Practice-changing publications

All areas of the UCCH are continuously active in clinical research and in conducting clinical trials. The researchers are involved in national and international consortia. The impact of these joint activities can be seen in the contribution of UCCH researchers as co-authors in groundbreaking studies and publications for the continuous development of cancer treatment.

In the following, we present selected publications of the most important practice-changing studies, i.e. studies in the field of oncology, which represent a significant improvement of the current standard of treatment. Listed here are publications from the year 2018 ongoing with UCCH participation that have appeared in the leading journals (e. g. New England Journal of Medicine, Lancet Oncology or Journal of Clinical Oncology).

  • Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma: The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial.

    Thuss-Patience P, Högner A, Goekkurt E, Stahl M, Kretzschmar A, Götze T, Stocker G, Reichardt P, Kullmann F, Pink D, Bartels P, Jarosch A, Hinke A, Schultheiß C, Paschold L, Stein A, Binder M. JAMA Netw Open. 2024 Jan 2;7(1):e2352830. doi: 10.1001/jamanetworkopen.2023.52830. PMID: 38261316; PMCID: PMC10807255. PubMed

    Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial.

    Lorenzen S, Götze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, Lindig U, Heuer V, Kretzschmar A, Goekkurt E, Haag GM, Riera-Knorrenschild J, Bolling C, Hofheinz RD, Zhan T, Angermeier S, Ettrich TJ, Siebenhuener AR, Elshafei M, Bechstein WO, Gaiser T, Loose M, Sookthai D, Kopp C, Pauligk C, Al-Batran SE; AIO and SAKK Study Working Groups. J Clin Oncol. 2024 Feb 1;42(4):410-420. doi: 10.1200/JCO.23.00975. Epub 2023 Nov 14. PMID: 37963317. PubMed

    Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

    Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O'Reilly EM, Hackert T, Golan T, Prager G, Haustermans K, Vogel A, Ducreux M; ESMO Guidelines Committee. Ann Oncol. 2023 Sep 5:S0923-7534(23)00824-4. doi: 10.1016/j.annonc.2023.08.009. Epub ahead of print. PMID: 37678671. PubMed

    Body mass index and molecular subtypes of colorectal cancer.

    Murphy N, Newton CC, Song M, Papadimitriou N, Hoffmeister M, Phipps AI, Harrison TA, Newcomb PA, Aglago EK, Berndt SI, Brenner H, Buchanan DD, Cao Y, Chan AT, Chen X, Cheng I, Chang-Claude J, Dimou N, Drew D, Farris AB, French AJ, Gallinger S, Georgeson P, Giannakis M, Giles GG, Gruber SB, Harlid S, Hsu L, Huang WY, Jenkins MA, Laskar RS, Le Marchand L, Limburg P, Lin Y, Mandic M, Nowak JA, Obón-Santacana M, Ogino S, Qu C, Sakoda LC, Schoen RE, Southey MC, Stadler ZK, Steinfelder RS, Sun W, Thibodeau SN, Toland AE, Trinh QM, Tsilidis KK, Ugai T, Van Guelpen B, Wang X, Woods MO, Zaidi SH, Gunter MJ, Peters U, Campbell PT. J Natl Cancer Inst. 2023 Feb 8;115(2):165-173. doi: 10.1093/jnci/djac215. PMID: 36445035; PMCID: PMC9905970. PubMed

    FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group.

    Hofheinz RD, Merx K, Haag GM, Springfeld C, Ettrich T, Borchert K, Kretzschmar A, Teschendorf C, Siegler G, Ebert MP, Goekkurt E, Mahlberg R, Homann N, Pink D, Bechstein W, Reichardt P, Flach H, Gaiser T, Battmann A, Oduncu FS, Loose M, Sookthai D, Pauligk C, Göetze TO, Al-Batran SE. J Clin Oncol. 2022 Nov 10;40(32):3750-3761. doi: 10.1200/JCO.22.00380. Epub 2022 Jun 16. PMID: 35709415. PubMed

    Efficacy of Ipilimumab vs FOLFOX in Combination With Nivolumab and Trastuzumab in Patients With Previously Untreated ERBB2-Positive Esophagogastric Adenocarcinoma: The AIO INTEGA Randomized Clinical Trial.

    Stein A, Paschold L, Tintelnot J, Goekkurt E, Henkes SS, Simnica D, Schultheiss C, Willscher E, Bauer M, Wickenhauser C, Thuss-Patience P, Lorenzen S, Ettrich T, Riera-Knorrenschild J, Jacobasch L, Kretzschmar A, Kubicka S, Al-Batran SE, Reinacher-Schick A, Pink D, Sinn M, Lindig U, Hiegl W, Hinke A, Hegewisch-Becker S, Binder M. JAMA Oncol. 2022 Jun 23. doi: 10.1001/jamaoncol.2022.2228. Epub ahead of print. PMID: 35737383. PubMed

    FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group.

    Hofheinz RD, Merx K, Haag GM, Springfeld C, Ettrich T, Borchert K, Kretzschmar A, Teschendorf C, Siegler G, Ebert MP, Goekkurt E, Mahlberg R, Homann N, Pink D, Bechstein W, Reichardt P, Flach H, Gaiser T, Battmann A, Oduncu FS, Loose M, Sookthai D, Pauligk C, Göetze TO, Al-Batran SE. J Clin Oncol. 2022 Jun 16:JCO2200380. doi: 10.1200/JCO.22.00380. Epub ahead of print. PMID: 35709415. PubMed

    Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212).

    Modest DP, Karthaus M, Fruehauf S, Graeven U, Müller L, König AO, Fischer von Weikersthal L, Caca K, Kretzschmar A, Goekkurt E, Haas S, Kurreck A, Stahler A, Held S, Jarosch A, Horst D, Reinacher-Schick A, Kasper S, Heinemann V, Stintzing S, Trarbach T. J Clin Oncol. 2022 Jan 1;40(1):72-82. doi: 10.1200/JCO.21.01332. Epub 2021 Sep 17. PMID: 34533973; PMCID: PMC8683209. PubMed

    The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality.

    Karlsen TH, Sheron N, Zelber-Sagi S, Carrieri P, Dusheiko G, Bugianesi E, Pryke R, Hutchinson SJ, Sangro B, Martin NK, Cecchini M, Dirac MA, Belloni A, Serra-Burriel M, Ponsioen CY, Sheena B, Lerouge A, Devaux M, Scott N, Hellard M, Verkade HJ, Sturm E, Marchesini G, Yki-Järvinen H, Byrne CD, Targher G, Tur-Sinai A, Barrett D, Ninburg M, Reic T, Taylor A, Rhodes T, Treloar C, Petersen C, Schramm C, Flisiak R, Simonova MY, Pares A, Johnson P, Cucchetti A, Graupera I, Lionis C, Pose E, Fabrellas N, Ma AT, Mendive JM, Mazzaferro V, Rutter H, Cortez-Pinto H, Kelly D, Burton R, Lazarus JV, Ginès P, Buti M, Newsome PN, Burra P, Manns MP. Lancet. 2022 Jan 1;399(10319):61-116. doi: 10.1016/S0140-6736(21)01701-3. Epub 2021 Dec 2. PMID: 34863359. PubMed

    Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study.

    Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. PMID: 34454674. PubMed

    Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212).

    Modest DP, Karthaus M, Fruehauf S, Graeven U, Müller L, König AO, Fischer von Weikersthal L, Caca K, Kretzschmar A, Goekkurt E, Haas S, Kurreck A, Stahler A, Held S, Jarosch A, Horst D, Reinacher-Schick A, Kasper S, Heinemann V, Stintzing S, Trarbach T. J Clin Oncol. 2021 Sep 17:JCO2101332. doi: 10.1200/JCO.21.01332. Epub ahead of print. PMID: 34533973. PubMed

    Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer.

    Yin J, Cohen R, Jin Z, Liu H, Pederson L, Adams R, Grothey A, Maughan TS, Venook A, Van Cutsem E, Punt C, Koopman M, Falcone A, Tebbutt NC, Seymour MT, Bokemeyer C, Rubio ED, Kaplan R, Heinemann V, Chibaudel B, Yoshino T, Zalcberg J, Andre T, De Gramont A, Shi Q, Lenz HJ. J Natl Cancer Inst. 2021 Jun 1:djab112. doi: 10.1093/jnci/djab112. Epub ahead of print. PMID: 34061178. PubMed

    BRAF V600E Mutation in First-line Metastatic Colorectal Cancer: an Analysis of Individual Patient Data from the ARCAD Database.

    Cohen R, Liu H, Fiskum J, Adams R, Chibaudel B, Maughan TS, Van Cutsem E, Venook A, Douillard JY, Heinemann V, Punt CJA, Falcone A, Bokemeyer C, Kaplan R, Lenz HJ, Koopman M, Yoshino T, Zalcberg J, Grothey A, de Gramont A, Shi Q, André T. J Natl Cancer Inst. 2021 Mar 18:djab042. doi: 10.1093/jnci/djab042. Online ahead of print. PMID: 33734401, PubMed

    Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial.

    Kunzmann V, Siveke JT, Algül H, Goekkurt E, Siegler G, Martens U, Waldschmidt D, Pelzer U, Fuchs M, Kullmann F, Boeck S, Ettrich TJ, Held S, Keller R, Klein I, Germer CT, Stein H, Friess H, Bahra M, Jakobs R, Hartlapp I, Heinemann V; German Pancreatic Cancer Working Group (AIO-PAK) and NEOLAP investigators. Lancet Gastroenterol Hepatol. 2020 Dec 15:S2468-1253(20)30330-7. PubMed

    Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial.

    Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. PubMed

    Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD.

    Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K.Schmoll HJ, et al. J Clin Oncol. 2020 Oct 1:JCO2001740. Online ahead of print. J Clin Oncol. 2020., PubMed

    Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial

    Shitara K,Van Cutsem E, Bang J-Y, Fuchs C, Wyrwicz L, Lee K-W, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J, JAMA Oncol. 2020 Sep 3., PubMed

    The Keynote 062 trial is the first large randomized trial to evaluate the role of first line immunotherapy with pembrolizumab either alone or in addition to standard first line chemotherapy both compared to chemotherapy alone, pointing out the high relevance of CPS and MSI status.

    Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer

    Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll H-J, Di Maio M, J Clin Oncol. 2020 Aug 20; JCO2001225., PubMed

    This large meta analysis defines the role of FOLFOXIRI and bevacizumab in first line metastatic colorectal cancer and will lead to a revision of current guidelines still recommending this regimen in BRAF mutant tumors despite no impact on survival.

    Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial.

    Subbiah V, Lassen U, Élez E, Italiano A, Curigliano G, Javle M, de Braud F, Prager GW, Greil R, Stein A, Fasolo A, Schellens JHM, Wen PY, Viele K, Boran AD, Gasal E, Burgess P, Ilankumaran P, Wainberg ZA, Lancet Oncology 2020 August 17, 2020., PubMed

    This phase 2 trial established BRAF/MEK inhibition as new standard of care in previously treated BRAF mutated biliary tract cancers.

    Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

    Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators., Lancet. 2019 May 11;393(10184):1948-1957., PubMed

    This German multicenter DKH-funded trial showed that in locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT in comparison to perioperative ECF/ECX improved overall survival.

    Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial.

    Phelip JM, Pelletier G, Bronowicki JP, Touchefeu Y, Pageaux G, Gerolami R, Habersetzer F, Nguyen-Khac E, Casadei-Gardini A, Borbath I, Tran A, Wege H, Saad AS, Colombo M, Abergel A, Richou C, Waked I, Yee NS, Molé A, Attali P, Le Boulicaut J, Vasseur B; RELIVE Investigators., Lancet Gastroenterol Hepatol. 2019 Jun;4(6):454-465., PubMed

    This is a negative trial showing that doxorubicin-loaded nanoparticles are not active in the treatment of sorafinib resistant hepatocellular carcinoma.

    Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial.

    Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group., Lancet Oncol. 2019 Mar;20(3):420-435., PubMed

    This large trial showed no beneficial impact of the addition of ramucirumab to standard first line chemotherapy, despite the clear effect seen in second and third line esophagogastric adenocarcinoma.

    Sequential Versus Combination Therapy of Metastatic Colorectal Cancer Using Fluoropyrimidines, Irinotecan, and Bevacizumab: A Randomized, Controlled Study-XELAVIRI (AIO KRK0110).

    Modest DP, Fischer von Weikersthal L, Decker T, Vehling-Kaiser U, Uhlig J, Schenk M, Freiberg-Richter J, Peuser B, Denzlinger C, Peveling Genannt Reddemann C, Graeven U, Schuch G, Schwaner I, Stahler A, Jung A, Kirchner T, Held S, Stintzing S, Giessen-Jung C, Heinemann V; XELAVIRI/AIO KRK0110 Investigators., J Clin Oncol. 2019 Jan 1;37(1):22-32., PubMed

    This trial demonstrated the clinical relevance of an upfront combination compared to a sequential escalation strategy in mainly elderly patients with metastatic colorectal cancer based on RAS/BRAF status.

    Evaluation of Continuous Tumor-Size-Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer.

    Burzykowski T, Coart E, Saad ED, Shi Q, Sommeijer DW, Bokemeyer C, Díaz-Rubio E, Douillard JY, Falcone A, Fuchs CS, Goldberg RM, Hecht JR, Hoff PM, Hurwitz H, Kabbinavar FF, Koopman M, Maughan TS, Punt CJA, Saltz L, Schmoll HJ, Seymour MT, Tebbutt NC, Tournigand C, Van Cutsem E, de Gramont A, Zalcberg JR, Buyse M; Aide et Recherche en Cancerologie Digestive Group., JAMA Netw Open. 2019 Sep 4;2(9):e1911750, PubMed

    This study indicates that the deepness of response and continuous evaluation of the size of lesions may be good surrogate parameters for the individual prediction of overall survival in metastatic colorectal cancer patients.

    Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial.

    Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS, Lancet. 2018 Jul 14;392(10142):123-133., PubMed

    This phase 3 trial showed an overall similar efficacy but better tolerability of pembrolizumab compared to paclitaxel and established the clinical relevance of PD-L1 combined positivity score (CPS) in esophagogastric adenocarcinoma.

    Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

    Sjoquist KM, Renfro LA, Simes RJ, Tebbutt NC, Clarke S, Seymour MT, Adams R, Maughan TS, Saltz L, Goldberg RM, Schmoll HJ, Van Cutsem E, Douillard JY, Hoff PM, Hecht JR, Tournigand C, Punt CJA, Koopman M, Hurwitz H, Heinemann V, Falcone A, Porschen R, Fuchs C, Diaz-Rubio E, Aranda E, Bokemeyer C, Souglakos I, Kabbinavar FF, Chibaudel B, Meyers JP, Sargent DJ, de Gramont A, Zalcberg JR; Fondation Aide et Recherche en Cancerologie Digestive Group (ARCAD)., J Natl Cancer Inst. 2018 Jun 1;110(6):638-648, PubMed

    The study group has developed a nomogram to predict survival outcome of patients based on several patient and disease characteristics in metastatic colorectal cancer undergoing first line chemotherapy plus/minus targeted antibody-based therapy.

    Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancérologie Digestive Database.

    Renfro LA, Goldberg RM, Grothey A, Sobrero A, Adams R, Seymour MT, Heinemann V, Schmoll HJ, Douillard JY, Hurwitz H, Fuchs CS, Diaz-Rubio E, Porschen R, Tournigand C, Chibaudel B, Hoff PM, Kabbinavar FF, Falcone A, Tebbutt NC, Punt CJA, Hecht JR, Souglakos J, Bokemeyer C, Van Cutsem E, Saltz L, de Gramont A, Sargent DJ; ARCAD Clinical Trials Program., J Clin Oncol. 2017 Jun 10;35(17):1929-1937., PubMed

    Based on the results of this pooled data set upfront identification of patient at risk for early mortality was established.

  • Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium.

    Gillessen S, Sauvé N, Collette L, Daugaard G, de Wit R, Albany C, Tryakin A, Fizazi K, Stahl O, Gietema JA, De Giorgi U, Cafferty FH, Hansen AR, Tandstad T, Huddart RA, Necchi A, Sweeney CJ, Garcia-Del-Muro X, Heng DYC, Lorch A, Chovanec M, Winquist E, Grimison P, Feldman DR, Terbuch A, Hentrich M, Bokemeyer C, Negaard H, Fankhauser C, Shamash J, Vaughn DJ, Sternberg CN, Heidenreich A, Beyer J; International Germ Cell Cancer Classification Update Consortium. J Clin Oncol. 2021 Apr 6:JCO2003296. doi: 10.1200/JCO.20.03296. Online ahead of print.PMID: 33822655, PubMed

    Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.

    Beyer J, Collette L, Sauvé N, Daugaard G, Feldman DR, Tandstad T, Tryakin A, Stahl O, Gonzalez-Billalabeitia E, De Giorgi U, Culine S, de Wit R, Hansen AR, Bebek M, Terbuch A, Albany C, Hentrich M, Gietema JA, Negaard H, Huddart RA, Lorch A, Cafferty FH, Heng DYC, Sweeney CJ, Winquist E, Chovanec M, Fankhauser C, Stark D, Grimison P, Necchi A, Tran B, Heidenreich A, Shamash J, Sternberg CN, Vaughn DJ, Duran I, Bokemeyer C, Patrikidou A, Cathomas R, Assele S, Gillessen S; International Germ Cell Cancer Classification Update Consortium. J Clin Oncol. 2021 Mar 17:JCO2003292. doi: 10.1200/JCO.20.03292. Online ahead of print. PMID: 33729863, PubMed

    Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma.

    Fischer S, Tandstad T, Cohn-Cedermark G, Thibault C, Vincenzi B, Klingbiel D, Albany C, Necchi A, Terbuch A, Lorch A, Aparicio J, Heidenreich A, Hentrich M, Wheater M, Langberg CW, Ståhl O, Fankhauser CD, Hamid AA, Koutsoukos K, Shamash J, White J, Bokemeyer C, Beyer J, Gillessen S; Global Germ-Cell Cancer Group., J Clin Oncol. 2020 Apr 20;38(12):1322-1331., PubMed

    This investigation shows that even after adjuvant chemotherapy the few patients who relapse have an excellent outcome.

    Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study.

    Dieckmann KP, Radtke A, Geczi L, Matthies C, Anheuser P, Eckardt U, Sommer J, Zengerling F, Trenti E, Pichler R, Belz H, Zastrow S, Winter A, Melchior S, Hammel J, Kranz J, Bolten M, Krege S, Haben B, Loidl W, Ruf CG, Heinzelbecker J, Heidenreich A, Cremers JF, Oing C, Hermanns T, Fankhauser CD, Gillessen S, Reichegger H, Cathomas R, Pichler M, Hentrich M, Eredics K, Lorch A, Wülfing C, Peine S, Wosniok W, Bokemeyer C, Belge G., J Clin Oncol. 2019 Jun 1;37(16):1412-1423., PubMed

    This milestone paper establishes a novel Marker, the micro RNA 371 as a potential novel serum marker for disease stage and response to therapy in both seminomatous and non-semino´matous germ cell tumors.

    Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry.

    Cathomas R, Klingbiel D, Bernard B, Lorch A, Garcia Del Muro X, Morelli F, De Giorgi U, Fedyanin M, Oing C, Haugnes HS, Hentrich M, Fankhauser C, Gillessen S, Beyer J., J Clin Oncol. 2018 Oct 4:JCO1800210., PubMed

    This re-evalution shows that the role of FDG-PET to study residual vital disease in seminoma pts after chemotherapy is less secure as initially thought.

  • Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial.

    Oaknin A, Gladieff L, Martínez-García J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Fariñas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcón J, Follana P, Romero I, Lebreton C, Pérez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030 Investigators. Lancet. 2023 Dec 1:S0140-6736(23)02405-4. doi: 10.1016/S0140-6736(23)02405-4. Epub ahead of print. PMID: 38048793. PubMed

    Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial.

    Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. doi: 10.1200/JCO.23.00529. Epub 2023 Aug 29. PMID: 37643382; PMCID: PMC10602539. PubMed

    Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial.

    Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Lück HJ, Emons G, Meier W, Gropp-Meier M, Schröder W, de Gregorio N, Hilpert F, Harter P. J Clin Oncol. 2022 Nov 4:JCO2201010. doi: 10.1200/JCO.22.01010. Epub ahead of print. PMID: 36332161. PubMed

    Intelligent Vacuum-Assisted Biopsy to Identify Breast Cancer Patients With Pathologic Complete Response (ypT0 and ypN0) After Neoadjuvant Systemic Treatment for Omission of Breast and Axillary Surgery.

    Pfob A, Sidey-Gibbons C, Rauch G, Thomas B, Schaefgen B, Kuemmel S, Reimer T, Hahn M, Thill M, Blohmer JU, Hackmann J, Malter W, Bekes I, Friedrichs K, Wojcinski S, Joos S, Paepke S, Degenhardt T, Rom J, Rody A, van Mackelenbergh M, Banys-Paluchowski M, Große R, Reinisch M, Karsten M, Golatta M, Heil J. J Clin Oncol. 2022 Jun 10;40(17):1903-1915. doi: 10.1200/JCO.21.02439. Epub 2022 Feb 2. PMID: 35108029. PubMed

    Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer.

    Nitz UA, Gluz O, Kümmel S, Christgen M, Braun M, Aktas B, Lüdtke-Heckenkamp K, Forstbauer H, Grischke EM, Schumacher C, Darsow M, Krauss K, Nuding B, Thill M, Potenberg J, Uleer C, Warm M, Fischer HH, Malter W, Hauptmann M, Kates RE, Gräser M, Würstlein R, Shak S, Baehner F, Kreipe HH, Harbeck N; West German Study Group. J Clin Oncol. 2022 Apr 11:JCO2102759. doi: 10.1200/JCO.21.02759. Epub ahead of print. PMID: 35404683. PubMed

    Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes.

    Breast Cancer Association Consortium, Mavaddat N, Dorling L, Carvalho S, Allen J, González-Neira A, Keeman R, Bolla MK, Dennis J, Wang Q, Ahearn TU, Andrulis IL, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Blomqvist C, Bogdanova NV, Bojesen SE, Briceno I, Brüning T, Camp NJ, Campbell A, Castelao JE, Chang-Claude J, Chanock SJ, Chenevix-Trench G, Christiansen H, Czene K, Dörk T, Eriksson M, Evans DG, Fasching PA, Figueroa JD, Flyger H, Gabrielson M, Gago-Dominguez M, Geisler J, Giles GG, Guénel P, Hadjisavvas A, Hahnen E, Hall P, Hamann U, Hartikainen JM, Hartman M, Hoppe R, Howell A, Jakubowska A, Jung A, Khusnutdinova EK, Kristensen VN, Li J, Lim SH, Lindblom A, Loizidou MA, Lophatananon A, Lubinski J, Madsen MJ, Mannermaa A, Manoochehri M, Margolin S, Mavroudis D, Milne RL, Mohd Taib NA, Morra A, Muir K, Obi N, Osorio A, Park-Simon TW, Peterlongo P, Radice P, Saloustros E, Sawyer EJ, Schmutzler RK, Shah M, Sim X, Southey MC, Thorne H, Tomlinson I, Torres D, Truong T, Yip CH, Spurdle AB, Vreeswijk MPG, Dunning AM, García-Closas M, Pharoah PDP, Kvist A, Muranen TA, Nevanlinna H, Teo SH, Devilee P, Schmidt MK, Easton DF. JAMA Oncol. 2022 Jan 27:e216744. doi: 10.1001/jamaoncol.2021.6744. Epub ahead of print. PMID: 35084436; PMCID: PMC8796069. PubMed

    Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.

    Harter P, Sehouli J, Vergote I, Ferron G, Reuss A, Meier W, Greggi S, Mosgaard BJ, Selle F, Guyon F, Pomel C, Lécuru F, Zang R, Avall-Lundqvist E, Kim JW, Ponce J, Raspagliesi F, Kristensen G, Classe JM, Hillemanns P, Jensen P, Hasenburg A, Ghaem-Maghami S, Mirza MR, Lund B, Reinthaller A, Santaballa A, Olaitan A, Hilpert F, du Bois A; DESKTOP III Investigators. N Engl J Med. 2021 Dec 2;385(23):2123-2131. doi: 10.1056/NEJMoa2103294. Erratum in: N Engl J Med. 2022 Feb 17;386(7):704. PMID: 34874631. PubMed

    Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis.

    Fasching PA, Yadav S, Hu C, Wunderle M, Häberle L, Hart SN, Rübner M, Polley EC, Lee KY, Gnanaolivu RD, Hadji P, Hübner H, Tesch H, Ettl J, Overkamp F, Lux MP, Ekici AB, Volz B, Uhrig S, Lüftner D, Wallwiener M, Müller V, Belleville E, Untch M, Kolberg HC, Beckmann MW, Reis A, Hartmann A, Janni W, Wimberger P, Taran FA, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Hartkopf AD, Couch FJ. J Clin Oncol. 2021 May 20;39(15):1619-1630. doi: 10.1200/JCO.20.01200. Epub 2021 Mar 29. PMID: 33780288 PubMed

    Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.

    Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Lancet Oncol. 2021 May;22(5):609-619. doi: 10.1016/S1470-2045(21)00056-5. Epub 2021 Apr 9. PMID: 33845034 PubMed

    Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial.

    Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Lancet Oncol. 2021 Mar 4:S1470-2045(20)30754-3. doi: 10.1016/S1470-2045(20)30754-3. Online ahead of print. PMID: 33676601, PubMed

    Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial.

    Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP., J Clin Oncol. 2020 May 29:JCO2000775., PubMed

    In this randomized, controlled trial in patients with HER2-positive breast cancer with brain metastases, the addition of tucatinib to trastuzumab and capecitabine significantly improved response, reduced risk of intracranial progression and reduced risk of death. This is the first regimen to demonstrate improved antitumor activity against brain metastases in patients with HER2-positive breast cancer.

    Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial.

    Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators., Lancet Oncol. 2020 May;21(5):699-709., PubMed

    In this randomized phase III trial, the combination of carboplation with pegylated liposomal doxorubicin and bevacizumab was established as a new standard of care in the treatment of recurrent platinum sensitive ovarian cancer.

    Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.

    Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP., N Engl J Med. 2020 Feb 13;382(7):597-609., PubMed

    This trial showed, that addition of the highly selective HER2 inhibitor tucatinib to standard treatment with capacetabine and trastuzumab resulted in heavily pretreated HER2-positive metastatic breast cancer patients in better progression-free survival and overall survival than adding placebo with a median 1 year PFS of 33.1% in the tucatinib-combination group compared to 12.3% in the placebo-combination group.

    Prospective, Multicenter, Randomized Phase III Trial Evaluating the Impact of Lymphoscintigraphy as Part of Sentinel Node Biopsy in Early Breast Cancer: SenSzi (GBG80) Trial.

    Kuemmel S, Holtschmidt J, Gerber B, Von der Assen A, Heil J, Thill M, Krug D, Schem C, Denkert C, Lubitz J, Blohmer JU, Reinisch M, Hötzeldt M, Seither F, Nekljudova V, Schwidde I, Uhrhan K, Von Minckwitz G, Rezai M, Mulowski J, Loibl S, Kuehn T., J Clin Oncol. 2019 Jun 10;37(17):1490-1498., PubMed

    In this German prospective, multicenter, randomized phase III trial, patients with cN0 early breast cancer or extensive/high-grade ductal carcinoma in situ planned for standard radioactive-labeled colloid Lymphoscintigraphy (LSG) with subsequent Sentinel Node Biopsy (SLNB) were randomly assigned biopsy either with knowledge of the LSG findings or without. It was shown, that SLNB is equally effective irrespective of the surgeon's knowledge of preoperative LSG results.

    A Randomized Trial of Lymphadenectomy in Patients with Advanced Ovarian Neoplasms.

    Harter P, Sehouli J, Lorusso D, Reuss A, Vergote I, Marth C, Kim JW, Raspagliesi F, Lampe B, Aletti G, Meier W, Cibula D, Mustea A, Mahner S, Runnebaum IB, Schmalfeldt B, Burges A, Kimmig R, Scambia G, Greggi S, Hilpert F, Hasenburg A, Hillemanns P, Giorda G, von Leffern I, Schade-Brittinger C, Wagner U, du Bois A., N Engl J Med. 2019 Feb 28;380(9):822-832., PubMed

    In this trial, a randomized comparison of systematic pelvic and paraaortic lymphadenectomy versus no lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery showed, that additional lymphadenectomy was not associated with longer overall or progression-free survival than no lymphadenectomy but was associated with a higher incidence of postoperative complications.

    Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.

    von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators., N Engl J Med. 2019 Feb 14;380(7):617-628., PubMed

    Her-2 positive breast cvancer patients received in this trial in case of residual invasive disease after completion of neoadjuvant therapy in a randomized comparison either trastuzumab or trastuzumab emtansine. It was shown, that treatment with trastuzumab emtansine led to a 50% reduction in progression compared to trastuzumab.

    Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

    Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N, Fridrich C, Markmann S, Potenberg J, Lorenz R, Oskay-Oezcelik G, Schmidt M, Krabisch P, Lueck HJ, Richter R, Braicu EI, du Bois A, Sehouli J; NOGGO; AGO TRIAS Investigators., Lancet Oncol. 2018 Sep;19(9):1247-1258., PubMed

    In this randomized trial, the role of antiangiogenesis in the treatment of platinum-resistant ovarian cancer was investigated. Sorafenib, in combination with topotecan and continued as maintenance therapy, showed a statistically significant improvement in progression-free survival in women with platinum-resistant ovarian cancer.

    Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial.

    Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E., Lancet Oncol. 2018 Aug;19(8):1126-1134., PubMed

    In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy.The here conducted prospective analyyses showed that olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo despite the known side effects of olaparib.

    Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial.

    Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vázquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR., Lancet Oncol. 2018 Aug;19(8):1117-1125., PubMed

    The ENGOT-OV16/NOVA trial was a multicentre, double-blind, phase 3, randomised controlled trial in patients with recurrent ovarian cancer who were in response to their last platinum-based chemotherapy and investigated either niraparib as a maintenance treatment or placebo. In this analyis, PRO data suggest that women who receive niraparib as maintenance treatment for recurrent ovarian cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo.

    BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study.

    Fasching PA, Loibl S, Hu C, Hart SN, Shimelis H, Moore R, Schem C, Tesch H, Untch M, Hilfrich J, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm T, Huober J, Liedtke C, Weinshilboum RM, Wang L, Ingle JN, Müller V, Nekljudova V, Weber KE, Rack B, Rübner M, von Minckwitz G, Couch FJ., J Clin Oncol. 2018 Aug 1;36(22):2281-2287., PubMed

    The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with triple-negative breast cancer with BRCA1/2 mutations.

    Survival Analysis After Neoadjuvant Chemotherapy With Trastuzumab or Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the GeparQuinto (G5) Study (GBG 44).

    Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG and the AGO-B Study Group., J Clin Oncol. 2018 May 1;36(13):1308-1316., PubMed

    In this analysis, it was shown, that in patients with hormone receptor-positive tumors, prolonged anti-HER2 treatment-neoadjuvant lapatinib for 6 months, followed by adjuvant trastuzumab for 12 months-significantly improved survival compared with anti-HER2 treatment with trastuzumab alone.

    Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

    Bidard FC, Michiels S, Riethdorf S, Mueller V, Esserman LJ, Lucci A, Naume B, Horiguchi J, Gisbert-Criado R, Sleijfer S, Toi M, Garcia-Saenz JA, Hartkopf A, Generali D, Rothe F, Smerage J, Muinelo-Romay L, Stebbing J, Viens P, Magbanua MJM, Hall CS, Engebraaten O, Takata D, Vidal-Martinez J, Onstenk W, Fujisawa N, Diaz-Rubio E, Taran FA, Cappelletti MR, Ignatiadis M, Proudhon C, Wolf DM, Bauldry JB, Borgen E, Nagaoka R, Caranana V, Kraan J, Maestro M, Brucker SY, Weber K, Reyal F, Amara D, Karhade MG, Mathiesen RR, Tokiniwa H, Llombart-Cussac A, Meddis A, Blanche P, d'Hollander K, Cottu P, Park JW, Loibl S, Latouche A, Pierga JY, Pantel K., J Natl Cancer Inst 2018;110: 560-7., PubMed

    In this multi-national metaanalysis on thousands of breast cancer patients receiving neoadjuvant therapy from 21 studies showed that the CTC count was an independent, strong prognostic factor for disease-free and overall survival. As highlighted in the accompanying Editorial, the results of this study will refine the paradigm of prognosis and treatment individualization. CTCs have been included into the AJCC Cancer Staging Manual 2018 for breast cancer as new staging category (cM0(i+), which allows now a better risk stratification.

  • Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma.

    Leypoldt LB, Tichy D, Besemer B, Hänel M, Raab MS, Mann C, Munder M, Reinhardt HC, Nogai A, Görner M, Ko YD, de Wit M, Salwender H, Scheid C, Graeven U, Peceny R, Staib P, Dieing A, Einsele H, Jauch A, Hundemer M, Zago M, Požek E, Benner A, Bokemeyer C, Goldschmidt H, Weisel KC. J Clin Oncol. 2023 Sep 27:JCO2301696. doi: 10.1200/JCO.23.01696. Epub ahead of print. PMID: 37753960. PubMed

    Improved post-transplant outcomes in recent years for AML patients with FLT3-ITD and wild-type NPM1: a report from the EBMT acute leukemia working party.

    Bazarbachi A, Labopin M, Gedde-Dahl T, Remenyi P, Forcade E, Kröger N, Socié G, Craddock C, Bourhis JH, Versluis J, Yakoub-Agha I, Salmenniemi U, El-Cheikh J, Bug G, Esteve J, Nagler A, Ciceri F, Mohty M. Clin Cancer Res. 2023 Aug 21:CCR-23-0954. doi: 10.1158/1078-0432.CCR-23-0954. Epub ahead of print. PMID: 37603683. PubMed

    Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial.

    Sonneveld P, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Levin MD, Ahmadi T, Qin X, Garvin Mayo W, Gai X, Carey J, Carson R, Spencer A. J Clin Oncol. 2022 Nov 22:JCO2102734. doi: 10.1200/JCO.21.02734. Epub ahead of print. PMID: 36413710. PubMed

    Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study.

    Platzbecker U, Götze KS, Kiewe P, Germing U, Mayer K, Radsak M, Wolff T, Chromik J, Sockel K, Oelschlägel U, Haase D, Illmer T, Al-Ali HK, Silling G, Reynolds JG, Zhang X, Attie KM, Shetty JK, Giagounidis A. J Clin Oncol. 2022 Nov 20;40(33):3800-3807. doi: 10.1200/JCO.21.02476. Epub 2022 Aug 23. PMID: 35998303; PMCID: PMC9671752. PubMed

    Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial.

    Goldschmidt H, Mai EK, Bertsch U, Fenk R, Nievergall E, Tichy D, Besemer B, Dürig J, Schroers R, von Metzler I, Hänel M, Mann C, Asemissen AM, Heilmeier B, Weinhold N, Huhn S, Kriegsmann K, Luntz SP, Holderried TAW, Trautmann-Grill K, Gezer D, Klaiber-Hakimi M, Müller M, Khandanpour C, Knauf W, Scheid C, Munder M, Geer T, Riesenberg H, Thomalla J, Hoffmann M, Raab MS, Salwender HJ, Weisel KC; German-Speaking Myeloma Multicenter Group (GMMG) HD7 investigators. Lancet Haematol. 2022 Nov;9(11):e810-e821. doi: 10.1016/S2352-3026(22)00263-0. PMID: 36328040. PubMed

    Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial.

    Dimopoulos MA, Richardson PG, Bahlis NJ, Grosicki S, Cavo M, Beksaç M, Legieć W, Liberati AM, Goldschmidt H, Belch A, Magen H, Larocca A, Laubach JP, Petrucci MT, Reece D, White D, Mateos MV, Špička I, Lazaroiu M, Berdeja J, Kaufman JL, Jou YM, Ganetsky A, Popa McKiver M, Lonial S, Weisel K; ELOQUENT-1 investigators. Lancet Haematol. 2022 Jun;9(6):e403-e414. doi: 10.1016/S2352-3026(22)00103-X. Epub 2022 May 9. PMID: 35550060. PubMed

    Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

    Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631. PMID: 34192431. PubMed

    Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study.

    Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, Dimopoulos M. Lancet Oncol. 2021 Dec 3:S1470-2045(21)00579-9. doi: 10.1016/S1470-2045(21)00579-9. Epub ahead of print. PMID: 34871550. PubMed

    Comparison Between 5-Azacytidine Treatment and Allogeneic Stem-Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability (VidazaAllo Study).

    Kröger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, Stadler M, Kobbe G, Wulf G, Bug G, Schäfer-Eckart K, Scheid C, Nolte F, Krönke J, Stelljes M, Beelen D, Heinzelmann M, Haase D, Buchner H, Bleckert G, Giagounidis A, Platzbecker U. J Clin Oncol. 2021 Oct 20;39(30):3318-3327. doi: 10.1200/JCO.20.02724. Epub 2021 Jul 20. PMID: 34283629. PubMed

    Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial.

    Thierry Facon, Shaji K Kumar, Torben Plesner, Robert Z Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O’Dwyer, Aurore Perrot, Christopher P Venner, Katja Weisel, Joseph R Mace, Noopur Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Tahamtan Ahmadi, Jianping Wang, Rian Van Rampelbergh, Clarissa M Uhlar, Brenda Tromp, Maria Delioukina, Jessica Vermeulen, Saad Z Usmani. Lancet Oncol 2021 Published Online October 13, 2021 https://doi.org/10.1016/ S1470-2045(21)00466-6. PubMed

    Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

    Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. N Engl J Med. 2021 Jul 1;385(1):46-58. doi: 10.1056/NEJMoa2028631. PMID: 34192431. PubMed

    Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group.

    Moreau P, Kumar SK, San Miguel J, Davies F, Zamagni E, Bahlis N, Ludwig H, Mikhael J, Terpos E, Schjesvold F, Martin T, Yong K, Durie BGM, Facon T, Jurczyszyn A, Sidana S, Raje N, van de Donk N, Lonial S, Cavo M, Kristinsson SY, Lentzsch S, Hajek R, Anderson KC, João C, Einsele H, Sonneveld P, Engelhardt M, Fonseca R, Vangsted A, Weisel K, Baz R, Hungria V, Berdeja JG, Leal da Costa F, Maiolino A, Waage A, Vesole DH, Ocio EM, Quach H, Driessen C, Bladé J, Leleu X, Riva E, Bergsagel PL, Hou J, Chng WJ, Mellqvist UH, Dytfeld D, Harousseau JL, Goldschmidt H, Laubach J, Munshi NC, Gay F, Beksac M, Costa LJ, Kaiser M, Hari P, Boccadoro M, Usmani SZ, Zweegman S, Holstein S, Sezer O, Harrison S, Nahi H, Cook G, Mateos MV, Rajkumar SV, Dimopoulos MA, Richardson PG. Lancet Oncol. 2021 Mar;22(3):e105-e118. doi: 10.1016/S1470-2045(20)30756-7, PubMed

    Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

    Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. N Engl J Med. 2021 Feb 25;384(8):705-716. doi: 10.1056/NEJMoa202485, PubMed

    Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR.

    Avet-Loiseau H, San-Miguel J, Casneuf T, Iida S, Lonial S, Usmani SZ, Spencer A, Moreau P, Plesner T, Weisel K, Ukropec J, Chiu C, Trivedi S, Amin H, Krevvata M, Ramaswami P, Qin X, Qi M, Sun S, Qi M, Kobos R, Bahlis NJ. J Clin Oncol. 2021 Jan 29:JCO2001814. doi: 10.1200/JCO.20.01814. Online ahead of print. PMID: 3351303, PubMed

    Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial.

    Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, Hulin C, Orlowski RZ, Nahi H, Mollee P, Ramasamy K, Roussel M, Jaccard A, Delforge M, Karlin L, Arnulf B, Chari A, He J, Ho KF, Van Rampelbergh R, Uhlar CM, Wang J, Kobos R, Gries KS, Fastenau J, Weisel K. J Clin Oncol. 2020 Dec 16:JCO2001370. Online ahead of print. PubMed

    Clinical Features Associated with COVID-19 Outcome in MM: First Results from International Myeloma Society Dataset

    Chari A, Samur MK, Martinez-Lopez J, Cook G, Biran N, Yong KL, Tietsche de Moraes Hungria V, Engelhardt M, Gay F, Garcia-Feria A, Oliva S, Oostvogels R, Gozzetti A, Rosenbaum CA, Kumar SK, Stadtmauer E, Einsele H, Beksac M, Weisel KC, Anderson KC, Mateos M-V, Moreau P, San Miguel J, Munshi NC, Avet-Loiseau H, Blood 2020 Nov 6; blood.2020008150., PubMed

    Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial.

    Knörr F, Brugières L, Pillon M, Zimmermann M, Ruf S, Attarbaschi A, Mellgren K, Burke GAA, Uyttebroeck A, Wróbel G, Beishuizen A, Aladjidi N, Reiter A, Woessmann W; European Inter-Group for Childhood Non-Hodgkin Lymphoma. J Clin Oncol. 2020 Dec 1;38(34):3999-4009. Epub 2020 Jul 30., PubMed

    Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.

    Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Yang H, Klippel Z, Zahlten-Kumeli A, Usmani SZ., Lancet. 2020 Jul 18;396(10245):186-197., PubMed

    In this large phase III trial, the addition of the monolonal antibody daratumumab to carfilzomib and dexamethasone lead to a significant benefit in response and PFS compared to carfilzomib and dexamethasone in 1.-3. Relapse of multiple myeloma and so set a new standard of care in this indication.

    Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN).

    Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, Schmid C, Crysandt M, Eßeling E, Wolf D, Wang Y, Böhm A, Thiede C, Haferlach T, Michel C, Bethge W, Wündisch T, Brandts C, Harnisch S, Wittenberg M, Hoeffkes HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK., J Clin Oncol. 2020 Jul 16:JCO1903345., PubMed

    In this randomized, phase II trial patients with FLT3-ITD-positive AML in complete hematologic remission after HCT were randomly assigned to receive sorafenib or placebo maintenance treatment. It was shown, that sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD-positive AML.

    Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study.

    Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD., Lancet Oncol. 2020 Feb;21(2):207-221., PubMed

    Belantamab mafodotin is the first anti-BCMA immunoconjugate showing marked efficacy in refractory multiple myeloma. Results of this phase II pivotal trial will lead to approval in this indication.

    Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study.

    Schlenk RF, Paschka P, Krzykalla J, Weber D, Kapp-Schwoerer S, Gaidzik VI, Leis C, Fiedler W, Kindler T, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Horst HA, Koller E, Wulf G, Schleicher J, Bentz M, Greil R, Hertenstein B, Krauter J, Martens U, Nachbaur D, Abu Samra M, Girschikofsky M, Basara N, Benner A, Thol F, Heuser M, Ganser A, Döhner K, Döhner H., J Clin Oncol. 2020 Feb 20;38(6):623-632., PubMed

    This randomized phase III study showed a clear increase in CR rate and EFS by addition of Gemtuzumab Ozogamicin to standard chemotherapy in a molecularly defined subgroup of AML patients.

    Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.

    Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance., Lancet. 2019 Dec 21;394(10216):2271-2281., PubMed

    The FLYER trial established in a non-inferiority setting the treatment of 4 cycles R-CHOP in patients with stage I-II disease and favorable prognosis with a comparable outcome to the 6 cycle treatment with significant reduction of overall toxicity.

    Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.

    Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, Moreau P, Dingli D, Cole C, Lonial S, Dimopoulos M, Stewart AK, Richter J, Vij R, Tuchman S, Raab MS, Weisel KC, Delforge M, Cornell RF, Kaminetzky D, Hoffman JE, Costa LJ, Parker TL, Levy M, Schreder M, Meuleman N, Frenzel L, Mohty M, Choquet S, Schiller G, Comenzo RL, Engelhardt M, Illmer T, Vlummens P, Doyen C, Facon T, Karlin L, Perrot A, Podar K, Kauffman MG, Shacham S, Li L, Tang S, Picklesimer C, Saint-Martin JR, Crochiere M, Chang H, Parekh S, Landesman Y, Shah J, Richardson PG, Jagannath S., N Engl J Med. 2019 Aug 22;381(8):727-738., PubMed

    In this pivotal trial for highly refractory multiple myeloma, treatment with Selinexor and dexamethasone was established as a new standard of care.

    Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial.

    Richardson PG, Oriol A, Beksac M, Liberati AM, Galli M, Schjesvold F, Lindsay J, Weisel K, White D, Facon T, San Miguel J, Sunami K, O'Gorman P, Sonneveld P, Robak P, Semochkin S, Schey S, Yu X, Doerr T, Bensmaine A, Biyukov T, Peluso T, Zaki M, Anderson K, Dimopoulos M; OPTIMISMM trial investigators., Lancet Oncol. 2019 Jun;20(6):781-794., PubMed

    After showing a significant benefit in response and PFS compared to bortezomib and dexamethasone, the triple combination treatment of pomalidomide, bortezomib and dexamethasone was established as a new standard of care for patients with 1.-3. Relapse of multiple myeloma after treatment with lenalidomide.

    Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.

    Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ., J Clin Oncol. 2019 May 20;37(15):1277-1284., PubMed

    Although venetoclax had been approved by the FDA in combination with low dose Ara-C due to our preceding phase I/II study, this randomized phase III definitely proved the advantage of addition of venetoclax to low doses ARA-C in elderly AML patients.

    Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma.

    Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ; MAIA Trial Investigators., N Engl J Med. 2019 May 30;380(22):2104-2115., PubMed

    This large phase III trial established with the combination treatment of the monoclonal Antibody Daratumumab to the standard of care regimen of lenalidomide and dexamethasone an new standard of care for first-line treatment of non-transplant eligible patients with multiple myeloma after showing significant benefit in response and PFS compared to lenalidomide and dexamethasone.

    Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation.

    Frick M, Chan W, Arends CM, Hablesreiter R, Halik A, Heuser M, Michonneau D, Blau O, Hoyer K, Christen F, Galan-Sousa J, Noerenberg D, Wais V, Stadler M, Yoshida K, Schetelig J, Schuler E, Thol F, Clappier E, Christopeit M,Ayuk F, Bornhäuser M, Blau IW, Ogawa S, Zemojtel T, Gerbitz A, Wagner EM, Spriewald BM, Schrezenmeier H, Kuchenbauer F, Kobbe G, Wiesneth M, Koldehoff M, Socié G, Kroeger N, Bullinger L, Thiede C, Damm F., J Clin Oncol. 2019 Feb 10;37(5):375-385., PubMed

    In patients with AML who underwent allogeneic stem cell transplantation, clonal donor hematopoiesis of unknown significance significantly influences relapse and GvHD risk.

    Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M., Leukemia. 2019 Feb;33(2):379-389., PubMed

    This is the only randomized study of glasdegib in AML. Since a clear survival advantage for the combination low dose Ara-C (LDAC) plus glasdegib vs. LDAC plus placebo was demonstrated, glasdegib was approved by the FDA.

    PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group.

    Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, Zijlstra JM, Markova J, Meissner J, Feuring-Buske M, Hüttmann A, Dierlamm J, Soekler M, Beck HJ, Willenbacher W, Ludwig WD, Pabst T, Topp MS, Hitz F, Bentz M, Keller UB, Kühnhardt D, Ostermann H, Schmitz N, Hertenstein B, Aulitzky W, Maschmeyer G, Vieler T, Eich H, Baues C, Stein H, Fuchs M, Kuhnert G, Diehl V, Dietlein M, Engert A., Lancet. 2018 Dec 23;390(10114):2790-2802., PubMed

    This German multicenter trial established the PET-guided treatment in advanced stage Hodgkin’s disease allowing treatment shortening in PET negative patients when evaluated after two treatment cycles.

  • Outcome of first-line treatment with pembrolizumab according to KRAS/TP53 mutational status for non-squamous PD-L1 high (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer (nNGM).

    Bischoff P, Reck M, Overbeck T, Christopoulos P, Rittmeyer A, Lüders H, Kollmeier J, Kulhavy J, Kemper M, Reinmuth N, Röper J, Janning M, Sommer L, Aguinarte L, Koch M, Wiesweg M, Wesseler C, Waller CF, Kauffmann-Guerrero D, Stenzinger A, Stephan-Falkenau S, Trautmann M, Lassmann S, Tiemann M, Klauschen F, Sebastian M, Griesinger F, Wolf J, Loges S, Frost N; National Network Genomic Medicine Lung Cancer (nNGM) collaborator group. J Thorac Oncol. 2023 Dec 12:S1556-0864(23)02423-1. doi: 10.1016/j.jtho.2023.12.015. Epub ahead of print. PMID: 38096950. PubMed

    Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.

    Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20. PMID: 37861218. PubMed

    Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

    Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. N Engl J Med. 2023 Nov 2;389(18):1672-1684. doi: 10.1056/NEJMoa2304875. Epub 2023 Oct 23. PMID: 37870974. PubMed

    Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial.

    Cho BC, Lee JS, Wu YL, Cicin I, Dols MC, Ahn MJ, Cuppens K, Veillon R, Nadal E, Dias JM, Martin C, Reck M, Garon EB, Felip E, Paz-Ares L, Mornex F, Vokes EE, Adjei AA, Robinson C, Sato M, Vugmeyster Y, Machl A, Audhuy F, Chaudhary S, Barlesi F. J Thorac Oncol. 2023 Aug 18:S1556-0864(23)00738-4. doi: 10.1016/j.jtho.2023.08.018. Epub ahead of print. PMID: 37597750. PubMed

    Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.

    Nakamura Y, Mizuno N, Sunakawa Y, Canon JL, Galsky MD, Hamilton E, Hayashi H, Jerusalem G, Kim ST, Lee KW, Kankeu Fonkoua LA, Monk BJ, Nguyen D, Oh DY, Okines A, O'Malley DM, Pohlmann P, Reck M, Shin SJ, Sudo K, Takahashi S, Van Marcke C, Yu EY, Groisberg R, Ramos J, Tan S, Stinchcombe TE, Bekaii-Saab T. J Clin Oncol. 2023 Sep 26:JCO2300606. doi: 10.1200/JCO.23.00606. Epub ahead of print. PMID: 37751561. PubMed

    First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.

    Lee SM, Schulz C, Prabhash K, Kowalski D, Szczesna A, Han B, Rittmeyer A, Talbot T, Vicente D, Califano R, Cortinovis D, Le AT, Huang D, Liu G, Cappuzzo F, Reyes Contreras J, Reck M, Palmero R, Mak MP, Hu Y, Morris S, Höglander E, Connors M, Biggane AM, Vollan HK, Peters S. Lancet. 2023 Aug 5;402(10400):451-463. doi: 10.1016/S0140-6736(23)00774-2. Epub 2023 Jul 6. Erratum in: Lancet. 2023 Aug 5;402(10400):450. PMID: 37423228. PubMed

    Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1.

    Reck M, Ciuleanu TE, Lee JS, Schenker M, Zurawski B, Kim SW, Mahave M, Alexandru A, Peters S, Pluzanski A, Caro RB, Linardou H, Burgers JA, Nishio M, Martinez-Marti A, Azuma K, Axelrod R, Paz-Ares LG, Ramalingam SS, Borghaei H, O'Byrne KJ, Li L, Bushong J, Gupta RG, Grootendorst DJ, Eccles LJ, Brahmer JR. J Thorac Oncol. 2023 Aug;18(8):1055-1069. doi: 10.1016/j.jtho.2023.04.021. Epub 2023 May 3. PMID: 37146754. PubMed

    Comparative evaluation of PD-L1 expression in cytology imprints, circulating tumour cells and tumour tissue in non-small cell lung cancer patients.

    Abdo M, Belloum Y, Heigener D, Welker L, von Weihe S, Schmidt M, Heuer-Olewinski N, Watermann I, Szewczyk M, Kropidlowski J, Pereira-Veiga T, Elmas H, Perner S, Steurer S, Wikman H, Pantel K, Reck M. Mol Oncol. 2023 Mar 9. doi: 10.1002/1878-0261.13415. Epub ahead of print. PMID: 36892210. PubMed

    First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes.

    Reck M, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, Richardet E, Bennouna J, Felip E, Juan-Vidal O, Alexandru A, Cheng Y, Sakai H, Paz-Ares L, Lu S, John T, Sun X, Moisei A, Taylor F, Lawrance R, Zhang X, Sylvester J, Yuan Y, Blum SI, Penrod JR, Carbone DP. Eur J Cancer. 2023 Apr;183:174-187. doi: 10.1016/j.ejca.2023.01.015. Epub 2023 Jan 28. PMID: 36871487. PubMed

    Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.

    Socinski MA, Jotte RM, Cappuzzo F, Nishio M, Mok TSK, Reck M, Finley GG, Kaul MD, Yu W, Paranthaman N, Bara I, West HJ. JAMA Oncol. 2023 Feb 16:e227711. doi: 10.1001/jamaoncol.2022.7711. Epub ahead of print. PMID: 36795388; PMCID: PMC9936386. PubMed

    Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study.

    Garassino MC, Gadgeel S, Speranza G, Felip E, Esteban E, Dómine M, Hochmair MJ, Powell SF, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Kurata T, Gray JE, Schwarzenberger P, Jensen E, Pietanza MC, Rodríguez-Abreu D. J Clin Oncol. 2023 Apr 10;41(11):1992-1998. doi: 10.1200/JCO.22.01989. Epub 2023 Feb 21. PMID: 36809080; PMCID: PMC10082311. PubMed

    Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227.

    Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, Audigier-Valette C, Lupinacci L, Sangha R, Pluzanski A, Burgers J, Mahave M, Ahmed S, Schoenfeld AJ, Paz-Ares LG, Reck M, Borghaei H, O'Byrne KJ, Gupta RG, Bushong J, Li L, Blum SI, Eccles LJ, Ramalingam SS. J Clin Oncol. 2023 Feb 20;41(6):1200-1212. doi: 10.1200/JCO.22.01503. Epub 2022 Oct 12. PMID: 36223558; PMCID: PMC9937094. PubMed

    Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817.

    Paz-Ares LG, Ciuleanu TE, Pluzanski A, Lee JS, Gainor JF, Otterson GA, Audigier-Valette C, Ready N, Schenker M, Linardou H, Caro RB, Provencio M, Zurawski B, Lee KH, Kim SW, Caserta C, Ramalingam SS, Spigel DR, Brahmer JR, Reck M, O'Byrne KJ, Girard N, Popat S, Peters S, Memaj A, Nathan F, Aanur N, Borghaei H. J Thorac Oncol. 2022 Aug 30:S1556-0864(22)01556-8. doi: 10.1016/j.jtho.2022.08.014. Epub ahead of print. PMID: 36049658. PubMed

    Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM).

    Janning M, Süptitz J, Albers-Leischner C, Delpy P, Tufman A, Velthaus-Rusik JL, Reck M, Jung A, Kauffmann-Guerrero D, Bonzheim I, Brändlein S, Hummel HD, Wiesweg M, Schildhaus HU, Stratmann JA, Sebastian M, Alt J, Buth J, Esposito I, Berger J, Tögel L, Saalfeld FC, Wermke M, Merkelbach-Bruse S, Hillmer AM, Klauschen F, Bokemeyer C, Buettner R, Wolf J, Loges S; National Network Genomic Medicine Lung Cancer (nNGM). Ann Oncol. 2022 Jun;33(6):602-615. doi: 10.1016/j.annonc.2022.02.225. Epub 2022 Mar 6. PMID: 35263633. PubMed

    Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

    Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum in: J Clin Oncol. 2022 Jun 10;40(17):1965. PMID: 35108059; PMCID: PMC9015199. PubMed

    Analysis of Outcomes With Addition of Immunotherapy to Chemoradiation Therapy for Non-Small Cell Lung Cancer-Reply.

    Jabbour SK, Keller SM, Reck M. JAMA Oncol. 2022 Jan 1;8(1):168-169. doi: 10.1001/jamaoncol.2021.5611. PMID: 34734971. PubMed

    Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

    Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. J Clin Oncol. 2022 Feb 2:JCO2101308. doi: 10.1200/JCO.21.01308. Epub ahead of print. PMID: 35108059. PubMed

    First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial.

    Paz-Ares LG, Ramalingam SS, Ciuleanu TE, Lee JS, Urban L, Caro RB, Park K, Sakai H, Ohe Y, Nishio M, Audigier-Valette C, Burgers JA, Pluzanski A, Sangha R, Gallardo C, Takeda M, Linardou H, Lupinacci L, Lee KH, Caserta C, Provencio M, Carcereny E, Otterson GA, Schenker M, Zurawski B, Alexandru A, Vergnenegre A, Raimbourg J, Feeney K, Kim SW, Borghaei H, O'Byrne KJ, Hellmann MD, Memaj A, Nathan FE, Bushong J, Tran P, Brahmer JR, Reck M. J Thorac Oncol. 2022 Feb;17(2):289-308. doi: 10.1016/j.jtho.2021.09.010. Epub 2021 Oct 12. PMID: 34648948. PubMed

    Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV.

    Brueckl WM, Reck M, Rittmeyer A, Kollmeier J, Wesseler C, Wiest GH, Christopoulos P, Stenzinger A, Tufman A, Hoffknecht P, Ulm B, Reich F, Ficker JH, Laack E. Transl Lung Cancer Res. 2021 Jul;10(7):3093-3105. doi: 10.21037/tlcr-21-197. PMID: 34430350; PMCID: PMC8350088. PubMed

    Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50.

    Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. J Clin Oncol. 2021 Apr 19:JCO2100174. doi: 10.1200/JCO.21.00174. Epub ahead of print. PMID: 33872070. PubMed

    Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial.

    Jabbour SK, Lee KH, Frost N, Breder V, Kowalski DM, Pollock T, Levchenko E, Reguart N, Martinez-Marti A, Houghton B, Paoli JB, Safina S, Park K, Komiya T, Sanford A, Boolell V, Liu H, Samkari A, Keller SM, Reck M. JAMA Oncol. 2021 Jun 4. doi: 10.1001/jamaoncol.2021.2301. Epub ahead of print. PMID: 34086039. PubMed

    Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study.

    Boyer M, Şendur MAN, Rodríguez-Abreu D, Park K, Lee DH, Çiçin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. J Clin Oncol. 2021 Jan 29:JCO2003579. doi: 10.1200/JCO.20.03579. Epub ahead of print. PMID: 33513313., PubMed

    Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell LungCancer.

    Reck M, Wehler T, Orlandi F, Nogami N, Barone C, Moro-Sibilot D, Shtivelband M, González Larriba JL, Rothenstein J, Früh M, Yu W, Deng Y, Coleman S, Shankar G, Patel H, Kelsch C, Lee A, Piault E, Socinski MA., J Clin Oncol. 2020 Aug 1;38(22):2530-2542., PubMed

    Updated analysis of the efficacy data, extended and updated safety analysis on induction and maintenance treatment as well as Quality of Life analysis of the IMpower 150 trial. No relevant worsening of Symptom and Quality of Life parameter during treatment were reported and in particular no impact by the addition of bevacizumab to the combination of atezolizumab and chemotherapy. No new safety signals were reported.

    Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell LungCancer.

    Gadgeel S, Rodríguez-Abreu D, Speranza G, Esteban E, Felip E, Dómine M, Hui R, Hochmair MJ, Clingan P, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Garon EB, Novello S, Rubio-Viqueira B, Boyer M, Kurata T, Gray JE, Yang J, Bas T, Pietanza MC, Garassino MC., J Clin Oncol. 2020 May 10;38(14):1505-1517., PubMed

    Efficacy of the combination Carboplatin/Pemetrexed/Pembrolizumab was confirmed in this updated analysis. No new safety signals were reported with longer follow up.

    Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lungcancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

    Garassino MC, Gadgeel S, Esteban E, Felip E, Speranza G, Domine M, Hochmair MJ, Powell S, Cheng SY, Bischoff HG, Peled N, Reck M, Hui R, Garon EB, Boyer M, Wei Z, Burke T, Pietanza MC, Rodríguez-Abreu D.,Lancet Oncol. 2020 Mar;21(3):387-397., PubMed

    No Impact on Quality of Life and Symptom scores by the addition of pembrolizumab to carboplatin/pembrolizumab was observed, in some Quality of Life and Symptom categories patient reported better outcomes for this combination.

    Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lungcancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators., Lancet Oncol. 2019 Dec;20(12):1655-1669., PubMed

    Combination of ramucirumab and erlotinib compared to erlotinib and placebo demonstrated a significant improvement of PFS and an improvement of DOR with comparable response rates. No new safety signals were observed.

    Nivolumab plus Ipilimumab in Advanced Non-Small-Cell LungCancer.

    Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS., N Engl J Med. 2019 Nov 21;381(21):2020-2031., PubMed

    In this second analysis a significant prolongation of survival was observed for the combination of nivolumab and ipilimumab compared to platinum based chemotherapy in untreated patients with advanced non oncogenic addicted PDL expressing NSCLC. Consistent efficacy was observed in PD-L 1 negative patients. Efficacy was independent from TMB.

    First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell LungCancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers.

    Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, Brahmer J, Rabinowitz I, Reddy PS, Chesney J, Orcutt J, Spigel DR, Reck M, O'Byrne KJ, Paz-Ares L, Hu W, Zerba K, Li X, Lestini B, Geese WJ, Szustakowski JD, Green G, Chang H, Ramalingam SS., J Clin Oncol. 2019 Apr 20;37(12):992-1000., PubMed

    Feasibility and tolerability of nivolumab and low dose ipilimumab in NSCLC was confirmed. TMB threshold of =/> 10 mut/MB was determined as threshold for efficacy assessed by response and PFS.

    Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell LungCancer With PD-L1 Tumor Proportion Score of 50% or Greater.

    Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR., J Clin Oncol. 2019 Mar 1;37(7):537-546., PubMed

    Consistent survival benefit for pembrolizumab monotherapy compared to platinum based chemotherapy in untreated patients with oncogenic wild type high PD-L1 expressing (=/> 50% TPS score) was confirmed with longer follow-up. No relevant safety signals were observed.

    Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.

    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Özgüroğlu M; PACIFIC Investigators., N Engl J Med. 2018 Dec 13;379(24):2342-2350., PubMed

    Besides PFS also the second coprimary endpoint survival was significantly prolonged by a consolidation treatment with durvalumab in patients with locally advanced NSCLC after simultaneous chemoradiotherapy.

    First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell LungCancer.

    Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group.,N Engl J Med. 2018 Dec 6;379(23):2220-2229., PubMed

    Combination of atezolizumab with carboplatin and etoposide led to a significant improvement of PFS and survival in untreated patients with metastatic SCLC compared to chemotherapy alone.

    Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC.

    Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Kelsch C, Lee A, Coleman S, Deng Y, Shen Y, Kowanetz M, Lopez-Chavez A, Sandler A, Reck M; IMpower150 Study Group., N Engl J Med. 2018 Jun 14;378(24):2288-2301., PubMed

    Combination of atezolizumab, bevacizumab, carboplatin and paclitaxel led to a significant improvement of PFS and OS in untreated population of patients with advanced non squamous NSCLC. Safety results were as expected and enhanced efficacy was seen in patients with liver metastases.

    Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell LungCancer.

    Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators., N Engl J Med. 2018 May 31;378(22):2078-2092., PubMed

    Combination of pembrolizumab with carboplatin and pemetrexed led to a significant improvement of PFS and OS in untreated oncogenic wild type patients with advanced non squamous NSCLC. Efficacy was seen across all PD-L1 expression levels and safety signals were as expected.

    Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden.

    Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L., N Engl J Med. 2018 May 31;378(22):2093-2104., PubMed

    Combination of nivolumab and ipilimumab led to a significant improvement of PFS in patients with untreated TMB high NSCLC independent from PD-L1 expression compared to platinum based chemotherapy. In addition DOR was in favor of this combination and no new safety signals were observed.

    Molecular Testing Guideline for the Selection of Patients With LungCancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of LungCancer/Association for Molecular Pathology Clinical Practice Guideline Update.

    Kalemkerian GP, Narula N, Kennedy EB, Biermann WA, Donington J, Leighl NB, Lew M, Pantelas J, Ramalingam SS, Reck M, Saqi A, Simoff M, Singh N, Sundaram B., J Clin Oncol. 2018 Mar 20;36(9):911-919., PubMed

    Update of the joint molecular testing guidelines of ASCO, CAP, ASCO and the Association for Molecular Pathology for patients with NSCLC implementing new and larger testing panels including testing for ROS-1, RET, ERB2, KRAS and MET.

  • Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations.

    Menzer C, Menzies AM, Carlino MS, Reijers I, Groen EJ, Eigentler T, de Groot JWB, van der Veldt AAM, Johnson DB, Meiss F, Schlaak M, Schilling B, Westgeest HM, Gutzmer R, Pföhler C, Meier F, Zimmer L, Suijkerbuijk KPM, Haalck T, Thoms KM, Herbschleb K, Leichsenring J, Menzer A, Kopp-Schneider A, Long GV, Kefford R, Enk A, Blank CU, Hassel JC., J Clin Oncol. 2019 Nov 20;37(33):3142-3151., PubMed

    This paper describes respoonse and efficacy of targeted therapy in unusual non-V600 BRAF mutations in melanoma.

  • Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials.

    Raetz EA, Rebora P, Conter V, Schrappe M, Devidas M, Escherich G, Imai C, De Moerloose B, Schmiegelow K, Burns MA, Elitzur S, Pieters R, Attarbaschi A, Yeoh A, Pui CH, Stary J, Cario G, Bodmer N, Moorman AV, Buldini B, Vora A, Valsecchi MG. Clin Oncol. 2023 Nov 10;41(32):5025-5034. doi: 10.1200/JCO.23.00088. Epub 2023 Jul 24. PMID: 37487146; PMCID: PMC10642910. PubMed

    Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma.

    Hargrave DR, Terashima K, Hara J, Kordes UR, Upadhyaya SA, Sahm F, Bouffet E, Packer RJ, Witt O, Sandalic L, Kieloch A, Russo M, Cohen KJ; all the Investigators involved in the high-grade glioma cohort. J Clin Oncol. 2023 Aug 29:JCO2300558. doi: 10.1200/JCO.23.00558. Epub ahead of print. PMID: 37643378. PubMed

    Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia.

    van der Sluis IM, de Lorenzo P, Kotecha RS, Attarbaschi A, Escherich G, Nysom K, Stary J, Ferster A, Brethon B, Locatelli F, Schrappe M, Scholte-van Houtem PE, Valsecchi MG, Pieters R. N Engl J Med. 2023 Apr 27;388(17):1572-1581. doi: 10.1056/NEJMoa2214171. PMID: 37099340. PubMed

    Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

    Erker C, Mynarek M, Bailey S, Mazewski CM, Baroni L, Massimino M, Hukin J, Aguilera D, Cappellano AM, Ramaswamy V, Lassaletta A, Perreault S, Kline CN, Rajagopal R, Michaiel G, Zapotocky M, Santa-Maria Lopez V, La Madrid AM, Cacciotti C, Sandler ES, Hoffman LM, Klawinski D, Khan S, Salloum R, Hoppmann AL, Larouche V, Dorris K, Toledano H, Gilheeney SW, Abdelbaki MS, Wilson B, Tsang DS, Knipstein J, Oren MY, Shah S, Murray JC, Ginn KF, Wang ZJ, Fleischhack G, Obrecht D, Tonn S, Harrod VL, Matheson K, Crooks B, Strother DR, Cohen KJ, Hansford JR, Mueller S, Margol A, Gajjar A, Dhall G, Finlay JL, Northcott PA, Rutkowski S, Clifford SC, Robinson G, Bouffet E, Lafay-Cousin L. J Clin Oncol. 2022 Dec 22:JCO2102968. doi: 10.1200/JCO.21.02968. Epub ahead of print. PMID: 36548930. PubMed

    High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma.

    Koch R, Gelderblom H, Haveman L, Brichard B, Jürgens H, Cyprova S, van den Berg H, Hassenpflug W, Raciborska A, Ek T, Baumhoer D, Egerer G, Eich HT, Renard M, Hauser P, Burdach S, Bovee J, Bonar F, Reichardt P, Kruseova J, Hardes J, Kühne T, Kessler T, Collaud S, Bernkopf M, Butterfaß-Bahloul T, Dhooge C, Bauer S, Kiss J, Paulussen M, Hong A, Ranft A, Timmermann B, Rascon J, Vieth V, Kanerva J, Faldum A, Metzler M, Hartmann W, Hjorth L, Bhadri V, Dirksen U. J Clin Oncol. 2022 Jul 20;40(21):2307-2320. doi: 10.1200/JCO.21.01942. Epub 2022 Apr 15. PMID: 35427190. PubMed

    Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

    Durno C, Ercan AB, Bianchi V, Edwards M, Aronson M, Galati M, Atenafu EG, Abebe-Campino G, Al-Battashi A, Alharbi M, Azad VF, Baris HN, Basel D, Bedgood R, Bendel A, Ben-Shachar S, Blumenthal DT, Blundell M, Bornhorst M, Bronsema A, Cairney E, Rhode S, Caspi S, Chamdin A, Chiaravalli S, Constantini S, Crooks B, Das A, Dvir R, Farah R, Foulkes WD, Frenkel Z, Gallinger B, Gardner S, Gass D, Ghalibafian M, Gilpin C, Goldberg Y, Goudie C, Hamid SA, Hampel H, Hansford JR, Harlos C, Hijiya N, Hsu S, Kamihara J, Kebudi R, Knipstein J, Koschmann C, Kratz C, Larouche V, Lassaletta A, Lindhorst S, Ling SC, Link MP, Loret De Mola R, Luiten R, Lurye M, Maciaszek JL, MagimairajanIssai V, Maher OM, Massimino M, McGee RB, Mushtaq N, Mason G, Newmark M, Nicholas G, Nichols KE, Nicolaides T, Opocher E, Osborn M, Oshrine B, Pearlman R, Pettee D, Rapp J, Rashid M, Reddy A, Reichman L, Remke M, Robbins G, Roy S, Sabel M, Samuel D, Scheers I, Schneider KW, Sen S, Stearns D, Sumerauer D, Swallow C, Taylor L, Thomas G, Toledano H, Tomboc P, Van Damme A, Winer I, Yalon M, Yen LY, Zapotocky M, Zelcer S, Ziegler DS, Zimmermann S, Hawkins C, Malkin D, Bouffet E, Villani A, Tabori U. J Clin Oncol. 2021 May 4:JCO2002636. doi: 10.1200/JCO.20.02636. Online ahead of print. PMID: 33945292 PubMed

    Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma.

    Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P Jr, Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V, Northcott PA. J Clin Oncol. 2021 Mar 1;39(7):807-821. doi: 10.1200/JCO.20.01359. Epub 2021 Jan 27. PMID: 33502920, PubMed

    Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol.

    Stutterheim J, van der Sluis IM, de Lorenzo P, Alten J, Ancliffe P, Attarbaschi A, Brethon B, Biondi A, Campbell M, Cazzaniga G, Escherich G, Ferster A, Kotecha RS, Lausen B, Li CK, Lo Nigro L, Locatelli F, Marschalek R, Meyer C, Schrappe M, Stary J, Vora A, Zuna J, van der Velden VHJ, Szczepanski T, Valsecchi MG, Pieters R. J Clin Oncol. 2021 Feb 20;39(6):652-662. doi: 10.1200/JCO.20.02333. Epub 2021 Jan 6. PMID: 33405950, PubMed

    Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial.

    Knörr F, Brugières L, Pillon M, Zimmermann M, Ruf S, Attarbaschi A, Mellgren K, Burke GAA, Uyttebroeck A, Wróbel G, Beishuizen A, Aladjidi N, Reiter A, Woessmann W; European Inter-Group for Childhood Non-Hodgkin Lymphoma., J Clin Oncol. 2020 Jul 30:JCO2000157., PubMed

    To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial stratified patients according to the time of relapse and CD3 expression to prospectively test re-induction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy. The results of this study showed, that allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse. Nevertheless, for early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy also achieved cure in patients with late relapse; however, it was again not effective for early relapses.

    Germline GPR161 Mutations Predispose to Pediatric Medulloblastoma.

    Begemann M, Waszak SM, Robinson GW, Jäger N, Sharma T, Knopp C, Kraft F, Moser O, Mynarek M, Guerrini-Rousseau L, Brugieres L, Varlet P, Pietsch T, Bowers DC, Chintagumpala M, Sahm F, Korbel JO, Rutkowski S, Eggermann T, Gajjar A, Northcott P, Elbracht M, Pfister SM, Kontny U, Kurth I., J Clin Oncol. 2020 Jan 1;38(1):43-50., PubMed

    The authors describe a novel brain tumor predisposition syndrome that is caused by germline GPR161 mutations and characterized by MB-SHH in infants.

    Improving Stratification for Children With Late Bone Marrow B-Cell Acute Lymphoblastic Leukemia Relapses With Refined Response Classification and Integration of Genetics.

    Eckert C, Groeneveld-Krentz S, Kirschner-Schwabe R, Hagedorn N, Chen-Santel C, Bader P, Borkhardt A, Cario G, Escherich G, Panzer-Grümayer R, Astrahantseff K, Eggert A, Sramkova L, Attarbaschi A, Bourquin JP, Peters C, Henze G, von Stackelberg A; ALL-REZ BFM Trial Group., J Clin Oncol. 2019 Dec 20;37(36):3493-3506., PubMed

    Minimal residual disease (MRD) helps to accurately assess when children with late bone marrow relapses of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) will benefit from allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The authors presumed that more detailed dissection of MRD response heterogeneity and the specific genetic aberrations could improve current practice. Therefore, MRD was assessed after induction treatment and at different times during relapse treatment until allo-HSCT in 413 patients. The MRD-response was then used for further treatment stratification. Results showed, that after induction treatment, MRD-based treatment stratification resulted in excellent survival in patients with late relapsed BCP-ALL and prognosis could be further improved in very poor responders by intensifying treatment directly after induction. Furthermore, TP53 alterations was identified as a novel genetic high-risk marker in all MRD response groups in late relapsed BCP-ALL. Furthermore the authors proposed to consider early and late non-responders as events in future trials.

    Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study.

    Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, Campbell M, Escherich G, Ferster A, Gardner RA, Kotecha RS, Lausen B, Li CK, Locatelli F, Attarbaschi A, Peters C, Rubnitz JE, Silverman LB, Stary J, Szczepanski T, Vora A, Schrappe M, Valsecchi MG., J Clin Oncol. 2019 Sep 1;37(25):2246-2256., PubMed

    Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. In this study, early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.

    Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group.

    Hoeben BA, Carrie C, Timmermann B, Mandeville HC, Gandola L, Dieckmann K, Ramos Albiac M, Magelssen H, Lassen-Ramshad Y, Ondrová B, Ajithkumar T, Alapetite C, Balgobind BV, Bolle S, Cameron AL, Davila Fajardo R, Dietzsch S, Dumont Lecomte D, van den Heuvel-Eibrink MM, Kortmann RD, Laprie A, Melchior P, Padovani L, Rombi B, Scarzello G, Schwarz R, Seiersen K, Seravalli E, Thorp N, Whitfield GA, Boterberg T, Janssens GO., Lancet Oncol. 2019 Mar;20(3):e155-e166., PubMed

    This is a consensus recommendation of paediatric radiation oncologists from leading centres in 11 European countries based on available information on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimize the risk of long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia.

    Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT/non-SHH medulloblastoma: a retrospective, molecular analysis of the HIT-SIOP PNET 4 trial.

    Goschzik T, Schwalbe EC, Hicks D, Smith A, Zur Muehlen A, Figarella-Branger D, Doz F, Rutkowski S, Lannering B, Pietsch T, Clifford SC., Lancet Oncol. 2018 Dec;19(12):1602-1616., PubMed

    In order to achieve a more risk-adapted and personalized therapeutic approach in the treatment of medulloblastoma, out of the HIT-SIOP PNET 4 trial a whole chromosomal signature was developed that allows the assignment of non-WNT/non-SHH medulloblastoma patients normally classified as standard-risk into favourable-risk and high-risk categories. A subgroup of children was defined according to the chromosomal and molecular signature who should be considered for therapy de-escalation in future biomarker-driven, risk-adapted clinical trials.

    High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008.

    Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Juergens H, Oberlin O; Euro-E.W.I.N.G.99 and EWING-2008 Investigators., J Clin Oncol. 2018 Sep 6;36(31):JCO2018782516., PubMed

    For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. It was shown by this study that, BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.

    Biological material collection to advance translational research and treatment of children with CNS tumours: position paper from the SIOPE Brain Tumour Group.

    Rutkowski S, Modena P, Williamson D, Kerl K, Nysom K, Pizer B, Bartels U, Puget S, Doz F, Michalski A, von Hoff K, Chevignard M, Avula S, Murray MJ, Schönberger S, Czech T, Schouten-van Meeteren AYN, Kordes U, Kramm CM, van Vuurden DG, Hulleman E, Janssens GO, Solanki GA, van Veelen MC, Thomale U, Schuhmann MU, Jones C, Giangaspero F, Figarella-Branger D, Pietsch T, Clifford SC, Pfister SM, Van Gool SW., Lancet Oncol. 2018 Aug;19(8):e419-e428., PubMed

    During the last decade new methods of molecular tumor tissue analysis have been developed in order to improve the identification of high-risk and low-risk diseases and subsequent treatment-stratification. Therefore, retrospective analysis of tumor material according to new methods is a key determinant in this improvement process. However, deficits in organisational structures and interdisciplinary cooperation are impeding the collection of high-quality biomaterial from CNS tumours. Thus, the authors recommend to implement practical, legal, and ethical guidelines for consent, storage, material transfer, biobanking, data sharing, and funding should be established by research consortia and local institutions to allow optimal collection of primary and subsequent tumour tissue, body fluids, and normal tissue. Furthermore, procedures for the collection and storage of biomaterials and related data should be implemented according to the individual and organisational structures of the local institutions.

    Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

    Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S, Grund KB, Brugières L, Jones DTW, Pajtler KW, Morrissy AS, Kool M, Sturm D, Chavez L, Ernst A, Brabetz S, Hain M, Zichner T, Segura-Wang M, Weischenfeldt J, Rausch T, Mardin BR, Zhou X, Baciu C, Lawerenz C, Chan JA, Varlet P, Guerrini-Rousseau L, Fults DW, Grajkowska W, Hauser P, Jabado N, Ra YS, Zitterbart K, Shringarpure SS, De La Vega FM, Bustamante CD, Ng HK, Perry A, MacDonald TJ, Hernáiz Driever P, Bendel AE, Bowers DC, McCowage G, Chintagumpala MM, Cohn R, Hassall T, Fleischhack G, Eggen T, Wesenberg F, Feychting M, Lannering B, Schüz J, Johansen C, Andersen TV, Röösli M, Kuehni CE, Grotzer M, Kjaerheim K, Monoranu CM, Archer TC, Duke E, Pomeroy SL, Shelagh R, Frank S, Sumerauer D, Scheurlen W, Ryzhova MV, Milde T, Kratz CP, Samuel D, Zhang J, Solomon DA, Marra M, Eils R, Bartram CR, von Hoff K, Rutkowski S, Ramaswamy V, Gilbertson RJ, Korshunov A, Taylor MD, Lichter P, Malkin D, Gajjar A, Korbel JO, Pfister SM., Lancet Oncol. 2018 Jun;19(6):785-798., PubMed

    Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not yet been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. The authors aimed to assess and define these genes to provide evidence for future screening guidelines. The analysis of 1022 cases from retrospective and prospective studies let to the conclusion, that genetic counselling and testing should be used as a standard-of-care procedure in patients with MB-WNT and MB-SHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. Criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics are proposed by the authors.

  • Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial.

    Oudard S, Ratta R, Voog E, Barthelemy P, Thiery-Vuillemin A, Bennamoun M, Hasbini A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Lange C, Phan L, Belhouari H, Tran Y, Kotti S, Helissey C. JAMA Oncol. 2023 Dec 1;9(12):1629-1638. doi: 10.1001/jamaoncol.2023.4255. PMID: 37883073; PMCID: PMC10603579. PubMed

    Randomized Phase II Cabazitaxel Dose Individualization and Neutropenia Prevention Trial in Patients with Metastatic Castration-Resistant Prostate Cancer.

    Omlin A, Cathomas R, von Amsberg G, Reuter C, Feyerabend S, Loidl W, Boegemann M, Lorch A, Heidenreich A, Tsaur I, Larcher-Senn J, Buck SAJ, Mathijssen RHJ, Jaehde U, Gillessen S, Joerger M. Clin Cancer Res. 2023 May 15;29(10):1887-1893. doi: 10.1158/1078-0432.CCR-22-3360. PMID: 36917691. PubMed

    Prostate-Specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death.

    Tilki D, Chen MH, Wu J, Huland H, Graefen M, Mohamad O, Cowan JE, Feng FY, Carroll PR, D'Amico AV. J Clin Oncol. 2023 Mar 1:JCO2202489. doi: 10.1200/JCO.22.02489. Epub ahead of print. PMID: 36857638. PubMed

    Cohort Study of Oligorecurrent Prostate Cancer Patients: Oncological Outcomes of Patients Treated with Salvage Lymph Node Dissection via Prostate-specific Membrane Antigen-radioguided Surgery.

    Knipper S, Mehdi Irai M, Simon R, Koehler D, Rauscher I, Eiber M, van Leeuwen FWB, van Leeuwen P, de Barros H, van der Poel H, Budäus L, Steuber T, Graefen M, Tennstedt P, Heck MM, Horn T, Maurer T. Eur Urol. 2023 Jan;83(1):62-69. doi: 10.1016/j.eururo.2022.05.031. Epub 2022 Jun 17. PMID: 35718637. PubMed

    Adjuvant Versus Early Salvage Radiation Therapy After Radical Prostatectomy for pN1 Prostate Cancer and the Risk of Death.

    Tilki D, Chen MH, Wu J, Huland H, Graefen M, D'Amico AV. J Clin Oncol. 2022 Jul 10;40(20):2186-2192. doi: 10.1200/JCO.21.02800. Epub 2022 Mar 15. PMID: 35290082. PubMed

    Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts.

    Kishan AU, Steigler A, Denham JW, Zapatero A, Guerrero A, Joseph D, Maldonado X, Wong JK, Stish BJ, Dess RT, Pilar A, Reddy C, Wedde TB, Lilleby WA, Fiano R, Merrick GS, Stock RG, Demanes DJ, Moran BJ, Tran PT, Martin S, Martinez-Monge R, Krauss DJ, Abu-Isa EI, Pisansky TM, Choo CR, Song DY, Greco S, Deville C, McNutt T, DeWeese TL, Ross AE, Ciezki JP, Tilki D, Karnes RJ, Tosoian JJ, Nickols NG, Bhat P, Shabsovich D, Juarez JE, Jiang T, Ma TM, Xiang M, Philipson R, Chang A, Kupelian PA, Rettig MB, Feng FY, Berlin A, Tward JD, Davis BJ, Reiter RE, Steinberg ML, Elashoff D, Boutros PC, Horwitz EM, Tendulkar RD, Spratt DE, Romero T. JAMA Oncol. 2022 Jan 20:e216871. doi: 10.1001/jamaoncol.2021.6871. Epub ahead of print. PMID: 35050303; PMCID: PMC8778608. PubMed

    Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study.

    Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Lancet Oncol. 2021 Nov;22(11):1541-1559. doi: 10.1016/S1470-2045(21)00402-2. Epub 2021 Sep 30. PMID: 34600602. PubMed

    Adjuvant Versus Early Salvage Radiation Therapy for Men at High Risk for Recurrence Following Radical Prostatectomy for Prostate Cancer and the Risk of Death.

    Tilki D, Chen MH, Wu J, Huland H, Graefen M, Wiegel T, Böhmer D, Mohamad O, Cowan JE, Feng FY, Carroll PR, Trock BJ, Partin AW, D'Amico AV. J Clin Oncol. 2021 Jun 4:JCO2003714. doi: 10.1200/JCO.20.03714. Online ahead of print. PMID: 34086480 PubMed

    Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy.

    Knipper S, Ascalone L, Ziegler B, Hohenhorst JL, Simon R, Berliner C, van Leeuwen FWB, van der Poel H, Giesel F, Graefen M, Eiber M, Heck MM, Horn T, Maurer T. Eur Urol. 2021 Apr;79(4):537-544. doi: 10.1016/j.eururo.2020.11.012. Epub 2020 Dec 11. PMID: 33317857, PubMed

    Timing of radiotherapy after radical prostatectomy.

    Tilki D, D'Amico AV. Lancet. 2020 Oct 31;396(10260):1374-1375. Epub 2020 Sep 28. Lancet., PubMed

    Persistent Prostate-Specific Antigen After Radical Prostatectomy and Its Impact on Oncologic Outcomes.

    Preisser F, Chun FKH, Pompe RS, Heinze A, Salomon G, Graefen M, Huland H, Tilki D., Eur Urol. 2019 Jul;76(1):106-114. doi: 10.1016/j.eururo.2019.01.048. Epub 2019 Feb 14. PMID: 3077203, PubMed

    A persistently increased PSA value after surgery is associated with a higher risk of biochemical relapse (BCR), metastatic disease and overall mortality. Recently published data from Martini Clinic confirmed these findings of earlier clinical trials: Thus, in this single center trial, 8.8% (n=1025) of 11 604 patients were identified with persistent PSA value after radical prostatectomy. Metastasis-free survival rates, OS and CSS rates were 53.0 vs. 93.2% (p < 0.001), 64.7 vs. 81.2% (p < 0.001) and 75.5 vs. 96.2% (p < 0.001) for persistent vs. undetectable PSA 15 years after surgery. Salvage radiotherapy was associated with improved OS (HR: 0.37, p=0.02) and CSS (HR: 0.12, p<0.01). Based on these results salvage radiotherapy is now recommended for patients with persistent PSA with no evidence of metastatic disease in EAU guidelines (EAU guidelines 6.2.6.6. Recommendations for the management of persistent PSA after radical prostatectomy).

    External Validation of the European Association of Urology Biochemical Recurrence Risk Groups to Predict Metastasis and Mortality After Radical Prostatectomy in a European Cohort.

    Tilki D, Preisser F, Graefen M, Huland H, Pompe RS., Eur Urol. 2019 Jun;75(6):896-900. doi: 10.1016/j.eururo.2019.03.016. Epub 2019 Apr 5., PubMed

    In this retrospective analysis of 1125 patients, the European Association of Urology biochemical risk (BCR) stratification was verified. In fact, 5yr. metastatic progression free survival and prostate cancer specific mortality free survival rates were significantly higher in patients with low BCR risk compared to their high-risk counterparts. Consequently, the EAU guidelines now recommend that patients with PSA recurrence assigned to the low risk BSC category can be monitored without immediate intervention (EAU guidelines 6.3.3 Natural History of PSA recurrence and 6.3.9 Guidelines for second-line therapy after treatment with curative intend)

    MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

    Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, Briganti A, Budäus L, Hellawell G, Hindley RG, Roobol MJ, Eggener S, Ghei M, Villers A, Bladou F, Villeirs GM, Virdi J, Boxler S, Robert G, Singh PB, Venderink W, Hadaschik BA, Ruffion A, Hu JC, Margolis D, Crouzet S, Klotz L, Taneja SS, Pinto P, Gill I, Allen C, Giganti F, Freeman A, Morris S, Punwani S, Williams NR, Brew-Graves C, Deeks J, Takwoingi Y, Emberton M, Moore CM; PRECISION Study Group Collaborators. N Engl J Med. 2018 May 10;378(19):1767-1777. doi: 10.1056/NEJMoa1801993. Epub 2018 Mar 18, PubMed

    This randomized controlled trial established MRI guided biopsy in the diagnostic of prostate cancer. In comparison to ultrasound-guided biopsy, the use of risk assessment with MRI before biopsy and MRI-targeted biopsy showed significant superiority in men at clinical risk for prostate cancer who had not undergone biopsy previously.

    Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial

    Azzouzi A-R, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel HG, Stief CG, Rassweiler J, Salomon G, Solsona E, Alcaraz A, Tammela TT, Rosario DJ, Gomez-Veiga F, Ahlgren G, Benzaghou F, Gaillac B, Amzal B, Debruyne FMJ, Fromont G, Gratzke C, Emberton M, PCM301 Study Group, Lancet Oncol. 2017 Feb;18(2):181-191. doi: 10.1016/S1470-2045(16)30661-1., PubMed

    Padeliporfin vascular-targeted photodynamic therapy as a tissue-preserving approach is a safe and effective treatment for low-risk, localised prostate cancer and may defer or avoid radical therapy.

  • High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma.

    Koch R, Gelderblom H, Haveman L, Brichard B, Jürgens H, Cyprova S, van den Berg H, Hassenpflug W, Raciborska A, Ek T, Baumhoer D, Egerer G, Eich HT, Renard M, Hauser P, Burdach S, Bovee J, Bonar F, Reichardt P, Kruseova J, Hardes J, Kühne T, Kessler T, Collaud S, Bernkopf M, Butterfaß-Bahloul T, Dhooge C, Bauer S, Kiss J, Paulussen M, Hong A, Ranft A, Timmermann B, Rascon J, Vieth V, Kanerva J, Faldum A, Metzler M, Hartmann W, Hjorth L, Bhadri V, Dirksen U. J Clin Oncol. 2022 Apr 15:JCO2101942. doi: 10.1200/JCO.21.01942. Epub ahead of print. PMID: 35427190. PubMed

    Efficacy of Pazopanib With or Without Gemcitabine in Patients With Anthracycline- and/or Ifosfamide-Refractory Soft Tissue Sarcoma: Final Results of the PAPAGEMO Phase 2 Randomized Clinical Trial

    Schmoll H-J, Lindner LH, Reichardt P, Heißner K, Kopp H-G, Kessler T, Mayer-Steinacker R, Rüssel J, Egerer G, Crysandt M, Kasper B, Niederwieser D, Kunitz A, Eigendorff E, Petersen I, Steighardt J, Cygon F, Meinert F, Stein A, JAMA Oncol. 2020 Dec 23; e206564., PubMed

    This trial evaluated a new combination approach in advanced and treatment refractory soft tissue sarcoma, which may be beneficial particularly in leiomyosarcoma patients after standard chemotherapy. The combination is well tolerated and improves progression free survival.

    Randomized comparison of pazopanib and doxorubicin as first line treatment in metastatic soft tissue sarcoma patients ≥60 years of age - results of an German intergroup study

    Grünwald V, Karch A, Schuler M, Schöffski P, Kopp H-G, Bauer S, Kasper B, Lindner LH, Chemnitz J-M, Crysandt M, Stein A, Steffen B, Richter S, Egerer G, Ivanyi P, Zimmermann S, Liu X, Kunitz A, J Clin Oncol. 2020 Aug 24; JCO2000714., PubMed

    This randomized German intergroup study showed comparable efficacy for single agent pazopanib or doxorubicin in elderly patients with previously untreated metastatic soft tissue sarcoma and thus established an additional treatment option in this patient group.

  • Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial.

    Guigay J, Aupérin A, Fayette J, Saada-Bouzid E, Lafond C, Taberna M, Geoffrois L, Martin L, Capitain O, Cupissol D, Castanie H, Vansteene D, Schafhausen P, Johnson A, Even C, Sire C, Duplomb S, Evrard C, Delord JP, Laguerre B, Zanetta S, Chevassus-Clément C, Fraslin A, Louat F, Sinigaglia L, Keilholz U, Bourhis J, Mesia R; GORTEC; AIO; TTCC, and UniCancer Head and Neck groups. Lancet Oncol. 2021 Mar 5:S1470-2045(20)30755-5. doi: 10.1016/S1470-2045(20)30755-5. Online ahead of print. PMID: 33684370, PubMed

  • Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

    Maas SLN, Stichel D, Hielscher T, Sievers P, Berghoff AS, Schrimpf D, Sill M, Euskirchen P, Blume C, Patel A, Dogan H, Reuss D, Dohmen H, Stein M, Reinhardt A, Suwala AK, Wefers AK, Baumgarten P, Ricklefs F, Rushing EJ, Bewerunge-Hudler M, Ketter R, Schittenhelm J, Jaunmuktane Z, Leu S, Greenway FEA, Bridges LR, Jones T, Grady C, Serrano J, Golfinos J, Sen C, Mawrin C, Jungk C, Hänggi D, Westphal M, Lamszus K, Etminan N, Jungwirth G, Herold-Mende C, Unterberg A, Harter PN, Wirsching HG, Neidert MC, Ratliff M, Platten M, Snuderl M, Aldape KD, Brandner S, Hench J, Frank S, Pfister SM, Jones DTW, Reifenberger G, Acker T, Wick W, Weller M, Preusser M, von Deimling A, Sahm F; German Consortium on Aggressive Meningiomas (KAM). J Clin Oncol. 2021 Dec 1;39(34):3839-3852. doi: 10.1200/JCO.21.00784. Epub 2021 Oct 7. PMID: 34618539; PMCID: PMC8713596. PubMed

    Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial.

    Wen PY, Stein A, van den Bent M, De Greve J, Wick A, de Vos FYFL, von Bubnoff N, van Linde ME, Lai A, Prager GW, Campone M, Fasolo A, Lopez-Martin JA, Kim TM, Mason WP, Hofheinz RD, Blay JY, Cho DC, Gazzah A, Pouessel D, Yachnin J, Boran A, Burgess P, Ilankumaran P, Gasal E, Subbiah V. Lancet Oncol. 2021 Nov 24:S1470-2045(21)00578-7. doi: 10.1016/S1470-2045(21)00578-7. Epub ahead of print. PMID: 34838156. PubMed

  • Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline.

    Falanga A, Ay C, Di Nisio M, Gerotziafas G, Jara-Palomares L, Langer F, Lecumberri R, Mandala M, Maraveyas A, Pabinger I, Sinn M, Syrigos K, Young A, Jordan K; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Ann Oncol. 2023 Jan 10:S0923-7534(22)04786-X. doi: 10.1016/j.annonc.2022.12.014. Epub ahead of print. PMID: 36638869. PubMed

    ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group.

    Pascual J, Attard G, Bidard FC, Curigliano G, De Mattos-Arruda L, Diehn M, Italiano A, Lindberg J, Merker JD, Montagut C, Normanno N, Pantel K, Pentheroudakis G, Popat S, Reis-Filho JS, Tie J, Seoane J, Tarazona N, Yoshino T, Turner NC. Ann Oncol. 2022 Aug;33(8):750-768. doi: 10.1016/j.annonc.2022.05.520. Epub 2022 Jul 6. PMID: 35809752. PubMed