memo - Magazine of European Medical Oncology

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00749-7

Wöll, Ewald

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00768-4

Geissler, Klaus

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00767-5

Pircher, Andreas

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00761-x

Weiss, Lukas

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00763-9

Summary The 2021 ASCO Annual Meeting provided updates on novel therapies in rare subgroups of metastatic colorectal cancer, such as immunotherapy in microsatellite instable colorectal cancer and antibody–drug conjugate therapy in HER2-positive disease. Furthermore, the concept of anti-EGFR rechallenge therapy has received additional momentum with data from the CHRONOS trial in regard to treating patients in later lines as well as how to integrate analysis of circulating tumor DNA in clinical decision-making.

Mair, Maximilian J.; Berghoff, Anna S.

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00752-y

Summary More than 140 abstracts were presented in the Central Nervous System Tumors track during the 2021 American Society of Clinical Oncology (ASCO) virtual meeting. Here, we review our personal highlights of the presented data. In rare entities such as papillary craniopharyngioma and neurotrophic tyrocine receptor kinase (NTRK)-fusion-positive tumors, promising data on targeted therapies were reported. In addition, early data on olaparib in high-grade glioma and combinational immunotherapy approaches will be briefly reviewed. Furthermore, the eagerly awaited results of the EORTC-1709 phase III trial on the pan-proteasome inhibitor marizomib in newly diagnosed glioblastoma were shown at the meeting. Although no practice-changing trials were presented for glioma patients, new treatments are on the horizon and results from modern platform trials are awaited in the near future.

Singer, Christian

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00750-0

Summary This year’s ASCO Annual Meeting has been a showcase for the overwhelming success of novel, targeted therapies, particularly in a tumor entity that has – until recently – been felt to be only treatable with chemotherapy. New data are extremely encouraging, but also highlight the need for target identification beyond the classical clinicopathological factors. Both, the Olympia and the Neotala study have been performed in BRCA-mutated tumors, and their results clearly point to the necessity to offer germline testing to HER2-negative high risk early breast cancer. In addition, GeparNuevo once more highlights the fact that immunotherapy is here to stay, not only in the advanced breast cancer setting, but also in early stage breast cancer. The side effect profile is acceptable, and long-term outcome a real improvement to conventional chemotherapy.

Fuereder, Thorsten

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00758-6

Summary During the ASCO 2021 virtual meeting, multiple clinically relevant studies were presented addressing open questions regarding the therapy of nasopharyngeal carcinomas (NPC): Is immunotherapy plus chemotherapy the new first line standard of care for patients in the recurrent/metastatic setting? Is adjuvant therapy with capecitabine in high risk NPC patients post chemoradiation (CRT) beneficial? Is there a role for treatment intensification by adjuvant metronomic capecitabine in NPC patients post induction chemotherapy and CRT? This article summarizes the most significant NPC studies presented at the ASCO 2021 virtual meeting and discusses the data in the context of the current literature.

Mayrhofer, Karl; Niedersüß-Beke, Dora

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00765-7

Summary Three trials presented at the meeting investigated the incorporation of immunotherapy into a multimodal bladder-sparing treatment approach. The results of these phase 2 trials are so far promising with most patients achieving complete remission (CR) and estimated bladder-intact disease-free survival (BIDFS) in these patients ranges between 73 and 88%. Additionally, the up to 5-year follow-up data from the KEYNOTE-052 study were discussed. The results confirm the efficacy of pembrolizumab as first-line monotherapy in cisplatin-ineligible patients with a programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10.

Ilhan-Mutlu, Aysegül

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00751-z

Summary The oncological community witnessed several practice-changing clinical reports in this years’ annual congress of the American Society of Clinical Oncology (ASCO). Many immunotherapeutic agents were shown to be beneficial for upper gastrointestinal tumors. For advanced squamous cell carcinoma, immunotherapy and chemotherapy combinations revealed by the CheckMate 648 and ESCORT-1st trials have been implemented into the clinical practice. The updates on the CheckMate 649 and CheckMate 577 trials again underlined the significant clinical contribution of nivolumab in advanced and localized gastroesophageal cancer, respectively. However, this effect seems to be dependent to PD-L1 expression. Not only immunotherapy trials, but also targeted therapy studies such as the FIGHT trial investigating the anti-FGFR2b monoclonal antibody bemarituzumab attracted huge interest, not only due to extension of survival in experimental group, but also due to the innovative design of this trial. This review summarizes the highlights regarding gastroesophageal tumors at the ASCO 2021 congress.

Schöche, Johannes; Strasser-Weippl, Kathrin

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00772-8

Summary The 2021 ASCO annual meeting did not change clinical practice in the treatment of ovarian cancer, but several interesting studies were presented that might have clinical impact in the future. One phase III study, by demonstrating no improved overall survival for an extended maintenance duration of bevacizumab treatment, supports the current standard of care of 15 months of bevacizumab for first-line maintenance. Data on Poly(ADP-ribose)-polymerase inhibitors (PARP inhibitors) again confirmed their marked clinical benefit, most prominently in certain biomarker subpopulations. Finally, new drug candidates with promising clinical activity include agents targeting ATR, Wee1, and folate receptor alpha.

Absenger, Gudrun; Pircher, Andreas

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00770-w

Summary This article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

Fillitz, Michael; Dixer, Barbara; Keil, Felix

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00771-9pmid: 34691269

Summary Immune thrombocytopenic purpura (ITP) is a rare hematological disorder with an autoimmune-mediated, often dramatic reduction of platelets in peripheral blood. Thrombocytopenia results from a reduced life span of thrombocytes and an additionally decreased production in bone marrow. For decades, the first-line therapy for ITP has been corticosteroids. As significant thrombocytopenic bleedings occur, the use of additional medication may be needed. Recent updates on therapy guidelines recommend the shortest possible use of corticosteroids. Thrombopoietin-receptor agonists are often used second line. Today splenectomy, which was previously recommended after unsuccessful first-line therapy, is usually considered much later. Patients who do not respond even after multiple lines of therapy continue to pose a major challenge. New drugs for ITP treatment are now available after steroid failure and will be discussed. This review gives a short summary on actual therapy guidelines taking into account newly available therapy options. In addition, comparisons between selected published data and experience at our department are made.

Geissler, Klaus

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00757-7

Summary Pancytopenia is a condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood. The spectrum of causes for the decrease of one or more blood cell lineages is broad including increased destruction, pooling by spleen, loss of blood cells, decreased production due to toxic and/or immune-mediated mechanisms and abnormalities due to clonal/malignant hematopoiesis. In this article common and/or typical causes of pancytopenia are presented with special emphasis on more or less disease specific features that may be useful clues in the differential diagnosis of this blood picture abnormality.

Kyrle, Paul A.

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00769-3

Summary Venous thromboembolism (VTE) is a chronic disease which tends to recur, in particular in patients with a first unprovoked VTE. Recurrence can be prevented by anticoagulants but at the price of bleeding. Identification of patients at high recurrence risk is therefore warranted. One such attempt consists of the routine determination of risk factors of VTE in the laboratory. However, laboratory thrombophilia screening has failed for the following reasons: it consists of measurement of risk factors for a first VTE rather than a second event; a parge proportion of patients with negative thrombophilia screening suffer from recurrence; studies showing a beneficial effect of thrombophilia screening do not exist; thrombophilia screening may confer emotional stress and anxiety. Therefore, patients with VTE should not be routinely screened for laboratory thrombophilia with the intention to optimize the duration of secondary thromboprophylaxis or to identify asymptomatic relatives who may harbor the same defect and may benefit from individual thromboprophylaxis.

Ibrahim, Rasha I.; Mohamed, Haydi S.; Nagib, Mary G.; Fares, Hebatullah M.; Saeed, Alia M.

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00715-3

Summary Background Autophagy is considered a pivotal cellular mechanism to cope with stress and maintain homeostasis. It is frequently dysregulated in various types of cancers with some exhibiting excessive and others having reduced autophagy levels. Aim The goal was to determine autophagy status in newly diagnosed adult acute lymphoblastic leukaemia (ALL) patients compared to age- and sex-matched controls. Moreover, its prognostic impact on disease characteristics and response to treatment were evaluated. Patients and methods Thirty-five newly diagnosed adult ALL patients were recruited and age and sex matched to 15 healthy control subjects. ATG5 expression was measured on diagnosis using real-time quantitative polymerase chain reaction (qPCR). Cases have been followed up for one year after enrolment into the study. Results Mean ATG5 expression in ALL was twice that of controls, which is a high statistically significant difference (2.15 ± 2.2 vs 1.09 ± 0.47, P value = 0.01). High ATG5 expression has been significantly associated with B‑ALL phenotype, lower haemoglobin and lower platelet counts. Of note, the higher expressor group had higher bone marrow and peripheral blood blast percentages and greater likelihood to develop chemoresistance to frontline agents, but this was not statistically significant. Further studies with larger numbers of patients are needed to examine the relationship between autophagy activation and therapeutic outcome in ALL.

Jungraithmayr, Wolfgang

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00737-x

Absenger, Gudrun; Terbuch, Angelika

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00727-z

Summary Malignant pleural mesothelioma (MPM) is a rare tumour that originates from the inner linings of the pleural cavity. The majority of cases are associated with exposure to asbestos for what was banned in the European Union in 1991. Due to the long latency between exposure and onset (20–40 years) the peak of MPM in Western Europe will be reached within the next years. Often diagnosed at an unresectable stage, treatment options remain palliative in the majority of cases. The highly aggressive nature of MPM leads to a dismal prognosis with a median overall survival of approximately one year. Platinum-based chemotherapy in combination with pemetrexed has been the mainstay of first line treatment in unresectable MPM for many years. Only recently, check point inhibitors have found their way into MPM treatment. The results of the phase III CheckMate 743 trial last year have finally led to a paradigm shift in the treatment of unresectable MPM. This trial showed a significant overall survival benefit for the combination of nivolumab and ipilimumab over standard chemotherapy, especially in nonepithelioid histology. Apart from histology, predictive biomarkers have not been identified for the treatment of MPM so far. Several trials investigating combination therapies with checkpoint inhibitors are currently ongoing and give hope to further improve prognosis for our patients.

Metovic, Jasna; Barella, Marco; Pelosi, Giuseppe

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00681-w

Summary Purpose Neuroendocrine tumors and neuroendocrine carcinomas in the lung are distinct and separate entities featuring neuroendocrine differentiation, for which an accurate classification is clinically warranted. Materials and methods Three perspectives were addressed: (i) diagnostic tools, with the terminology to be used in either resection specimen or small-sized material; (ii) the so-called carcinoid tumors with elevated proliferation rates (mitotic and/or Ki-67 activity); (iii) predictive biomarkers based on immunohistochemical characterization. Results We herein provide a pathology update on lung neuroendocrine neoplasm classification that will appear in the forthcoming 5th edition of the WHO Blue Book, including a short discussion about biomarkers, which are presently given full consideration in clinical practice. Conclusion The WHO classification on lung neuroendocrine neoplasms is the cornerstone to provide the best clinical management of patients and is the starting point for any investigative insight.

Hempel, Louisa; Molnar, Jakob; Gaumann, Andreas; Robert, Sebastian; Scheiber, Josef; Kleespies, Axel; Riedmann, Kristina; Schreiber, Susanne; Gandorfer, Beate; Piehler, Armin; Hempel, Dirk

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00724-2

Summary In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described.

Nagl, Laurenz; Seeber, Andreas; Widmann, Gerlig; Schmitz, Katja; Maier, Herbert; Pall, Georg; Wolf, Dominik; Pircher, Andreas

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00738-w

Summary Primary pulmonary sarcomas (PPS) are rare mesenchymal lung cancers, which do not present clinically or radiological different to lung carcinomas. Definite PPS diagnosis can only be made by histological analysis and detailed staging examinations in order to exclude a secondary pulmonary malignancy such as metastatic soft tissue sarcoma or another solid tumour. Here we present the case of a 66-year-old woman with a pulmonary mass infiltrating the diaphragm and the mediastinal adipose tissue, which was identified as leiomyosarcoma. The patient received curative surgery with complete tumour R0 resection. The prognosis of PPS is defined by tumour size, lymph node status and histological grading. Surgery is the mainstay of therapy and there is no definitive indication for adjuvant therapy for R0-resected and lymph-node-negative patients like in our case. However, multimodal therapy approaches such as (neo)adjuvant chemo- and radiotherapy can contribute to improving locoregional tumour control, which is the most important prognostic factor. With our case report we want to raise awareness for pulmonary sarcomas as a relevant proportion of rare lung cancers which have to be kept in mind during the differential diagnosis. Moreover, we aim to discuss the complex and individual interdisciplinary management.

Salzer, Elisabeth; Attarbaschi, Andishe

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00764-8

Summary Leukemia and lymphoma are a leading cause of cancer-related mortality in children and the prognosis for patients with relapsed or refractory disease remains poor. Standard therapies are associated with a wide array of acute and long-term toxicities. Immunotherapy is changing the treatment landscape for pediatric leukemia and lymphoma patients and has advanced at a tremendous pace over the last decade. Immunotherapies are thought to exhibit fewer long-term toxicities than chemotherapy and radiation, which makes it very appealing in the field of pediatrics. These novel therapeutic concepts may overcome resistance to and decrease side effects of standard therapy. Many therapies are currently being investigated, from immunomodulatory agents to adoptive cell therapy, bispecific T‑cell engagers, oncolytic virotherapy, and checkpoint inhibition. A critical challenge that must be overcome is the identification of biomarker(s) to identify patients who would benefit from immunotherapy.

Jaeger, Johannes B.; Jaeger, Thomas; Preuner, Sandra; Pusic, Petra; Sponseiler, Isabella; Lion, Thomas; Winder, Thomas; Hartmann, Bernd Lorenz

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00742-0

Summary Background Chronic myeloid leukemia (CML) is a hematological malignancy characterized by BCR-ABL1-derived permanent proliferation of myeloid progenitor cells. BCR-ABL1 tyrosine kinase inhibitors (TKI) are effective first-line therapeutic options to suppress tumor proliferation. However, TKI therapy is not always curative and drug-related side effects as well as drug resistance may evolve over time, necessitating salvage therapies. Methods In this case report we present a 68-year-old woman who developed second- and third-generation TKI therapy resistance with BCR-ABL1T315I and BCR-ABL1E255V mutation. Considering contraindication for hematopoietic stem cell transplantation, we treated the patient in an individual treatment attempt with a third-generation TKI ponatinib in combination with palbociclib, a CDK4/CDK6 inhibitor, which has been shown to effectively inhibit proliferation of BCR-ABL1T315I-mutated cells in vitro. Results Our case study shows strong antineoplastic effects using this combination in an advanced CML patient resistant to ponatinib monotherapy as a fourth-line treatment. Combined administration of ponatinib/palbociclib at full dose showed almost a tenfold decrease (42.6 to 4.4 IS%) of BCR-ABL1-positive cells but with simultaneous hematopoietic toxicity, necessitating dose reduction. Conclusion This combination treatment showed high clinical activity. However, biological activity needs to be further characterized in prospective clinical trials.

Khair, Wael

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00753-x

Summary Objective The objective of this paper is to elucidate the role of thymus and activation-regulated chemokine (TARC) as a marker of treatment response in classical Hodgkin lymphoma (cHL). Background Most patients diagnosed with cHL can be cured today but about 20–30% still experience refractoriness/relapse. Positron emission tomography (PET) has been shown to not be the optimal tool, since 15–20% of patients relapse despite negative PET. There is an unmet need for new markers to predict response to treatment as early as possible and for surveillance of patients after completion of treatment to allow prompt intervention in case of signs of evolving relapse. Methods Literature regarding the role of thymus and activation-regulated chemokine (TARC) in cHL was searched and 13 studies between 2005 and 2020 with a total of 1433 patients were identified and reviewed. Conclusion Reviewed studies suggest that TARC is one of the most promising markers, which can be used to improve treatment outcome in cHL.