Long-term survival in advanced and metastatic pancreatic carcinoma - prognosis-defining factors

Background: Advanced pancreatic carcinoma is incurable and ranks fourth in cancer-related causes of death in Germany. Yet in rare cases patients on palliative therapy achieve prolonged survival. Until now no bigger cohort of such long-term-survivors has been described with regard to their constitutional and tumor-related factors. The identification of potential long-term survivors should improve individual prognostic assessment therefore lead to better therapeutic decisions in the clinical routine. Methods: Patients with advanced pancreatic carcinoma treated between 1997 and 2012 in the Department of Hematology, Oncology and Tumor Immunology at the Charité - University Medicine Berlin, Campus Virchow-Klinikum, who survived more than 36 months, were analyzed retrospectively with focus on their tumor characteristics, laboratory results, treatment regimens and survival data. Results: Out of a total of 510 patients 18 could be identified, who survived more than 36 months after the initiation of the palliative first-line therapy. 16 of them were in good clinical performance status (ECOG 0-1). Median CA 19-9 was 198 (range 0-4592) U/ml. 17 patients were treated with Gemcitabin alone or Gemcitabin-combination regimes in the first-line. Progression-free survival after initiation of first-line was 11 (range 3-40) months. A median of 3.5 (range 1-6) treatment-lines was performed. Discussion: Long-term-survival in advanced pancreatic carcinoma is a rare phenomenon and potentially linked to factors like good clinical performance-status and low initial CA 19-9. The use of multiple palliative treatment-lines to achieve prolonged survival seems justified in the setting of sustained clinical performance status. New therapeutic targets are necessary to reach higher rates of long-term-survival.Einleitung: Das fortgeschrittene Pankreaskarzinom hat eine infauste Prognose und gehört zu den 4 häufigsten krebsbedingten Todesursachen in Deutschland. Dennoch überleben einzelne Patienten durch palliative Therapieverfahren überdurchschnittlich lange. Bisher konnte jedoch keine größere Kohorte von Langzeitüberlebenden in Bezug auf konstitutionelle und tumorspezifische Faktoren charakterisiert werden. Die Identifizierung möglicher Langzeitüberlebender erlaubt letztendlich eine bessere Prognoseabschätzung und Therapieentscheidung im klinischen Alltag. Methodik: Patienten mit fortgeschrittenem Pankreaskarzinom, die zwischen 1997 und 2012 an der medizinischen Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie der Charité Campus Virchow-Klinikum behandelt wurden und über 36 Monate überlebten, wurden retrospektiv hinsichtlich ihrer Tumorcharakteristika, Laborwerte, verwendeter Behandlungs-regime und Überlebensdaten analysiert. Ergebnisse: Aus insgesamt 510 Patienten konnten 18 identifiziert werden, die mehr als 36 Monate von Beginn der ersten palliativen Therapielinie überlebten. 16 befanden sich zu diesem Zeitpunkt in einem guten klinischen Performance-Status (ECOG 0-1). Das CA 19-9 lag im Median bei 198 (Range 0-4592) U/ml. In 17 Fällen wurden Gemcitabin oder Gemcitabin-haltige Chemotherapien in der Erstlinie eingesetzt. Das Progressionsfreie Überleben der ersten Therapielinie betrug 11 (Range 3-40) Monate. Im Median kamen 3,5 (Range 1-6) Therapielinien zum Einsatz. Diskussion: Langzeitüberleben bei fortgeschrittenem Pankreaskarzinom ist ein seltenes Phänomen und wird vermutlich durch Faktoren wie ein guter klinischer Performance-Status und niedriges Ausgangs-CA 19-9 günstig beeinflusst. Der Einsatz multipler palliativer Therapielinien erscheint bei erhaltenem klinischem Performance-Status zur Verbesserung des Gesamtüberlebens gerechtfertigt. Neue therapeutische Angriffspunkte sind notwendig um höhere Langzeitüberlebensraten zu erzielen

VEXAS and Myelodysplastic Syndrome: An Interdisciplinary Challenge

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical–rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the UBA1 codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18–68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for UBA1 mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for UBA1 mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease