Retinoblastoma

Retinoblastoma constitutes a global disease that burdens many families all over the world. This book highlights the essential basic information needed by every ophthalmologist and covers all aspects of this tumor: history, genetics, epidemiology, clinical features, diagnosis, imaging, management, and prognosis. The book includes basic knowledge, but is also designed to discuss current treatment modalities showing improved survival compared to the past. A whole chapter is dedicated to histopathological features and the American Joint Commission on Cancer staging system, with the aim of having it internationally used in all countries to improve outcomes and for research purposes. Readers will find the book enjoyable, comprehensive, and easy to understand

Towards patient selection for cranial proton beam therapy – Assessment of current patient-individual treatment decision strategies

Proton beam therapy shows dosimetric advantages in terms of sparing healthy tissue compared to conventional photon radiotherapy. Those patients who are supposed to experience the greatest reduction in side effects should preferably be treated with proton beam therapy. One option for this patient selection is the model-based approach. Its feasibility in patients with intracranial tumours is investigated in this thesis. First, normal tissue complication probability models for early and late side effects were developed and validated in external cohorts based on data of patients treated with proton beam therapy. Acute erythema as well as acute and late alopecia were associated with high-dose parameters of the skin. Late mild hearing loss was related to the mean dose of the ipsilateral cochlea. Second, neurocognitive function as a relevant side effect for brain tumour patients was investigated in detail using subjective and objective measures. It remained largely stable during recurrence-free follow-up until two years after proton beam therapy. Finally, potential toxicity differences were evaluated based on an individual proton and photon treatment plan comparison as well as on models predicting various side effects. Although proton beam therapy was able to achieve a high relative reduction of dose exposure in contralateral organs at risk, the associated reduction of side effect probabilities was less pronounced. Using a model-based selection procedure, the majority of the examined patients would have been eligible for proton beam therapy, mainly due to the predictions of a model on neurocognitive function.:1. Introduction 2. Theoretical background 2.1 Treatment strategies for tumours in the brain and skull base 2.1.1 Gliomas 2.1.2 Meningiomas 2.1.3 Pituitary adenomas 2.1.4 Tumours of the skull base 2.1.5 Role of proton beam therapy 2.2 Radiotherapy with photons and protons 2.2.1 Biological effect of radiation 2.2.2 Basic physical principles of radiotherapy 2.2.3 Field formation in radiotherapy 2.2.4 Target definition and delineation of organs at risk 2.2.5 Treatment plan assessment 2.3 Patient outcome 2.3.1 Scoring of side effects 2.3.2 Patient-reported outcome measures – Quality of life 2.3.3 Measures of neurocognitive function 2.4 Normal tissue complication probability models 2.4.1 Types of NTCP models 2.4.2 Endpoint definition and parameter fitting 2.4.3 Assessment of model performance 2.4.4 Model validation 2.5 Model-based approach for patient selection for proton beam therapy 2.5.1 Limits of randomised controlled trials 2.5.2 Principles of the model-based approach 3. Investigated patient cohorts 4. Modelling of side effects following cranial proton beam therapy 4.1 Experimental design for modelling early and late side effects 4.2 Modelling of early side effects 4.2.1 Results 4.2.2 Discussion 4.3 Modelling of late side effects 4.3.1 Results 4.3.2 Discussion 4.4 Interobserver variability of alopecia and erythema assessment 4.4.1 Patient cohort and experimental design 4.4.2 Results 4.4.3 Discussion 4.5 Summary 5. Assessing the neurocognitive function following cranial proton beam therapy 5.1 Patient cohort and experimental design 5.2 Results 5.2.1 Performance at baseline 5.2.2 Correlation between subjective and objective measures 5.2.3 Time-dependent score analyses 5.3 Discussion and conclusion 5.4 Summary 6. Treatment plan and NTCP comparison for patients with intracranial tumours 6.1 Motivation 6.2 Treatment plan comparison of cranial proton and photon radiotherapy 6.2.1 Patient cohort and experimental design 6.2.2 Results 6.2.3 Discussion 6.3 Application of NTCP models 6.3.1 Patient cohort and experimental design 6.3.2 Results 6.3.3 Discussion 6.4 Summary 7. Conclusion and further perspectives 8. Zusammenfassung 9. Summar

Quantifying, Understanding and Predicting Differences Between Planned and Delivered Dose to Organs at Risk in Head & Neck Cancer Patients Undergoing Radical Radiotherapy to Promote Intelligently Targeted Adaptive Radiotherapy

Introduction: Radical radiotherapy (RT) is an effective but toxic treatment for head and neck cancer (HNC). Contemporary radiotherapy techniques sculpt dose to target disease and avoid organs at risk (OARs), but anatomical change during treatment mean that the radiation dose delivered to the patient – delivered dose (DA), is different to that anticipated at planning – planned dose (DP). Modifying the RT plan during treatment – Adaptive Radiotherapy (ART) – could mitigate these risks by reducing dose to OARs. However, clinical data to guide patient selection for, and timing of ART, are for lacking. Methods: 337 patients with HNC were recruited to the Cancer Research UK VoxTox study. Demographic, disease and treatment data were collated, and both DP and DA to organs at risk (OARs) were computed from daily megavoltage CT image guidance scans, using an open-source deformable image registration package (Elastix). Toxicity data were prospectively collected. Relationships between DP, DA and late toxicities were investigated with univariate, and logistic regression normal tissue complication probability (NTCP) modelling approaches. A sub-study of VoxTox recruited 18 patients who had MRI scans before RT fractions 1, 6, 16, and 26. Changes in salivary gland volumes and relative apparent diffusion coefficient (ADC) values were measured and related to toxicity events. Results: Spinal cord dose differences were small, and not predicted by weight loss or shape change. Mean DA to all other OARs was higher than DP; factors predicting higher DA included primary disease site, concomitant therapy, shape change and advanced neck disease. Nine patients (3.7%) saw DA>DP by 2Gy to more than half of the OARs assessed. These patients all had received bilateral neck RT for N-stage 2b oropharyngeal cancer. Strong uni- and multivariate relationships between OAR dose and toxicity were seen. Differences between DA and DP-based dose-toxicity models were minimal, and not statistically significant. On MRI, both parotid and submandibular glands shrank during treatment, whilst relative ADC rose. Relationships with toxicity were inconclusive. Conclusions: Small differences between OAR DP and DA mean that DA-based toxicity prediction models confer negligible additional benefit at the population level. Factors such as primary disease sub-site, concomitant systemic therapy, staging and shape change may help to select the patients that do develop clinically significant dose differences, and would benefit most from ART for toxicity reduction

Thyroid Disorders

The thyroid disorders are one of the most common and exciting areas of endocrinology. Hypothyroidism, multinodular goiter, hyperthyroidism and thyroid cancer are only few of the several implications that the thyroid disorders have in health. In fact, thyroid hormones regulate not only metabolism process, but also many other molecular and physiological systems. From this point of view, hyperthyroidism complications are a good example of the significance of thyroid hormone actions. This book aims to provide a general view of thyroid disorders, and a deeper explanation of hyperthyroidism and its complications and impact in health