Influence of demographic change on the demand for radiotherapy using forecasted predictions for prostate cancer in Germany.

PURPOSE: Demographic change will lead to an increase in age-associated cancers. The demand for primary treatment, especially oncologic therapies, is difficult to predict. This work is an attempt to project the demand for radiation therapy (RT) in 2030, taking into account demographic changes using prostate cancer (PC) as an example. MATERIALS AND METHODS: Using the GENESIS database of the Federal Statistical Office, we retrieved demographic population projections for 2030 and retrospective demographic surveys from 1999 to 2019. Additionally, we queried incidence rates for PC in the respective age groups of 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, and +85 years from 1999-2019 via the Federal Cancer Registry of the Robert Koch Institute. We used a regression method to determine the age-dependent correlation between the incidence of PC and the population size of the respective age group by combining the data from 1999 to 2019. This information was used to calculate the incidence rates in the age groups of the expected population for 2030 and the expected new cases of PC in 2030. Finally, we extrapolated the indications for the demand for RT based on data from the Report on Cancer Incidence in Germany from 2016. RESULTS: Considering a population-dependent incidence rate, an increase in new cases of PC is expected. This increase is particularly evident in the age groups of 70-74 and 80-84 years. With regards to RT, the estimate indicates an overall increase of 27.4% in demand. There is also a shift in RT demands towards older patients, especially in the 80- to 84-year-old age group. CONCLUSION: We observe an age-associated increase in primary cases of PC. This is likely to result in an increased demand for RT. The exact demand cannot be predicted. However, trends can be estimated to plan for the demand. This, though, requires a good database from cancer registries.

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.

Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study.

PURPOSE: Approximately 40-70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). METHODS: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. RESULTS: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04-47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03-18.30). After a median follow-up of 16 months (1-57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. CONCLUSION: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.

PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T­category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (

Valuing and understanding fish populations in the Anthropocene: key questions to address.

Research on the values of fish populations and fisheries has primarily focused on bio-economic aspects; a more nuanced and multidimensional perspective is mostly neglected. Although a range of social aspects is increasingly being considered in fisheries research, there is still no clear understanding as to how to include these additional values within management policies nor is there a cogent appreciation of the major knowledge gaps that should be tackled by future research. This paper results from a workshop held during the 50th anniversary symposium of the Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017. Here, we aim to highlight the current knowledge gaps on the values of fish populations and fisheries thus directing future research. To this end, we present eight questions that are deeply relevant to understanding the values of fish populations and fisheries. These can be applied to all habitats and fisheries, including freshwater, estuarine and marine.

Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations.

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

[Fear of progression in parents of children with cancer: adaptation of the Fear of Progression Questionnaire and correlates]. / Progredienzangst bei Eltern krebskranker Kinder: Adaptation eines Fragebogens und Korrelate.

BACKGROUND: Fear of Progression (FoP), the fear of further disease progression, is one of the most common psychological strains of chronically ill patients and can also be found in healthy partners of cancer patients. Parents of children with cancer are also at risk of developing distinct fears that may persist after medical treatment. This study aimed to assess FoP in parents of children with cancer and to investigate relationships between FoP in parents of children with cancer and disease- and treatment-related issues, the child's current medical condition and parents' quality of life. PATIENTS: In this study 76 parents (51 mothers, 25 fathers) whose children were in inpatient treatment or follow-up care were surveyed. METHOD: The short form of the FoP Questionnaire was adapted by rephrasing the items for the parental perspective (FoP-Q-SF/PR). RESULTS: The FoP-Q-SF/PR is a short questionnaire with adequate psychometric properties (e. g. Cronbach's α=0.90) and satisfying results in terms of construct validity. Significant correlations with FoP are found for the child's current medical condition (r=0.35), time since diagnosis (r=- 0.30), parents' capacity to cope with disease-related fears (r=- 0.45) and parents' quality of life (r=- 0.55). A cut-off value of 46 points is recommended. CONCLUSION: The FoP-Q-SF/PR offers a feasible and sensitive battery to assess disease-related fears. For clinicians, evaluation of individual results can provide insight into specific problem areas for parents of children with cancer. The questionnaire is thus well suited for use in psychosocial care of families within the field of paediatric oncology.

Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

Transgenerational transmission of psychopathology: when are adaptive emotion regulation strategies protective in children?

BACKGROUND: Children of parents with a mental illness (COPMI) have multiple psychological and developmental risks, including an increased lifetime risk of developing a mental illness themselves. Emotion regulation (ER) has been identified as a potential underlying mechanism of the transgenerational transmission of mental disorders. This study compares ER strategies in parents with and without a mental illness and their children. Further, it aims to examine the relationship between parents and children's psychopathology with a focus on the role of parental and child ER. METHODS: Participants were 96 COPMI (77% female) and 99 children of parents without mental illness (COPWMI, 83% female) aged 4-16 years and their parents. Psychopathology and ER strategies of parents and children were assessed with a series of questionnaires. RESULTS: Both COPMI and their parents showed significantly more psychopathology and more maladaptive and adaptive ER strategies in comparison with COPWMI and their parents. Parent and child adaptive ER strategies mediated the relationship between the psychopathology of parents and children only when child maladaptive ER strategies were low. CONCLUSIONS: The findings further our understanding of the processes by which parental psychopathology affects child outcomes. Our findings highlight the importance of implementing preventive programs that specifically target the reduction of maladaptive ER in children to interrupt the transgenerational transmission of psychopathological symptoms.

Prevalence of suicidal ideation in German psychotherapy outpatients: A large multicenter assessment.

BACKGROUND: Suicidal ideation is a major concern in clinical practice. Yet, little is known about prevalence rates of suicidal ideation in patients undergoing outpatient psychotherapeutic treatment. Therefore, the aim of the current study is to assess the prevalence of suicidal ideation in a large sample of psychotherapy outpatients in Germany. The data analyzed in this study is taken from the KODAP-project on the coordination of data collection and analysis at German university-based research and training outpatient clinics for psychotherapy. METHODS: A total of N = 10,357 adult outpatients (64.4 % female; age: M(SD) = 35.94 (13.54), range: 18-92 years of age) starting cognitive-behavioral therapy at one of 27 outpatient clinics in Germany were included in the current study. Prevalence of suicidal ideation was assessed with the Suicide Item (Item 9) of the Beck-Depression Inventory II. RESULTS: Suicidal ideation was reported by 36.7 % (n = 3795) of the participants. Borderline Personality Disorder, Posttraumatic Stress Disorder, and recurrent Major Depression were the diagnoses most strongly associated with the presence and severity of suicidal ideation. LIMITATION: Suicide ideation was assessed only with the respective item of the Beck Depression Inventory II. CONCLUSION: Suicidal ideation is very common among adult patients who start psychotherapy in Germany. A well-founded knowledge of risk assessment in suicidal patients and suicide-specific treatment options is therefore highly relevant.

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.

Second primary malignancies in head and neck cancer patients: high prevalence of curable-stage disease.

BACKGROUND AND PURPOSE: Patients treated for squamous cell carcinoma of the head and neck (HNSCC) carry a high risk of second primary malignancies (SPM). Recently, computed tomography (CT) of the chest was shown to significantly decrease the risk of death due to bronchial carcinoma (BC) in a cohort of smokers whose risk of BC is increased but might be lower than that of patients previously treated for HNSCC. Thus, the present study evaluated the potential benefit of CT and other examinations in the detection of SPM in HNSCC patients. PATIENTS AND METHODS: Between July 2008 and November 2011, 118 participants underwent a prospective, systematic examination for SPM (13 women, 105 men, median age 62 years). All patients had been previously treated for HNSCC and showed no recurrence or distant metastases at the time of the study start. CT scans, ear-nose-throat endoscopy, and endoscopy of the esophagus and stomach were performed. RESULTS: Overall, 33 suspicious findings were clarified by additional investigations. In all, 26 SPM were confirmed in 21 of 118 patients (18%; 10 lung, 7 HNSCC, 3 gastrointestinal, 1 renal). Eighteen of these 21 patients (86%) underwent therapy with curative intent. CONCLUSION: The examinations revealed a high prevalence of curable stage SPM in HNSCC patients. Adapting a surveillance scheme including a chest CT is recommended.

The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors.

INTRODUCTION: Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. PATIENTS AND METHODS: In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3-18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. RESULTS: The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. CONCLUSION: The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

HDR brachytherapy: an option for preventing nonmalignant obstruction in patients after lung transplantation.

PURPOSE: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. PATIENTS AND METHODS: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. RESULTS: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. CONCLUSIONS: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.