Das Jahr 2025 war busy. Im Folgenden die wesentlichen Schwerpunkte:

• CUPISCO – Studie: weitere Auswertungen, incl. translationaler Forschungsprojekte:
  • Zielgerichtete Therapie bei primär chemotherapierefraktären Pat.
  • Multiomic Profiling of Patient Derived CUP Tumor Organoid Models
  • Analysis of ctDNA for Molecularly Guidet Treatment And Risk Stratifikation
  • a.
• Neufassung der Onkopedia-Leitlinie, publiziert 09/2025
• Vorbereitung der SaciCUP – Studie: Sacituzumab-Govitecan vs BAT – Best Available Therapy – in Pretreated CUP
• Vorbereitung und Mitgestaltung der weltweit ersten internationalen CUP Conference in Berlin am 16.10.25 im Vorfeld des ESMO-Kongresses in Berlin
• Gewinnung neuer aktiver YMO für die Arbeitsgruppe aus Mainz
• Phophoproteomics zur besseren molekularen Profilierung des CUP-Syndroms
• Vorbereitung CUP – Session: Für den Deutschen Krebskongress 2026 hat unsere AG eine Fortbildungssitzung gestaltet.
• Zwei junge Onkologen – YMO – haben am Mentoring-Projekt der AIO beim ESMO-Kongress 2025 mit Erfolg und Gewinn teilgenommen

Bochtler T, Christopoulos P, Schlamp K, Winkler F, Krämer A. Management of a Pregnant ALK-Positive Lung Cancer Patient With Alectinib-Induced Pneumonitis and Bilateral Globus Pallidus Necrosis Postpartum. Clin Lung Cancer. 2024 Jan;25(1):72-76. doi: 10.1016/j.cllc.2023.08.016.

Bochtler T, Becker H, Stenzinger A. „Cancer of unknown primary” – histologische und molekularpathologische Grundlagen in der Diagnostik. Die Onkologie. Ausgabe 03/2024.

Boosfeld, L., Lang, S., Mattheis, S., Peis, M., Zaun, G., Waßenberg, S., Baba, H. A., Hussain, T., & Kürten, C. (2025). Diagnosis, treatment and oncological outcome of cervical CUP-syndrome depending on p16 status. Laryngo- rhino- otologie, 104(6), 361–370. https://doi.org/10.1055/a-2468-6211

Pouyiourou M, Bochtler T, Pauli C, Moch H, Brobeil A, Pantel K, Stenzinger A, Krämer A. Rethinking cancer of unknown primary: from diagnostic challenge to targeted treatment. Nat Rev Clin Oncol. 2025 Oct;22(10):781-799. doi: 10.1038/s41571-025-01060-8.

Kubuschok, B., Claus, R. & Stahl, M. Interdisziplinäre Therapiestruktur beim CUP-Syndrom. InFo Hämatol Onkol 28, 14–18 (2025). https://doi.org/10.1007/s15004-025-0889-x

Maximilian Werner; Tobias Mundt; Annika Schneider; Waqar Hussain; Jonas Arnold; Cecilia Bang Jensen; Martina Fröhlich; Barbara Hutter; Jennifer Hüllein; Nagarajan Paramasivam; Amirhossein Sakhteman; Matthew The; Daniela Richter; Simon Kreutzfeldt; Christoph E. Heilig; Maria-Veronica Teleanu; Daniel B. Lipka; Annika Baude; Katja Beck; Katrin Pfütze; Maren Knödler; Damian Rieke; Johanna Falkenhorst; Ilektra Antonia Mavroeidi; Christian Brandts; Anna L. Illert; Melanie Börries; Thomas Kindler; Tobias Marcus Herold; Nicole Pfarr; Albrecht Stenzinger; Christoph Heining; Irina Kerle; Evelin Schröck; Peter Horak; Daniel Hübschmann; Lino Möhrmann; Bernhard Küster; Stefan Fröhling; Hanno Glimm Cancer Res (2025) 85 (8_Supplement_1): 6373. https://doi.org/10.1158/1538-7445.AM2025-6373

Hübner G, Bochtler T, Borner M, Stöger H, Neben K, Ernst T, et al. Onkopedia Leitlinien 09/25: CUP-Syndrom - Krebserkrankungen mit unbekanntem Primärtumor 09/2025. Available from: https://www.onkopedia.com/de/onkopedia/guidelines/cup-syndrom-krebserkrankungen-mit-unbekanntem-primaertumor/@@guideline/html/index.html

Abu Sabbah T, Theurer S, Baba HA, Lueong S, Rashidi-Alavijeh J, Hilser T, Zaun Y, Metzenmacher M, Pogorzelski M, Virchow I, Pretzell I, Kostbade K, Treckmann J, Wiesweg M, Schuler M, Kasper S, Zaun G. PD-L1 expression associates with favorable survival of patients with cancer of unknown primary (CUP) not treated with checkpoint inhibitors. Eur J Cancer. 2024 Oct;210:114268. doi: 10.1016/j.ejca.2024.114268. Epub 2024 Aug 10. PMID: 39153343.

Budczies J, Kazdal D, Menzel M, Beck S, Kluck K, Altbürger C, Schwab C, Allgäuer M, Ahadova A, Kloor M, Schirmacher P, Peters S, Krämer A, Christopoulos P, Stenzinger A. Tumour mutational burden: clinical utility, challenges and emerging improvements. Nat Rev Clin Oncol. 2024 Oct;21(10):725-742. doi: 10.1038/s41571-024-00932-9. Epub 2024 Aug 27. PMID: 39192001.

Krämer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomášek J, Arslan C, Özgüroğlu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Durán-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. doi: 10.1016/S0140-6736(24)00814-6. Epub 2024 Jul 31. PMID: 39096924.

Le Tourneau C, André F, Helland Å, Mileshkin L, Minnaard W, Schiel A, et al. Modified study designs to expand treatment options in personalised oncology: a multistakeholder view. European journal of cancer (Oxford, England : 1990). 2023;194:113278.

Mosele MF, Westphalen CB, Stenzinger A, Barlesi F, Bayle A, Bièche I, Bonastre J, Castro E, Dienstmann R, Krämer A, Czarnecka AM, Meric-Bernstam F, Michiels S, Miller R, Normanno N, Reis-Filho J, Remon J, Robson M, Rouleau E, Scarpa A, Serrano C, Mateo J, André F. Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2024 Jul;35(7):588-606. doi: 10.1016/j.annonc.2024.04.005. Epub 2024 May 27. PMID: 38834388.

Pouyiourou M, Bochtler T, Coith C, Wikman H, Kraft B, Hielscher T, Stenzinger A, Riethdorf S, Pantel K, Krämer A. Frequency and Prognostic Value of Circulating Tumor Cells in Cancer of Unknown Primary. Clin Chem. 2024 Jan 4;70(1):297-306. doi: 10.1093/clinchem/hvad180. PMID: 38175594.

Pouyiourou M, Mokry T, Feszler M, Teifke A, Kreft A, Krämer A. Cancer of unknown primary derived from regressed breast cancer. J Cancer Res Clin Oncol. 2024 May 4;150(5):229. doi: 10.1007/s00432-024-05768-5. PMID: 38703270; PMCID: PMC11069480.

Pouyiourou M, Reitnauer LE, Ballhausen A, Alig AHS, Bleckmann A, Westphalen CB, Kloft M. Highlights of Translational and Molecular Research Presented at the European Society for Medical Oncology Annual Meeting 2023. Oncol Res Treat. 2024;47(4):149-153. doi: 10.1159/000537940. Epub 2024 Feb 28. PMID: 38417407.

Zaun G, Borchert S, Metzenmacher M, Lueong S, Wiesweg M, Zaun Y, Pogorzelski M, Behrens F, Schildhaus HU, Virchow I, Kasper S, Schuler M, Theurer S, Liffers S. Comprehensive biomarker diagnostics of unfavorable cancer of unknown primary to identify patients eligible for precision medical therapies. Eur J Cancer. 2024 Mar;200:113540. doi: 10.1016/j.ejca.2024.113540. Epub 2024 Jan 26. PMID: 38316065.

Bochtler T, Pouyiourou M, Krämer A. [Cancer of unknown primary-The new ESMO guidelines]. Radiologie (Heidelberg, Germany). 2023;63(5):329-35.

Delorme S, Krämer A. [The big mystery-a second look] Das große Rätsel – ein zweiter Blick. Radiologie (Heidelberg, Germany). 2023;63(5):327-8.

Hübner G, Bochtler T, Borner M, Stöger H, Neben K, Ernst T, et al. Onkopedia Leitlinien 06/23: CUP-Syndrom - Krebserkrankungen mit unbekanntem Primärtumor2023 06/2023. Available from: https://www.onkopedia.com/de/onkopedia/guidelines/cup-syndrom-krebserkrankungen-mit-unbekanntem-primaertumor/@@guideline/html/index.html.

Krämer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of oncology: official journal of the European Society for Medical Oncology. 2023;34(3):228-46.

Mileshkin L, Bochtler T, Pauli C, Durán-Pacheco G, Arslan C, Bigot F, et al. LBA16 Primary analysis of efficacy and safety in the CUPISCO trial: A randomised, global study of targeted therapy or cancer immunotherapy guided by comprehensive genomic profiling (CGP) vs platinum-based chemotherapy (CTX) in newly diagnosed, unfavourable cancer of unknown primary (CUP). Annals of oncology : official journal of the European Society for Medical Oncology. 2023;34:S1254-55.

Pouyiourou M, Kraft BN, Wohlfromm T, Stahl M, Kubuschok B, Löffler H, et al. Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial. Nature communications. 2023;14(1):6761.

Pouyiourou M, Regnery S, Bochtler T, Herfarth K, Krämer A. [Cancer of unknown primary (CUP)-single-site, oligometastatic, and in the head and neck region]. Radiologie (Heidelberg, Germany). 2023;63(5):358-65.

Zaun G, Weber M, Metzenmacher M, Wiesweg M, Hilser T, Zaun Y, et al. SUV(max) Above 20 in (18)F-FDG PET/CT at Initial Diagnostic Workup Associates with Favorable Survival in Patients with Cancer of Unknown Primary. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2023;64(8):1191-4.

Mileshkin L, Bochtler T, Gatta G, Kurzrock R, Beringer A, Müller-Ohldach M, Surinach A, Perret C, Thomas M, Gondos A, Krämer A: Cancer-of-unknown-primary-origin: A SEER – Medicare study of patterns of care and outcomes among elderly patients in clinical practice. Cancers 14: 2905, 2022.

Bochtler T, Wohlfromm T, Hielscher T, Stichel D, Pouyiourou M, Kraft B, Neumann O, Endris V, von Deimling A, Stenzinger A, Krämer A: Prognostic impact of copy number alterations and tumor mutational burden in carcinoma of unknown primary. Genes Chromosomes Cancer 61: 551-560, 2022.

Pouyiourou M, Wohlfromm T, Kraft B, Hielscher T, Stichel D, von Deimling A, Delorme S, Endris V, Neumann O, Stenzinger A, Krämer A, Bochtler T: Local ablative treatment with surgery and/or radiotherapy in single-site and oligo-metastatic carcinoma of unknown primary (CUP). Eur J Cancer 157: 179-189, 2021.

Pauli C, Bochtler T, Mileshkin L, Baciarello G, Losa F, Ross J, Pentheroudakis G, Zarkavelis G, Yalcin S, Özgüroğlu M, Beringer A, Scarato J, Mueller-Ohldach M, Thomas M, Moch H, Krämer A: A challenging task – Identifying patients with cancer of unknown primary (CUP) according to ESMO guidelines: the CUPISCO trial experience. Oncologist 26: e769-e779, 2021.

Folprecht G, Trautmann K, Stein A, Hübner G, Stahl M, Kasper S, Kretzschmar A, Köhne CH, Grünwald V, Hofheinz R, Schütte K, Löffler H, Bokemeyer C, Krämer A, Arbeitsgemeinschaft Internistische Onkologie (AIO) - CUP group: Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the phase II PACET-CUP trial. Br J Cancer 124: 721-727, 2021.

Ross JS, Sokol ES, Moch H, Mileshkin L, Baciarello G, Losa F, Beringer A, Thomas M, Elvin J, Ngo N, Jin DX, Krämer A: Comprehensive genomic profiling of carcinoma-of-unknown-primary-origin: retrospective molecular classification considering the CUPISCO study design. Oncologist 26: e394-e402, 2021.

Pauli C, Bochtler T, Mileshkin L, Baciarello G, Losa F, Ross JS, et al. A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience. The oncologist. 2021;26(5):e769-e79.

Ross JS, Sokol ES, Moch H, Mileshkin L, Baciarello G, Losa F, et al. Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Origin: Retrospective Molecular Classification Considering the CUPISCO Study Design. The oncologist. 2021;26(3):e394-e402.

Westphalen CB, Karapetyan A, Beringer A, Krämer A, al. e. Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO. Ann Oncol. 2021;32:1227-8.

Pouyiourou M, Wohlfromm T, Kraft B, Hielscher T, Stichel D, von Deimling A, et al. Local ablative treatment with surgery and/or radiotherapy in single-site and oligometastatic carcinoma of unknown primary. European journal of cancer (Oxford, England : 1990). 2021;157:179-89.

Folprecht G, Trautmann K, Stein A, Huebner G, Stahl M, Kasper S, et al. Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the Phase 2 AIO trial PACET-CUP. Br J Cancer. 2021;124(4):721-7.

Hübner G, Borner M, Neben K, Stöger H. Onkopedia Leitlinien 02/20: CUP-Syndrom - Krebserkrankungen mit unbekanntem Primärtumor2020 02/2020. Available from: https://www.dgho-onkopedia.de/de/ onkopedia/leitlinien/cup-syndrom-krebserkrankungen-mit-unbekanntem.

Bochtler T, Reiling A, Endris V, Hielscher T, Volckmar AL, Neumann O, Kirchner M, Budczies J, Heukamp LC, Leichsenring J, Allgäuer M, Kazdal D, Löffler H, Weichert W, Schirmacher P, Stenzinger A, Krämer A: Integrated clinico-molecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary. Int J Cancer 146: 3053-3064, 2020.

Bochtler T, Endris V, Leichsenring J, Reiling A, Neumann O, Volckmar A-L, Kirchner M, Allgäuer M, Schirmacher P, Krämer A, Stenzinger A: Comparative genetic profiling aids diagnosis and clinical decision making in challenging cases of CUP syndrome. Int J Cancer 145: 2963-2973, 2019.

Meyer M., Schenkirsch G., Claus R., Schaller T., Märkl B., König C., Schmutz M., Trepel M., Kubuschok B. Liver biomarkers in Carcinoma of Unknown Primary (CUP): Impact on prognosis. Oncology Research and Treatment, 43(suppl 4): 480, 2020.

Kirchner M, Neumann O, Volckmar AL, Stögbauer F, Allgäuer M, Budczies J, Rempel E, Brandt R, von Winterfeld M, Leichsenring J, Bochtler T, Krämer A, Springfeld C, Schirmacher P, Penzel R, Endris V, Stenzinger A: Reliable and fast RNA-based detection of gene fusions in formalin-fixed and paraffin-embedded carcinoma samples. Cancers 11: E1309, 2019.

Ross JS, Sokol ES, Moch H, Mileshkin L, Baciarello G, Losa F, Beringer A, Thomas M, Elvin J, Ngo N, Jin DX, Krämer A: Comprehensive genomic profiling of carcinoma-of-unknown-primary-origin: retrospective molecular classification considering the CUPISCO study design. Oncologist (in press), 2020.