Survey of treatment and care practices in small-cell lung cancer among German radiation oncologists.

BACKGROUND: The management of small-cell lung cancer shows differences, particularly with regard to the use of radio- (RT), chemo-, and immunotherapy. We performed a survey among German radiation oncologists to assess the management of small-cell lung cancer (SCLC). METHODS: A 34-question online survey was created and sent out by e­mail to radiation oncologists throughout Germany. The survey period extended from August 2020 to January 2021. The questions addressed indications for RT, planning techniques, dosing/fractionation, target volume definition for consolidative thoracic irradiation, and the use of prophylactic cranial irradiation (PCI). At the same time, we surveyed the use of atezolizumab. The survey addressed the treatment practice for limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC). RESULTS: We received 74 responses. In LS-SCLC, treatment is planned predominantly based on diagnostic information from computed tomography (CT) of the thorax/abdomen/pelvis (88%), PET-CT (86%), and pulmonary function testing (88%). In LS-SCLC, 99% of respondents perform radiation concurrently with chemotherapy, preferably starting with cycle one or two (71%) of chemotherapy. The most common dose and fractionation schedule was 60-66 Gy in 30-33 fractions (once daily: 62% of all respondents). In ES-SCLC, 30 Gy in 10 fractions (once daily: 33% of all respondents) was the most commonly used regimen in consolidative thoracic irradiation. Only 25% use chemosensitization with RT. The inclusion criteria for PCI were similar for limited and extensive disease, with Karnofsky index (78% and 75%) being the most important decision factor. Respondents use a schedule of 30 Gy in 15 fractions most frequently in both stages (68% limited stage [LS], 60% extensive stage [ES]). Immunotherapy was used regularly or occasionally in LS-SCLC by 45% of respondents, with reduced lung function (37%), cardiac comorbidities (30%), and hepatic insufficiency (30%) being the most commonly mentioned exclusion criteria for this form of therapy. In ES-SCLC, atezolizumab use was reported in 78% of all questionnaires. Half of the respondents (49%) administer it simultaneously with cranial irradiation. CONCLUSION: Our survey showed variability in the management of SCLC. Results from future studies might help to clarify open questions regarding the optimal treatment paradigms. In addition, new treatment modalities, such as immunotherapy, might change practices in the near future.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

[Hearing classification in patients with vestibular schwannoma using German-language test procedures]. / Hörklassen bei Patienten mit Vestibularisschwannom bei Verwendung deutschsprachiger Testverfahren.

BACKGROUND: Hearing function in patients with vestibular schwannoma is often classified according to the Gardner and Robertson (1988) or the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS, 1995) systems. These classification systems are based on English-language test procedures, there is no German-language equivalent. The aim of the study was to investigate the influence of various target parameters on hearing classification and to derive a recommendation for the use of German-language test methods. MATERIALS AND METHODS: The rules for speech audiometry based on English-language test procedures were applied to German speech test materials. In 91 patients with vestibular schwannoma, pure tone hearing thresholds, speech recognition thresholds, and speech discrimination at different sound pressure levels were measured. The patients were categorized according to the Gardner and Robertson and AAO-HNS classifications. RESULTS: In both the Gardner-Robertson and the AAO-HNS classifications, the number of patients in the hearing classes with serviceable hearing function (measured as Pure Tone Average across three (3PTA) or four (4PTA) frequencies) was highest when using the 3PTA0,5;1;2 kHz condition, followed by 4PTA0,5;1;2;3 kHz, 4PTA0,5;1;2;4 kHz, and 4PTA0,5;1;2;"3"kHz. If maximum word recognition score (WRSmax) was used instead of word recognition 40 dB above the sensation level (WRS40SL), more patients were classified into the hearing classes with serviceable hearing function, irrespective of the mean pure tone hearing threshold. CONCLUSION: The Gardner-Robertson and AAO-HNS classifications can be used in German-speaking settings. The Freiburg monosyllabic test can be used to determine speech discrimination scores or maximum word recognition.

Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

Radiation treatment of hemato-oncological patients in times of the COVID-19 pandemic : Expert recommendations from the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance.

PURPOSE: The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care. METHODS: A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally. RESULTS: Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24 h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative). CONCLUSION: RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.

[Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation. German version]. / Management transmodiolärer und transmakulärer Vestibularis- und Cochlearisschwannome mit und ohne Cochleaimplantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

Radiotherapy for prostate cancer: DISCERN quality assessment of patient-oriented websites in 2018.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men. Radiotherapy represents one major treatment option in different therapeutic settings. As patients increasingly rely on internet-based medical information, we examined the quality of information on radiotherapy and prostate cancer in websites used by laypersons. METHODS: An Internet search from a patients` perspective was carried out using different search engines (Google, Yahoo and Bing, search terms: "prostate cancer" and "radiotherapy"). The quality of search results was analyzed with regard to the DISCERN score, HON code certification, the JAMA criteria and the ALEXA traffic rank. RESULTS: In general, websites were of good quality. The highest quality was found for websites operated by charity organizations. No significant differences in results obtained via the above-mentioned tools were seen for the examined search engines, but Google revealed the most stable search results in terms of temporal changes. CONCLUSION: Patients with prostate cancer can sufficiently inform themselves on general treatment options including radiotherapy on websites directed at laypersons. However, no simple strategy could identify high quality websites in general. For treating physicians, it is important to support patients in interpreting and ranking the vast quantity of information.

Side effects of radiotherapy in breast cancer patients : The Internet as an information source.

AIM: Breast cancer is the most common cancer type among women necessitating adjuvant radiotherapy. As the Internet has become a major source of information for cancer patients, this study aimed to evaluate the quality of websites giving information on side effects of radiotherapy for breast cancer patients. METHODS: A patients' search for the English terms "breast cancer - radiotherapy - side effects" and the corresponding German terms "Brustkrebs - Strahlentherapie - Nebenwirkungen" was carried out twice (5 months apart) using the search engine Google. The first 30 search results each were evaluated using the validated 16-question DISCERN Plus instrument, the Health on the Net Code of Conduct (HONcode) certification and the Journal of the American Medical Association (JAMA) benchmark criteria. The overall quality (DISCERN score) of the retrieved websites was further compared to queries via Bing and Yahoo search engines. RESULTS: The DISCERN score showed a great range, with the majority of websites ranking fair to poor. Significantly superior results were found for English websites, particularly for webpages run by hospitals/universities and nongovernmental organizations (NGO), when compared to the respective German categories. In general, only a minority of websites met all JAMA benchmarks and was HONcode certified (both languages). We did not determine a relevant temporal change in website ranking among the top ten search hits, while significant variation occurred thereafter. Mean overall DISCERN score was similar between the various search engines. CONCLUSION: The Internet can give breast cancer patients seeking information on side effects of radiotherapy an overview. However, based on the currently low overall quality of websites and the lack of transparency for the average layperson, we emphasize the value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.

Prognostic implications of the co-detection of the urokinase plasminogen activator system and osteopontin in patients with non-small-cell lung cancer undergoing radiotherapy and correlation with gross tumor volume.

BACKGROUND: The urokinase plasminogen activator system (uPA, uPAR, PAI­1) is upregulated in cancer and high plasma levels are associated with poor prognosis. Their interaction with hypoxia-related osteopontin (OPN) which is also overexpressed in malignant tumors suggests potential clinical relevance. However, the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell lung cancer (NSCLC), particularly in combination with OPN, has not been investigated so far. METHODS: uPA, uPAR, PAI­1 and OPN plasma levels of 81 patients with locally advanced or metastasized NSCLC were prospectively analyzed by ELISA before RT and were correlated to clinical patient/tumor data and prognosis after RT. RESULTS: uPAR plasma levels were higher in M1; uPA and PAI­1 levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001) which also correlated with PAI­1 (p < 0.001). The prognostic impact of OPN plasma levels in the RT of NSCLC was previously reported by our group. PAI­I plasma levels significantly impacted overall (OS) and progression-free survival (PFS). Low PAI­1 levels were associated with a significantly reduced OS and PFS with a nearly 2­fold increased risk of death (p = 0.029) and tumor progression (p = 0.029). In multivariate analysis, PAI­1 levels remained an independent prognostic factor for OS and PFS with a 3­fold increased risk of death (p = 0.001). If PAI­1 plasma levels were combined with OPN or tumor volume, we found an additive prognostic impact on OS and PFS with a 2.5- to 3­fold increased risk of death (p = 0.01). CONCLUSION: Our results suggest that PAI-1 but not uPA and uPAR might add prognostic information in patients with advanced NSCLC undergoing RT. High pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients and indicate a favorable prognosis as opposed to OPN where high plasma levels are associated with poor survival and metastasis. In combination, PAI-1 and OPN levels successfully predicted outcome and additively correlated with prognosis. These findings support the notion of an antidromic prognostic impact of OPN and PAI-1 plasma levels in the RT of advanced NSCLC.

Malignization of a vestibular schwannoma 13 years after radiation therapy.

This article presents a case of malignant transformation of vestibular schwannoma 13 years after stereotactic radiation therapy, which lead to an acute life-threatening condition. Although the observation is currently only based on case reports, an increasing number of these support the hypothesis that there is a relevant risk of malignant transformation in the long-term course of previously irradiated vestibular schwannomas. Therefore, long-term MRI follow-up should be considered.

[Malignization of vestibular schwannoma 13 years after radiation therapy]. / Malignisierung eines Vestibularisschwannoms 13 Jahre nach Bestrahlung.

This article presents a case of malignant transformation of vestibular schwannoma 13 years after stereotactic radiation therapy, which lead to an acute life-threatening condition. Although the observation is currently only based on case reports, an increasing number of these support the hypothesis that there is a relevant risk of malignant transformation in the long-term course of previously irradiated vestibular schwannomas. Therefore, long-term MRI follow-up should be considered.

Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group.

Nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is a very rare disease in childhood and adolescence. In Germany, about 15 newly diagnosed patients present with this disease annually; this number comprises less than 10% of all pediatric Hodgkin lymphoma cases. Since the EuroNet-PHL-LP1 trial for early stage nLPHL patients stopped recruiting in Germany in October 2014, the GPOH-HD writing committee reviewed the literature and decided to deliver treatment recommendations for childhood and adolescent nLPHL patients. These guidelines shall be applicable to young nLPHL patients in European countries that will no longer be able to participate in nLPHL trials for young patients. Therefore, the EuroNet-PHL-nLPHL-registry will be installed to provide quality assured central review of staging and response assessment for registered patients by the Central Review Board of EuroNet-PHL in Halle/Leipzig, Germany.

[What does the general and abdominal surgeon need to know about radiotherapy? - aspects of radiotherapy in general and abdominal surgery]. / Was muss der Allgemein- und Viszeralchirurg von der Strahlentherapie wissen? - Strahlentherapeutische Aspekte in der Allgemein- und Viszeralchirurgie.

Radiooncological therapies are an integral part of the multimodal oncological treatment concepts in general and abdominal surgery. These include therapeutic approaches with a curative intention such as the neoadjuvant (pre-operative) radiotherapy of locoregionally advanced and/or N+ oesophageal and rectal cancer, definitive combined chemoradiotherapy of locally advanced, unresectable oesophageal cancer or oesophageal tumour lesions of the upper third, definitive radiotherapy of anal cancer (sphincter sparing) and pre- or post-operative radiotherapy of soft tissue sarcoma on the one hand. A yT0 stage achieved as characteristic of a curative effect by radiation in oesophageal and rectal cancer (omitting subsequent surgical intervention, naturally under clinical and imaging-based controls within short-term follow-up intervals) can be considered as a very interesting set-up with regard to its reasonable integration in daily clinical practice, which needs to be further and critically discussed. By integrating radiotherapy in interdisciplinary therapy concepts, improved tumour control and survival rates with clinically acceptable toxicity can be achieved. On the other hand, non-invasive, locally ablative radiooncological therapies such as extracranial stereotactic body radiotherapy constitute an effective and feasible treatment method for liver metastases in oligometastatic colorectal cancer or other tumour entities according to the decisions by the institutional tumour board, offering high local tumour control rates which can be part of multistep, multimodal procedures with curative intention. This review aims at providing an overview for the general and abdominal surgeon, outlining relevant radiooncological treatment aspects in the multimodal cancer therapy with a focus on the treatment of rectal, oesophageal and anal cancer as well as soft tissue sarcoma and hepatic metastases in oligometastatic colorectal cancer.

A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor.

BACKGROUND: Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. MATERIAL AND METHODS: Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. RESULTS: All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. CONCLUSION: This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.

Proxy assessment of patients before and after radiotherapy for brain metastases. Results of a prospective study using the DEGRO brain module.

PURPOSE: Proxies of patients with poor performance status could give useful information about the patients' quality of life (QoL). We applied a newly developed questionnaire in a prospective QoL study of patients undergoing radiotherapy for brain metastases in order to make the first move to validate this instrument, and we compared the results with scores obtained using validated patient-completed instruments. MATERIALS AND METHODS: From January 2007 to June 2010, 166 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module BN20 were used to assess QoL in patients at the start of treatment and 3 months later. At the same time points, 141 of their proxies estimated the QoL with the new DEGRO brain module (DBM), a ten-item questionnaire rating the general condition as well as functions and impairment by symptoms in areas relevant to patients with brain metastases. RESULTS: At 3 months, 85 of 141 patients (60%) with initial response by a proxy were alive. Sixty-seven of these patients (79% of 3-month survivors) and 65 proxies completed the second set of questionnaires. After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL except headache. Correlations between self-assessed and proxy-assessed QoL were high in single items such as nausea, headache, and fatigue. CONCLUSIONS: The high correlation between self-assessment and proxy ratings as well as a similar change over time for both approaches suggest that in patients with brain metastases, proxy assessment using the DBM questionnaire can be an alternative approach to obtaining QoL data when patients are unable to complete questionnaires themselves. Our self-constructed and first applied DBM is the only highly specific instrument for patients with brain metastases, but further tests are needed for its final validation.

Craniospinal irradiation with concurrent temozolomide and nimotuzumab in a child with primary metastatic diffuse intrinsic pontine glioma. A compassionate use treatment.

Primary metastatic diffuse intrinsic pontine glioma (DIPG) is relatively rare and associated with a dismal prognosis. Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival. However, little is known about the feasibility and toxicity of this treatment approach. Here, we describe the case of an 8-year-old girl with primary metastatic DIPG who received craniospinal radiotherapy, a local boost, and concurrent temozolomide and nimotuzumab treatment based on an individual therapy recommendation. Radiotherapy could be completed without any interruption. However, concurrent temozolomide had to be disrupted several times due to considerable acute myelotoxicity (grade III-IV).Maintenance immunochemotherapy could be started with a delay of 5 days and was performed according to treatment schedule. The disease could be stabilized for a few months. A routine MRI scan finally depicted disease progression 5.7 months after the start of irradiation. The patient died 1.9 months later.

Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH).

PURPOSE: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. PATIENTS AND METHODS: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. RESULTS: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 ± 5 % after EFRT and 65 ± 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. CONCLUSION: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative.

The development of a hiPSC-based platform to identify tissue-dependencies of IDH1 R132H.

The application of patient-derived (PD) in vitro tumor models represents the classical strategy for clinical translational oncology research. Using these cellular heterogeneous cultures for the isolation of cancer stem cells (CSCs), suggested to be the main driver for disease malignancy, relies on the use of surrogate biomarkers or is based on CSC-enriching culture conditions. However, the ability of those strategies to exclusively and efficiently enrich for CSC pool has been questioned. Here we present an alternative in vitro CSC model based on the oncogenic transformation of single clone-derived human induced pluripotent stem cells (hiPSC). Hotspot mutations in the DNA encoding for the R132 codon of the enzyme isocitrate dehydrogenase 1 (IDH1) and codon R175 of p53 are commonly occurring molecular features of different tumors and were selected for our transformation strategy. By choosing p53 mutant glial tumors as our model disease, we show that in vitro therapy discovery tests on IDH1-engineered synthetic CSCs (sCSCs) can identify kinases-targeting chemotherapeutics that preferentially target tumor cells expressing corresponding genetic alteration. In contrast, neural stem cells (NSCs) derived from the IDH1R132H overexpressing hiPSCs increase their resistance to the tested interventions indicating glial-to-neural tissue-dependent differences of IDH1R132H. Taken together, we provide proof for the potential of our sCSC technology as a potent addition to biomarker-driven drug development projects or studies on tumor therapy resistance. Moreover, follow-up projects such as comparing in vitro drug sensitivity profiles of hiPSC-derived tissue progenitors of different lineages, might help to understand a variety of tissue-related functions of IDH1 mutations.

[Radiation-related caries: etiology and possible preventive strategies. What should the radiotherapist know?]. / Radiogene Karies: Ätiologie und Möglichkeiten der Prävention. Was sollte der Strahlentherapeut wissen?

BACKGROUND: After radiation treatment of head-and-neck cancer, the impairment of patient's quality of life still remains an issue. After completion of the treatment course, a substantial number of patients develop so-called radiation caries. In addition, almost 50% of all cases of infectious osteoradionecrosis (iORN) of the jaws are directly associated with radiation caries. This review addresses our current knowledge on the etiology and pathogenesis of radiation caries including possible preventive strategies. MATERIALS AND METHODS: A PubMed search using the terms "radiation caries" ("radiation related caries", "radiation related damage to dentition") and "radiogenic caries" ("postradiation caries", "dental complications and radiotherapy") was performed. The analysis of its content focused on the etiology, the pathogenesis, and the available knowledge on prophylaxis as well as treatment of radiation caries. RESULTS: For this review, 60 publications were selected. As main causal factors for radiogenic caries, either indirect impairment, resulting from alterations in the oral environment (e.g., radiation-induced xerostomia) or direct radiation-induced damage in teeth hard tissues are discussed. Radiation caries remains a lifelong threat and, therefore, requires permanent prevention programs. CONCLUSION: To enable optimal medical care of the patients during the time course of radiotherapy as well as afterwards, close interdisciplinary cooperation between radiotherapists, oral surgeons, otorhinolaryngologists, and dentists is absolutely essential.