Multidisciplinary survey on use of feeding tubes in head and neck cancer patients undergoing chemoradiotherapy in Germany-the SUFEETUBE project.

BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (n = 52; 74.3%) and came from a radiation oncology background (n = 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (n = 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (n = 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations.

OBJECTIVES: Long-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging. METHODS: Asymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping. RESULTS: Forty-four survivors (age 44 [interquartile range, IQR 37-52] years; follow-up time 10 [IQR 5-15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50-54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001). CONCLUSION: Based on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors. CLINICAL RELEVANCE STATEMENT: Platinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy. KEY POINTS: • Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement. • Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of  ≥ 200 mg/m2. • Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.

Targeting cyclin-dependent kinase 7-association between CDK7 and pMED1 expression in prostate cancer tissue.

Cyclin-dependent kinase (CDK) 7-mediated phosphorylation of Mediator-complex subunit 1 (MED1) enhances androgen receptor (AR) activity in prostate cancer (PCa). Hyperactive AR-signalling plays a key role for the development of castration resistance. Several CDK7 inhibitors are currently under investigation in Phase I/II trials addressing solid tumours, including PCa. Aim of this study was to characterize the CDK7/phospho-(p)MED1 axis in human tissue. Immunohistochemistry was performed on 595 PCa samples including 394 primary tumour foci obtained by radical prostatectomy (RP), 64 advanced or recurrent tumours obtained by palliative transurethral resection of the prostate (pTUR), 65 lymph node metastases (LNM), 35 distant metastases (DM) and 36 benign samples. CDK7 is expressed in 79.3% of PCa tissues and protein levels are significantly higher in LNM, pTUR and DM and lower in benign tissues compared to primary tumours. CDK7 and pMED1 expression show strong positive correlation. High expression of CDK7 associated with shorter 5-year biochemical recurrence-free-survival (63.0% vs. 85.0%) and reduced survival persists when adjusted for T-Stage, nodal status, resection boundaries, grade group and pre-operative prostate-specific antigen in multivariate Cox-regression (hazard ratio 4.30; 95% CI, 1.43 to 12,40, P = 0.007). High CDK7 and pMED1 levels correlate with nuclear AR expression. CDK7 positive tumours harbour higher Ki67 expression indices and show more frequently positive ERG (ETS-related gene)-status. In conclusion, CDK7 is frequently expressed in human PCa and predicts disease recurrence after RP. Therapeutical inhibition of CDK7 might be a promising approach in treatment of advanced PCa.

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG).

PURPOSE: To report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out. METHODS: A multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint. RESULTS: Collaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0-177) and two consecutive treatment lines (range 0-5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47-1.30) associated with an overall 2-year CSS rate of 30%. CONCLUSION: PC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

The influence of the explosive decompression in steam-explosion pretreatment on the enzymatic digestibility of different biomasses.

For the production of second generation biofuels from lignocellulosic biomass, pretreatment of the biomass feedstock is necessary to overcome its recalcitrance in order to gain fermentable sugars. Due to many reasons, steam-explosion pretreatment is currently the most commonly used pretreatment method for lignocellulosic biomass on a commercial scale [S. Brethauer and M. H. Studer, CHIMIA, 2015, 69, 572-581]. In contrast to others, we showed that the explosive decompression at the end of this pretreatment step can have a positive influence on the enzymatic digestibility of softwood, especially in combination with high enzyme dosages [T. Pielhop, et al., Biotechnology for Biofuels, 2016, 9, 152]. In this study, the influence of the explosive decompression on the enzymatic digestibility of hardwood and herbaceous plants was systematically studied. Beech and corn stover were pretreated under different pretreatment conditions and enzymatically hydrolysed with different enzyme dosages. The maximum enhancement of the digestibility of corn stover was 16.53% after a 2.5 min pretreatment step at 15 barg steam pressure. For beech, a maximum relative enhancement of 58.29% after a 10 min pretreatment step at 15 barg steam pressure could be reached. With this, we show that the explosive decompression can also enhance the enzymatic cellulose digestibility of hardwood and herbaceous plants.

Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond-A Comprehensive Review of the Current Literature.

PURPOSE: We comprehensively reviewed current efforts and advances in the field of chemotherapeutic and biologically targeted treatment options after the failure of cisplatin based, first line regimens for urothelial carcinoma. MATERIALS AND METHODS: We searched MEDLINE®, Central®, and meeting abstracts of ASCO (American Society of Clinical Oncology) and ESMO (European Society for Medical Oncology) to identify original articles, reviews and retrospective analyses on second line treatment of urothelial carcinoma. Articles were included in analysis if they described prospective phase II/III studies or larger high quality retrospective studies of second line treatment of urothelial carcinoma. RESULTS: Although considered a chemosensitive disease, most patients with advanced or metastatic urothelial carcinoma relapse after cisplatin based first line treatment. Today none of the commonly used drugs, ie paclitaxel, carboplatin and/or gemcitabine, are approved by the FDA (Food and Drug Administration) for second line systemic treatment. In Europe vinflunine plus best supportive care is the only option approved by the EMA (European Medicines Agency) with moderate clinical efficacy. Responses to combined chemotherapy approaches are often better but associated with remarkable toxicity. In patients who respond well to first line treatment and, thus, are considered cisplatin sensitive readministration of a platinum based combination regimen may be an option. To date targeted therapies do not have a role in second line treatment of urothelial cancer. Immunotherapeutic strategies to target the PD-1/PD-L1 axis are emerging. In a recent phase I trial evaluating the PD-L1 targeted monoclonal antibody MPDL3280A a promising 43% response rate with good tolerability was achieved, which led to an immediate breakthrough therapy designation by the FDA. Combining chemotherapy with targeted agents, eg weekly paclitaxel and pazopanib, also shows promising activity in this prognostically poor treatment situation. CONCLUSIONS: Response rates and survival are poor after second line chemotherapy for advanced or metastatic urothelial carcinoma. To improve outcomes of salvage treatment novel biologically targeted drugs as monotherapy or as part of a combination with conventional cytostatics are urgently needed.

Hyperthyroidism in non-seminomatous testicular germ cell tumors: two case reports and literature review.

Background: Human chorionic gonadotropin (hCG)-induced hyperthyroidism is a rare paraneoplastic syndrome observed in non-seminomatous testicular germ cell tumors, due to a cross-reaction between the ß-subunit of hCG with the thyroid-stimulating hormone receptor. The precise prevalence of this paraneoplastic phenomenon is unclear as, in the majority of cases, hyperthyroidism remains subclinical. Case presentation: Here, we present two cases of advanced metastatic non-seminomatous testicular germ cell tumors where patients exhibited signs and symptoms of thyrotoxicosis at primary diagnosis due to excessive serum ß-hCG elevation, with complete remission of symptomatology after the start of oncological treatments and no signs of relapse at the time of publication of this report. Additionally, we provide a comprehensive review of the existing literature concerning this uncommon occurrence. Conclusion: Despite being a rare event, the presence of hyperthyroidism or thyrotoxicosis without clear etiology in a young man should lead to consider less frequent causes such as testicular tumors. Even if patients typically have mild symptoms that resolve after chemotherapy, in rare cases, it can be a life-threatening condition that requires prompt recognition and specific intervention.

Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. RESULTS: The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP ≤5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels ≤ and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. CONCLUSIONS: A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.

Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors.

Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case-control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in 129 TGCT cases unselected for age of onset, histology, clinical outcome, and family history of any cancer, and the frequency of identified variants was compared to findings in 27,173 ancestry-matched cancer-free men. We identified four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%), which reached statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59-10.54) as compared to the control group. Cases with P/LP variants in CHEK2 developed TGCT almost 6 years earlier than individuals with CHEK2 wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between CHEK2 status and further clinical and histopathological characteristics, including histological subtypes, the occurrence of aggressive TGCT, family history of TGCT, and family history of any cancer. In addition, we found significant enrichment for the low-penetrance CHEK2 variant p.Ile157Thr (p = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45-9.55). Thus, we provide further independent evidence of CHEK2 being a moderate-penetrance TGCT predisposition gene.

Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum.

Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224-40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2-/CDX2-. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.

Misuse of tumor marker levels leads to an insufficient International Germ Cell Consensus Classification (IGCCCG) risk group assignment and impaired treatment.

BACKGROUND: Metastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels. METHODS: A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen's kappa. RESULTS: A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow-up data points. By using pre-orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy-two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen's kappa was 0.69 (p < 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 72 patients or undertreatment of 34 patients. CONCLUSIONS: The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients.

Imatinib-induced liver cirrhosis in a patient with advanced gastrointestinal stroma tumor (GIST).

BACKGROUND: The use of imatinib mesylate is associated with a progression free survival of 41 months in first line treatment of metastatic or locally advanced gastrointestinal stromal tumors (GIST) and other studies approved that adjuvant imatinib treatment improves the recurrence-free survival in patients with GIST. Current recommendations include 1 year adjuvant treatment in GIST patients at risk but active studies explore different durations of treatment with an interval of up to 5 years. While the most frequent adverse events (AEs) are blood count alterations, abdominal discomfort and edema, the occurrence of grade 3 or 4 increase of AST or ALT is specified with 2.1% and 2.7% respectively. CASE PRESENTATION: We report a 49-year old male with a gastrointestinal stromal tumor (GIST) of the small bowel who developed liver cirrhosis under adjuvant imatinib treatment. CONCLUSIONS: Our report supports the notion that imatinib-induced hepatotoxicity may lead to acute liver damage with subsequent cirrhotic remodelling. Patients developing grade 3 or 4 hepatotoxicity during imatinib treatment should therefore be carefully evaluated for chronic liver disease.

Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients.

BACKGROUND: To evaluate the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). METHODS: We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three subgroups (CRP ≤ 4, 4-10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4-10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP ≤4 mg/l, respectively. CONCLUSIONS: A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.

The prognostic impact of the smoking status of cancer patients receiving systemic treatment, radiation therapy, and surgery: A systematic review and meta-analysis.

INTRODUCTION: Cigarette smoking represents the main risk factor for cancer development; however, less is known about the effects of active smoking on the outcome of cancer patients receiving systemic treatment, radiation therapy, or surgery. METHODS: A systematic review and meta-analysis were conducted searching the PubMed® and Web of Science® Library databases using specific Medical Subject Headings terms. Studies reporting on the prognostic impact of the smoking status concerning survival endpoints in cancer patients treated with systemic treatment, radiation therapy, or surgery were eligible for inclusion. RESULTS: Of 1.380 articles reviewed, 12 reports including data from 31.785 patients with six different cancer types were considered eligible for inclusion. According to the meta-analysis of the overall effect, active smoking during cancer treatment was associated with an impaired overall survival (OS) and cancer-specific mortality (CSM) as compared to former or never smokers (OS: hazard ratio (HR) = 1.61, 95% CI: 1.19-2.17, p = 0.007; CSM: HR = 1.25, 95% CI: 1.01-1.54, p = 0.046). Moreover, smoking cessation led to a similar OS and CSM when comparing former to never smoking patients (OS: HR = 1.01, 95% CI: 0.87-1.18, p = 0.818; CSM: HR = 1.04, 95% CI: 0.91-1.20, p = 0.324). CONCLUSION: These results underline active smoking during cancer treatment as an independent adverse prognostic factor, while smoking cessation can result in similar outcomes compared to never smokers. Limitations of the study were a substantial study heterogeneity concerning different cancer entities and variations of treatment modalities.

[Multimodal treatment of testicular cancer: chemotherapy, surgery or radiotherapy?] / Multimodale Therapie des Hodentumors: wann Chemotherapie, Operation oder Strahlentherapie?

BACKGROUND: Metastatic testicular germ cell tumors patients require histology- and stage-appropriate therapy to achieve optimal therapeutic outcomes. OBJECTIVES: This work focuses on the interdisciplinary presentation of current recommendations for the treatment of metastatic germ cell tumor patients. MATERIALS AND METHODS: The interdisciplinary recommendations were formulated based on the German S3 guideline and supplemented by recent literature. RESULTS: Using a stage-specific and guideline-based treatment approach, interdisciplinary cooperation between urology, oncology, and radiotherapy is mandatory to successfully achieve a high rate of cure and, in the case of complex advanced tumors, also the most effective therapy possible. The question of optimal treatment approaches for seminoma in cSII A/B remains particularly challenging. CONCLUSION: Since treatment of advanced or multiple relapsed germ cell tumor patients remains complex, patients should be referred for an online second opinion ( https://urologie.ekonsil.org ).

Approaches of stem cell mobilization in a large cohort of metastatic germ cell cancer patients.

High-dose chemotherapy (HD-Cx) in refractory germ cell cancer (GCC) is effective but limited data are available concerning the optimal approach for stem cell mobilization (SCM) in these patients. In this analysis 102 patients undergoing SCM during first (n = 25) or subsequent treatment lines (n = 77) were analyzed. Subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) were given once daily (group 1) in 52 patients (51%), twice daily (group 2) in 39 patients (38%) or one injection Pegylated-G-CSF (PegG-CSF) (group 3) in eleven patients (11%) after one cycle of mobilization chemotherapy. Plerixafor was administered 13 times in group 1, seven times in group 2 and once in group 3. Overall, 77 (75%) patients achieved successful SCM defined as ≥8*106 CD34+ cells/kg body weight for three consecutive HD-Cx plus one backup dose. In group 1, 40 of 52 patients (77%) achieved successful SCM with a median of 11 G-CSF injections, in group 2, 27 of 39 patients (69%) with a median of 14 G-CSF injections and in group 3, 10 of 11 patients (91%) with one injection of PegG-CSF. SCM was more successful if conducted during first-line chemotherapy (p = 0.016) and associated with a beneficial outcome concerning overall survival (p = 0.02) if performed satisfactorily.