Nicolaus Andratschke

Bio: Nicolaus Andratschke is an academic researcher from University of Zurich. The author has contributed to research in topics: Medicine & Radiation therapy. The author has an hindex of 32, co-authored 164 publications receiving 3802 citations. Previous affiliations of Nicolaus Andratschke include European Organisation for Research and Treatment of Cancer & University of Texas MD Anderson Cancer Center.

MR-guidance in clinical reality: Current treatment challenges and future perspectives

Abstract: Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites. MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.

ICRU report 91 on prescribing, recording, and reporting of stereotactic treatments with small photon beams : Statement from the DEGRO/DGMP working group stereotactic radiotherapy and radiosurgery.

Abstract: The International Commission on Radiation Units and Measurements (ICRU) report 91 with the title "prescribing, recording, and reporting of stereotactic treatments with small photon beams" was published in 2017. This extensive publication covers different relevant aspects of stereotactic radiotherapy such as small field dosimetry, accuracy requirements for volume definition and planning algorithms, and the precise application of treatment by means of image guidance. Finally, recommendations for prescribing, recording and reporting are given.

Update of human spinal cord reirradiation tolerance based on additional data from 38 patients

Abstract: Purpose: To update a combined analysis of all published clinical data. Methods and Materials: We collected data from 38 additional patients treated in our department or published in four different reports and calculated the biologically effective dose (BED) according to the linear-quadratic model using an α/β value of 2 Gy for cervical and thoracic cord and 4 Gy for lumbar cord. In this model, a dose of 50 Gy given in single daily fractions of 2 Gy is equivalent to a BED of 100 Gy 2 or 75 Gy 4 . Results: The 2005 risk score based on three variables (cumulative BED, highest BED of all treatment series in a particular individual, and interval), which discriminate three different risk groups, does not require modification. The low-risk group now contains 1 case of radiation myelopathy (RM) after hypofractionated stereotactic reirradiation. Therefore, the rate increased from 0% to 3%. Intermediate-risk patients developed RM in 25%, and high-risk patients in 90%. When the interval between the two treatment courses is not shorter than 6 months and the dose of each course is ≤98 Gy 2 , the cumulative BED where no case of RM has yet been reported is 120 Gy 2 . Conclusions: Based on these updated results, the risk of RM appears small after ≤135.5 Gy 2 when the interval is not shorter than 6 months and the dose of each course is ≤98 Gy 2 . We would recommend limiting the dose to the lowest feasible level. The influence of very steep dose gradients from stereotactic and intensity-modulated approaches (i.e., a more complex volume-effect) requires further evaluation.

Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies.

Abstract: Purpose Evidence is rapidly mounting that dysregulated epidermal growth factor receptor (EGFR) signaling is one of the underlying mechanisms of more aggressive tumor behavior and increased tumor resistance to cytotoxic agents, including radiotherapy (RT). This has led to extensive preclinical and clinical studies aimed at developing effective treatment strategies that counteract EGFR-mediated signaling. In this article, we review preclinical studies, primarily from our laboratory, addressing the role of EGFR in tumor radioresponse and the use of C225, a human-mouse chimeric anti-EGFR monoclonal antibody, to improve the results of RT. Methods and materials Mouse carcinomas were used to study the influence of EGFR on tumor radioresponse. EGFR expression was assessed by Western blot analysis, and cDNA transfection experiments were performed to determine a causal relationship between EGFR and tumor cell radioresistance. A431 human tumor xenografts growing in nude mice were used to test whether blockade of EGFR with C225 anti-EGFR antibody enhances tumor radioresponse. Results Our studies showed that high levels of EGFR were associated with decreased tumor radiocurability of murine carcinomas. The causal role of EGFR in mediating cellular resistance to RT was demonstrated by transfecting the EGFR cDNA into the cells with low levels of EGFR. The EGFR-high expression-transfected clones became more resistant to RT. RT activated EGFR and its downstream signaling pathways in radioresistant, but not in radiosensitive, tumors, which can be regarded as an adaptive response to radiation damage. Additional studies investigated whether blockade of EGFR and inhibition of EGFR-mediated downstream signaling can be exploited for therapeutic purposes. The results described here showed that treatment of human tumor xenografts with C225 can markedly enhance the tumor response to RT, as assessed by both tumor growth delay and the tumor cure rate. Conclusion The findings from our in vivo preclinical studies suggest that overexpression of EGFR could serve as a predictor of tumor treatment outcome by RT and as a therapeutic target to enhance the efficacy of RT. This therapeutic strategy is currently being explored in patients with head-and-neck cancers.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Multiple Imputation for Nonresponse in Surveys

Abstract: 25. Multiple Imputation for Nonresponse in Surveys. By D. B. Rubin. ISBN 0 471 08705 X. Wiley, Chichester, 1987. 258 pp. £30.25.

Hypoxia, HIF1 and glucose metabolism in the solid tumour

Abstract: It has been known for many years that cellular metabolism within the solid tumour is markedly different from that of the corresponding normal tissue. The transcription factor hypoxia-inducible factor 1 (HIF1) has been implicated in regulating many of the genes that are responsible for the metabolic difference. However, it remains unclear how this 'aerobic glycolysis', originally described by Otto Warburg, offers tumour cells a growth advantage. As discussed in this Perspective, new data suggests that this metabolic switch may provide a benefit to the tumour not by increasing glycolysis but by decreasing mitochondrial activity.

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs – Threshold Doses for Tissue Reactions in a Radiation Protection Context

Abstract: This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.