memo - Magazine of European Medical Oncology

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00697-2

Füreder, Thorsten

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00711-7

Troch, Marlene

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00704-6

Bartsch, Rupert

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00712-6pmid: 34178160

Hofer, Silvia

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00707-3

Sillaber, Alois

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00716-2

Zila, Nina; Hoeller, Christoph; Paulitschke, Verena

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00699-0

Summary In malignant diseases, targeting of immune checkpoints successfully changed the therapeutic landscape and helped to unleash anti-tumor T cell responses, resulting in durable clinical outcomes, but only in up to 50% of patients. The success of these therapies and the need to overcome intrinsic and acquired therapy resistance stimulated research to identify new pathways and targets. Numerous clinical trials are currently evaluating novel checkpoint inhibitors or recently developed strategies like modulating the tumor microenvironment, mostly in combination with approved therapies. This short review briefly discusses promising therapeutic targets, currently still under investigation, with the chance to realize clinical application in the foreseeable future.

Umut, Öykü; Gottschlich, Adrian; Endres, Stefan; Kobold, Sebastian

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00703-7pmid: 34777609

Summary Chimeric antigen receptor (CAR) T cell therapy has been established in the treatment of hematological malignancies. However, in solid tumors its efficacy remains limited. The aim of this article is to give an overview of the field of cell therapy itself, to introduce the underlying concepts of CAR T cell-based treatment approaches and to address its limitations in advancing the treatment for solid malignancies.

Heller, Gerwin

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00696-3

Summary Immunotherapy is one of the major breakthroughs in cancer treatment. However, many patients do not benefit from this type of therapy. Thus, there is an urgent need for a strategy to predict treatment efficacy before start of therapy. The role of certain genetic and epigenetic factors as potential predictive markers for response to immunotherapy is discussed in this short review.

Kiesl, David

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00698-1

Summary Background This review summarizes current data on the effects of exercise interventions and physical activity in cancer prevention, treatment and related side effect management, as well as on the rehabilitation of cancer patients. Patients and methods The overall quality of patient studies is still poor due to methodological limitations. Major limitations of the interventional exercise studies conducted include their designs, with regard to missing randomization or the absence of control groups, and the use of heterogeneous assessment methods to quantify and objectify physical activity. As a result, there are no specific exercise recommendations in cancer patients as yet that would essentially differ from exercise recommendations for healthy subjects. Nevertheless, due to major findings and empirical data, the field of research into exercise- and physical activity-related effects on disease and therapy-associated aspects is young and rapidly emerging. Conclusion Exercise potentially contributes to the prevention and rehabilitation of cancer and represents a powerful tool in the prevention of various side effects under chemotherapy. Current data from interventional studies show preliminary positive effects for diverse movement programs and especially through specific combinations of endurance and resistance training. Additional randomized controlled trials with standardized assessments and controlling for potential confounders are needed to confirm and expand these findings.

Hutterer, Markus; Oberndorfer, Stefan

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00690-9

Summary Cognitive impairment by neurotoxic substances, administered alone or in a multidrug regimen, affects a large number of patients treated for noncentral nervous system cancer during and after chemotherapy with variable onset, severity and duration, but sustainably affecting the patients’ individual health-related quality of life. Depending on the mechanism of action, the ability to cross the blood–brain barrier into the central nervous system and the cumulative total dose of the cytotoxic drugs results in functional and structural brain changes. This neurotoxicity leads to negative effects on neural precursor cells (neurogenesis), microglia (neuroinflammation), neurons (cortical dysfunction with altered brain networks), and astro-/oligodendroglia (white matter tract demyelination) and therefore on patients’ cognitive performance. Memory and executive functions, attention/concentration, and processing speed are the cognitive domains commonly impaired by chemotherapy. Importantly, numerous simultaneously occurring risk factors may also have distinct restrictions on cognitive function. For this reason, the term cancer-related cognitive impairment (CRCI), implicating neurotoxicity in cancer patients with simultaneous consideration of other causes on cognitive performance, should be used. The aim of this review is to provide an update of the most recent clinical and pathophysiological findings, self-reported and neuropsychological testing methods, and the current management strategies of CRCI.

Beirer, Angelika

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-020-00672-3

Summary Background The prevalence of malnutrition in cancer patients ranges from about 20% to more than 70%. However, 10–20% of cancer patients’ deaths are related to malnutrition, not the malignancy itself. To reverse the pattern of weight loss, improve the patients’ quality of life, reduce the treatment toxicity, the psychological stress and the risk of mortality, the diagnosis of malnutrition should be made as early as possible to facilitate the best possible treatment. Methods A systematic literature search was conducted following guidelines of ESPEN (European Society for Clinical Nutrition), DGEM (German Society for Nutritional Medicine) and ASPEN (American Society for Parenteral and Enteral Nutrition). Results and conclusion To assess the risk of malnutrition, all cancer patients should be screened regularly with a valid screening tool (e.g., MUST [Malnutrition Universal Screening Tool], NRS [Nutritional Risk Screening] or PG-SGA [Scored Patient-Generated Subjective Global Assessment]). If risk of malnutrition is present, adequate nutritional therapy is recommended to stop involuntary weight loss. Patients should engage in exercise to maintain and improve muscle mass, strength and function. They should be offered regular dietetic counselling, and their muscle depletion should be monitored by determining fat-free mass. As cachectic patients in particular are at risk, the presence of cachexia should also be recognized at an early stage. Three consensus-based definitions are widely accepted: Fearon et al. and the EPCRC (European Palliative Care Research Collaborative) propose definitions specifically for cancer cachexia, while Evans et al. put forward a definition for cachexia associated with all types of underlying chronic diseases. However, if there is a cancer cachexia diagnosis, additional pharmacological and psychological treatment should be considered.

Kiesewetter, Barbara

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00700-w

Summary This year’s virtual version of the European Society for Medical Oncology (ESMO) presidential sessions included three “late breaking” non-small cell lung cancer (NSCLC) abstracts, discussing strategies for adjuvant therapy of localized disease and up-front treatment of advanced anaplastic lymphoma kinase(ALK)-positive lung cancer.

Bergen, Elisabeth Sophie

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00692-7

Summary At the ESMO (European Society for Medical Oncology) 2020 several interesting albeit not practice-changing studies in the field of pancreatic cancer were presented. The Canadian phase II randomized PA.7 trial investigated the additional benefit of dual checkpoint inhibition with durvalumab and tremelimumab to a standard chemotherapy regimen as first-line treatment in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Unfortunately, no significant improvement of responses or outcome could be achieved rendering this study a negative trial. Within the German platform-based QoliXane trial, quality of life was shown to be an essential prognosticator of survival with fatigue and nausea being independently associated with outcome of patients. Moreover, promising results could be observed with new targeted therapy approaches, which may lead to its investigation in larger randomized clinical trials.

Popper, Ulrich; Rumpold, Holger

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00694-5

Summary During this year’s virtual congress of the European Society of Oncology (ESMO) some practice-changing abstracts were presented. Especially immunotherapy (IO) has found its way into the treatment of esophageal (EC) and gastric cancer (GC) in both the adjuvant and palliative setting. The CheckMate 577 trial, which was presented in EMSO Presidential Symposium III, showed a doubling in disease-free survival (DFS) for patients with resected esophageal (EC) or esophagogastric junction cancer (EGJC) following neoadjuvant chemoradiation therapy (CRT), who had not achieved a pathological complete response, treated with nivolumab versus placebo. For advanced disease, the KEYNOTE-590 trial revealed a benefit of adding pembrolizumab to chemotherapy for patients with locally advanced or metastatic adenocarcinoma (EAC) or squamous cell carcinoma of the esophagus (ESCC) or EGJC Siewert type 1. In the CheckMate 649 study, patients (predominantly Caucasians) with advanced gastric, EGJC or EAC benefitted from the addition of nivolumab to chemotherapy in terms of overall survival (OS) and progression-free survival (PFS). In contrast, in the ATTRACTION‑4 trial, the Asian population gained a prolongation of PFS but not of OS by adding IO to chemotherapy.

Bartsch, Rupert

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00713-5pmid: 33968263

Summary Despite the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, results of several pertinent studies in the field of breast cancer (BC) were presented in a virtual format at the 2020 European Society of Medical Oncology (ESMO) Congress. Early results of the MonarchE trial investigating the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to standard adjuvant endocrine therapy indicated a lower recurrence rate in the combination group in a high-risk population of patients with early stage hormone receptor (HR)-positive/HER2-negative BC. In contrast, the PALLAS study evaluating adjuvant palbociclib could not confirm these results. Subtle differences in the respective trial populations, a higher discontinuation rate in PALLAS, or substance-specific differences may be responsible. In HER2-positive early stage BC, long-term results of the ADAPT-TP trial support the notion that chemotherapy-free treatment may be possible in a subset of patients with favourable response to HER2-directed therapy without compromising long-term outcome. The phase III IMpassion031 trial evaluated the addition of atezolizumab to neoadjuvant anthracycline/taxane-containing chemotherapy in triple-negative BC (TNBC). A significant improvement in terms of pathologic complete remission rate was observed but data concerning long-term outcome must be awaited. Final overall survival (OS) analysis of IMpassion130 confirmed the clinically relevant OS improvement observed with the addition of atezolizumab to first-line nab-paclitaxel in metastatic PD-L1 positive TNBC. In contrast, no benefit was observed with the addition of atezolizumab to solvent-based paclitaxel in a similar population. This contradiction is commonly explained by the need for corticosteroid co-medication with conventional paclitaxel, but the exact reason remains poorly understood. Antibody–drug conjugates (ADCs) have been successfully established in HER2-positive breast cancer; in TNBC, the phase III ASCENT trial compared the ADC sacituzumab govitecan with chemotherapy by physician’s choice in pretreated metastatic patients. A significant improvement in terms of progression-free survival and OS was observed rendering this drug a potential novel standard in this patient population.

Rushing, Elisabeth J.

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00680-x

Summary Identification of the underlying genetic and epigenetic alterations in an increasing number of tumors of the nervous system is contributing to a more clinically relevant classification. In the following article, the 7 cIMPACT-NOW publications, which adumbrate the upcoming 5th edition of the WHO Classification of Tumours of the Central Nervous Sytem are summarized.

Hofer, Silvia; Le Rhun, Emilie

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00693-6

Summary Leptomeningeal metastases from solid tumours are increasingly being diagnosed and require a careful assessment by an interdisciplinary neuro-oncological tumour board for adequate diagnosis, therapy planning and optimal care of the affected patients.

Steindl, Ariane; Berghoff, Anna Sophie

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00709-1

Summary Background Brain metastases (BM) still present a clinical challenge in oncology. Treatment of BM was mainly based on local approaches including neurosurgery and radiation. However, the fraction of patients with asymptomatic BM has risen over the last decade. Recent clinical trials on immune- and targeted therapies showed promising intracranial responses—especially in neurological asymptomatic status. Therefore, systemic treatment presents an emerging therapy approach specifically in patients with asymptomatic BM. Methods The present review highlights the recent advances in systemic therapeutic and preventive approaches in BM focusing on the main BM causing tumors: non-small cell lung cancer (NSCLC), melanoma and breast cancer. Results Remarkable intracranial efficacies were presented for several next-generation tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors, especially in asymptomatic BM patients. In NSCLC, osimertinib and afatinib presented intracranial response rates over 80%. Osimertinib showed even a potential for primary BM prevention. Considerable intracranial response rates were observed for the combination of dabrafenib and trametinib in BRAF mutated melanoma BM. Combined ipilimumab and nivolumab treatment in asymptomatic melanoma BM even presented with similar intra- and extracranial response rates. In breast cancer, HER2-targeted TKIs like lapatinib in combination with chemotherapy, or trastuzumab deruxtecan monotherapy presented also notable intracranial response rates. Conclusion New developments in targeted and immune-modulating therapies have postulated high intracranial efficacies in patients with BM from different solid tumors. However, more BM-specific studies and BM-specific endpoints in registration trials are warranted to underscore the role of systemic treatment in patients with BM.

Dieckmann, Karin; Herrmann, Harald

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00710-8

Summary Brain metastases (BM) are the most frequent intracranial tumors in adults. About 10–20% of the patients with cancer will develop them. Historically, most of the patients with brain metastases were treated with whole brain radiotherapy (WBRT). The intention was to control the metastases and to eliminate distant micrometastases. Randomized control trials showed no difference in survival in patients with single and oligometastases treated with WBRT compared with stereotactic radiosurgery (SRS). To avoid treatment-related toxicities with neurocognitive decline, indications for WBRT are changing. High precision therapy with SRS or postoperative stereotactic treatments have become increasingly important. Only in exceptional cases is WBRT still the treatment of choice.

Kuczkiewicz-Siemion, Olga; Dansonka-Mieszkowska, Agnieszka; Rutkowski, Piotr; Klimczak, Anna; Tysarowski, Andrzej; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna

2021 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-021-00708-2

Summary Most gastrointestinal stromal tumors (GISTs) are associated with molecular changes in two genes, KIT and platelet-derived growth factor receptor‑α (PDGFRA). However, only 5–10% of GISTs harbor PDGFRA mutation. Most tumors carry substitution affecting codon D842 in exon 18, which entails imatinib resistance. The other substitutions in this codon are extremely rare mutations (only 13 reported cases) involving D842Y substitution. This report presents a case of gastric GIST infiltrating liver segment III in a 70-year-old man. The tumor was studied histologically, immunohistochemically, and genetically. Mutational analysis revealed PDGFRA exon 18 mutation—p.(D842Y), c.2524G > T. Diagnosis of GIST with a high risk of progression was made. Due to subsequent liver metastases, imatinib therapy was commenced, which resulted in a minor disease response at a higher dose of imatinib. Our case is a unique, comprehensive report of in vivo PDGFRA D842Y-mutated GIST partial sensitivity to imatinib.