memo - Magazine of European Medical Oncology

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0464-3

Thaler, Josef

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0453-6

Heidegger, Isabel

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0459-0

Erdel, Martin

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0436-7

In tumor cytogenetics, individual cancer cells are genetically analyzed, either conventionally by studying the mitotic chromosomes of dividing tumor cells from in vitro cultures (metaphase analysis; karyotyping) or molecularly by identifying specific DNA sequences or chromosomal regions in the nucleus of nondividing tumor cells in situ (interphase fluorescence in situ hybridization). In a typical cytogenetic study, 20 metaphase cells and/or 200 interphase cells are microscopically investigated for visible somatic chromosome changes that might occur in a given neoplastic clone. The detection sensitivity for aberrant cells, therefrom, ranges roughly between 1 and 10% in both, conventional and molecular cytogenetics. This and the need for a culturable testing material is why cytogenetics is completely different to the more sensitive molecular genetic methods (polymerase chain reaction, deep sequencing). The great strength of cytogenetics is the acquisition of substantial amounts of information about the whole genome of a tumor, cell per cell, in a single assay, such as detection of previously unknown chromosome anomalies, revealing of primary and secondary changes, proof of clonality and cell lineage origin, positional evidence for tumor-relevant genes, knowledge of the proliferating ability of an aberrant clone, and conclusions for staging and prognosis at diagnosis, as well as information about disease regression and clonal evolution during follow-up.

Richtig, Erika

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0455-4pmid: 30595751

The 2018 ASCO Annual Meeting provided a closer look on the details of studies already presented. In melanoma, the interest was on neoadjuvant treatment options with high pathological response rates as well as updates on large phase III studies in stage IV disease. Further new targets were discussed focusing on additional drugs to a PD-1 backbone treatment.

Gamerith, Gabriele; Kocher, Florian; Rudzki, Jakob; Pircher, Andreas

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0444-7pmid: 30595752

Non-small cell lung cancer (NSCLC) treatment was booming at this year’s ASCO 2018 meeting as several well-performed phase III trials with practice-changing potential were presented. Thereby immune checkpoint blockade (ICB) consolidated its major role in the treatment of NSCLC patients without genetic alterations and extended its use by showing impressive data on ICB combination therapies (mainly combined with chemotherapy). Furthermore the role of predictive biomarkers for ICB therapy (Programmed death-ligand 1 [PD-L1] expression, tumor mutational burden [TMB] testing and others) have been further developed and blood-based tests were presented with promising data revealing the potential of this minimally invasive method for treatment monitoring and guidance in the future. Nevertheless the best biomarker is still elusive and future research is ongoing and might be a multimodal approach combining different modalities. No major studies concerning new genetic alterations or innovative targets were presented and the focus in genetic driven NSCLC was the evaluation of combinational approaches (e.g. in epidermal growth factor receptor [EGFR] mutation positve patients, EGFR tyrosine kinase inhibitor [TKI] plus anti-angiogenic agent or chemotherapy backbone). The presented results showed some benefit for the combinational approach; however toxicity might be an issue and further validation is necessary. Summarizing, ASCO 2018 showed that combinational approaches will be the future standard treatment in NSCLC and that biomarker identification is more heterogeneous and complex than anticipated, but presented next generation techniques may pave the way to a more personalized cancer therapy.

Dormann, Clemens; Aichberger, Karl

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0448-3

At this year’s American Society of Clinical Oncology (ASCO) annual meeting two large phase 3 trials, the ABCSG-18 and the D‑CARE study, analysed the effects of adjuvant denosumab in breast cancer patients and reported different outcomes. Another phase 3 study, the ASTRRA trial, investigated the use of adjuvant ovarian function suppression (OFS) in high-risk premenopausal patients. This trial confirmed the benefit of OFS similar to the results of the already published SOFT/TEXT trials but raises some crucial questions on the optimal duration of OFS in these patients. The results of the SOFT/TEXT trials were also updated at this meeting.

Rinnerthaler, Gabriel; Gampenrieder, Simon; Greil, Richard

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0450-9pmid: 30595753

This article reviews the clinically most relevant presentations at the American Society of Clinical Oncology (ASCO) annual meeting 2018 on the topic of metastatic breast cancer. In the randomized placebo-controlled phase 3 trial MONALEESA-3, testing ribociclib vs. placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative (HER2−) advanced breast cancer (ABC), an increase of median progression-free survival (PFS) from 12.8 months to 20.5 months by the addition of the CDK4/6 inhibitor was reported (HR 0.59; P > 0.01). Taselisib, an alpha specific PI3K inhibitor, was tested in combination with fulvestrant in pretreated HR+/HER2− ABC patients with PIK3CA mutations in the placebo-controlled phase 3 trial SANDPIPER. PFS was significantly longer (7.4 months vs 5.4 months; HR 0.70, P < 0.01) but severe adverse events were more frequent (32% and 9%) in the taselisib group. In triple-negative breast cancer, the AKT inhibitor capivasertib (AZD5363) was combined with paclitaxel as first-line treatment in the placebo-controlled phase 2 trial PAKT. In patients with altered PIK3CA, AKT1 or PTEN, median PFS increased from 3.7 months to 9.3 months (HR 0.30; two-sided P = 0.01). No treatment effect was shown in the non-altered group. The most common adverse events attributed to capivasertib were diarrhea, fatigue and stomatitis. Results of two phase I trials of trastuzumab antibody-drug conjugates (ADCs) indicated HER2 as a non-oncogenic surface target in breast cancer patients expressing HER2.

Bartsch, Rupert; Bergen, Elisabeth

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0441-xpmid: 30595754

At the 2018 ASCO Annual Meeting, data from several interesting studies in HER2-positive metastatic breast cancer were presented. While not immediately practice changing, these trials indicate the future directions of drug development in this field. Early phase studies with novel antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan and trastuzumab-duocarmazine suggest relevant clinical activity of these drugs in pretreated patients; in addition, these ADCs may offer activity in low HER2-expressing tumours as well. ZW25, a bispecific HER2-directed antibody targeting the extracellular domains 2 and 4, showed excellent tolerability and considerable single-agent activity. A combination of T‑DM1 with the tyrosine-kinase inhibitor neratinib yielded high response rates, while a study of trastuzumab plus durvalumab reported disappointing results. Although formally negative, overall survival data from the PHEREXA trial suggest clinical activity of dual HER2-inhibition with trastuzumab and pertuzumab in patients with prior trastuzumab treatment for advanced disease. A combined analysis of two tucatinib studies showed that systemic therapy is active when continued in case of isolated central nervous system progression and stable extracranial disease after local therapy of brain metastases; finally, a small prospective observation in asymptomatic patients with reduced left ventricular ejection fraction suggests that anti-HER2 treatment may be reasonably safe in this population.

Pichler, Renate; Horninger, Wolfgang; Heidegger, Isabel

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0422-0pmid: 30595755

Prostate cancer and urothelial carcinoma are the two most common urological cancers. The aim of this short review is to highlight abstracts from this year’s ASCO Annual Meeting. The phase III SPCG-13 trial showed no difference in biochemical disease-free survival by the addition of docetaxel after primary radiation therapy of localized high-risk prostate cancer. In bone dominant metastatic castration resistant prostate cancer, the phase II radium-223 dose escalation study concluded that the currently used dose with 6 cycles of 55 kBq/kg remains the standard of care. The PARP inhibitor olaparib plus abiraterone provided a significant benefit in radiological progression-free survival compared with abiraterone alone, independent of homologous recombination repair (HRR) mutation status. In localized muscle-invasive urothelial carcinoma, two phase II trials (ABACUS and PURE-01) exploring the pathological complete remission rate of atezolizumab and pembrolizumab prior to cystectomy in cisplatin-unfit or cisplatin-fit patients are presented. Novel targeted therapies such as fibroblast growth factor receptor (FGFR) inhibitors or monoclonal antibodies against nectin-4 confirmed astonishing objective response rates in heavily pretreated metastatic urothelial carcinoma (mUC) patients, resulting in a median overall survival (OS) up to 13.8 months. Finally, updated 1‑year and 2‑year OS survival rates of pembrolizumab and atezolizumab in the first line setting of mUC are presented.

Sonnweber, Bettina; Wöll, Ewald

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0447-4

Results from studies in upper gastrointestinal cancer presented at the 2018 American Society of Clinical Oncology (ASCO) meeting are promising. Prophylactic treatment of Barrett’s esophagus with high proton pump inhibitor therapy plus aspirin showed positive results on death, esophageal adenocarcinoma and dysplasia. Current studies on the treatment of gastric cancer included the following: S‑1 plus docetaxel as postoperative adjuvant chemotherapy in Asian patients, triplet therapy (cisplatin, S1, and docetaxel) in Asian patients, paclitaxel vs. pembrolizumab, and a biomarker study for trastuzumab continuation. Advances in the treatment of pancreatic cancer are likely to be practice changing: combined chemotherapy mFOLFIRINOX clearly improved disease-free survival in patients with resected pancreatic ductal adenocarcinomas. In the palliative setting, the introduction of FOLFIRINOX and gemcitabine/nab-paclitaxel may allow treatment with lower toxicity and allow broader patient selection. In the treatment of cholagiocellular cancer, gemcitabine plus S‑1 was non-inferior to gemcitabine plus cisplatin. Preliminary data in the treatment of neoendocrine tumors with temozolomide plus capecitabine are promising. Finally, the second-line treatment of hepatocellular carcinoma with ramucirumab showed a significant survival benefit.

Strasser, Christa; Graf, Sebastian; Tauber, Volkmar; Krause, Steffen

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0451-8

The intestinal microbiome plays a significant role in modulation of the immune system and carcinogenesis. An increasing number of studies are now investigating the microbiome and the effect of dysbiosis on urological diseases.

Tsaur, Igor; Thomas, Christian

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0442-9

Previously assumed to be rare, the prevalence of aggressive variants of prostate cancer has increased rapidly. This histologically heterogeneous group of cancers, including different forms of the neuroendocrine carcinoma of the prostate, share a common clinical course associated with a poor response to androgen deprivation treatment and fatal prognosis. Currently, the most commonly used terms are aggressive variant of prostate cancer and treatment-related neuroendocrine prostate cancer. The best treatment of these tumors in clinical routine is still being debated. Here, we highlight the clinically most relevant aspects of this heterogeneous disease and summarize recommendations for clinical routine.

Ladurner, Michael; Horninger, Wolfgang; Bektic, Jasmin

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0452-7

Although localized prostate cancer (PC) is a curable disease, a significant proportion of patients progress from advanced PC to metastatic castration-resistant prostate cancer (mCRPC). Several new treatments for mCRPC were approved including new hormonal therapies, chemotherapies, and radium-223. For patients with disease progression after the standard therapies, lutetium-prostate-specific membrane antigen (Lu-PSMA) therapy could be an option.

Bektic, Jasmin; Horninger, Wolfgang

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0456-3

Oligometastatic prostate cancer has been considered an intermediate state between localized disease and widespread metastases, but there is no consensus on the definition of oligometastasis in prostate cancer. At present, a clinical diagnosis made on the basis of up to five extrapelvic lesions is reasonable for use. Retrospective studies and post hoc analyses suggest that local or metastasis-directed interventions could have benefits in the oligometastatic state including a better response to systematic therapy, lower risk of local complications, and possible positive impact on cancer-specific survival and overall survival; however, insufficient data are available to draw reliable conclusions. In this short review, we summarize the current available data on the role of surgery in oligometastatic prostate cancer.

Steinkohl, Fabian; Pichler, Renate; Junker, Daniel

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0458-1pmid: 30595756

Magnetic resonance imaging (MRI) of the prostate has become the gold standard for visualization of prostate cancer. Prostate MRI is usually performed as multiparametric MRI (mpMRI). Since mpMRI has several drawbacks, a biparametric MRI (bpMRI) of the prostate has been proposed. Many studies have been published on mpMRI and bpMRI in recent years. This short review offers an overview of the latest developments in this rapidly evolving field of research.

Kiesewetter, Barbara; Raderer, Markus

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0449-2pmid: 30595757

Several compounds have recently been approved for the systemic treatment of advanced well-differentiated neuroendocrine tumours (NET) of gastroenteropancreatic (GEP) or lung origin. Based on the PROMID and CLARINET trials, somatostatin analogues (SSA) are the preferred first-line approach for all GEP-NET and offer—in addition to antiproliferative effects—durable symptomatic relief for hormonally active tumours. The mTOR inhibitor everolimus has been approved for progressive GEP- and lung-NET and is a widely used drug in this setting. Furthermore, recent results have underlined the high efficacy of somatostatin-receptor targeting radionuclide therapy (PRRT) in somatostatin-receptor positive midgut tumours and PRRT is now considered standard treatment for midgut-NET progressing on SSA. The optimal application of PRRT in somatostatin receptor positive NET with non-midgut site is currently an issue of discussion and should be decided on an individually basis in multidisciplinary boards. Following new insights in the genetic landscape of NET, “hot topics” in recent months include optimal treatment of the recently defined NET G3 and preliminary data on immunotherapy.

Gruenberger, Thomas; Jonas, Phillip; Lutz, Rebecca; Gruenberger, Birgit

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0443-8

Metastatic colorectal cancer was long considered for palliative therapy, until significant improvement in surgical techniques and more effective chemotherapeutic regimens changed the way metastatic colon cancer patients are being treated today. Prospective trials were designed to answer the question which patient with metastatic disease could potentially be cured by a multidisciplinary approach with medical oncologists, surgeons and radiation oncology using an induction chemotherapy in combination with a targeted agent and being monitored for resectability in multidisciplinary tumor boards. Patients with oligometastatic disease should be treated with the goal of curative resection. This review will highlight studies conducted over the past 15 years addressing this issue. An algorithm is proposed illustrating how every newly diagnosed mCRC (metastatic colorectal cancer) patient could be discussed in the tumor board to decide the best treatment sequence with the best chance of cure.

Niedersüß-Beke, Dora; Simon, Judit; Schiffinger, Michael; Mader, Robert

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0440-y

Asnafi, Ali; Farshchi, Niloofar; Khosravi, Abbas; Ketabchi, Neda; Behzad, Masumeh; Shahrabi, Saeid

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0446-5

Yolcu, Alkim; Dirican, Ahmet; Ozturk, Gamze; Cetin, Cigdem; Aydogdu, Ismet

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0437-6

We present a case of Visceral Leishmaniasis (VL) in a patient with gastric cancer treated with chemoradiotherapy. A 69-year-old man with gastric carcinoma had been treated with total gastrectomy, lymphadenectomy and postoperative radiotherapy with chemotherapy. Then 3 years after treatment, due to pancytopenia with progressive trombocytopenia and splenomegaly, bone marrow examination was performed and Leishmania spp. amastigotes were diagnosed. When antibiotherapy was completed, splenomegaly was eliminated and the laboratory results became normal. VL should be kept in mind in the differential diagnosis of patients, even adults, with splenomegaly, trombocytopenia and a history of contact with dogs in endemic countries such as Turkey.

Chakrabarti, Amrita; Sood, Nitin

2018 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-018-0435-8

Ruxolitinib is a Janus kinase (JAK) 2 inhibitor that is an effective therapeutic agent for primary myelofibrosis (PMF), which helps significantly to reduce constitutional symptoms and spleen size. However, this drug has significant immunomodulatory effects that may lead to various opportunistic infections. Reactivation of tuberculosis and certain viral infections have been well documented. Although a few reports of patients with pulmonary cryptosporidiosis on ruxolitinib exist, an extensive literature review shows only one previously reported case of cryptococcal meningoencephalitis in an immunocompetent patient on ruxolitinib, with a history of avian exposure. Here we report another extremely rare incidence of cryptococcal meningitis in a fully immunocompetent male patient on ruxolitinib, with no history of contact with birds. Although this is an approved and effective therapy for PMF, careful evaluation, screening, and prophylaxis in susceptible individuals should be considered before starting therapy.