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Objectives: Circulating levels of activin A (ActA) and follistatin (FST) have been investigated in various disorders including malignancies. However, to date, their diagnostic and prognostic relevance is largely unknown in small cell lung cancer (SCLC). Our aim was to evaluate circulating ActA and FST levels as potential biomarkers in this devastating disease. Methods: Seventy-nine Caucasian SCLC patients and 67 age- and sex-matched healthy volunteers were included in this study. Circulating ActA and FST concentrations were measured by ELISA and correlated with clinicopathological parameters and long-term outcomes. Results: Plasma ActA and FST concentrations were significantly elevated in SCLC patients when compared to healthy volunteers (p < 0.0001). Furthermore, extensive-stage SCLC patients had significantly higher circulating ActA levels than those with limited-stage disease (p = 0.0179). Circulating FST concentration was not associated with disease stage (p = 0.6859). Notably, patients with high (≥548.8 pg/ml) plasma ActA concentration exhibited significantly worse median overall survival (OS) compared to those with low (

Összefoglaló. Bevezetés: Az öngyilkosság régóta jelentős probléma hazánkban. Célkitűzés: Az elmúlt 20 év során elkövetett, befejezett öngyilkosságok elemzése három időintervallumban (2000–2006, 2006–2010, 2010–2019) nemek, korcsoportok, az elkövetési mód, a családi állapot és a munkanélküliség szempontjából. További célunk volt a pszichiátriai ellátást negatívan érintő, 2007. évi egészségügyi reform suicid halálozással való összefüggéseinek vizsgálata. Módszer: A suicid halálozást a Központi Statisztikai Hivatal adatainak felhasználásával elemeztük. Az évenkénti suicid rátát 100 000 lakosra adtuk meg. Az adatok statisztikai feldolgozásához az Excel 2011-es, az SPSS 23-as és az amerikai NIH Jointpoint programjának 4.8.0.1-as verzióját használtuk. Eredmények: 2000 és 2019 között 51,4%-kal csökkent a suicid halálozás (nők: 15,57 vs. 7,69/100 000 fő; férfiak: 51,5 vs. 24,73/100 000 fő, összlakosság: 32,61 vs. 15,85/100 000 fő). A legnagyobb mértékben a férfiak és a középkorúak körében csökkent a mortalitási ráta, a legkevésbé a fiatal, egyedülálló nőknél. A leggyakoribb elkövetési mód változatlanul az akasztás (58,4%). A 20 évig tartó rátacsökkenés 2006 után több évre megtorpant, és egészen 2010-ig nagyjából konstans maradt (24,43 vs. 24,88/100 000 fő). Azt feltételezzük, hogy ennek hátterében jelentős részben a pszichiátriai ellátórendszert negatívan érintő, 2007-ben bevezetett egészségügyi reform állt. Ez a megtörés kimutatható volt szinte minden korcsoportnál, a leggyakoribb elkövetési módoknál, és egyaránt érintette a hajadonokat/nőtleneket, a házasokat, az özvegyeket és az elváltakat. Csak 2010 után kezdődött újra a suicid mortalitás szignifikáns csökkenése. Az utolsó 10 év alatt 36,3%-kal csökkent a suicid mortalitás (24,88 vs. 15,85/100 000 fő), ami kiemelkedő eredmény az európai országok körében. Következtetés: Egy elhibázott, a pszichiátriai ellátórendszert sújtó egészségügyi reform következményeként az addig egyenletesen csökkenő suicid halálozás üteme 2006 után megtört, és néhány évig stagnált. Több évig tartott, mire bizonyos mértékig rendeződött a pszichiátriai ellátórendszer, és ennek köszönhetően 2010 után ismét folyamatosan és szignifikánsan csökkent a suicid mortalitás. Orv Hetil. 2021; 162(32): 1283–1296. Summary. Introduction: In Hungary, suicide has been a major public health issue for a long time. Objective: Our objective was to examine data on completed suicide cases in Hungary from a 20-year period divided into three intervals (2000–2006; 2006–2010; 2010–2019) grouped by sex, age, methods of commitment, marital and employment statuses. An auxiliary aim was to assess the associations between the healthcare reform in 2007 (with unfavourable impacts on the psychiatric care system) and suicide mortality. Method: Data on suicide were provided by the Hungarian Central Statistical Office. In all cases, the yearly suicide rates were given for 100 000 inhabitants. For statistical calculations, we used Excel 2011, SPSS v. 23 and NIH Joinpoint Regression Program v. 4.8.0.1. Results: Between 2000 and 2019, there was a 51.4% reduction in the suicide mortality (females: 15.57 vs. 7.69/100 000; males: 51.5 vs. 24.73/100 000; total population: 32.61 vs. 15.85/100 000). The greatest declines occurred among males and middle-aged. At the same time, the rate of young single females declined only slightly. The most common method of commitment remained hanging (58.4%). During the 20-year-long period investigated, there was a temporary halt between 2006 (24.43/100 000) and 2010 (24.88/100 000) in the otherwise steadily declining trend of the rate. One of the major underlying causes of this plateau is presumed to be the healthcare reform commenced in 2007 with negative impacts on psychiatric services. This plateau was observable in almost all subpopulations irrespective of their age, marital status and the suicide method they used. The decline of the rate restarted only after 2010. In the last 10 years, suicide mortality has decreased by 36.3% (from 24.88 to 15.85/100 000) in Hungary, which is a very good result in a European comparison. Conclusion: Due to an unsound health reform threatening the psychiatric care, the previously experienced declining trend of the suicide rate halted in 2006 and has remained almost unchanged for a few years during which psychiatric services could be restored in some degree. From 2010, as a consequence of this restoration, the marked decline of the suicide rate restarted and has been remained stable. Orv Hetil. 2021; 162(32): 1283–1296.

Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of

Background Early metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood‐borne metastases in a comprehensive large cohort of SCLC patients. Methods In this retrospective non‐interventional cross‐sectional study of 1009 Caucasian SCLC patients, we investigated the correlation between the distinct locations of the primary tumor and metastatic sites. Results The onset of bone (p, In this study, our aim was to examine the organ specificity and timing of blood‐borne metastases in a comprehensive large cohort of Caucasian SCLC patients (n =1009). We report here that the onset of bone, brain, and pericardial metastases are late events, whereas adrenal gland and liver metastases occur earlier during tumor progression. We also show that several metastatic sites, such as bone and liver, and brain and adrenal gland intend to co‐metastasize preferentially. Of note, however, no significant associations were observed with regards to the timing and organ preference of distant metastases when comparing central and peripheral primary tumors.

To the authors' knowledge, AREN0321 is the first prospective clinical study of pediatric and adolescent renal cell carcinoma (RCC). Goals of the study included establishing epidemiological, treatment, and outcome data and confirming that patients with completely resected pediatric RCC, including lymph node-positive disease (N1), have a favorable prognosis without adjuvant therapy.From 2006 to 2012, patients aged30 years with centrally reviewed pathology of RCC were enrolled prospectively.A total of 68 patients were enrolled (39 of whom were male; median age of 13 years [range, 0.17-22.1 years]). Stage was classified according to the American Joint Committee on Cancer TNM stage seventh edition as stage I in 26 patients, stage II in 7 patients, stage III in 26 patients, and stage IV in 8 patients, and was not available in 1 patient. Sixty patients underwent resection of all known sites of disease, including 2 patients with stage IV disease. Surgery included radical nephrectomy (53 patients [81.5%]), partial nephrectomy (12 patients [18.5%]), and unknown (3 patients [4.4%]). Histology was TFE-associated RCC (translocation-type RCC; tRCC) in 40 patients, RCC not otherwise specified and/or other in 13 patients, papillary RCC in 9 patients, and renal medullary carcinoma (RMC) in 6 patients. Lymph node status was N0 in 21 patients, N1 in 21 patients (tRCC in 15 patients, RMC in 3 patients, papillary RCC in 2 patients, and not otherwise specified and/or other in 1 patient), and Nx in 26 patients. The 4-year event-free survival and overall survival rates were 80.2% (95% CI, 69.6%-90.9%) and 84.8% (95% CI, 75.2%-94.5%), respectively, overall and 87.5% (95% CI, 68.3%-100%) and 87.1% (95% CI, 67.6%-100%), respectively, for the 16 patients with N1M0 disease. Among patients presenting with metastases, 2 of 8 patients (2 of 5 patients with RMC) were alive (1 with disease) at the time of last follow-up, including 1 patient who was lost to follow-up (succinate dehydrogenase deficiency). The predominant RCC subtypes associated with mortality were tRCC and RMC.Favorable short-term outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected RCC, independent of lymph node status. A prospective study of patients with tRCC and RMC with M1 or recurrent disease is needed to optimize treatment.

Background Lorvotuzumab mertansine (IMGN901) is an antibody-drug conjugate linking an antimitotic agent (DM1) to an anti-CD56 antibody (lorvotuzumab). Preclinical efficacy has been noted in Wilms tumor, rhabdomyosarcoma, and neuroblastoma. Synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), and pleuropulmonary blastoma also express CD56. A phase 2 trial of lorvotuzumab mertansine was conducted to assess its efficacy, recommended phase 2 dose, and toxicities. Methods Eligible patients had relapsed after or progressed on standard therapy for their tumor type. Lorvotuzumab mertansine (110 mg/m2 per dose) was administered at the adult recommended phase 2 dose intravenously on days 1 and 8 of 21-day cycles. Dexamethasone premedication was used. Pharmacokinetic samples, peripheral blood CD56-positive cell counts, and tumor CD56 expression were assessed. Results Sixty-two patients enrolled. The median age was 14.3 years (range, 2.8-29.9 years); 35 were male. Diagnoses included Wilms tumor (n = 17), rhabdomyosarcoma (n = 17), neuroblastoma (n = 12), synovial sarcoma (n = 10), MPNST (n = 5), and pleuropulmonary blastoma (n = 1). Five patients experienced 9 dose-limiting toxicities: hyperglycemia (n = 1), colonic fistula (n = 1) with perforation (n = 1), nausea (n = 1) with vomiting (n = 1), increased alanine aminotransferase in cycle 1 (n = 2), and increased alanine aminotransferase in cycle 2 (n = 1) with increased aspartate aminotransferase (n = 1). Non-dose-limiting toxicities (grade 3 or higher) attributed to lorvotuzumab mertansine were rare. The median values of the maximum concentration, half-life, and area under the curve from zero to infinity for DM1 were 0.87 µg/mL, 35 hours, and 27.9 µg/mL h, respectively. Peripheral blood CD56+ leukocytes decreased by 71.9% on day 8. One patient with rhabdomyosarcoma had a partial response, and 1 patient with synovial sarcoma achieved a delayed complete response. Conclusions Lorvotuzumab mertansine (110 mg/m2 ) is tolerated in children at the adult recommended phase 2 dose; clinical activity is limited.

Background A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to facilitate partial nephrectomy in 25% of children with bilaterally predisposed unilateral tumors (Wilms tumor/aniridia/genitourinary anomalies/range of developmental delays [WAGR] syndrome; and multifocal and overgrowth syndromes). The purpose of this prospective study was to achieve excellent event-free survival (EFS) and overall survival (OS) while preserving renal tissue through preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response. Methods The treating institution identified whether a predisposition syndrome existed. Patients underwent a central review of imaging studies through the biology and classification study AREN03B2 and then were eligible to enroll on AREN0534. Patients were treated with induction chemotherapy determined by localized or metastatic disease on imaging (and histology if a biopsy had been undertaken). Surgery was based on radiographic response at 6 or 12 weeks. Further chemotherapy was determined by histology. Patients who had stage III or IV disease with favorable histology received radiotherapy as well as those who had stage I through IV anaplasia. Results In total, 34 patients were evaluable, including 13 males and 21 females with a mean age at diagnosis of 2.79 years (range, 0.49-8.78 years). The median follow-up was 4.49 years (range, 1.67-8.01 years). The underlying diagnosis included Beckwith-Wiedemann syndrome in 9 patients, hemihypertrophy in 9 patients, multicentric tumors in 10 patients, WAGR syndrome in 2 patients, a solitary kidney in 2 patients, Denys-Drash syndrome in 1 patient, and Simpson-Golabi-Behmel syndrome in 1 patient. The 4-year EFS and OS rates were 94% (95% CI, 85.2%-100%) and 100%, respectively. Two patients relapsed (1 tumor bed, 1 abdomen), and none had disease progression during induction. According to Response Evaluation Criteria in Solid Tumor 1.1 criteria, radiographic responses included a complete response in 2 patients, a partial response in 21 patients, stable disease in 11 patients, and progressive disease in 0 patients. Posttherapy histologic classification was low-risk in 13 patients (including the 2 complete responders), intermediate-risk in 15 patients, and high-risk in 6 patients (1 focal anaplasia and 5 blastemal subtype). Prenephrectomy chemotherapy facilitated renal preservation in 22 of 34 patients (65%). Conclusions A standardized approach of preoperative chemotherapy, surgical resection within 12 weeks, and histology-based postoperative chemotherapy results in excellent EFS, OS, and preservation of renal parenchyma.

PURPOSE AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes. PATIENTS AND METHODS Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I. RESULTS Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5. CONCLUSION VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.

OBJECTIVE. Distinguishing nephrogenic rests from small Wilms tumors can be challenging. This retrospective study was performed to determine if imaging characteristics can be used to distinguish nephrogenic rests from Wilms tumors. MATERIALS AND METHODS. All cases of pathologically confirmed nephrogenic rests and Wilms tumors smaller than 5 cm in maximum dimension on imaging in patients younger than 5 years old were identified from the Children’s Oncology Group AREN03B2 study (July 2006–August 2016). Exclusion criteria were chemotherapy before pathologic evaluation or more than 30 days between imaging and surgery; in addition, patients with nephrogenic rests occurring within or juxtaposed to a Wilms tumor and patients with diffuse hyperplastic perilobar nephroblastomatosis were excluded. Two radiologists who were blinded to pathology results assessed all lesions. The two-sample t test was used for continuous variables, and the Fisher exact test was used for categoric variables. ROC analysis was performed to determine the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors. RESULTS. Thirty-one pathologically confirmed rests (20 perilobar, 11 intralobar) and 26 Wilms tumors smaller than 5 cm met the eligibility criteria for study inclusion. The median diameter of the nephrogenic rests was 1.3 cm (range, 0.7–3.4 cm) and the median diameter of the Wilms tumor was 3.2 cm (range, 1.8–4.9 cm) (p < 0.001). Imaging findings supportive of Wilms tumors were spherical (p < 0.001) and exophytic (p < 0.001) lesions. Perilobar rests (17/20) were more likely to be homogeneous than intralobar rests (3/11) or Wilms tumor (3/26) (p < 0.001). ROC analysis showed that the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors was 1.75 cm. CONCLUSION. In children younger than 5 years old, the diagnosis of a Wilms tumor should be favored over a nephrogenic rest when a renal mass is spherical, exophytic, or larger than 1.75 cm. Homogeneity favors the diagnosis of perilobar nephrogenic rests, whereas intralobar rests and Wilms tumors are more likely to be inhomogeneous.

Both depressive and malignant disorders are endemic, furthermore, they are also frequently comorbid. In this narrative review, we briefly discuss the epidemiological aspects of the association between depression and cancer, including the following: 1) the prevalence of depression among patients with cancer is higher than that of the general population; 2) the incidence of cancer is higher among subjects with depression; 3) depression is associated with elevated cancer-specific mortality; and 4) the suicide mortality among cancer patients. Furthermore, we also discuss the possible etiological explanations of the frequent co-occurrence of depression and malignancies, including those biological and psychological factors that may explain how depression (and/or its treatment) may lead to the development of malignancies and vice versa. Finally, some aspects of screening and treatment of depression in cancer patients are also considered. Related to this, we may state that, taking into consideration that depression is frequently underdiagnosed in cancer patients, screening is recommended in this population. However, screening for depression is valueable only if the screened patients found depressed have access to psychiatric services where the final diagnosis can be made and some kind of antidepressive treatment is available. Orv Hetil. 2020; 161(22): 908-916.Both depressive and malignant disorders are endemic, furthermore, they are also frequently comorbid. In this narrative review, we briefly discuss the epidemiological aspects of the association between depression and cancer, including the following: 1) the prevalence of depression among patients with cancer is higher than that of the general population; 2) the incidence of cancer is higher among subjects with depression; 3) depression is associated with elevated cancer-specific mortality; and 4) the suicide mortality among cancer patients. Furthermore, we also discuss the possible etiological explanations of the frequent co-occurrence of depression and malignancies, including those biological and psychological factors that may explain how depression (and/or its treatment) may lead to the development of malignancies and vice versa. Finally, some aspects of screening and treatment of depression in cancer patients are also considered. Related to this, we may state that, taking into consideration that depression is frequently underdiagnosed in cancer patients, screening is recommended in this population. However, screening for depression is valueable only if the screened patients found depressed have access to psychiatric services where the final diagnosis can be made and some kind of antidepressive treatment is available. Orv Hetil. 2020; 161(22): 908-916.

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO2 coincides with an increase in certain species and the "GABA shunt" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity.

Background In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10) or diffuse (n = 19) anaplastic Wilms' tumour (AWT) treated with vincristine and dactinomycin without flank radiation were 69.5% and 82.6%, respectively. The Children's Oncology Group AREN0321 study evaluated whether adding doxorubicin and flank radiation improves survival for these patients. Patients and methods Tumour histology and stage were confirmed by real-time central pathology, surgery and radiology review. The patients received 25 weeks of vincristine, dactinomycin and doxorubicin (cumulative dose 150 mg/m2) with flank radiation (1080 cGy). We retrospectively analysed outcomes of all patients with stage I AWT enrolled in NWTSs 1–5 and AREN0321 with respect to treatment regimens. Results Eighteen patients with stage I AWT (8 focal and 10 diffuse) were enrolled on AREN0321. With a median follow-up of 4.6 years, the 4-year EFS and OS were 100%. One patient with diffuse AWT had pulmonary relapse 4.12 years after diagnosis. In the 112 patients with stage I AWT treated in NWTSs 1–5 and AREN0321, the EFS was significantly improved with doxorubicin treatment (p = 0.01; 4-year EFS: 97.2% [95% confidence interval {CI}: 91.3–100] vs. 77.5% [95% CI: 67.6–87.4]) but not by flank radiation (p = 0.15). Conclusions Treatment of stage I AWT with vincristine, dactinomycin, doxorubicin and flank radiation in AREN0321 yielded excellent survival outcomes. Retrospective analysis of AREN0321 and NWTS patients suggests that doxorubicin had a greater contribution to the excellent outcomes than radiation.

BACKGROUND: Molecular underpinnings that may prognosticate survival could increase understanding of small cell lung cancer (SCLC) tumor behavior. Here, we report the clinicopathological characteristics and biomarker profiles of short-term (ST) versus long-term (LT) survival in patients with metastatic SCLC. METHODS: Of the 876 consecutive metastatic SCLC patients receiving standard of care therapy, 44 met the definition of LT and 91 for ST, respectively. Available FFPE tumor tissue blocks were analyzed by next-generation sequencing (NGS). Analysis included gene mutations, copy number variations, mRNA expression, and protein expression by immunohistochemistry, followed by correlation with clinicopathological characteristics. RESULTS: There were no statistically significant and clinically relevant differences in cases with or without FFPE according to major clinicopathological variables in ST and LT. However, according to NGS, five mutually exclusive gene mutations were identified (E1A binding protein P300 [EP300] p.N217S; p.E152K; human epidermal growth factor receptor 4 [ERBB4] p.E317K; BRCA1, DNA repair associated [BRCA1] p.E1661N, and epidermal growth factor receptor [EGFR] p.V742A). Comparing LT vs. ST survivals, a twofold increase was found in the average predicted number of drugs per patient off compendium. We found high SSTR2 mRNA expressions in all LT patients (vs. two [20%] ST patients), which may reflect more benign neuroendocrine tumor characteristics. CONCLUSIONS: Consolidation radiation therapy and higher predicted drug sensitivity for off compendium were associated with LT compared to ST patients in SCLC. NGS profiling of extreme survivals may improve classification of SCLC and possibly identify clinically relevant new targets.

Background After its initial difficulties were overcome, lung transplantation became an accepted and effective treatment for end-stage lung disease. Patients can take part in almost all kinds of sports after lung transplantation, including high-altitude mountaineering, which is an extreme sport even for healthy individuals. Several articles have been published about high-altitude tolerance of transplanted patients. However, this was the first high-altitude expedition that included only lung transplant patients. Methods The Vienna lung transplantation team organized an expedition in 2017 to conquer the peak of Mount Kilimanjaro, which consisted of 10 lung transplanted patients and 24 accompanying medical personnel. The participants were tested before and several times during the hike to evaluate their general and cardiopulmonary status, the severity of altitude sickness, and radio-morphologic changes. The results of the lung transplanted patients were compared to the results of their healthy companions. Results The group started at 2360 meters and reached the 5895-meter-high summit of Mount Kilimanjaro after 6 days on June 18, 2017. Eight transplant patients and 24 escorting medical personnel reached the peak. This means that the success rate was 94%, which is significantly higher than the reported 85% for this route. The 2 transplant patients who did not make the summit turned back on the first and second day because they lacked the necessary fitness for the trip. We did not see a significant difference in the results regarding cardiopulmonary status or the severity of altitude sickness, although we observed mildly higher blood pressure and altitude sickness score results in the lung transplant group. Conclusion Based on our experiences, we can state that a stable patient after lung transplantation who attains the necessary physical fitness can achieve similar or even better physical results than an average healthy individual.

Given the moderate efficacy of the currently available antidepressants (ADs) in the treatment of major depressive disorder (MDD), the identification of agents that are both able to enhance the effectiveness of ADs and have a good safety profile is a reasonable task for current psychopharmacology. In addition to the well-known drugs (second-generation antipsychotics, levothyroxine, dopaminergic agents, etc.) for augmentation, investigations suggest that several nutraceuticals and over-the-counter (OTC) drugs may be effective and safe as adjunct therapeutic agents to conventional ADs. To identify such active ingredients we first performed a systematic literature search using PubMed and then conducted both backward and forward citation searches. For the PubMed search, we used the following combinations of keywords: 1) "adjunctive" + "therapy" + "antidepressant"; 2) "add-on" + "therapy" + "antidepressant"; 3) "supplementation" + "therapy" + "antidepressant". As a result of those efforts, we found more than 20 agents (e.g. S-Adenosyl-L-Methionine; folate; ω-3 fatty acids; curcumin; N-acetylcysteine; saffron; 5-hydroxytryptophan; NSAIDs) that are supposedly effective in the augmentation of standard AD treatment. We discussed the possible mechanisms of the antidepressant actions of those agents, as well as the preclinical and clinical evidence for their efficacy as stand-alone and adjunct treatments for MDD.

Recurrent respiratory papillomatosis is a condition caused by human papilloma virus, usually sub types 6 and 11. Papillomas are benign neoplasms that are most commonly found on the larynx and can be often associated with significant airway involvement. Frequency of episodes varies among patients as do the clinical symptoms. Patients often present with symptoms such as hoarseness but there is potential for respiratory compromise and even complete airway obstruction.

Background Sorafenib,an orally bioavailable, multitarget tyrosine kinase inhibitor, and irinotecan, a topoisomerase I inhibitor, have demonstrated activity in pediatric and adult malignancies. We evaluated the toxicity, pharmacokinetic (PK), and pharmacogenomic (PGX) profile of sorafenib with irinotecan in children with relapsed or refractory solid tumors and assessed the feasibility of incorporating patient-reported outcome (PRO) measures as an adjunct to traditional endpoints. Methods Sorafenib, continuous oral twice daily dosing, was administered with irinotecan, orally, once daily days 1-5, repeated every 21 days (NCT01518413). Based on tolerability, escalation of sorafenib followed by escalation of irinotecan was planned. Three patients were initially enrolled at each dose level. Sorafenib and irinotecan PK analyses were performed during cycle 1. PRO measurements were collected during cycles 1 and 2. Results Fifteen patients were evaluable. Two of three patients at dose level 2 experienced dose-limiting toxicity (DLT), grade 3 diarrhea, and grade 3 hyponatremia. Therefore, dose level 1 was expanded to 12 patients and two patients had DLT, grade 4 thrombocytopenia, grade 3 elevated lipase. Nine of 15 (60%) patients had a best response of stable disease with four patients receiving ≥6 cycles. Conclusions The recommended dose for pediatric patients was sorafenib 150 mg/m2 /dose twice daily with irinotecan 70 mg/m2 /dose daily × 5 days every 21 days. This oral outpatient regimen was well tolerated and resulted in prolonged disease stabilization. There were no significant alterations in the PK profile of either agent when administered in combination. Patients were willing and able to report their subjective experiences with this regimen.

Background: Patients with advanced-stage lung adenocarcinoma (LADC) often develop distant metastases in the skeletal system. Yet, the bone-specific metastasis pattern is still controversial. We, therefore, aimed to examine how the primary tumor location affects bone specificity and survival in LADC patients diagnosed with skeletal metastases.Methods: In total, 209 bone-metastatic Caucasian LADC patients from two thoracic centers were included in this study. Focusing on the specific location of primary tumors and bone metastatic sites, clinicopathological variables were included in a common database and analyzed retrospectively. Skeletal metastases were diagnosed according to the contemporary diagnostic guidelines and confirmed by bone scintigraphy. Besides region- and side-specific localization, primary tumors were also classified as central or peripheral tumors based on their bronchoscopic visibility.Results: The most common sites for metastasis were the spine (n = 103) and the ribs (n = 60), followed by the pelvis (n = 36) and the femur (n = 22). Importantly, femoral (p = 0.022) and rib (p = 0.012) metastases were more frequently associated with peripheral tumors, whereas centrally located LADCs were associated with humeral metastases (p = 0.018). Moreover, we deduced that left-sided tumors give rise to skull metastases more often than right-sided primary tumors (p = 0.018). Of note, however, the localization of the primary tumor did not significantly influence the type of affected bones. Multivariate Cox regression analysis adjusted for clinical parameters demonstrated that central localization of the primary tumor was an independent negative prognostic factor for overall survival (OS). Additionally, as expected, both chemotherapy and bisphosphonate therapy conferred a significant benefit for OS.Conclusion: The present study demonstrates unique bone-specific metastasis patterns concerning primary tumor location. Peripherally located LADCs are associated with rib and femoral metastases and improved survival outcomes. Our findings might contribute to the development of individualized follow‐up strategies in bone-metastatic LADC patients and warrant further clinical investigations on a larger sample size.

In our brief literature review, we discuss the changes in the concept of catatonia as well as its various types and symptoms. We also succinctly review the possible symptoms of clozapine withdrawal. In addition, we analyze the main features of the very few published cases of clozapine withdrawal-induced catatonia and the relationship between neuroleptic malignant syndrome and the malignant subtype of catatonia. Furthermore, we present the case of a 29-year-old male patient with schizophrenia in whom a malignant catatonic episode/neuroleptic malignant syndrome (with negativism, stupor, mutism, autonomic signs [eg, fever, hyperhidrosis], and elevated creatine kinase levels) began 5 days after the patient decided arbitrarily to cease his clozapine treatment. His catatonic symptoms quickly (ie, within a few days) resolved after the reinstitution of clozapine. Finally, we attempt to provide a theoretical explanation for the surprising finding in the literature that the withdrawal of clozapine, unlike the withdrawal of any other antipsychotics, may be associated with catatonia (frequently its malignant subtype). The take-home message of our case is that clinicians should bear in mind the risk of catatonia (especially the malignant subtype of it) after the prompt withdrawal of clozapine therapy.

Background: Suboptimal treatment response during anti-depressive treatment is fairly common with the first antidepressant (AD) choice, followed by switching to another agent in the majority of cases. However, the efficacy of this strategy over continuation of the original agent is less solidly documented in real-life studies. The aim of our present study was to ascertain the effects of switching to duloxetine following inadequate response to prior ADs on general illness severity, pain, and health-related quality of life in a large sample of major depressive disorder (MDD) and generalized anxiety disorder (GAD) patients in a prospective, real-world, multicenter, observational study.Methods: A total of 578 participants with MDD or GAD were enrolled in 58 outpatient sites in an 8-week, single-arm, open-label, flexible-dose trial with duloxetine. Severity of symptoms [with Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I)], severity of pain (with a Visual Analog Scale), satisfaction with current treatment, and health-related quality of life [with the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L)] measures were recorded at baseline and at follow-up visits 4 and 8 weeks after initiation of treatment. Data were analyzed using ANOVA and mixed linear models.Results: 565 patients completed the study and comprised the analyzed dataset. Results indicated that severity of illness significantly decreased over the 8 weeks of the study and already at 4 weeks in both patient groups. Overall quality of life and all of its subindicators also significantly improved in both patient groups and so did subjective experience of pain. Satisfaction with current treatment also significantly increased during the study period. Frequency of side effects was low. In both GAD and MDD groups, two patients dropped out of the study due to adverse effects, leading to treatment termination in four cases (0.7%).Conclusions: This 8-week, multicenter, flexible-dosing, single-arm, open-label, observational real-life study in MDD and GAD patients switched to duloxetine after inadequate response or low tolerability to other ADs showed a significant positive effect on all outcome measures, including a significant decrease in illness severity as well as significant overall symptomatic improvement, with good tolerability.

BACKGROUND: Although lung adenocarcinoma (LADC) with sensitizing mutations of the epidermal growth factor receptor (EGFR) is highly sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), in most cases disease progression inevitably occurs. Our aim was to investigate the predictive and prognostic significance of adjusted tumoral EGFR variant allele frequency (EGFR-aVAF) in the above setting. METHODS: Eighty-nine Caucasian advanced-stage LADC patients with known exon-specific EGFR mutations undergoing EGFR-TKI treatment were included. The correlations of EGFR-aVAF with clinicopathological variables including progression-free and overall survival (PFS and OS, respectively) were retrospectively analyzed. RESULTS: Of 89 EGFR-mutant LADC patients, 46 (51.7%) had exon 19 deletion, while 41 (46.1%) and 2 (2.2%) patients had exon 21- and exon 18-point mutations, respectively. Tumoral EGFR-aVAF was significantly higher in patients harboring EGFR exon 19 mutations than in those with exon 21-mutant tumors (P

Background: KRAS mutation is the most common genetic alteration in lung adenocarcinoma (LADC) in Western countries and is associated with worse outcome in bone-metastatic cases. Yet, to date, no effective treatment guidelines were developed for these patients. Accordingly, our aim was to investigate the impact of KRAS mutation on bisphosphonate (BTx) and radiation therapy (RTx) in bone-metastatic LADC patients. Methods: Clinicopathological variables of 134 consecutive LADC patients with bone metastases at diagnosis and known KRAS status were retrospectively analyzed. The effects of BTx, RTx and KRAS mutation on overall survival (OS) were investigated. Results: Of the total cohort, 93 patients were identified as KRAS wild-type (WT) (69.4%) and 41 (30.6%) as KRAS mutant patients. The presence of KRAS mutation was associated with significantly reduced median OS (5.1 vs. 10.2 months in KRAS WT patients; P=0.008). Irrespective of KRAS mutational status both BTx (P=0.007) and RTx (P=0.021) conferred a significant benefit for OS. Notably, however, when analyzing the patients with KRAS-mutant and KRAS WT tumors separately, the benefit from BTx and RTx on OS remained statistically significant only in KRAS WT patients (P=0.032 and P=0.031, respectively). Conclusions: KRAS mutation is a strong negative prognostic factor in bone-metastatic LADC patients. Both BTx and RTx can increase the OS with a pronounced benefit for patients with KRAS WT tumors. Altogether, KRAS mutational status should be considered during therapeutic decision making in bone-metastatic LADC patients. CA extern und UDE (Hegedus)

PURPOSE OF REVIEW The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor. RECENT FINDINGS Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials. SUMMARY The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.

Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). ----- Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. ------ Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. ----- Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.

Background Thymomas and thymic carcinomas (TC) are intrathoracic malignancies that, although rare, represent the most common anterior mediastinal tumors in adults (comprising approximately 0.2-1.5% of all malignancies).1 Recent accumulating evidence on immune checkpoint pathways suggests that immunotherapy might be a promising therapeutic option for refractory TCs.2 We herein report two cases of a pembrolizumab-treated TC patient. Methods Immunotherapy is accessible through individual permission for the treatment of TC in Hungary. We retrospectively collected data of two TC patients treated with pembrolizumab in one institute. Results The first patient was a 66-year-old woman. Squamous cell TC was diagnosed in her left parasternal region. She was a former smoker, had no history of autoimmune disorders, and had no associated symptoms at the time of diagnosis. She underwent open thymectomy. The histology proved type C (WHO classification) TC with a pathological TNM of T1aN0 and microscopic-positive margins. Consequently, the patient received 60 Gy of postoperative radiotherapy. Nine months after the surgery local recurrence and multiple hepatic metastases appeared. Six cycles of chemotherapy (ADOC regimen) were introduced as first-line systemic therapy which resulted in stable disease (SD) for 8 months. Pembrolizumab was administered as second-line treatment (200 mg every 3 weeks) for 6 cycles. The best result was SD. Due to progression, third-line docetaxel treatment was initiated. Shortly after, ptosis and diplopia developed. Myasthenia gravis was diagnosed, and third-line chemotherapy was judged ineffective. The second patient was a 63-year-old man. He was diagnosed with unresectable TC and treated with chemotherapy (ADOC regimen) up-front. After six cycles the tumor regressed, and surgery was performed with R2 result. Postoperatively, the patient was given six cycles of chemotherapy (cisplatin/etoposide) and radiotherapy. Six months later local progression was detected and pembrolizumab was commenced. Eight cycles of pembrolizumab produced SD as best response. No immune-related adverse effects (irAEs) were detected. After progression Sunitinib therapy was started. In both cases, additional immunohistochemistry investigations were performed. Conclusions In the literature, there is no phase 3 trial on immune-checkpoint inhibitor (ICI) therapy of TC. Phase 2 trials reported promising results with pembrolizumab.3 4 However, there are conflicting results with other ICIs.5 Before starting, it is important to rule out autoimmune disorders to evade serious, even life-threatening immune-complications. The high likelihood of irAEs in TC also underpin the importance of predictive biomarkers. Further studies are required to evaluate the efficacy and safety of immunotherapy in TC. Acknowledgements The authors thank the multidisciplinary clinical teams involved in the treatment and management of the patient. References Bushan K, Sharma S, Verma H. A review of thymic tumors. Indian Journal of Surgical Oncology 2013;4(2):112–116. https://doi.org/10.1007/s13193-013-0214-2 Isshiki T, Isobe K, Tochigi N, et al. Successful use of pembrolizumab to treat refractory thymic carcinoma with high PD-L1 expression. Case Rep Oncol2018;11(3):688–692. Published 2018 Oct 31. doi:10.1159/000493187 Giaccone G, Kim C, Thompson J, McGuire C, Kallakury B, Chahine JJ, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol 2018;19:247–255. Cho J, Kim HS, Ku BM, Choi YL, Cristescu R, Han J, et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: an open-label phase II trial. J Clin Oncol 2019;37(JCO2017773184):2162–2170. Katsuya Y, Horinouchi H, Seto T, Umemura S, Hosomi Y, Satouchi M, et al. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer 2019;113:78e86.

Background Patients with relapsed or refractory Wilms tumor (WT) have poor prognoses with limited treatment options.1–3 Immunotherapy offers a promising alternative for targeted therapy but has been limited by immune evasion tactics.4–6 Adoptive cell therapy with patient-derived tumor-associated antigen-specific T cells (TAA-T) targeting 3 antigens (WT1, PRAME, and survivin) has the potential to overcome antigen loss. The objective of this phase I clinical trial is to determine the safety of administering TAA-T to patients with high-risk, relapsed/refractory solid tumors. Secondary objectives include determination of clinical efficacy and immunobiology following infusion. Methods T cells expanded from patient peripheral blood are stimulated weekly with antigen presenting cells expressing an overlapping peptide library spanning the tumor antigens WT1, PRAME, and survivin. Following release testing, patients are infused with TAA-T on a dose escalation study, ranging from a dose of 1 x 107/m2 (dose level 1) to 4 x 107/m2 (dose level 3). Clinical and immunobiological studies performed post-infusion monitor for adverse effects and assess immune and disease responses. Results Therapy with TAA-T was shown to be safe and well-tolerated in patients with high-risk solid tumors on this dose-escalation study.7 A total of 18 patients have been infused, with WT as the predominant diagnosis, accounting for 10 patients. We elucidated a dose-response relationship, with a prolonged median time to progression for patients treated on dose level 3 (recommended dose level [RDL]) compared to those on dose level 1 and 2 combined (5.2 vs 2.8 months, respectively) (figure 1). Patients demonstrated prolonged progression-free survival (PFS) compared to therapy received just prior to TAA-T (figure 2). Best response observed was stable disease. A majority of patients demonstrated improved anti-tumor immunity as evidenced by antigen spreading (figure 3). Conclusions In long-term follow up, the 1-year progression-free survival (PFS) remains improved for patients treated at the recommended dose level compared to the PFS observed with therapy received immediately prior to TAA-T (29% vs 15%, respectively). Three patients are long-term (28–38 months) survivors without disease progression or further therapy. This unique immunotherapeutic has been well-tolerated without life-threatening cytokine release syndrome. To enhance TAA-T activity further in vivo, we will evaluate the safety of prescribed lymphodepletion prior to TAA-T infusion and assess anti-tumor immunity. We expect that lymphodepletion will enhance T cell persistence and expansion and recruit endogenous immune response with altered kinetics. Ethics Approval The study was approved by the Children’s National Hospital Institutional Review Board, approval number NCT02789228. References Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, Van den Heuvel-Eibrink M, Pritchard-Jones K. Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration. J Clin Oncol 2015;33(27):2999–3007. Mullen EA, Chi YY, Hibbitts E, Anderson JR, Steacy KJ, Geller JI, Green DM, Khanna G, Malogolowkin MH, Grundy PE and others. Impact of Surveillance Imaging Modality on Survival After Recurrence in Patients With Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group. J Clin Oncol 2018:JCO1800076. Malogolowkin MH, Hemmer MT, Le-Rademacher J, Hale GA, Mehta PA, Smith AR, Kitko C, Abraham A, Abdel-Azim H, Dandoy C and others. Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms’ tumor: a CIBMTR retrospective analysis. Bone Marrow Transplant 2017;52(11):1549–1555. Heczey A, Louis CU. Advances in chimeric antigen receptor immunotherapy for neuroblastoma. Discov Med 2013;16(90):287–94. Park JR, Digiusto DL, Slovak M, Wright C, Naranjo A, Wagner J, Meechoovet HB, Bautista C, Chang WC, Ostberg JR and others. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther 2007;15(4):825–33. Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, Vulto A, den Bakker M, Oosterwijk E, Debets R and others. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther 2013;21(4):904–12. Hont AB, Cruz CR, Ulrey R, O’Brien B, Stanojevic M, Datar A, Albihani S, Saunders D, Hanajiri R, Panchapakesan K and others. Immunotherapy of relapsed and refractory solid tumors with ex vivo expanded multiantigen-associated specific cytotoxic T lymphocytes: A Phase I Study. J Clin Oncol 2019:JCO1900177.

Purpose Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD. Patients and methods This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database. Results Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212–1.571]; p Discussion To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of “Neurotic, stress-related and somatoform disordersˮ and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.

Background: Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. Method: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. Results: Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. Conclusions: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern., SCOPUS: ar.j, info:eu-repo/semantics/published

Aims Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. Methods and results Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. Conclusions Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.

Background Metastatic lung cancer is a debilitating disease, but with the advances in immunotherapy, therapeutic options have vastly increased. Numerous complete blood count parameters (CBC) have been described as easily accessible biomarkers that might predict response to immunotherapy. However, to date, no comprehensive study has been performed on the longitudinal changes of these parameters during cancer progression. Methods The clinicopathological variables and CBC parameters of 986 advanced stage lung cancer patients were retrospectively analyzed. Blood tests were performed as part of the routine checkup and the results were recorded at the time of the diagnosis of the primary tumor, the diagnosis of brain or bone metastases, and also during the last available follow‐up. Results In the experimental subcohort, 352 and 466 patients were diagnosed with brain and bone metastases, respectively. The control group consisted of 168 patients without clinically detectable or other distant organ metastases. In our longitudinal analyses, we found significantly decreasing absolute lymphocyte count (ALC: P, In our longitudinal analyses, we found significantly decreasing ALC, and significantly increasing ANC levels in advanced‐stage lung cancer patients during disease progression. Interestingly, patients with brain metastases have descending‐ascending PLT trendlines, while patients with bone metastases exhibit ascending‐descending trendlines during disease progression. The current study might help to improve patient selection and treatment strategies for brain and bone metastatic lung cancer patients.

Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.

We determined the prevalence of untreated depression in patients with hypertension (HT) and/or diabetes (DM) and estimated the extra health care use and expenditures associated with this comorbidity in a rural Hungarian adult population. We also assessed the potential workload of systematic screening for depression in this patient group. General health check database from a primary care programme containing survey data of 2027 patients with HT and/or DM was linked to the outpatient secondary care use database of National Institute of Health Insurance Fund Management. Depression was ascertained by Beck Depression Inventory score and antidepressant drug use. The association between untreated depression and secondary healthcare utilization indicated by number of visits and expenses was evaluated by multiple logistic regression analysis controlled for socioeconomic/lifestyle factors and comorbidity. The age-, sex- and education-specific observations were used to estimate the screening workload for an average general medical practice. The frequency of untreated depression was 27.08%. The untreated severe depression (7.45%) was associated with increased number of visits (OR 1.60, 95% CI 1.11–2.31) and related expenses (OR 2.20, 95% CI 1.50–3.22) in a socioeconomic status-independent manner. To identify untreated depression cases among patients with HT and/or DM, an average GP has to screen 42 subjects a month. It seems to be reasonable and feasible to screen for depression in patients with HT and/or DM in the primary care, in order to detect cases without treatment (which may be associated with increase of secondary care visits and expenditures) and to initiate the adequate treatment of them.

Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

Lung transplant is an effective way to treat many end-stage lung diseases. However, one of the main barriers of allograft organ transplant is still the immunologic rejection of transplanted tissue, which is a response of the HLA molecules. Rejection is a complex process involving both T-cell-mediated delayed-type hypersensitivity reactions and antibody-mediated hypersensitivity reactions to histocompatibility molecules on foreign grafts. We report the case of a 25-year-old female patient with cystic fibrosis who underwent 2 lung transplants because of her initial diagnosis and appearance of bronchiolitis obliterans syndrome after the first transplant. Only 13 months after the second transplant, despite the therapies applied, a new rejection occurred associated with high mean fluorescent intensity donor-specific antibody levels, which resulted later in the death of the patient. The present case draws attention to the importance of matching HLA molecules between donor and recipient in addition to immunosuppressive therapy.

Background: Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies with an expected 1-year overall survival (OS) of Methods: Lymphocytes obtained from the BMT donor were manufactured to target TAAs; WT1, PRAME and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5-4x10 7/m 2. Patients were evaluated for acute infusion-related toxicity, cytokine release syndrome (CRS), neurotoxicity, GVHD and monitored for clinical response post-infusion. T-cell receptor sequencing was conducted on the TAA-T product and the recipients' peripheral blood prior to and post-infusion to monitor persistence and expansion of the product. Results: Twenty-three BMT recipients with relapsed/refractory (n=11) and/or high-risk (n=12) acute myeloid leukemia (n=20) and acute lymphoblastic leukemia (n=3) were infused post-transplant. No patient developed CRS or neurotoxicity, and only one patient developed grade III GVHD. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n=9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post-TAA-T (Figure 1A and B). The poorest prognosis patients (relapsed less than 6 months after transplant) exhibited a 1-year OS of 42.8% post-relapse (n=7) (Figure 1C). Median survival was not reached for high-risk patients who received pre-emptive TAA-T post-transplant (n=12) with eight of the nine (88.9%) evaluable patients at 1-year post-infusion remaining alive (Figure 1B). Of those, five (62.5%) were alive and in continued remission at the time of submission. Evaluation of unique T-cell receptor clonotypes (present in the product but not the recipient prior to infusion) demonstrated expansion and persistence in patients up to 1-year post-infusion (Figure 1D). Conclusions: Although as a Phase-I study, concomitant anti-leukemic therapy was allowed, TAA-T cell therapy was shown to be safe and well-tolerated with sustained remissions observed in high-risk and relapsed patients. Moreover, adoptively transferred TAA-T expanded in vivo as detected by T-cell receptor V-beta (TCRVb) sequencing persisted up to at least 1-year post-infusion (Figure 1D). (ClinicalTrials.gov numbers, NCT002203902) Figure 1 Figure 1. Disclosures Cruz: Mana Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Catamaran Bio: Consultancy, Patents & Royalties, Research Funding. Hanley: Mana Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellevolve: Consultancy; Maxcyte: Membership on an entity's Board of Directors or advisory committees. Bollard: SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cabaletta Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Catamaran Bio: Membership on an entity's Board of Directors or advisory committees; Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees; ROCHE: Consultancy, Honoraria; Repertoire Immune Medicines: Current equity holder in publicly-traded company; Neximmune: Current equity holder in publicly-traded company; Mana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

The Children's Oncology Group study AREN0534 aimed to improve event-free survival (EFS) and overall survival (OS) while preserving renal tissue by intensifying preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response.No prospective therapeutic clinic trials in children with bilateral Wilms tumors (BWT) exist. Historical outcomes for this group were poor and often involved prolonged chemotherapy; on NWTS-5, 4-year EFS for all children with BWT was 56%.Patients were enrolled and imaging studies were centrally reviewed to assess for bilateral renal lesions. They were treated with 3-drug induction chemotherapy (vincristine, dactinomycin, and doxorubicin) for 6 or 12 weeks based on radiographic response followed by surgery and further chemotherapy determined by histology. Radiation therapy was provided for postchemotherapy stage III and IV disease.One hundred eighty-nine of 208 patients were evaluable. Four-year EFS and OS were 82.1% (95% CI: 73.5%-90.8%) and 94.9% (95% CI: 90.1%-99.7%. Twenty-three patients relapsed and 7 had disease progression. After induction chemotherapy 163 of 189 (84.0%) underwent definitive surgical treatment in at least 1 kidney by 12 weeks and 39% retained parts of both kidneys. Surgical approaches included: unilateral total nephrectomy with contralateral partial nephrectomy (48%), bilateral partial nephrectomy (35%), unilateral total nephrectomy (10.5%), unilateral partial nephrectomy (4%), and bilateral total nephrectomies (2.5%).This treatment approach including standardized 3-drug preoperative chemotherapy, surgical resection within 12 weeks of diagnosis and response and histology-based postoperative therapy improved EFS and OS and preservation of renal parenchyma compared with historical outcomes for children with BWT.

Objective This study aims to evaluate the impact of T stage and extended surgery on the outcome of patients with Pancoast tumors after induction chemoradiation therapy. Methods Forty-six consecutive patients who underwent chemoradiation therapy (platin-based, 45-66 Gy) followed by surgery between 1998 and 2013 were retrospectively reviewed and analyzed. Results In 28 (61%) patients with T4 tumors, extended procedures (more than rib resection) were performed. There were 37 (80%) lobectomies, 6 (13%) pneumonectomies, and 3 (7%) sublobar resections. A total of 44 (96%) patients had R0 resection. About 30-day mortality was 0%, major surgical complications occurred in 9 (19.6%) patients. Overall survival (OS) at 5-years was 63%. Disease-free survival (DFS) at 5-years was 45%. At multivariate cox regression analysis adjusted for clinical factors, T factor (T3/T4) and extended surgical procedures did not impact survival. However, pathological positive N stage had a negative impact on OS and lack of pathological response negatively impacted both OS and DFS. Conclusion Trimodality treatment including radical resection for Pancoast tumors provides good surgical outcome and favorable long-term results. Survival of patients with T4 tumors and extended surgical procedures comparable to that of patients with T3 tumors undergoing rib resection only.

Background and Purpose— Stroke preparedness interventions are limited by the lack of psychometrically sound intermediate end points. We sought to develop and assess the reliability and validity of the video-Stroke Action Test (video-STAT) an English and a Spanish video-based test to assess people’s ability to recognize and react to stroke signs. Methods— Video-STAT development and testing was divided into 4 phases: (1) video development and community-generated response options, (2) pilot testing in community health centers, (3) administration in a national sample, bilingual sample, and neurologist sample, and (4) administration before and after a stroke preparedness intervention. Results— The final version of the video-STAT included 8 videos: 4 acute stroke/emergency, 2 prior stroke/nonemergency, 1 nonstroke/emergency, and 1 nonstroke/nonemergency. Acute stroke recognition and action response were queried after each vignette. Video-STAT scoring was based on the acute stroke vignettes only (score range 0–12 best). The national sample consisted of 598 participants, 438 who took the video-STAT in English and 160 who took the video-STAT in Spanish. There was adequate internal consistency (Cronbach α=0.72). The average video-STAT score was 5.6 (SD=3.6), whereas the average neurologist score was 11.4 (SD=1.3). There was no difference in video-STAT scores between the 116 bilingual video-STAT participants who took the video-STAT in English or Spanish. Compared with baseline scores, the video-STAT scores increased after a stroke preparedness intervention (6.2 versus 8.9, P Conclusions— The video-STAT yields reliable scores that seem to be valid measures of stroke preparedness.

OBJECTIVE To determine if observation alone after nephrectomy in very low-risk Wilms tumor (defined as stage I favorable histology Wilms tumors with nephrectomy weight

Wilms tumor (WT) is the most common renal malignancy of childhood and accounts for 6% of all childhood malignancies. With current therapies, the 5-yr overall survival (OS) for children with unilateral favorable histology WT is greater than 85%. The prognosis is worse, however, for the roughly 15% of patients who relapse, with only 50%–80% OS reported in those with recurrence. Herein, we describe the extended and detailed clinical course of a rare case of a child with recurrent, pulmonary metastatic, favorable histology WT harboring a BRAF V600E mutation. The BRAF V600E mutation, commonly found in melanoma and other cancers, and previously undescribed in WT, has recently been reported by our group in a subset of epithelial-predominant WT. This patient, who was included in that series, presented with unilateral, stage 1, favorable histology WT and was treated with standard chemotherapy. Following the completion of therapy, the patient relapsed with pulmonary metastatic disease, that then again recurred despite an initial response to salvage chemotherapy and radiation. Next-generation sequencing (NGS) on the metastatic pulmonary nodule revealed a BRAF V600E mutation. After weighing the therapeutic options, a novel approach with dual BRAF/MEK inhibitor combination therapy was initiated. Complete radiographic response was observed following 4 months of therapy with dabrafenib and trametinib. At 12 months following the start of BRAF/MEK combination treatment, the patient continues with a complete response and has experienced minimal treatment-related side effects. This represents the first case, to our knowledge, of effective treatment with BRAF/MEK molecularly targeted therapy in a pediatric Wilms tumor patient.

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597, p = 0.011) and OS (hazard ratio, 0.645, p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group, p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group, p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.

Stage I epithelial-predominant favorable-histology Wilms tumors (EFHWTs) have long been suspected to have an excellent outcome. This study investigates the clinical and pathologic features of patients with stage I EFHWTs to better evaluate the potential for a reduction of chemotherapy and its associated toxicity.All patients registered in the Children's Oncology Group (COG) AREN03B2 study between 2006 and 2017 with stage I EFHWTs were identified. EFHWTs were defined as tumors with at least 66% epithelial differentiation, regardless of the degree of differentiation. Clinical information was abstracted from COG records. Event-free survival (EFS) and overall survival (OS) were calculated and compared between groups based on age and therapy.The 4-year EFS rate was 96.2% (95% confidence interval, 92%-100%), and the OS rate was 100%; EFS and OS did not statistically significantly differ with the age at diagnosis (48 vs ≥48 months; P = .37) or treatment (EE4A vs observation only; P = .55). Six events were reported. Three patients developed contralateral tumors and did not otherwise relapse; none of these had nephrogenic rests or a recognized predisposition syndrome. Three patients developed metastatic recurrence; all 3 had received EE4A as their primary therapy after nephrectomy.These findings demonstrate an excellent outcome for stage I EFHWTs with95% EFS and OS. These data support the utility of investigating the treatment of stage I EFHWTs with observation alone after nephrectomy.

We report on two cases of severe recurrent respiratory papillomatosis (RRP) involvement where the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab IV has been administered for treatment. Notably, there have not been any episodes of urgent transfer to the hospital for obstructive events since the bevacizumab was started. It is important to note however, that the disease has not been eliminated. While some pulmonary nodules continue to grow, they have become cavitated. Overall, the number and size of pulmonary lesions has decreased. Therefore, VEGF-targeted therapies, Bevacizumab, could prove to be a promising novel approach for long-term treatment of severe RRP.

PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P = .042), and 61.3% for patients with stage III/IV disease ( P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%). CONCLUSION Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Introduction Lung transplantation is the only successful treatment option for patients experiencing end-stage lung disease. Results have improved significantly in the last decade; however, the number one limiting factor is still the shortage of donor lungs. Due to the discrepancy between available donor lungs and patients awaiting lung transplantation, many centers have reintroduced donation after cardiac death (DCD). According to their results, DCD and donation after brain death (DBD) are comparable in terms of survival and graft function. Currently in Hungary, donation is only allowed from DBD donors; however, due to the Eurotransplant agreement, non-heart-beating donation (NHBD) organs can be transplanted into Hungarian patients, and in some cases Hungarian transplant teams can also take part in NHBDs within the Eurotransplant region. The Hungarian experience. A Hungarian patient received a lung from a 15-year-old uncontrolled DCD in Vienna. The donor was reanimated for 54 minutes and after lung procurement the lungs were put on ex vivo lung perfusion and later successfully implanted into the Hungarian recipient. The recovery was very successful and the patient is still alive. The Hungarian Lung Transplantation Team was involved in a controlled Maastricht III donation in 2017. A 49-year-old female donor was reported from Ghent, Belgium. A multiorgan donation was carried out with 15 minutes of warm ischemic time in the case of the lungs. Conclusion DCD is an effective, safe, and available method to increase the donor pool. In the case of controlled donations, the necessary protocols have already been prepared. Although DBD is working very successfully in Hungary, infrastructural developments, education of professionals, and social preparations are all needed to implement a DCD protocol in Hungary.