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Stege, Henner Maximilian ; Haist, Maximilian ; Schultheis, Michael ; Fleischer, Maria Isabel ; Mohr, Peter ; Meier, Friedegund ; Schadendorf, Dirk ; Ugurel, Selma ; Livingstone, Elisabeth ; Zimmer, Lisa ; Herbst, Rudolf ; Pföhler, Claudia Ursula ; Kähler, Katharina ; Weichenthal, Michael ; Terheyden, Patrick ; Nashan, Dorothée ; Debus, Dirk ; Kaatz, Martin ; Ziller, Fabian ; Haferkamp, Sebastian ; Forschner, Andrea Lydia ; Leiter, Ulrike ; Kreuter, Alexander ; Ulrich, Jens ; Kleemann, Johannes ; Bradfisch, Fabienne ; Grabbe, Stephan ; Loquai, Carmen
Simple Summary: The introduction of BRAF/MEK-directed targeted therapy (TT) has significantly improved the management of patients with advanced BRAF-V600-mutant melanoma. Although resistance occurs, there is a subgroup of patients showing a complete response (CR) to TT and who maintain durable disease control. For these patients with durable CR, it is not clear whether it is safe to cease therapy. In this retrospective, multicenter study we have analyzed 37 patients who received TT and achieved a CR upon treatment. We identified 15 patients with a durable CR to TT. Overall, patients who discontinued TT (n = 26) were at higher risk of tumor progression compared to patients receiving ongoing TT. Sustained CR was however not restricted to patients with ongoing TT (n = 11) but was also found in patients who ceased TT (n = 4). Finally, our analysis indicated which patients with an initial CR might be most likely to maintain durable CR upon discontinuation of TT.
Abstract: The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.
Heppt, Markus V. ; Amaral, Teresa ; Kähler, Katharina C. ; Heinzerling, Lucie ; Hassel, Jessica C. ; Meissner, Markus ; Kreuzberg, Nicole ; Loquai, Carmen ; Reinhardt, Lydia ; Utikal, Jochen ; Dabrowski, Evelyn ; Gesierich, Anja ; Pföhler, Claudia Ursula ; Terheyden, Patrick ; Thoms, Kai-Martin ; Zimmer, Lisa ; Eigentler, Thomas Kurt ; Kirchberger, Michael Constantin ; Stege, Henner Maximilian ; Meier, Friedegund ; Schlaak, Max ; Berking, Carola
Background: Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages. The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear.
Methods: Patients with metastatic or unresectable UM treated with ipilimumab in combination with a PD-1 inhibitor were collected from 16 German skin cancer centers. Patient records of 64 cases were analyzed for response, progression-free survival (PFS), overall survival (OS), and safety. Clinical parameters and serum biomarkers associated with OS and treatment response were determined with Cox regression modelling and logistic regression.
Results: The best overall response rate to combined checkpoint blockade was 15.6% with 3.1 and 12.5% complete and partial response, respectively. The median duration of response was 25.5 months (range 9.0–65.0). Stable disease was achieved in 21.9%, resulting in a disease control rate of 37.5% with a median duration of the clinical benefit of 28.0 months (range 7.0–65.0). The median PFS was 3.0 months (95% CI 2.4–3.6). The median OS was estimated to 16.1 months (95% CI 12.9–19.3). Regarding safety, 39.1% of treated patients experienced a severe, treatment-related adverse event according to the CTCAE criteria (grade 3: 37.5%; grade 4: 1.6%). The most common toxicities were colitis (20.3%), hepatitis (20.3%), thyreoiditis (15.6%), and hypophysitis (7.8%). A poor ECOG performance status was an independent risk factor for decreased OS (p = 0.007).
Conclusions: The tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.
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Vodopyanov, Alexander ; Volkl, Martin Andreas ; Voloshin, Kirill ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Voscek, Dominik ; Vranić, Danilo ; Vrlakova, Janka ; Vulpescu, Bogdan ; Wagner, Boris ; Wang, Hongkai ; Wang, Mengliang ; Wang, Yifei ; Watanabe, Daisuke ; Watanabe, Kengo ; Watanabe, Yosuke ; Weber, Michael ; Weber, Steffen Georg ; Wegerle, Dominik ; Weiser, Dennis ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Westerhoff, Uwe ; Whitehead, Andile Mothegi ; Wiechula, Jens ; Wikne, Jon ; Wilk, Alexander ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy John ; Willems, Guido Alexander ; Williams, M. Crispin S. ; Willsher, Emily ; Windelband, Bernd Stefan ; Winn, Michael ; Witt, William Edward ; Xu, C ; Yalcin, Serpil ; Yamakawa, Kosei ; Yang, Ping ; Yano, Satoshi ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-kwon ; Yoon, Jin Hee ; Yurchenko, Volodymyr ; Yurevich, Vladimir ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zanevski, Yuri ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, Haitao ; Zhang, Xiaoming ; Zhang, Yonghong ; Chunhui, Zhang ; Zhang, Zuman ; Zhao, Chengxin ; Zhigareva, Natalia ; Zhou, Daicui ; Zhou, You ; Zhou, Zhuo ; Zhu, Hongsheng ; Zhu, Jianhui ; Zichichi, Antonino ; Zimmer, Stefan ; Zimmermann, Alice ; Zimmermann, Markus ; Zinovjev, Gennady M. ; Zmeskal, Johann ; Zou, Shuguang
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Acharya, Shreyasi ; Adam, Jaroslav ; Adamová, Dagmar ; Adler, Clemens ; Adolfsson, Jonatan ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Antonczyk, Dariusz ; Arend, Andreas ; Bazo Alba, José Luis ; Albuquerque, Danilo Silva de ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Prado, Caio Alves Garcia ; Andrei, Cristian ; Andreou, Dimitra ; Andrews, Harry Arthur ; Andronic, Anton ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Anwar, Rafay ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arnold, Oliver Werner ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Audurier, Benjamin ; Augustinus, Andre ; 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The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Acharya, Shreyasi ; Adam, Jaroslav ; Adamová, Dagmar ; Adler, Clemens ; Adolfsson, Jonatan ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Antonczyk, Dariusz ; Arend, Andreas ; Bazo Alba, José Luis ; Albuquerque, Danilo Silva de ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Prado, Caio Alves Garcia ; Andrei, Cristian ; Andreou, Dimitra ; Andrews, Harry Arthur ; Andronic, Anton ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Anwar, Rafay ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arnold, Oliver Werner ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Audurier, Benjamin ; Augustinus, Andre ; 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Lesser, F ; Lévai, Peter ; Li, Xiaomei ; Lien, Jørgen André ; Lietava, Roman ; Lim, Bong-Hwi ; Lindal, Svein ; Lindenstruth, Volker ; Lindsay, Scott William ; Lippmann, Christian ; Lisa, Michael A. ; Litichevskyi, Vladyslav ; Llope, William ; Lodato, Davide Francesco ; Lohner, Daniel ; Lønne, Per-Ivar ; Loginov, Vitaly ; Loizides, Constantinos ; Lončar, Petra ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lowe, Andrew John ; Lu, XianGuo ; Ludolphs, W ; Lüttig, Philipp ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Lupi, Matteo ; Lutz, Tyler Harrison ; Maevskaya, Alla ; Mager, Magnus ; Magureanu, C ; Mahajan, Sanjay ; Mahmoud, Tariq ; Mahmood, Sohail Musa ; Maire, Antonin ; Majka, Richard Daniel ; Malaev, Mikhail ; Malinina, Liudmila ; Mal’Kevich, Dmitry ; Malzacher, Peter ; Mamonov, Alexander ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Margutti, Jacopo ; 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Norman, Jaime ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Oeschler, Helmut ; Oh, Saehanseul ; Ohlson, Alice ; Okubo, Tsubasa ; Oláh, László ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Onderwaater, Jacobus ; Oppedisano, Chiara ; Orava, Risto ; Oravec, Matej ; Ortiz Velasquez, Antonio ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Pacik, Vojtech ; Pagano, Davide ; Pagano, Paola ; Paic, Guy ; Panebratsev, Yu ; Palni, Prabhakar ; Pan, Jinjin ; Pandey, Ashutosh Kumar ; Panebianco, Stefano Matthias ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Pareek, Pooja ; Park, Jonghan ; Park, WooJin ; Parmar, Sonia ; Passfeld, Annika ; Pathak, Surya Prakash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Pérez Lezama, Edgar ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petris, M ; Petrov, Viacheslav ; Petrovici, Mihai A. ; Petta, Catia ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Ozelin de Lima Pimentel, Laís ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, Nora ; Piyarathna, Danthasinghe ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Pluta, Jan Marian ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polishchuk, Boris ; Poljak, Nikola ; Poonsawat, Wanchaloem ; Pop, Amalia ; Poppenborg, Hendrik ; Porteboeuf, Sarah Julie ; Pozdniakov, Valeriy ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Puddu, Giovanna ; Pujahari, Prabhat Ranjan ; Punin, Valery ; Putschke, Jörn H. ; Radomski, Sylwester ; Rachevski, Alexandre ; Raha, Sibaji ; Rajput, Sonia ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rana, Dhan Bahadur ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Ratza, Viktor ; Ravasenga, Ivan ; Read, Kenneth Francis ; Redlich, Krzysztof ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Reischl, A ; Ren, Xiaowen ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Reygers, Klaus ; Riabov, Viktor ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Ristea, Cătălin-Lucian ; Rodrı́guez Cahuantzi, Mario ; Røed, Ketil ; Rogochaya, Elena ; Rohr, David ; Röhrich, Dieter ; Rokita, Przemyslaw Stefan ; Ronchetti, Federico ; Dominguez Rosas, Edgar ; Rosnet, Philippe ; Rossi, Andrea ; Rotondi, Alberto ; Roukoutakis, Filimon ; Roy, Ankhi ; Roy, Christelle Sophie ; Roy, Pradip Kumar ; Vazquez Rueda, Omar ; Rui, Rinaldo ; Rumyantsev, Boris ; Rusanov, Ivan ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej ; Saarinen, Sampo ; Sadhu, Samrangy ; Sadovskiy, Sergey ; Šafařík, Karel ; Saha, Sumit Kumar ; SahlmÜller, Baldo ; Sahoo, Baidyanath ; Sahoo, Pragati ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakai, Shingo ; Sakata, Dousatsu ; Saleh, Mohammad Ahmad ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sandoval, Andres ; Sann, Hans ; Sano, Masato ; Santo, Rainer ; Sarkar, Debojit ; Sarkar, Nachiketa ; Sarma, Pranjal ; Sas, Mike Henry Petrus ; Scapparone, Eugenio ; Scarlassara, Fernando ; Schaefer, Brennan ; Scharenberg, Rolf Paul ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmiederer, Stefan ; Schneider, R ; Schukraft, Jürgen ; Schulze, R ; Schutz, Yves Roland ; Schwarz, Kilian Eberhard ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Sedykh, S ; Šefčík, Michal ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senosi, Kgotlaesele ; Senyukov, Serhiy ; Serradilla Rodriguez, Eulogio ; Sett, Priyanka ; Sevcenco, Adrian ; Shabanov, Arseniy ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shaikh, Wadut ; Shangaraev, Artem ; Sharma, Anjali ; Sharma, Ankita ; Sharma, Mona ; Sharma, Monika ; Sharma, Natasha ; Sheikh, Ashik Ikbal ; Shigaki, Kenta ; Shimansky, S ; Shou, Qiye ; Shtejer Diaz, Katherin ; Shukla, P ; Sibiryak, Yury ; Sicking, Eva ; Siddhanta, Sabyasachi ; Sielewicz, Krzysztof Marek ; Siemiarczuk, Teodor ; Silaeva, Svetlana ; Silvermyr, David Olle Rickard ; Silvestre, Catherine Micaela ; Simatovic, Goran ; Simon, Reinhard S ; Simonetti, Giuseppe ; Singaraju, Rama Narayana ; Singh, Ranbir ; Singhal, Vikas ; Sarkar - Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Slupecki, Maciej ; Smirnov, Nikolai ; Smykov, L ; Snellings, Raimond ; Snellman, Tomas Wilhelm ; Solveit, Hans Kristian ; Sommer, Wolfgang ; Song, Jihye ; Song, Myunggeun ; Soramel, Francesca ; Sorensen, Soren Pontoppidan ; Sozzi, Federica ; Spiriti, Eleuterio ; Sputowska, Iwona Anna ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stankus, Paul William ; Stelzer, Herbert ; Stenlund, Evert Anders ; Stiller, Johannes ; Stocco, Diego ; Stockmeyer, M.R. ; Storetvedt, Maksim Melnik ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Sugitate, Toru ; Suire, Christophe Pierre ; Suleymanov, Mais Kazim Oglu ; Šuljić, Miljenko ; Sultanov, Rishat ; Šumbera, Michal ; Sumowidagdo, Suharyo ; Suzuki, Ken ; Swain, Sagarika ; Szabo, Alexander ; Szarka, Imrich ; Tabassam, Uzma ; Takahashi, Jun ; Tambave, Ganesh Jagannath ; Tanaka, Naoto ; Tarhini, Mohamad ; Tariq, Mohammad ; Tarzila, Madalina-Gabriela ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terasaki, Kohei ; Terrevoli, Cristina ; Teyssier, Boris ; Thakur, Dhananjaya ; Thakur, Sanchari ; Thomas, Deepa ; Thoresen, Freja ; Tieulent, Raphael Noel ; Tikhonov, Anatoly ; Tilsner, Heinz ; Timmins, Anthony Robert ; Toia, Alberica ; Rojas Torres, Solangel ; Tripathy, Sushanta ; Trogolo, Stefano ; Trombetta, Giuseppe ; Tropp, Lukas ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Trzeciak, Barbara Antonina ; Tsiledakis, Georgios ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Umaka, Ejiro Naomi ; Uras, Antonio ; Usai, Gianluca ; Utrobicic, Antonija ; Vala, Martin ; Maarel, Jasper van der ; Hoorne, Jacobus Willem van ; Leeuwen, Marco van ; Vanat, Tomas ; Vargas, H ; Vyvre, Pierre vande ; Varga, Dezsö ; Vargas Treviño, Maria Aurora Diozcora ; Vargyas, Márton ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vauthier, Astrid ; Vazquez Doce, Oton ; Vechernin, Vladimir ; Veen, Annelies Marianne ; Velure, Arild ; Vercellin, Ermanno ; Vergara Limon, Sergio ; Vernet, Renaud ; Vértesi, Róbert ; Vicković, Linda ; Vigolo, Sonia ; Viinikainen, Jussi Samuli ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Villatoro Tello, Abraham ; Vinogradov, Alexander ; Vinogradov, Leonid ; Virgili, Tiziano ; Vislavicius, Vytautas ; Vodopyanov, Alexander ; 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Crispin S. ; Willsher, Emily ; Windelband, Bernd ; Winn, Michael ; Witt, William Edward ; Xu, C ; Yalcin, Serpil ; Yamakawa, Kosei ; Yang, Ping ; Yano, Satoshi ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-kwon ; Yoon, Jin Hee ; Yurchenko, Volodymyr ; Yurevich, Vladimir ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zanevski, Yuri ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, Haitao ; Zhang, Xiaoming ; Zhang, Yonghong ; Chunhui, Zhang ; Zhang, Zuman ; Zhao, Chengxin ; Zhigareva, Natalia ; Zhou, Daicui ; Zhou, You ; Zhou, Zhuo ; Zhu, Hongsheng ; Zhu, Jianhui ; Zichichi, Antonino ; Zimmer, Stefan ; Zimmermann, Alice ; Zimmermann, Markus ; Zinovjev, Gennady M. ; Zmeskal, Johann ; Zou, Shuguang
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Hecht, Markus ; Meier, Friedegund ; Zimmer, Lisa ; Polat, Bülent ; Loquai, Carmen ; Weishaupt, Carsten ; Forschner, Andrea Lydia ; Gutzmer, Ralf ; Utikal, Jochen ; Goldinger, Simone M. ; Geier, Michael ; Hassel, Jessica C. ; Balermpas, Panagiotis ; Kiecker, Felix ; Rauschenberg, Ricarda ; Dietrich, Ursula ; Clemens, Patrick ; Berking, Carola ; Grabenbauer, Gerhard ; Schadendorf, Dirk ; Grabbe, Stephan ; Schuler, Gerold ; Fietkau, Rainer ; Distel, Luitpold Valentin Rudolf ; Heinzerling, Lucie
Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients.
Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi).
Results: The median duration of BRAFi treatment interruption prior to radiotherapy was 4 days and lasted for 17 days. Median OSRT and OSBRAFi in the entire cohort were 9.8 and 12.6 months in the interrupted group and 7.3 and 11.5 months in the concomitant group (P=0.075/P=0.217), respectively. Interrupted vemurafenib treatment with a median OSRT and OSBRAFi of 10.1 and 13.1 months, respectively, was superior to concomitant vemurafenib treatment with a median OSRT and OSBRAFi of 6.6 and 10.9 months (P=0.004/P=0.067). Interrupted dabrafenib treatment with a median OSRT and OSBRAFi of 7.7 and 9.8 months, respectively, did not differ from concomitant dabrafenib treatment with a median OSRT and OSBRAFi of 9.9 and 11.6 months (P=0.132/P=0.404). Median local control of the irradiated area did not differ in the interrupted and concomitant BRAFi treatment groups (P=0.619). Skin toxicity of grade ≥2 (CTCAE) was significantly increased in patients with concomitant vemurafenib compared to the group with treatment interruption (P=0.002).
Conclusions: Interruption of vemurafenib treatment during radiation was associated with better survival and less toxicity compared to concomitant treatment. Due to lower number of patients, the relevance of treatment interruption in dabrafenib treated patients should be further investigated. The results of this analysis indicate that treatment with the BRAFi vemurafenib should be interrupted during radiotherapy. Prospective studies are desperately needed.
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