Systematic risk analysis of radiation pneumonitis in breast cancer: role of cotreatment with chemo-, endocrine, and targeted therapy.

PURPOSE: A major complication of sequential and concomitant chemoradiation in breast cancer treatment is interstitial pneumonitis induced by radiation therapy (RT), systemic therapy, or a combination of both. Dose and volume of co-irradiated lung tissue directly correlate with the risk of radiation pneumonitis. Especially in case of combined treatment, it is often unclear which of the used therapeutic agents promote pneumonitis. METHODS: This was a prospective monocentric study including 396 breast cancer patients. A systematic analysis of single and combined therapeutic measures was performed in order to identify treatment-related factors enhancing the risk of pneumonitis post RT. RESULTS: Overall incidence of pneumonitis of any grade was 38%; 28% were asymptomatic (grade 1) and 10% were symptomatic (> grade 1). Pneumonitis > grade 2 did not occur. Beside age, smoking status, and mean lung dose, the combined treatment with goserelin and tamoxifen significantly enhanced the risk of pneumonitis in a supra-additive pattern (odds ratio [OR] 4.38), whereas each agent alone or combined with other drugs only nonsignificantly contributed to a higher pneumonitis incidence post RT (OR 1.52 and OR 1.16, respectively). None of the other systemic treatments, including taxanes, increased radiation pneumonitis risk in sequential chemoradiation. CONCLUSION: Common treatment schedules in sequential chemoradiation following breast-conserving surgery only moderately increase lung toxicity, mainly as an asymptomatic complication, or to a minor extent, as transient pneumonitis ≤ grade 2. However, combined treatment with tamoxifen and the LHRH analog goserelin significantly increased the risk of pneumonitis in breast cancer patients after chemoradiation. Thus, closer surveillance of involved patients is advisable.

Surgeons' non-transparent facemasks challenge the physician-patient relationship in the orthopedic outpatient clinic of a tertiary university hospital during the COVID-19 pandemic: a prospective cohort study of 285 patients.

Background and purpose - Facemasks play a role in preventing the respiratory spread of SARS-CoV-2, but their impact on the physician-patient relationship in the orthopedic outpatient clinic is unclear. We investigated whether the type of surgeons' facemask impacts patients' perception of the physician-patient relationship, influences their understanding of what the surgeon said, or affects their perceived empathy. Patients and methods - All patients with an appointment in the orthopedic outpatient clinic of a tertiary university hospital during the 2-week study period were included. During consultations, all surgeons wore a non-transparent (first study week) or transparent facemask (second study week). Results of 285 of 407 eligible patients were available for analysis. The doctor-patient relationship was evaluated using the standardized Patient Reactions Assessment (PRA) and a 10-point Likert-scale questionnaire ranging from 0 (strongly disagree) to 10 (strongly agree). Results - A non-transparent facemask led to more restrictions in the physician-patient communication and a worse understanding of what the surgeon said. Patients' understanding improved with a transparent facemask with greatest improvements reported by patients aged 65 years and older (non-transparent: 6 [IQR 5-10] vs. transparent: 10 [IQR 9-10], p < 0.001) and by patients with a self-reported hearing impairment (non-transparent: 7 [IQR 3-7] vs. transparent: 9 [IQR 9-10], p < 0.001). The median PRA score was higher when surgeons wore a transparent facemask (p= 0.003). Interpretation - Surgeons' non-transparent facemasks pose a new communication barrier that can negatively affect the physician-patient relationship. While emotional factors like affectivity and empathy seem to be less affected overall, the physician-patient communication and patients' understanding of what the surgeon said seem to be negatively affected.

Invasive diagnostic and therapeutic measures are unnecessary in patients with symptomatic van Neck-Odelberg disease (ischiopubic synchondrosis): a retrospective single-center study of 21 patients with median follow-up of 5 years.

Background and purpose - Van Neck-Odelberg disease (VND) is a self-limiting skeletal phenomenon characterized by a symptomatic or asymptomatic uni- or bilateral overgrowth of the pre-pubescent ischiopubic synchondrosis. It is frequently misinterpreted as a neoplastic, traumatic, or infectious process, often resulting in excessive diagnostic and therapeutic measures. This study assessed the demographic, clinical, and radiographic features of the condition and analyzed diagnostic and therapeutic pathways in a large single-center cohort.Patients and methods - We retrospectively analyzed 21 consecutive patients (13 male) with a median age of 10 years (IQR 8-13) and a median follow-up of 5 years (IQR 42-94 months), who were diagnosed at our department between 1995 and 2019.Results - VND was unilateral in 17 cases and bilateral in 4 cases. Initial referral diagnoses included suspected primary bone tumor (n = 9), fracture (n = 3), osteomyelitis (n = 2), and metastasis (n = 1). The referral diagnosis was more likely to be VND in asymptomatic than symptomatic patients (4/6 vs. 2/15). More MRI scans were performed in unilateral than bilateral VND (median 2 vs. 0). All 15 symptomatic patients underwent nonoperative treatment and reported a resolution of symptoms and return to physical activity after a median time of 5 months (IQR 0-6).Interpretation - By understanding the physiological course of VND during skeletal maturation, unnecessary diagnostic and therapeutic measures can be avoided and uncertainty and anxiety amongst affected patients, their families, and treating physicians can be minimized.

Interdigitated aluminium and titanium sensors for assessing epithelial barrier functionality by electric cell-substrate impedance spectroscopy (ECIS).

Electric cell-substrate impedance spectroscopy (ECIS) enables non-invasive and continuous read-out of electrical parameters of living tissue. The aim of the current study was to investigate the performance of interdigitated sensors with 50 µm electrode width and 50 µm inter-electrode distance made of gold, aluminium, and titanium for monitoring the barrier properties of epithelial cells in tissue culture. At first, the measurement performance of the photolithographic fabricated sensors was characterized by defined reference electrolytes. The sensors were used to monitor the electrical properties of two adherent epithelial barrier tissue models: renal proximal tubular LLC-PK1 cells, representing a normal functional transporting epithelium, and human cervical cancer-derived HeLa cells, forming non-transporting cancerous epithelial tissue. Then, the impedance spectra obtained were analysed by numerically fitting the parameters of the two different models to the measured impedance spectrum. Aluminium sensors proved to be as sensitive and consistent in repeated online-recordings for continuous cell growth and differentiation monitoring as sensors made of gold, the standard electrode material. Titanium electrodes exhibited an elevated intrinsic ohmic resistance in comparison to gold reflecting its lower electric conductivity. Analysis of impedance spectra through applying models and numerical data fitting enabled the detailed investigation of the development and properties of a functional transporting epithelial tissue using either gold or aluminium sensors. The result of the data obtained, supports the consideration of aluminium and titanium sensor materials as potential alternatives to gold sensors for advanced application of ECIS spectroscopy.

Cerebral and peripheral tissue oxygenation in stable neonates: Absent influence of cardiac function.

AIM: Cardiac function is a major factor for tissue perfusion and therefore may affect the tissue oxygen saturation. Aim was to analyse possible associations between cardiac function parameters and cerebral and peripheral tissue oxygenation in neonates on the first day after birth. METHODS: For the present study, we analysed secondary outcome parameters of a previously performed prospective single centre observational study. The prospective study was conducted at the Medical University of Graz, Austria between September 2011 and June 2013. We included preterm and term neonates who were admitted to the neonatal intensive care unit and in whom simultaneous near-infrared spectroscopy measurements and echocardiography were obtained on the first day after birth. Cardiac function parameters were correlated to cerebral and peripheral tissue oxygen saturation and cerebral and peripheral fractional tissue oxygen extraction at the time of echocardiography. RESULTS: A total of 60 neonates of whom 47 were preterm and 13 were term (median gestational age: 34; IQR 33-35 weeks, mean birth weight: 2276 ± 774 grams) were included. There were no statistically significant correlations between cardiac function parameters and regional tissue oxygenation parameters. CONCLUSION: In the present study, we found no correlation between regional tissue oxygenation and parameters of cardiac function in cardio-circulatory stable neonates on the first day after birth.

Case of nasogastric tube dysfunction.

CLINICAL PRESENTATION: An elderly female patient was admitted to intensive care for prolonged vasopressor therapy and mechanical ventilation after cardiac arrest and acute percutaneous coronary intervention. Antiplatelet, thyroid hormone replacement and statin therapies were administered through a 14-French nasogastric tube (Nestlé Health Science) and enteral feeding was initiated. Correct position of the nasogastric tube was confirmed radiologically. On the seventh day in the intensive care, our patient was seen to regurgitate soft crumbs into her mouth. The blocked nasogastric tube was removed, but attempts to reinsert another tube failed.Upper GI endoscopy revealed an obstruction of the oesophagus with a milky-yellowish caseous substance 20 cm from the incisors (figure 1). The proximal part of the mass showed a central hole and ring-shaped layers resembling the cut face of a tree trunk.gutjnl;68/2/206/F1F1F1Figure 1Obstruction of the oesophagus with a milky-yellowish caseous substance. QUESTIONS: What caused the obstruction?How should we manage such a problem?

Reconstructed evolution of insulin receptors in insects reveals duplications in early insects and cockroaches.

Social insects show an extreme degree of phenotypic plasticity. In highly eusocial species, this manifests in the generation of distinct castes with extreme differences in both morphology and life span. The molecular basis of these differences is highly entangled and not fully understood, but several recent studies demonstrated that insulin/insulin-like growth factor signaling (IIS) is one of the key pathways. Here, we investigate the molecular evolution of insect insulin receptors (InRs), which are membrane-bound dimers that enable IIS by relaying extracellular signals to intracellular signaling cascades. Classic models of invertebrate IIS include only one InR gene, but some recent studies on less commonly studied insects have found two InRs, which act in an antagonistic manner to facilitate polyphenism in at least one documented case. We search 22 arthropod genomes and identify several InR copies and their evolutionary origin that were lacking from previous annotations. Phylogenetic analysis shows that the two insect InR genes date back at least 400 million years to a common ancestor of winged insects. Most notably, we also identified the evolutionary origin of a third InR copy that is unique to the clade of Blattodea, just before therein the eusocial termites evolved. One of the InR paralogs consistently shows caste-biased expression in all three termites, which strongly suggests a role in caste differentiation. These results have important ramifications for past and future InR inhibition/InR knockdown experiments in insects and they provide a set of key genes regulating life span and morphology in termite castes.

Occurrence of pneumonitis following radiotherapy of breast cancer - A prospective study.

AIM: of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma. PATIENTS AND METHODS: A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment. RESULTS: A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis. CONCLUSIONS: The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

ÖGRO survey on radiotherapy capacity in Austria : Status quo and estimation of future demands.

BACKGROUND: A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO). MATERIALS AND METHODS: All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands. RESULTS: For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16-24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5-29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively. CONCLUSION: This ÖGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates.

INTRODUCTION: A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Ten consecutive mCRPC patients were selected for 177Lu-PSMA617 therapy on the basis of PSMA-targeted 68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and 18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to 177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. RESULTS: 177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased 177Lu-PSMA617 and 68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. CONCLUSION: Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following 177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

Sex Differences in Renal Proximal Tubular Cell Homeostasis.

Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase-α Additionally, we quantified urinary excretion of blood plasma proteins α1-microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase-α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1-microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ-derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

Crosstalk between DNA repair and cancer stem cell (CSC) associated intracellular pathways.

DNA damaging agents (ionizing radiation and chemotherapeutics) are considered as most effective in cancer treatment. However, there is a subpopulation of carcinoma cells within the tumour demonstrating resistance to DNA damaging treatment approaches. It is suggested that limited tumour response to this kind of therapy can be associated with specific molecular properties of carcinoma stem cells (CSCs) representing the most refractory cell subpopulation. This review article presents novel data about molecular features of CSCs underlying DNA damage response and related intracellular signalling.

(68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate?

PURPOSE: To assess the association between PSA levels, PSA kinetics and other factors and a pathological (68)Ga-PSMA PET/CT scan in patients with recurrent prostate cancer (rPCa) with biochemical relapse (BR) after radical therapy. METHODS: Seventy consecutive rPCA patients referred for (68)Ga-PSMA PET/CT, matching all the following criteria, were retrospectively evaluated: (a) previous radical prostatectomy or primary radiotherapy with curative intent; (b) BR or persisting high PSA levels after primary treatment; and (c) complete clinical and imaging information. The mean ± SD PSA level was 3.5 ± 5.3 ng/mL (median 1.7, range 0.2 - 32.2 ng/mL), the mean ± SD PSA doubling time (PSAdt) was 6.5 ± 5.5 months (median 5.5, range 1.3 - 31.6 months), and the mean ± SD PSA velocity was 7.9 ± 20.5 (median 2.1, range 0.2 - 147.5 ng/mL/year). Statistical analysis was performed to assess which factors were associated with the detection of rPCa on (68)Ga-PSMA PET/CT. RESULTS: (68)Ga-PSMA PET/CT was positive in 52 of 70 patients (74.2%). In 30 patients (42.8%) lesions limited to the pelvis were detected. Distant lesions were observed in 8 of patients (11.4%). Local plus systemic lesions were detected in 14 patients (20%). PSA level (p = 0.017) and PSAdt (p = 0.0001) were significantly different between PET-positive patients (higher PSA level, shorter PSAdt) and PET-negative patients (lower PSA, longer PSAdt). ROC analysis showed that PSAdt 6.5 months and PSA 0.83 ng/mL were optimal cut-off values. In multivariate analysis PSAdt was associated with (68)Ga-PSMA PET/CT positivity. (68)Ga-PSMA PET/CT was positive in 17 of 20 patients (85%) with PSA <2 ng/mL and PSAdt <6.5 months, and in 3 of 16 patients (18.7%) with PSA <2 ng/mL and PSAdt ≥6.5 months. CONCLUSION: The great potential of (68)Ga-PSMA PET/CT in patients with rPCa and BR was confirmed. PSA and PSAdt were valuable predictors of pathological (68)Ga-PSMA PET/CT findings.

Long-term surveillance of locally advanced rectal cancer patients with neoadjuvant chemoradiation and aggressive surgical treatment of recurrent disease: a consecutive single-centre experience.

PURPOSE: The aim of this study was to analyse the long-term outcome of rectal cancer patients who submitted to preoperative chemoradiation with consecutive intensive follow-up and aggressive surgical treatment of recurrent disease. METHODS: Patients with locally advanced (cT3-4 Nx M0-1) mid/low rectal cancer were treated at a tertiary university hospital with preoperative long-course chemoradiation followed by resection (according to a prospective study protocol). After resection, all patients were urged to participate in a standardised, risk-independent intensive follow-up program. All curatively treated patients (n = 153, 96 %) were included in our long-term analysis with respect to curative re-resection of recurrent disease. RESULTS: Of 153 patients, 143 (93 %) participated in our follow-up program: 63 % were surveyed longer than 5 years after primary therapy (mean follow-up 75 months, 95 % CI 67.8-82.2). Fifty-five (36 %) patients developed cancer recurrence (mean 27.8 months, 95 % CI 20.6-34.9, range 3-108), giving a disease-free survival rate of 68.5 and 60.7 % at 5 and 10 years; 21 (38 %) patients were re-resected curatively and 58 (38 %) patients died during the observation period, giving an overall survival rate of 70.8 and 57.5 % at 5 and 10 years. Multivariate analysis found tumour differentiation (P < 0.01), operative procedure (P < 0.05) and downstaging (P < 0.01) to be independent variables influencing overall survival. CONCLUSIONS: The combination of multimodal therapy and aggressive surgical treatment of metastases including repeated re-resections in curative intention is relevant in order to chronify the disease. Thus, both intensive and extended follow-up beyond 5 years appear to be mandatory.

Putative biomarkers and therapeutic targets associated with radiation resistance.

Radiation therapy plays an important role in the management of malignant tumors, however, the problem of radiation resistance resulting in tumor recurrences after treatment is still unsolved. The emergence of novel biomarkers to predict cancer cell insensitivity to ionizing radiation could help to improve therapy results in cancer patients receiving radiation therapy. The proteomic approach could be effectively used to identify proteins associated with cancer radiation resistance. It is generally believed that radiation resistance could be associated with cancer stem cell persistence within the tumor. Therefore, determination of the molecular characteristics of cancer stem cells could provide additional possibilities to discover novel biomarkers to predict radiation resistance in cancer patients. This review addresses proteome-based findings that could be used for further biomarker identification and preclinical and clinical validation.

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Clinician and patient perspectives on the ontology of mental disorder: a qualitative study.

Background: Psychiatry may face an "identity crisis" regarding its very foundations. The lack of consensus regarding the theoretical grounds of psychiatry as a discipline has its epicenter in the discussion about the Diagnostic and Statistical Manual (DSM). A growing number of academics considers the manual broken and a growing number of patients voice concern. Despite the huge body of critique, 90% of Randomized Trials are based on DSM definitions of mental disorder. Therefore, the question regarding the ontology of mental disorder remains: what is a mental disorder, exactly? Aims: We aim to identify ontologies that live among patients and clinicians, evaluate the degree of consistency and coherence between clinician and patient views and contribute to the establishment of a novel ontological paradigm of mental disorder that is aligned with patients' and clinicians' perspectives. Method: Eighty participants (clinicians/patients/clinicians with lived experience) were interviewed using a semi-structured interview, exploring their ideas on the ontology of mental disorder. This question was approached from different angles which led to comprising the interview schedule into different topics: "concept of disorder," "representation by DSM," "what is treated," "what is recovered," and "the right outcome measure." Interviews were transcribed and analyzed using inductive Thematic Analysis. Results: From all subthemes and main themes, a typology was constructed in which six, not necessarily mutually exclusive, ontological domains were identified: mental disorder as (1) disease, (2) functional impairment, (3) loss of adaptation, (4) existential problem, (5) highly subjective phenomenon, and (6) deviation from social norms. Common ground for the sample groups was that mental disorder is about functional impairment. Although about a fourth of sample clinicians holds an ontological concept of disease, only a small percentage of patients and none of the clinicians with lived experience adhered to an ontological concept of disease. The sample clinicians most often understand mental disorder to be a highly subjective phenomenon, and individuals with lived experience (patients and clinicians) most often understand mental (dis)order to be adaptational in nature: an (im)balance of burden in relation to strengths, skills, and recourses. Conclusion: The ontological palette is more diverse than what is taught about mental disorder in dominant scientific and educational discourse. There is a need to diversify the current, dominant ontology and make room for other ontologies. Investment is required in the development, elaboration and coming of age of these alternative ontologies, allowing them to reach their full potential and act as drivers of a landscape of promising novel scientific and clinical approaches.

Radiation doses to mediastinal organs at risk in early-stage unfavorable Hodgkin lymphoma- a risk stratified analysis of the GHSG HD17 trial.

Introduction: The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits. Methods: For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors. Results: Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found. Conclusion: Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory.