Plasmapheresis as therapeutic option in a 16-year-old with EVALI: A case report.

Since 2019 when a cluster of cases with acute respiratory distress syndrome (ARDS) associated with e-cigarettes in the United States was reported, there have been increasing numbers of reports. Electronic-cigarette or Vaping Use-associated Lung Injury (EVALI) represents a recent entity of respiratory clinical syndromes, primarily in young adults. We report a previously healthy 16-year-old boy who developed severe ARDS following a brief nonspecific prodromal phase after excessive consumption of e-cigarettes. Despite maximum intensive care therapy, including several weeks of venovenous extracorporeal membrane oxygenation, plasmapheresis and repeated administration of immunoglobulins seemed the only way to achieve therapeutic success. Although many case reports have been published, to our knowledge, there are none to date on the therapeutic use of plasmaphoresis in severe EVALI. This case highlights the clinical features of EVALI and the diagnostic dilemma that can arise with EVALI occurring against the background of an expired SARS-CoV-2 infection, with a paediatric inflammatory syndrome (PIMS) as differential diagnosis. EVALI is a diagnosis of exclusion, and the medical history of vaping and e-cigarette use can provide valuable clues. Ethical approval for this case report (protocol number 23-145 RS) was provided by the Ethical Committee of the Department of Medicine, Philipps-Universität Marburg, Germany on 13 th of June 2023. Written informed consent to publish this case and the associated images was obtained from the patient and his mother.

Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Single-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial.

BACKGROUND: Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. These options result in 3-year progression free survival rates of at least 90%, but bear risks for acute and late toxic effects, including secondary malignancies. We tested a novel approach combining de-escalated chemotherapy with de-escalated involved node radiotherapy, with the aim of reducing toxicity while preserving efficacy. METHODS: In the single-arm, multicentre, phase 2 SAKK 01/10 trial, patients with stage IIA or IIB classic seminoma (either at primary diagnosis or at relapse during active surveillance for stage I) were enrolled at ten centres of the Swiss Group for Clinical Cancer Research and ten centres of the German Testicular Cancer Study Group. WHO performance status 0-2, age 18 years or older, and adequate bone marrow and kidney function were required for eligibility. Treatment comprised one cycle of carboplatin (area under the curve 7) followed by involved-node radiotherapy (30 Gy in 15 fractions for stage IIA disease and 36 Gy in 18 fractions for stage IIB disease). The primary endpoint was 3-year progression-free survival. Efficacy analyses were done on the full analysis set, which comprised all patients who signed the informed consent, were registered in the trial, initiated trial treatment, and met all medically relevant inclusion or exclusion criteria. Safety was assessed in all patients who were treated at least once with one of the trial treatments. The study is ongoing but no longer recruiting, and is registered with Clinicaltrials.gov, NCT01593241. FINDINGS: Between Oct 18, 2012, and June 22, 2018, 120 patients were registered in the study. 116 patients were eligible and started treatment according to the study protocol (46 patients with stage IIA disease and 70 with stage IIB disease). After a median follow-up of 4·5 years (IQR 3·9-6·0), 3-year progression-free survival was 93·7% (90% CI 88·5-96·6). With a target progression-free survival of 95% at 3 years, the primary endpoint was not met. Acute treatment-related adverse events of any grade were noted in 58 (48%) of 116 patients, and grade 3 or 4 treatment-related adverse events occurred in the form of neutropenia in five (4%) patients, thrombocytopenia in three (3%) patients, and vomiting in one (1%) patient. No treatment-related deaths and no late treatment-related adverse events were reported. Serious adverse events were reported in five (4%) of 116 patients (one transient creatinine increase and four second primary tumours). INTERPRETATION: Despite the fact that the primary endpoint was not met, we observed favourable 3-year progression-free survival with single-dose carboplatin area under the curve 7 and involved-node radiotherapy, with minimal toxic effects. Our findings might warrant discussion with patients about the SAKK 01/10 regimen as an alternative to standard-of-care treatment, but more research on this strategy is needed. FUNDING: Swiss State Secretariat for Education, Research and Innovation and Rising Tide Foundation for Clinical Cancer Research.

On the probability of lymph node negativity in pN0-staged prostate cancer-a theoretically derived rule of thumb for adjuvant needs.

PURPOSE: The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment. METHODS: Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0. RESULTS: A theoretical formula of npv = p(N0IpN0) = (100 - prevalence) / (100 - sensitivityâ€¯× prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9â€¯× nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30. CONCLUSION: We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment.

Radiotherapy for hormone-sensitive prostate cancer with synchronous low burden of distant metastases.

PURPOSE: The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden. METHODS: The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden. RESULTS: In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases. CONCLUSION: Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging.

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset.

OBJECTIVES: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC® Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. PATIENTS AND METHODS: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC® Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC® Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. RESULTS: The sensitivity, specificity, and area under the curve for the UBC® Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58-0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70-0.76) for high-grade (HG) BC, respectively. Age, UBC® Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72-0.87) and 0.95 (95% CI: 0.92-0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC® Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. CONCLUSION: The UBC® Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC.

Radiotherapy and hyperthermia for breast cancer patients at high risk of recurrence.

PURPOSE: To evaluate the long-term efficacy of combined radiotherapy (RT) and hyperthermia (HT) in a large mono-institutional cohort of breast cancer (BC) patients affected by recurrent, newly diagnosed non-resectable or high risk resected tumor. MATERIALS AND METHODS: Records of BC patients treated with RT + HT between 1995 and 2018 were retrospectively analyzed. RT doses of 50-70 Gy concurrent to a twice per week superficial HT were applied. For HT, a temperature between 41 and 42 °C was applied for approximately 1 h. Primary endpoint was local control (LC), secondary endpoints comprised toxicity, overall survival (OS), and progression-free survival (PFS). RESULTS: A total of 191 patients and 196 RT + HT treatments were analyzed. In 154 cases (78.6%) RT + HT was performed for patients with recurrent BC. Among these, 93 (47.4% of the entire cohort) had received RT prior to RT + HT. Median follow up was 12.7 years. LC at 2, 5, and 10 years was 76.4, 72.8, and 69.5%, respectively. OS at 2, 5, and 10 years was 73.5, 52.3, and 35.5%, respectively. PFS at 2, 5, and 10 years was 55.6, 41, and 33.6%, respectively. Predictive factors for LC were tumor stage, distant metastases, estrogen/progesterone receptor expression, resection status and number of HT fractions. At multivariate analysis tumor stage and receptor expression were significant. No acute or late toxicities higher than grade 3 were observed. CONCLUSION: Combined RT + HT offers long-term high LC rates with acceptable toxicity for patients with recurrent, newly diagnosed non-resectable or resected BC at high risk of relapse.

[Rhabdomyolysis - the chamaeleon of the intensive care unit]. / Rhabdomyolyse ­ das Chamäleon auf der Intensivstation.

Myotonia congenita Thomsen is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1). Although this channelopathy may cause disabling muscle symptoms, patient's daily routine can be almost inconspicuous. Nevertheless, during illness or acute diseases this neuromuscular disease may worsen and get clinically apparent up to severe rhabdomyolysis. Within this case report we describe and discuss the treatment of a patient with Myotonia congenita Thomsen treated at our hospital's intensive care unit. Rhabdomyolysis with acute renal failure and necessity of dialysis during the ICU stay was attributed to the initial reason for emergency hospitalization - an aortic dissection. Nevertheless, in this case the patient's myotonia caused rhabdomyolysis and initially led us on a wrong path. Diagnosis of the real cause of rhabdomyolysis is often difficult, although an early and adequate therapy may prevent complications. This case report demonstrates the importance of a thorough anamnesis with all aspects of the patient's history.

Moderately hypofractionated radiotherapy as definitive treatment for localized prostate cancer: Pattern of practice in German-speaking countries : A survey of the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society (DKG-ARO).

PURPOSE: Various randomized phase III clinical trials have compared moderately hypofractionated to normofractionated radiotherapy (RT). These modalities showed similar effectiveness without major differences in toxicity. This project was conducted by the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society. We aimed to investigate expert opinions on the use of moderately hypofractionated RT as a definitive treatment for localized prostate cancer in German-speaking countries. METHODS: A 25-item, web-based questionnaire on moderate-hypofractionation RT was prepared by an internal committee. The experts of the DEGRO were asked to complete the questionnaire. RESULTS: Fourteen active members of DEGRO completed the questionnaire. The questions described indications for selecting patients eligible to receive moderate hypofractionation based on clinical and pathological factors such as age, urinary symptoms, and risk-group. The questions also collected information on the technical aspects of selection criteria, including the definition of a clinical target volume, the use of imaging, protocols for bladder and rectal filling, the choice of a fractionation schedule, and the use of image guidance. Moreover, the questionnaire collected information on post-treatment surveillance after applying moderately hypofractionated RT. CONCLUSION: Although opinions varied on the use of moderate-hypofractionation RT, the current survey reflected broad agreement on the notion that moderately hypofractionated RT could be considered a standard treatment for localized prostate cancer in German-speaking countries.

Radiotherapy in nodal oligorecurrent prostate cancer.

OBJECTIVE: The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. MATERIALS AND METHODS: A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. RESULTS: Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. CONCLUSION: ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.

Ultrahypofractionation of localized prostate cancer : Statement from the DEGRO working group prostate cancer.

Due to its low fractionation sensitivity, also known as "alpha/beta ratio," in relation to its surrounding organs at risk, prostate cancer is predestined for hypofractionated radiation schedules assuming an increased therapeutic ratio compared to normofractionated regimens. While moderate hypofractionation (2.2-4 Gy) has been proven to be non-inferior to normal fractionation in several large randomized trials for localized prostate cancer, level I evidence for ultrahypofractionation (>4 Gy) was lacking until recently. An accumulating body of non-randomized evidence has recently been strengthened by the publication of two randomized studies comparing ultrahypofractionation with a normofractionated schedule, i.e., the Scandinavian HYPO-RT trial by Widmark et al. and the first toxicity results of the PACE­B trial. In this review, we aim to give a brief overview of the current evidence of ultrahypofractionation, make an overall assessment of the level of evidence, and provide recommendations and requirements that should be followed before introducing ultrahypofractionation into routine clinical use.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Serological responses to koi herpesvirus (KHV) in a non-cyprinid reservoir host.

Koi herpesvirus (KHV) is a highly contagious virus that causes KHV disease (KHVD) inducing high mortality in carp and koi (Cyprinus carpio L.). In the late stage, latency occurs with very low, often non-detectable virus concentrations, which represents a challenge for virus detection. After validation according to OIE recommendations, an antibody ELISA was established to recognize antibodies of C. carpio against KHV infection. In this study, the ELISA was modified to detect anti-KHV antibodies from a non-cyprinid fish. Experimentally infected rainbow trout (Oncorhynchus mykiss) were able to transmit KHV to naïve carp at two different temperatures, demonstrating their potential as a reservoir host. At 20°C, KHVD was induced in carp but not at 15°C. Unexpectedly, rainbow trout developed humoral response against KHV at both temperatures. In contrast to carp, at 15°C trout produced neutralizing antibodies but not at 20°C. While antibodies obtained from infected carp sera reacted in a similar way against all KHV, antibodies from rainbow trout sera reacted differently to the same isolates by ELISA. The data show that even when non-cyprinid fish species are infected with KHV, they can produce antibodies that differ from those observed in carp.

[Primary treatment of prostate cancer using 1.5 T MR-linear accelerator]. / Stellenwert des 1,5-T-MR-Linearbeschleunigers für die primäre Therapie des Prostatakarzinoms.

BACKGROUND: Hybrid devices of MR-scanners and linear accelerators (MR-Linacs) represent a new and promising extension of radiotherapeutic options for prostate cancer. The potential advantage of magnetic resonance imaging (MRI) over computed tomography (CT) for soft tissue contrast is well-known and leads to more consistent and smaller target volumes and improved normal tissue sparing. OBJECTIVES: This article presents an overview of clinical experience, indications, advantages and challenges of utilizing a 1.5 T MR-Linac in the setting of radiotherapy of prostate cancer. RESULTS: All current indications for radiotherapy of prostate cancer can be treated with an MR-Linac. The advantages include daily MR-based imaging in treatment position and daily adaption of the treatment plan on current anatomy (adaptive radiotherapy). Additionally, functional MRI sequences might be exploited to enhance treatment individualization and response assessment. Ultimately treatment on an MR-Linac might further increase the therapeutic window. The limitations of using MR-Linac include treatment complexity and the duration of each session. CONCLUSIONS: MR-Linacs expand the spectrum of radiotherapeutic options for prostate cancer. Increased precision can be reached with daily MRI-based target volume definition and plan adaption. Clinical studies are necessary to identify patient groups who would benefit most from radiotherapy on a MR-Linac.

[Vitamin C - New Option in Sepsis Therapy?] / Vitamin C ­ neue Therapiemöglichkeit bei Sepsis?

Vitamin C deficiency often occurs in critical illness and especially in patients with sepsis. Low plasma levels correlate with organ dysfunction and outcome parameters. Vitamin C offers pleiotropic effects possibly attenuating pathophysiology in sepsis. This includes antioxidative effects like scavenging reactive oxygen species or restoring other antioxidants. Vitamin C is a cofactor for norepinephrine biosynthesis and it protects endothelial function. In addition, it modulates immune response. A combined therapy with vitamin C, hydrocortisone and thiamine could be beneficial because of synergistic effects. Some clinical studies have shown reduced mortality due to vitamin C alone or in combination with hydrocortisone and thiamine, others do not. Adverse events are rare. So data supporting a therapy with vitamin C is still unclear. Further randomised controlled trials are necessary.

Treatment strategies to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer : Statement from the DEGRO working group prostate cancer.

AIM: To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer. METHODS: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity. RESULTS: Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1â€¯× 10 Gy or 2â€¯× 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1â€¯× 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques. CONCLUSIONS: Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered.

Role of combined radiation and androgen deprivation therapy in intermediate-risk prostate cancer : Statement from the DEGRO working group on prostate cancer.

OBJECTIVE: This article aims to provide an overview of the role of combined radiation and androgen deprivation (ADT) therapy in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: The current German, European, and NCCN (National Comprehensive Cancer Network) guidelines as well as relevant literature in the PubMed database which provide information on sub-classification within the intermediate-risk group and the use of ADT in terms of oncological outcome were reviewed. RESULTS: Different recommendations for risk-group assessment of patients with localized prostate cancer are available. Subdivision of intermediate risk into a favorable and an unfavorable group seems to be justified to allow for a more individualized therapy in a quite heterogenous group of patients. So far, multiple randomized trials have shown a benefit when radiation therapy (RT) is combined with ADT. The use of dose-escalated RT without ADT also appears to be an adequate therapy associated with a very low rate of cancer-specific deaths. Therefore, taking into account the increased rate of toxicity associated with ADT, dose-escalated RT alone might be justified, especially in favorable intermediate-risk patients. CONCLUSION: Dose-escalated RT alone appears to be an appropriate treatment in favorable intermediate-risk patients. Addition of short course ADT (4-6 months) might improve outcomes in unfavorable intermediate-risk patients.

Prognostic risk classification for biochemical relapse-free survival in patients with oligorecurrent prostate cancer after [68Ga]PSMA-PET-guided metastasis-directed therapy.

PURPOSE: Since the success of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging for patients with oligorecurrent prostate cancer (ORPC), it is increasingly used for radiotherapy as metastasis-directed therapy (MDT). Therefore, we developed a prognostic risk classification for biochemical relapse-free survival (bRFS) for patients after PSMA-PET-guided MDT after radical prostatectomy. METHODS: We analyzed 292 patients with local recurrence (LR) and/or pelvic lymph node (LN) lesions and/or up to five distant LN, bone (BM), or visceral metastases (VM) detected with [68Ga]PSMA-PET imaging. Median follow-up was 16 months (range 0-57). The primary endpoint was bRFS after MDT. Cox regression analysis for risk factors was incorporated into a recursive partitioning analysis (RPA) with classification and regression tree method. RESULTS: PSA at recurrence ≥ 0.8 ng/mL, BM, and VM was significantly associated with biochemical relapse. RPA showed five groups with tenfold cross-validation of 0.294 (SE 0.032). After building risk classes I to IV (p < 0.0001), mean bRFS was 36.3 months (95% CI 32.4-40.1) in class I (PSA < 0.8 ng/mL, no BM) and 25.8 months (95% CI 22.5-29.1) in class II (PSA ≥ 0.8 ng/mL, no BM, no VM). LR and/or pelvic LNs caused relapse in classes I and II. Mean bRFS was 16.0 months (95% CI 12.4-19.6) in class III (PSA irrelevant, present BM) and 5.7 months (95% CI 2.7-8.7) in class IV (PSA ≥ 0.8 ng/mL, no BM, present VM). CONCLUSION: We developed and internally validated a risk classification for bRFS after PSMA-PET-guided MDT. Patients with PSA < 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) had the most promising bRFS. PSA ≥ 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) indicated intermediate risk for failure. Patients with BM were at higher risk regardless of the PSA. However, those patients still show satisfactory bRFS. In patients with VM, bRFS is heavily decreased. MDT in such cases should be discussed individually.