Retroperitoneal Lymph Node Dissection in Patients with Stage II Seminomatous Germ Cell Tumour.

Treatment de-escalation strategies in patients with seminoma with retroperitoneal metastases are being investigated in ongoing clinical trials. Primary retroperitoneal lymph node dissection conducted by expert surgeons may avoid any cytotoxic treatment and related long-term side effects in ≥70% of patients with clinical stage IIA/B seminoma.

The function of the complement system remains fully intact throughout the course of allogeneic stem cell transplantation.

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with immune complications and endothelial dysfunction due to intricate donor-recipient interactions, conditioning regimens, and inflammatory responses. Methods: This study investigated the role of the complement system during HSCT and its interaction with the cytokine network. Seventeen acute myeloid leukemia patients undergoing HSCT were monitored, including blood sampling from the start of the conditioning regimen until four weeks post-transplant. Clinical follow-up was 200 days. Results: Total complement functional activity was measured by WIELISA and the degree of complement activation by ELISA measurement of sC5b-9. Cytokine release was measured using a 27-multiplex immuno-assay. At all time-points during HSCT complement functional activity remained comparable to healthy controls. Complement activation was continuously stable except for two patients demonstrating increased activation, consistent with severe endotheliopathy and infections. In vitro experiments with post-HSCT whole blood challenged with Escherichia coli, revealed a hyperinflammatory cytokine response with increased TNF, IL-1ß, IL-6 and IL-8 formation. Complement C3 inhibition markedly reduced the cytokine response induced by Staphylococcus aureus, Aspergillus fumigatus, and cholesterol crystals. Discussion: In conclusion, HSCT patients generally retained a fully functional complement system, whereas activation occurred in patients with severe complications. The complement-cytokine interaction indicates the potential for new complement-targeting therapeutic strategies in HSCT.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

Long-term quality of life of testicular cancer survivors differs according to applied adjuvant treatment and tumour type.

PURPOSE: To evaluate the quality of life (QoL) in long-term testicular cancer (TC) survivors. METHODS: QoL was assessed in TC survivors treated between March 1976 and December 2004 (n = 625) using the EORTC-QLQ-C30 questionnaire, including a TC module. The assessment was performed at two time points (2006: response rate: n = 201/625 (32.2%), median follow-up (FU): 12.9 years (range 1.1-30.9); 2017: response rate: n = 95/201 (47.3%), median FU: 26.2 years (range: 13.0-41.2)). TC survivors were grouped according to treatment strategy, tumour entity, clinical stage and prognosis group. Linear and multiple linear regression analyses were performed, with age and time of follow-up as possible confounders. RESULTS: Radiation therapy (RT) compared to retroperitoneal lymph node dissection (RPLND) was associated with a higher impairment of physical function (2017: ß = - 9.038; t(84) = - 2.03; p = 0.045), role function (2017: ß = - 12.764; t(84) = - 2.00; p = 0.048), emotional function (2006: ß = - 9.501; t(183) = - 2.09; p = 0.038) and nausea (2006: ß = 6.679; t(185) = 2.70; p = 0.008). However, RT was associated with a lower impairment of sexual enjoyment (2017: symptoms: ß = 26.831; t(64) = 2.66; p = 0.010; functional: ß = 22.983; t(65) = 2.36; p = 0.021). Chemotherapy (CT), compared to RPLND was associated with a higher impairment of role (2017: ß = - 16.944; t(84) = - 2.62; p = 0.011) and social function (2017: ß = - 19.160; t(79) = - 2.56; p = 0.012), more insomnia (2017: ß = 19.595; t(84) = 2.25; p = 0.027) and greater concerns about infertility (2017: ß = 19.830; t(80) = 2.30; p = 0.024). In terms of tumour type, nonseminomatous germ cell tumour (NSGCT) compared to seminoma survivors had significantly lower impairment of nausea (2006: ß = - 4.659; t(187) = - 2.17; p = 0.031), appetite loss (2006: ß = - 7.554; t(188) = - 2.77; p = 0.006) and future perspective (2006: ß = - 12.146; t(175) = - 2.08; p = 0.039). On the other hand, surviving NSGCT was associated with higher impairment in terms of sexual problems (2006: ß = 16.759; t(145) = 3.51; p < 0.001; 2017: ß = 21.207; t(63) = 2.73; p = 0.008) and sexual enjoyment (2017: ß = - 24.224; t(66) = - 2.76; p = 0.008). CONCLUSIONS: The applied adjuvant treatment and the tumour entity had a significant impact on the long-term QoL of TC survivors, even more than 25 years after the completion of therapy. Both RT and CT had a negative impact compared to survivors treated with RPLND, except for sexual concerns. NSGCT survivors had a lower impairment of QoL compared to seminoma survivors, except in terms of sexual concerns. IMPLICATIONS FOR CANCER SURVIVORS: Implications for cancer survivors are to raise awareness of aspects of long-term and late effects on QoL in TC survivors; offer supportive care, such as psycho-oncological support or lifestyle modification, if a deterioration in QoL is noticed; and avoid toxic treatment without compromising a cure whenever possible.

Chimeric antigen receptor T cells targeting the GM3(Neu5Gc) ganglioside.

Chimeric antigen receptor (CAR) T cell technology has ushered in a new era of immunotherapy, enabling the targeting of a broad range of surface antigens, surpassing the limitations of traditional T cell epitopes. Despite the wide range of non-protein tumor-associated antigens, the advancement in crafting CAR T cells for these targets has been limited. Owing to an evolutionary defect in the CMP-Neu5Ac hydroxylase (CMAH) that abolishes the synthesis of CMP-Neu5Gc from CMP-Neu5Ac, Neu5Gc is generally absent in human tissues. Despite this, Neu5Gc-containing antigens, including the ganglioside GM3(Neu5Gc) have consistently been observed on tumor cells across a variety of human malignancies. This restricted expression makes GM3(Neu5Gc) an appealing and highly specific target for immunotherapy. In this study, we designed and evaluated 14F7-28z CAR T cells, with a targeting unit derived from the GM3(Neu5Gc)-specific murine antibody 14F7. These cells exhibited exceptional specificity, proficiently targeting GM3(Neu5Gc)-expressing murine tumor cells in syngeneic mouse models, ranging from B cell malignancies to epithelial tumors, without compromising safety. Notably, human tumor cells enhanced with murine Cmah were effectively targeted and eliminated by the 14F7 CAR T cells. Nonetheless, despite the detectable presence of GM3(Neu5Gc) in unmodified human tumor xenografts, the levels were insufficient to trigger a tumoricidal T-cell response with the current CAR T cell configuration. Overall, our findings highlight the potential of targeting the GM3(Neu5Gc) ganglioside using CAR T cells across a variety of cancers and set the stage for the optimization of 14F7-based therapies for future human clinical application.

During twenty years of Cisplatin-based therapy the face of nonseminomatous testicular germ cell tumors is still changing: an evaluation of presentation, management, predictive factors and survival

Purpose: To assess the changing presentation and treatment of nonseminomatous testicular germ cell tumors (NSGCT) and to investigate predictive factors for the status of metastasis at diagnosis and on relapse and death. Materials and Methods: Retrospective record review of 147 patients that underwent inguinal orchiectomy from 1987-2007. Follow-up data was available for 102 patients (median follow-up: 80 months (0-243); 96 patients alive). Results: Mean patients age increased (p = 0.015) and more patients were diagnosed in clinical stage I (CSI) (p = 0.040). The fraction of yolk sac (YS) elements inclined (p = 0.030) and pT2 tumors increased (p < 0.001). Retroperitoneal lymph node dissection (RPLND) declined whereas more patients were treated with chemotherapy (p < 0.001; p = 0.004). There was an increase in relapse free (RFS) and cancer specific survival (CSS) due to an improvement in patients with disseminated disease (p = 0.014; p < 0.001). The presence of YS and teratoma elements showed a reduction in the odds ratio (OR) for metastasis at diagnosis (p = 0.002, OR: 0.262; p = 0.009, OR: 0.428) whereas higher pT-stage was associated to their presence (p = 0.039). Patients with disseminated disease (CS > I) showed a declined CSS compared to CSI patients (p = 0.055). The presence of YS elements was associated to an improved RFS (p = 0.038). Conclusions: In our single institution study the face of NSGCT markedly changed over 20 years even after the introduction of Cisplatin-based chemotherapy. These changes were accompanied by an improvement in RFS and CSS. When dealing with NSGCT patients such observations now and in the future should be taken into account. .