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2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00624-x
Summary BRCA mutation-related DNA repair deficiencies increase the individual sensitivity to DNA-targeting agents. Therefore, the patient’s BRCA mutational status is evaluated in clinical practice as a predictive marker in response to platinum salts and poly-ADP-ribose polymerase (PARP) inhibitors for breast cancer treatment. A substantial subset of BRCA wild-type breast cancer lesions, however, share both prominent molecular characteristics and clinical behavior patterns with cancer that harbors BRCA mutations, including DNA repair deficiencies. Also referred to as “BRCAness”, this observation is related to aberrations of the homologous recombination (HR) repair pathway, which deprive cancer cells of the ability to adequately mend potentially lethal double-strand breaks and result in a BRCA-like genomic instability. Hence, HR deficiency is a promising target for related therapeutic options and the predictive potential of HR testing for treatment response has been increasingly studied. Several HR deficiency-testing assays have been proposed and prospectively validated for various cancer types; however, preliminary results in early breast cancer are inconsistent. As scientific evidence for a potential therapeutic benefit in breast cancer is scarce, HR testing remains highly experimental and should be limited to the boundaries of clinical studies until results of ongoing phase 3 trials are available.
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00658-1
Summary Molecular targeted therapies in pancreatic ductal adenocarcinoma (PDAC) lag behind treatment options in other tumor entities. The POLO trial has provided promising preliminary data for targeting gBRCA in PDAC by the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib. This review tries to show further potential approaches to exploit faulty DNA repair mechanisms beyond gBRCA and olaparib.
Strobl, Andreas; Hartl, Maximilian; Burian, Martin
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00638-5
Summary Robotic surgery in the field of head and neck cancer was initiated at the beginning of this century. In the last decade, transoral robotic surgery (TORS) had to prove its oncological equivalence to standardised conservative treatment regimens like radiotherapy and radiochemotherapy and to other transoral or open surgical procedures. The amount of data on oncological efficacy, cost effectiveness and long-term outcomes has continued to increase over the last few years. The transoral approach enables minimally invasive tumour resection, which helps to minimize functional postoperative deficits. Compared with traditional concurrent radiochemotherapy (CRCT), the radiation dose is lower in the adjuvant setting and therefore helps to reduce long-term toxicities. Moreover, in case of absent risk factors in the histological specimen, it might be possible to avoid additional chemotherapy. Thus, long-term toxicities eventually caused by CRCT might be decreased.
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00623-y
Summary The management of head and neck tumors is challenging and requires a multidisciplinary approach. Besides the common histology of squamous cell cancer, other histologies like adenoid cystic carcinoma, mucosal melanoma, and adenocarcinoma are often present. These tumors are radioresistant and need high radiation doses. Photon beam therapy is often limited by the normal tissue tolerance, and particle therapy using protons or carbon ions is a valuable treatment option. Due to their dosimetric advantages, protons enable deposition of high tumor doses, while optimally sparing the surrounding tissue. Carbon ions offer the additional advantage of a higher linear energy transfer (LET) which results in a higher biological effectiveness of tumor cell damage. Therefore, while protons can also be used in sterilizing microscopic disease, carbon ions should be considered in large macroscopic disease, where a significant tumor burden has to be managed.
Kloppenburg, Marcel; Mildner, Finn; Kasseroler, Maria Theresia; Dejaco, Daniel; Amann, Arno
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00645-6
Summary Background Recurrent and metastatic squamous cell carcinomas of the head and neck are still difficult to treat. The EXTREME regimen has been the standard of care for the last decade, but recent studies initiated a change. In this work we provide an overview of the established treatment concepts for recurrent and metastatic squamous cell carcinomas of the head and neck with palliative intent. Material and methods We performed a literature search using the key words: recurrent, metastatic, cancer, head and neck, HNSCC, treatment, chemotherapy, immunotherapy, salvage, and surgery. Furthermore, the presentations of the ASCO highlights of head and neck cancer from 2019 and 2020 were included. Results The KEYNOTE-048 and the TPEx randomized trial are the most relevant trials in the first line setting. The CheckMate 141 and KEYNOTE-040 have the greatest impact for the second line regimen. Conclusion The expression of PD-L1, prior treatment, performance status, local symptoms and tumor burden are the most important factors regarding choice of treatment. Pembrolizumab alone or in combination with chemotherapy can be recommend as the 1st line standard in patients with combined positive score (CPS) ≥20. The choice of therapy in patients with CPS 1-19 and CPS <1 has to be individually evaluated for each patient. Furthermore, TPEx is an encouraging alternative to the EXTREME regimen with less toxicity and improved quality of life.
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00614-z
Summary Salivary gland cancers (SGC) are a rare and heterogeneous group of malignancies. Most frequently tumors arise in the parotid gland. The most common histologic subtypes are adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Rare subtypes include salivary ductal carcinoma (SDC), mammary analogue secretory carcinoma (MASC) and adenocarcinoma not other specified (AC NOS). For locally advanced or metastatic disease, chemotherapy has been the mainstay of therapy. The course of disease differs markedly between the subtypes, especially ACC usually presents as slowly progressing disease. Due to the rarity of these tumors only small phase I/II studies exist, which report efficacy of cytotoxic regimens in advanced SGC. However, due to advances in the understanding of tumor biology and molecular testing, drugable genetic changes like androgen receptor (AR) status, HER2/neu overexpression and neurotrophic tyrosine receptor kinase (NTRK) gene fusion have evolved as potential therapy targets in subsets of SGC. Consequently therapy with androgen receptor blockade (ARB) can be offered to patients with AR expressing tumors. Anti-HER2 therapy with trastzumab is an option for the treatment of tumors with overexpression of HER2/neu and finally NTRAK inhibitors can be used for tumors harboring a NTRK gene fusion. Taken together, due to the small number of patients, data from large phase III studies for the treatment of SGC are missing. However, promising targeted therapy approaches have been recently undertaken.
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00613-0
Summary Background The majority of patients who suffer from head and neck cancer are malnourished even prior to treatment initiation. In addition, side effects from cancer therapy including change in taste, mucositis, nausea or diarrhea increase patients’ malnutrition. Therefore, early management is crucial to improve nutritional status, prognosis and quality of life of patients. Methods A literature research was performed in PubMed, Medline and other available databases. The guidelines of the German Society for Nutritional Medicine, the European Society for Clinical Nutrition and Metabolism and common recommendations of other countries were selected, analyzed and summarized. Results Early screening for malnutrition is recommended for all cancer patients. Adequate intake of energy and protein should be ensured which may be achieved by consumption of oral nutritional supplements or enteral nutrition such as tube feeding. Conclusion It is important to determine the best course of management to maintain body weight and reduce typical adverse effects of malnutrition to improve quality of life. All patients at any stage of their treatment should receive intensive dietary counseling.
Böttcher, Bettina; Goeckenjan, Maren
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00620-1
Summary Fertility preservation has become an integral part of standard treatment for young patients with planned gonadotoxic therapy. The decision-making process is an interdisciplinary challenge to both oncologists and radiotherapists involved in the process of diagnosis and treatment. Nevertheless, even today, not every patient receives adequate counselling about fertility preserving techniques. Current data on the options of fertility preservation for women, including cryopreservation of oocytes, embryos, ovarian tissue, transposition of ovaries and medical treatment, are summarized in this review.
Reiser, Elisabeth; Böttcher, Bettina; Minasch, Danijela; Mangesius, Julian; Toth, Bettina
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00646-5
Summary Cytotoxic chemotherapy regimens and radiotherapy can lead to acute ovarian failure, premature ovarian insufficiency and menopause. Fertility preservation options before radiotherapy include ovarian transposition, where one or both ovaries are placed outside the radiation field. However, the efficacy of ovarian transposition is questioned, as the conservation of ovarian function varies between 17 and 95% in the literature.
Böttcher, Bettina; Winkler-Crepaz, Katharina
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00626-9
Summary Fertility preservation in women has become well established over the last two decades. Nevertheless, options for cancer survivors need to be improved to regain ovarian functioning, ideally leading to pregnancy and live birth. Techniques to protect the ovary from the damage of cytotoxic agents, to improve the survival of follicles in the ovarian graft, and to minimize the risk of re-seeding malignant cells after ovarian tissue transplantation are the object of current research all over the world. The demand for fertility preservation procedures in patients with benign diseases like systemic lupus erythematosus before cytotoxic therapy, in patients with endometriosis before surgery, and in patients with genetic predispositions which can lead to a premature ovarian failure will further increase in coming years. In this short review, these future perspectives are presented.
Bralo, Helena; Roethlisberger, Maria; Nouri, Kazem
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00661-6
Summary Fertility preservation should only be offered to patients with endometrial cancer stage Ia grade 1 (G1), who present without myometrial invasion or where the cancer has invaded less than 50% of the myometrium, with no evidence of pathological lymph nodes or no evidence of synchronous or metachronous ovarian tumor. It is estimated that about 22% will achieve successful pregnancy.
Gasser, Elisabeth; Kogler, Pamela; Lorenz, Andreas; Kafka-Ritsch, Reinhold; Öfner, Dietmar; Perathoner, Alexander
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00647-4
Summary Peritoneal carcinomatosis from colorectal cancer is associated with a poor prognosis and is usually treated with systemic chemotherapy and immunotherapy alone. In patients with isolated peritoneal carcinomatosis (PC) without nonperitoneal metastases, however, cytoreductive surgery (CRS) has been shown to significantly improve outcome and to achieve even cure in selected patients in combination with systemic therapy. The additional use of a hyperthermic intraperitoneal chemotherapy (HIPEC) is primarily indicated to control microscopical residual tumor tissue in the peritoneal cavity after successful CRS. Another more recent option is the application of an adjuvant HIPEC to prevent peritoneal carcinomatosis in high risk patients with pT4 cancer or perforated cancer at the time of or after primary surgery. The aim of this short review is to highlight the corresponding available literature and assess the role of CRS and HIPEC in the context of modern chemotherapy and immunotherapy.
Yurttas, Can; Fisher, Oliver M.; Cortés-Guiral, Delia; Haen, Sebastian P.; Königsrainer, Ingmar; Königsrainer, Alfred; Beckert, Stefan; Liauw, Winston; Löffler, Markus W.
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00653-6
Summary Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a multimodal treatment approach combining surgical interventions of varying extent with administration of heated cytostatic drugs flushed through the abdominal cavity. Hitherto, this treatment has been popular for peritoneal metastasis (PM), e.g. from colorectal cancer (CRC). Recent randomized controlled trials (RCT) question the benefit of HIPEC in its present form for CRC treatment and raise fundamental issues, eliciting discussions and expert statements regarding HIPEC relevance and interpretation of these results. Unfortunately, such discussions have to remain uninformed, due to the lacking publication of crucial peer reviewed RCT results. Novel basic research aware of HIPEC futility suggests there may be systematic limitations. Innovative modelling approaches for HIPEC may shed light on the reasons for therapeutic failure of frequently used drugs and may lead the way to select better alternatives and/or more rational approaches for the design of HIPEC procedures (e.g. regarding exposure time or temperature). Available evidence strongly supports the notion that CRS is the mainstay for the treatment effects observed in PM from CRC. Unfortunately, HIPEC has become a surrogate for surgical expertise in the field and optimal surgery may therefore outweigh the potentially harmful effects of HIPEC treatment, particularly in lieu of modern systemic chemotherapies. The current situation which frequently is assumed to be deadlocked should be regarded as a challenge to investigate HIPEC with well-designed prospective clinical trials, potentially even constituting an opportunity for introducing innovative trial designs that solve the multifaceted issues of a very heterogeneous treatment approach.
Prager, Gerald; Gerger, Armin; Höfler, Gerald; Webersinke, Gerald; Rumpold, Holger; Winder, Thomas; Bartsch, Rupert; Preusser, Matthias; Eisterer, Wolfgang
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00662-5
Summary The Austrian Society for Hematology and Medical Oncology (OeGHO) aimed to define a clear position on the importance of molecular diagnostics in solid tumors. This position covers the following four points: the indication for the assessment of a molecular profile has to be given by the treating medical oncologist depending on the course of the patient’s disease; the requirement that the molecular profile might lead to a therapeutic intervention in the individual patient; quality control of the molecular analysis through proficiency testing and/or accreditation of the method used; and adherence to patient’s data safety according to data protection regulation. The present position paper does not cover the topic of germline mutations and other assessments in human genetics. Due to the fact that clinically relevant information on germline mutations may appear during the diagnostic processing we strongly recommend thorough patient education and documentation of patient consent.
Puhr, Hannah Christina; Ilhan-Mutlu, Aysegül
2020 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-020-00649-2
Summary The prognosis of patients with metastatic gastroesophageal cancer remains poor despite numerous promising clinical trials, and the clinical benefit of systemic therapies is under critical review. This case report of a patient with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric adenocarcinoma is an impulse for the importance of individual decision making and molecular guided treatment options.