour-specific variants, to analyse serial pre- and post-operative plasma samples for evidence of minimal residual disease and recurrence., Results: In 17 patients analysed, personalised panels were designed to detect 34 to 52 somatic variants. Data show ctDNA detection in baseline samples taken prior to surgery in 17 of 17 patients. In post-surgery samples, ctDNA could be detected at levels as low as 0.0006% variant allele frequency. In all cases with clinical recurrence to date, ctDNA was detected prior to progression, with lead times ranging from 108 to 253 days., Conclusions: This study illustrates the potential of ctDNA as a biomarker for detecting minimal residual disease and recurrence in HNSCC and demonstrates the feasibility of personalised ctDNA assays for the detection of disease prior to clinical recurrence., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
20. Progressive epigenetic dysregulation in neuroendocrine tumour liver metastases.
- Author
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Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, Serra S, Ogunbiyi O, Novelli M, Luong T, Asa SL, Kulke M, Toumpanakis C, Meyer T, Caplin M, Beck S, and Thirlwell C
- Subjects
- Epigenomics, Female, Humans, Liver Neoplasms pathology, Male, Neoplasm Metastasis, Neuroendocrine Tumors pathology, Liver Neoplasms secondary, Neuroendocrine Tumors complications
- Published
- 2017
- Full Text
- View/download PDF
21. Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor.
- Author
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Karpathakis A, Dibra H, Pipinikas C, Feber A, Morris T, Francis J, Oukrif D, Mandair D, Pericleous M, Mohmaduvesh M, Serra S, Ogunbiyi O, Novelli M, Luong T, Asa SL, Kulke M, Toumpanakis C, Meyer T, Caplin M, Meyerson M, Beck S, and Thirlwell C
- Subjects
- Adult, Aged, Chromosomes, Human, Pair 18, Cluster Analysis, Computational Biology methods, Cyclin-Dependent Kinase Inhibitor p27 genetics, DNA Copy Number Variations, DNA Methylation, DNA Mutational Analysis, Epigenesis, Genetic, Exome, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Intestinal Neoplasms diagnosis, Intestine, Small pathology, Male, Middle Aged, Mutation, Neoplasm Metastasis, Neoplasm Staging, Neuroendocrine Tumors diagnosis, Prognosis, Reproducibility of Results, Intestinal Neoplasms genetics, Intestinal Neoplasms mortality, Intestine, Small metabolism, Neuroendocrine Tumors genetics, Neuroendocrine Tumors mortality
- Abstract
Purpose: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type., Experimental Design: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43)., Results: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%)., Conclusions: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival., (©2015 American Association for Cancer Research.)
- Published
- 2016
- Full Text
- View/download PDF
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