Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells.

BACKGROUND: Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening of larger blood volumes. To leverage DLA's full potential, this study introduces a novel approach for CTC enrichment from DLAs. METHODS: DLA was applied to six advanced stage NSCLC patients. For an unbiased CTC enrichment, a two-step approach based on negative depletion of hematopoietic cells was used. Single-cell (sc) whole-transcriptome sequencing was performed, and CTCs were identified based on gene signatures and inferred copy number variations. RESULTS: Remarkably, this innovative approach led to the identification of unprecedented 3,363 CTC transcriptomes. The extensive heterogeneity among CTCs was unveiled, highlighting distinct phenotypes related to the epithelial-mesenchymal transition (EMT) axis, stemness, immune responsiveness, and metabolism. Comparison with sc transcriptomes from primary NSCLC cells revealed that CTCs encapsulate the heterogeneity of their primary counterparts while maintaining unique CTC-specific phenotypes. CONCLUSIONS: In conclusion, this study pioneers a transformative method for enriching CTCs from DLA, resulting in a substantial increase in CTC numbers. This allowed the creation of the first-ever single-cell whole transcriptome in-depth characterization of the heterogeneity of over 3,300 NSCLC-CTCs. The findings not only confirm the diagnostic value of CTCs in monitoring tumor heterogeneity but also propose a CTC-specific signature that can be exploited for targeted CTC-directed therapies in the future. This comprehensive approach signifies a major leap forward, positioning CTCs as a key player in advancing our understanding of cancer dynamics and paving the way for tailored therapeutic interventions.

A Combined Cyto- and Histopathological Diagnostic Approach Reduces Time to Diagnosis and Time to Therapy in First Manifestation of Metastatic Spinal Disease: A Cohort Study.

Malignant spinal lesions (MSLs) are frequently the first manifestation of malignant disease. Spinal care, diagnostic evaluation, and the initiation of systemic therapy are crucial for outcomes in patients (pts) with advanced cancer. However, histopathology (HP) may be time consuming. The additional evaluation of spinal lesions using cytopathology (CP) has the potential to reduce the time to diagnosis (TTD) and time to therapy (TTT). CP and HP specimens from spinal lesions were evaluated in parallel in 61 pts (CP/HP group). Furthermore, 139 pts in whom only HP was performed were analyzed (HP group). We analyzed the TTD of CP and HP within the CP/HP group. Furthermore, we compared the TTD and TTT between the groups. The mean TTD in CP was 1.7 ± 1.7 days (d) and 8.4 ± 3.6 d in HP (p < 0.001). In 13 pts in the CP/HP group (24.1%), specific therapy was initiated based on the CP findings in combination with imaging and biomarker results before completion of HP. The mean TTT in the CP/HP group was 21.0 ± 15.8 d and was significantly shorter compared to the HP group (28.6 ± 23.3 d) (p = 0.034). Concurrent CP for MSLs significantly reduces the TTD and TTT. As a result, incorporating concurrent CP for analyzing spinal lesions suspected of malignancy might have the potential to enhance pts' quality of life and prognosis in advanced cancer. Therefore, we recommend implementing CP as a standard procedure for the evaluation of MSLs.

Circulating Tumor Cells and Thromboembolic Events in Patients with Glioblastoma.

Patients with glioblastoma (GBM) are at increased risk for arterial and venous thromboembolism (TE). Risk factors include surgery, the use of corticosteroids, radiation, and chemotherapy, but also prothrombotic characteristics of the tumor itself such as expression of tissue factor, vascular endothelial growth factor, or podoplanin. Although distant metastases are extremely rare in this tumor entity, circulating tumor cells (CTCs) have been detected in a significant proportion of GBM patients, potentially linking local tumor growth characteristics to systemic hypercoagulability. We performed post hoc analysis of a study, in which GBM patients had been investigated for CTCs. Information on TE was retrieved from electronic patient charts. In total, 133 patients (median age, 63 years; interquartile range, 53-70 years) were analyzed. During follow-up, TE was documented in 14 patients (11%), including 8 venous and 6 arterial events. CTCs were detected in 26 patients (20%). Four (15%) patients with CTCs had a TE compared with 10 (9%) patients without CTCs. There was no difference in the frequency of TE events between patients with and those without detectable CTCs (p = 0.58). In summary, although our study confirms a high risk of TE in GBM patients, it does not point to an obvious association between CTCs and vascular thrombosis.

"Being an informal caregiver - strengthening resources": mixed methods evaluation of a psychoeducational intervention supporting informal caregivers in palliative care.

BACKGROUND: Informal caregivers are key support for patients with progressive incurable diseases. However, their own needs often remain unmet. Therefore, we developed, manualised and implemented the intervention "Being an informal caregiver - strengthening resources" aiming to support and empower informal caregivers by addressing relevant information-related, physical, psychological and social needs. METHODS: In this pilot study, we evaluated the acceptance and experiences with this psychoeducational intervention. The study was conducted over two years (2019-2021). Informal caregivers were recruited from the University Medical Centre Hamburg-Eppendorf and the metropolitan region of Hamburg, Germany. The intervention was aimed at adult persons who identified themselves as an informal caregiver to an adult patient with a progressive incurable cancer and non-cancer disease. For the evaluation we used a mixed methods approach, combining a longitudinal questionnaire survey (pre-intervention, after each module, 3-months follow-up) and semi-structured interviews post-intervention. Quantitative data were analysed using descriptive statistics and a paired t-Test, interviews were analysed based on the qualitative content analysis according to Mayring. Results were triangulated using a convergent triangulation design. RESULTS: Of 31 informal caregivers who received the intervention, 25 returned the follow-up questionnaire and 20 informal caregivers were interviewed. Triangulated results showed a high satisfaction with the implementation of the intervention. Of a broad range of subjective benefits, gaining knowledge, self-awareness and self-efficacy were most apparent. Informal caregivers reported improved preparedness, awareness of own needs as well as confidence regarding handling own emotions and interacting with the ill person. However, implementing the learned skills into daily life can be challenging due to internal and external factors. Motivations and challenges for participating as well as potential for improvement were identified. CONCLUSIONS: This pilot study showed an overall positive evaluation and several subjective benefits of the psychoeducational intervention "Being an informal caregiver - strengthening resources". Further research is needed to measure the efficacy of this intervention on informal caregivers' outcomes. Therefore, a multicentre randomized prospective study is planned.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

BCMA x CD3 T-cell engager in a patient with penta-refractory multiple myeloma and HIV: a clinical and immunological report.

Not available.

A Multimodal Lifestyle Psychosocial Survivorship Program in Young Cancer Survivors: The CARE for CAYA Program-A Randomized Clinical Trial Embedded in a Longitudinal Cohort Study.

Importance: There is a lack of trials examining the effect of counseling interventions for child, adolescent, and younger adult (CAYA) cancer survivors. Objective: To assess lifestyle habits and the psychosocial situation of CAYAs to determine the efficacy of needs-based interventions in the CARE for CAYA program (CFC-P). Design, Setting, and Participants: The CFC-P was conducted as a multicenter program in 14 German outpatient clinics, mainly university cancer centers. Recruitment began January 1, 2018; a randomized clinical trial was conducted until July 15, 2019; and intervention was continued as a longitudinal cohort study until March 31, 2021. Data preparation was conducted from April 1, 2021, and analysis was conducted from August 14, 2021, to May 31, 2022. Herein, predefined confirmatory analyses pertain to the RCT and descriptive results relate to the overall longitudinal study. Data analysis was based on the full analysis set, which is as close as possible to the intention-to-treat principle. Intervention: A comprehensive assessment determined needs in physical activity, nutrition and psychooncology. Those with high needs participated in 1 to 3 modules. In the RCT, the IG received 5 counseling sessions plus newsletters, while the control group CG received 1 counseling session. Main Outcomes and Measures: The primary outcome was the change in the rate of CAYAs with high needs at 52 weeks. Secondary outcomes were feasibility, modular-specific end points, satisfaction, quality of life, and fatigue. Results: Of 1502 approached CAYAs aged 15 to 39 years, 692 declined participation. Another 22 CAYAs were excluded, resulting in 788 participants. In the randomized clinical trial, 359 CAYAs were randomized (intervention group [IG], n = 183; control group [CG], n = 176), and 274 were followed up. In the RCT, the median age was 25.0 (IQR, 19.9-32.2) years; 226 were female (63.0%) and 133 male (37.0%). After 52 weeks, 120 CAYAs (87.0%) in the IG and 115 (86.5%) in the CG still had a high need in at least 1 module (odds ratio, 1.04; 95% CI, 0.51-2.11; P = .91). Both groups reported reduced needs, improved quality of life, reduced fatigue, and high satisfaction with the CFC-P. Conclusions and Relevance: In this randomized clinical trial, the implementation of a lifestyle program in this cohort was deemed necessary, despite not meeting the primary outcome. The interventions did not alter the rate of high needs. The results may provide guidance for the development of multimodal interventions in the follow-up care of CAYAs. Trial Registration: German Clinical Trial Register: DRKS00012504.

Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria.

CASE: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder caused by acquired mutations in the phosphatidylinositol glycan class A gene, which lead to a partial or total loss of the cellular complement regulators CD55 and CD59.1 In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication and occur in up to 44% of patients in historic PNH cohorts.1 2.

[Advanced renal cell carcinoma - an overview of current systemic therapy]. / Das fortgeschrittene Nierenzellkarzinom ­ Aktuelle Systemtherapie im Überblick.

Renal cell carcinoma (RCC) is one of the more common tumor diseases in older adults. The only curative treatment method is surgical resection in the localized stage. Based on current study data, drug (combination) therapy in the metastatic stage is the most effective treatment option for non-resectable/metastatic RCC (mRCC). Immuno-oncological combinations of 2 Checkpoint-Inhibitors (CPI) or CPIs and Tyrosine kinase inhibitors (TKI) are now standard in the first-line treatment of metastatic RCC. Since the results of foundational combination therapy studies are not fully comparable due to different study design and patient populations, additional clinical and patient-related criteria are required when making individual treatment decisions. The systemic therapy of advanced RCC is therefore based on tumor extent, treatment pressure, concomitant diseases, and personal circumstances. A decision on first-line therapy should be made individually as part of a "shared decision" with the patient. The selection of a second-line systemic therapy is based on individual criteria; the data available for a well-founded classification of a possible therapy sequence after progression to first-line therapy is sparse. Further investigations to optimize systemic therapy (expansion of combination therapy to triple combination of CPI+CPI+TKI) or evaluation of therapy in other histological subtypes of renal cell carcinoma are the subject of ongoing clinical studies.

Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies.

BACKGROUND: The search for biomarkers to identify suitable candidates for immune checkpoint inhibitor (ICI) therapy remains ongoing. We evaluate how soluble levels of the next generation immune checkpoint Lymphocyte Activation Gene-3 (sLAG-3) and its association with circulating T lymphocyte subsets could pose as a novel biomarker to predict outcome to ICI therapy. METHODS: Circulating levels of sLAG3 were analyzed using multiplex immunoassay in n = 84 patients undergoing ICI therapy for advanced solid cancer, accompanied by flow cytometry analyses of peripheral blood mononuclear cells (PBMCs). RESULTS: Uni- and multivariate analysis shows that patients with higher sLAG3 concentrations before ICI therapy had a significantly impaired progression-free (PFS) and overall survival (OS) (HRPFS: 1.005 [95%CI: 1.000-1.009], p = 0.039; HROS: 1.006 [95%CI: 1.001-1.011], p = 0.015). The CD4/CD8 cell ratio and its dynamics during therapy were strong predictors of PFS and OS with patients with a decreasing ratio between baseline and after 1-2 cycles having an improved median OS compared to patients with increasing values (p = 0.012, HR: 3.32). An immunological score combining sLAG3 and the CD4/CD8 ratio showed the highest predictive potential (HROS: 10.3). CONCLUSION: Pending prospective validation, sLAG3 and correlating circulating T-cell subsets can be used as a non-invasive predictive marker to predict outcome to ICI therapy to help identifying ideal ICI candidates in the future.

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma.

PURPOSE: The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with exclusively high-risk disease for whom prospective trials are limited, aiming to induce minimal residual disease (MRD) negativity. METHODS: This academic, investigator-initiated, multicenter, phase II trial enrolled patients with high-risk NDMM (HRNDMM) defined by mandatory International Staging System stage II/III combined with del17p, t(4;14), t(14;16), or more than three 1q21 copies as high-risk cytogenetic aberrations (HRCAs). Patients received Isa-KRd induction/consolidation and Isa-KR maintenance. TE patients received high-dose melphalan. TNE patients received two additional Isa-KRd cycles postinduction. This prespecified interim analysis (IA) reports the primary end point, MRD negativity (<10-5, next-generation flow), at the end of consolidation. The secondary end point was progression-free survival (PFS). RESULTS: Among 125 patients with HRNDMM (TE-intention-to-treat [ITT]-IA, 99; TNE-ITT, 26) of the IA population for the primary end point, the median age was 58 (TE-ITT-IA) and 74 (TNE-ITT) years. Del17p was the most common HRCA (TE, 44.4%; TNE, 42.3%); about one third of evaluable TE/TNE patients presented two or more HRCAs, respectively. The trial met its primary end point with MRD negativity rates after consolidation of 67.7% (TE) and 54.2% (TNE) of patients. Eighty-one of 99 TE-ITT-IA patients reached MRD negativity at any time point (81.8%). MRD negativity was sustained for ≥1 year in 62.6% of patients. With a median follow-up of 44 (TE) and 33 (TNE) months, median PFS was not reached in either arm. CONCLUSION: Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.

Cetuximab every 2 weeks versus standard weekly dosing administration schedule.

Cetuximab every 2 weeks (Q2W) dosing schedule is approved by the US FDA and by the Japanese Pharmaceuticals and Medical Devices Agency in patients with metastatic colorectal cancer and squamous cell carcinoma of the head and neck. Phase II trials have found comparable efficacy and safety for the weekly (Q1W) and Q2W schedules, and real-world studies have shown noninferiority of the Q2W compared with the Q1W schedule. Several guidelines recommend cetuximab Q2W administration as an alternative to the Q1W dosing schedule. Cetuximab Q2W can be administered with a Q2W dose of chemotherapy, making it a more convenient option to the Q1W schedule, potentially resulting in reduced costs for administration, increased flexibility for clinical staff and improved patient adherence.

Cetuximab is a drug for patients with colorectal cancer or cancer of the head and neck. It is usually administered once a week. However, studies have shown that cetuximab given once every 2 weeks instead has similar clinical benefits and side effects. Based on this evidence, the every 2 weeks dosing schedule has been approved for use in USA and Japan. The every 2 weeks dosing schedule is a convenient alternative to the weekly schedule. It may result in fewer hospital visits, improved patient quality of life, reduced healthcare costs and more flexibility for medical staff. This review summarizes the current evidence and benefits for the every 2 weeks dosing schedule.

Effect of factor XI inhibition on tumor cell-induced coagulation activation.

BACKGROUND: Cancer-associated thrombosis is a frequent complication in patients with malignancies. While factor XI (FXI)/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined. OBJECTIVES: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation. METHODS: Procoagulant activity (PCA) of 4 different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF served as positive control. RESULTS: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated recombinant human TF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 µM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 µM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels. CONCLUSION: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in vivo studies.

Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial.

BACKGROUND: FOLFOXIRI plus bevacizumab has demonstrated benefits for metastatic colorectal cancer (mCRC) patients. However, challenges arise in its clinical implementation due to expected side effects and a lack of stratification criteria. METHODS: The AIO "CHARTA" trial randomised mCRC patients into clinical Group 1 (potentially resectable), 2 (unresectable/risk of rapid progression), or 3 (asymptomatic). They received FOLFOX/bevacizumab +/- irinotecan. The primary endpoint was the 9-month progression-free survival rate (PFSR@9). Secondary endpoints included efficacy in stratified groups, QoL, PFS, OS, ORR, secondary resection rate, and toxicity. RESULTS: The addition of irinotecan to FOLFOX/bevacizumab increased PFSR@9 from 56 to 67%, meeting the primary endpoint. The objective response rate was 61% vs. 69% (P = 0.21) and median PFS was 10.3 vs. 12 months (HR 0.83; P = 0.17). The PFS was (11.4 vs. 12.9 months; HR 0.83; P = 0.46) in potentially resectable patients, with a secondary resection rate of 37% vs. 51%. Moreover, Group 3 (asymptomatic) patients had a PFS of 11.1 vs. 16.1 months (HR 0.6; P = 0.14). The addition of irinotecan did not diminish QoL. CONCLUSION: The CHARTA trial, along with other studies, confirms the efficacy and tolerability of FOLFOXIRI/bevacizumab as a first-line treatment for mCRC. Importantly, clinical stratification may lead to its implementation. TRIAL REGISTRATION: The trial was registered as NCT01321957.

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.

Effects of Exercise Training on Patient-Specific Outcomes in Pancreatic Cancer Patients: A Scoping Review.

BACKGROUND: International guidelines have already highlighted the beneficial effects of exercise in common cancer entities. However, specific recommendations for pancreatic cancer are still missing. This scoping review aimed to evaluate the impact of exercise training on patient-specific outcomes in pancreatic cancer patients. METHODS: A literature search was undertaken using PubMed, Web of Science, and Cochrane Library. We included randomized controlled trials (RCTs) published before August 2023 with structured exercise interventions during or after pancreatic cancer treatment. RESULTS: Seven articles that prescribed home-based or supervised exercise with aerobic or resistance training or both were reviewed. The results indicate that exercise is feasible and safe in pancreatic cancer patients. Furthermore, exercise was associated with improved quality of life, cancer-related fatigue, and muscle strength. Concerning other outcomes, heterogeneous results were reported. We identified a lack of evidence, particularly for patients with advanced pancreatic cancer. CONCLUSION: Exercise interventions in pancreatic cancer patients are feasible and can lead to improved quality of life, cancer-related fatigue, and muscle strength. However, further studies with larger sample sizes are needed to clarify the potential of exercise in pancreatic cancer, in particular for advanced stages.

Practice patterns, experiences, and challenges of German oncology health care staff with smoking cessation in patients with cancer: a cross-sectional survey study.

PURPOSE: Often, cancer patients do not receive education about the negative consequences of smoking on the treatment outcome. To support cancer patients in the process of smoking cessation, it is essential to involve oncology staff. This study aims to learn about the experiences and attitudes from the point of view of oncology staff and, thus, how a smoking intervention should be designed. The study aims to engage all oncology staff due to the unclear responsibility for providing smoking cessation education, support, and motivating cancer patients to quit smoking. METHODS: N = 354 German oncology staff (oncologists, nurses, psycho-oncologists, others) filled out a 5-point Likert scale-based questionnaire regarding practices, potential barriers, and attitudes towards smoking cessation between October 2021 and June 2022. The questionnaire was developed by Derksen et al. (2020), translated and slightly modified for the use of this study. It was distributed to all leading oncology staff in our Cancer Center Network with a request to share with all oncology staff. Flyers were also handed out in all oncology wards and outpatient clinics in the same Cancer Center Network. RESULTS: Most oncology staff ask cancer patients about their current smoking status (curative, M = 2.27; SD = 1.59; palliative, M = 2.90; SD = 1.83), but they rarely treat or refer patients for a smoking cessation intervention (curative, M = 4.78; SD = 1.20; palliative, M = 4.99; SD = 1.06). Smoking behavior of curative cancer patients is addressed more than that of palliative cancer patients (d = - 37). Regression analyses of key dependent variables showed that profession, setting, and the belief that continued smoking affects treatment outcome explained the variance of asking patients if they smoke, advising to stop smoking and lack of time (without profession). CONCLUSION: Involving oncology staff in motivating cancer patients who smoke to quit and referring them to smoking cessation services should take the different attitudes and knowledge of the staff into account to improve treatment that supports tobacco cessation. IMPLICATIONS FOR CANCER SURVIVORS: Cancer patients have special needs when it comes to a cessation program. In the long term, survivors will benefit from tailored smoking cessation education and services provided by oncology staff to help them quit smoking after a cancer diagnosis.

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.