Oncology Research and Treatment最新文献

Background: Advanced stages of prostate cancer (PCa), in particular metastatic castration-resistant prostate cancer, are associated with significant morbidity and mortality. The androgen receptor (AR) signaling pathway is a cornerstone of therapeutic intervention, but resistance mechanisms and disease progression demand increasingly complex treatment strategies.

Summary: We provide a comprehensive overview on the management of metastatic PCa, highlighting the evolution of treatment approaches and their clinical implications. Androgen deprivation therapy remains the backbone of therapy, enhanced by androgen synthesis inhibitors, AR inhibitors, and emerging AR degraders. Taxane-based chemotherapy, radiopharmaceuticals like radium-223 and lutetium-177 PSMA-617, and PARP inhibitors have expanded the therapeutic arsenal. Novel treatment approaches are in preclinical and clinical development. Various factors must be taken into account when deciding on the optimal treatment strategy including disease and patient-specific aspects. In addition, previous treatment lines may impact the efficacy of subsequent therapeutic approaches.

Key messages: The growing number of treatment options and a better understanding of the biological processes involved in tumor progression and the development of resistance are enabling increasingly individualized treatment of patients with advanced PCa.

Background: Male germ cell tumours are an exemplar of a highly curably malignancy and represent the most frequent solid malignancy among men under the age of 40. The majority of cases are detected while the tumour is confined to the testicle where cure rates exceed 99%. Even in cases of metastatic disease expansion, cure rates remain extraordinary compared to other malignancies, owing to the unique sensitivity of most germ cell tumour components to cisplatin-based chemotherapy.

Summary: The treatment of metastatic germ cell tumours is adapted to (i) primary histology (seminoma versus non-seminoma or mixed germ cell tumour), (ii) disease spread (clinical stage IIA/B versus IIC/III), and (iii) clinical risk according to the International Germ Cell Cancer Collaborative Group classification. Across all metastatic stages, the combination of bleomycin, etoposide, and cisplatin is most commonly used. In non-seminomas, post-chemotherapy residual mass resection is the second cornerstone of treatment. Among patients who relapse after first-line chemotherapy, platinum-based conventional dose or high-dose chemotherapy regimens can still achieve cure in 50% of patients. Outcomes for patients with multiple relapses, however, remain dissatisfactory and novel treatment approaches are urgently needed. High cure rates demand cautious consideration of possible long-term side effects. Novel strategies are being explored to mitigate the risk of long-term morbidity without lowering the outstanding cure rates.

Key messages: (i) Advanced germ cell tumours are highly curable with cisplatin-based combination chemotherapy and often surgical post-chemotherapy residual mass resection. (ii) Novel de-escalation strategies and survivorship programs aim to mitigate the risk of long-term treatment side effects. A lack of effective molecularly targeted treatment approaches pinpoints the need for novel treatments for multiply relapsed, platinum-resistant disease.

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is associated with poor prognosis in advanced stages. This study aims to develop a prognostic model for patients with ccRCC based on a lysosome-related gene signature.

Methods: The clinical and transcriptomic data of kidney renal clear cell carcinoma (KIRC) patients were downloaded from TCGA, cBioportal, and GEO databases, and lysosome-related gene sets were acquired in the previous study. TCGA data were used as a training set to investigate the prognostic role of lysosomal-related genes in ccRCC, and cBioportal and GEO databases were used for validation. After the lysosome-related differentially expressed genes were found, machine learning method was used to construct a risk model, and Kaplan-Meier (K-M) and receiver operating characteristic curves were used to evaluate the performance of the model.

Results: Machine learning methods were utilized to identify seven gene signatures related to lysosome, which accurately predict the prognosis of ccRCC. Patients with higher risk scores demonstrate poorer overall survival (OS; HR: 2.467, 95% CI: 1.642-3.706, p < 0.001), and significant disparities in immune infiltration, immune score, and response to anticancer drugs are observed between the high-risk group and the low-risk group (p < 0.001).

Conclusion: The prognostic model developed in this study demonstrates a high efficacy in accurately predicting the OS of ccRCC patients, thereby offering a novel perspective for the advancement of ccRCC treatment.

Introduction: Elderly, frail, or cisplatin-ineligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. To date, no standard of care has been defined for this population.

Methods: The randomized, open-label phase 2 study was conducted to determine whether first-line treatment with pembrolizumab (PEM) is superior to methotrexate (MTX) in elderly, frail, or cisplatin-ineligible patients with R/M HNSCC not amenable to local therapies. Patients were randomized 1:1 to receive PEM 200 mg q3w or MTX 40 mg/m2 IV weekly until disease progression or unacceptable toxicity. The primary end point was overall survival after 1 year (1YOS); secondary endpoints were time to failure of strategy (TTFS) at 1 year, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results: Of 100 planned participants, 47 (23 in the PEM and 24 in the MTX group) were enrolled. The trial was terminated prematurely. Efficacy did not differ between the treatment arms (1YOS 17.4% for PEM vs. 37.5% for MTX [p = 0.12]). ORR was 17.4% with PEM vs. 12.5% with MTX (p = 0.70), TTFS at 1 year was 91% vs. 100% (p = 0.47), median PFS was 1.8 vs. 2.7 months (p = 0.83), and median OS was 6.1 vs. 9.7 months (p = 0.50), respectively. PD-L1 expression did not impact primary and secondary endpoints. Safety parameters favored PEM.

Conclusion: ELDORANDO failed to demonstrate benefit of PEM over MTX regarding 1YOS, ORR, PFS, or OS. The optimal treatment strategy for fragile patients remains to be determined.

Objective: This study aims to explore the clinical efficacy of transarterial chemoembolization (TACE) combined with the immune checkpoint inhibitor nivolumab administered via hepatic arterial infusion (HAI) in inhibiting tumor angiogenesis in hepatocellular carcinoma (HCC).

Methods: A total of 140 patients diagnosed with HCC at our hospital from October 2021 to October 2022 were analyzed. They were randomly divided into a study group (n=70), receiving TACE combined with HAI of nivolumab, and a control group (n=70), receiving TACE alone. The efficacy and adverse reactions of both groups were compared. Levels of angiogenesis factors (VEGF, VEGFR-2, Ang-2) and tumor markers (CEA, AFP, CA19-9) were measured one day before and one month after treatment, followed by patient follow-up.

Results: The objective response rate (ORR) and disease control rate (DCR) in the study group were significantly higher than those in the control group (64.3% vs. 42.9%, P=0.006 and 91.4% vs. 70.0%, P=0.001, respectively). One day before treatment, there was no significant difference in the levels of VEGF, VEGFR-2, and Ang-2 between the two groups (P > 0.05). One month after treatment, the study group showed significantly lower levels of VEGF, VEGFR-2, and Ang-2 compared to the control group (all P < 0.001). Similarly, there was no significant difference in CEA, AFP, and CA19-9 levels before treatment (P > 0.05), but one month after treatment, the study group had significantly lower levels of these markers (P < 0.001). The incidence of adverse reactions between the two groups showed no significant difference (P > 0.05). All 140 patients were followed up for a median of 13.87 months. The median overall survival was 15.4 months in the study group versus 13.4 months in the control group (P < 0.05), and median progression-free survival was 9.5 months versus 9.0 months, respectively (P < 0.05).

Conclusion: TACE combined with hepatic arterial infusion of nivolumab can effectively inhibit tumor angiogenesis in HCC, improve clinical outcomes, and maintain a high safety profile, representing a promising therapeutic strategy for patients with unresectable HCC.

Introduction: Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous population that plays a key role in tumor-related immune suppression. MDSCs are immature cells that express the myeloid markers CD11b and Gr1 in mice and accumulate in tumor-bearing mice, including those with HER2/neu+ breast cancer. We previously reported that tumor regression by anti-neu antibodies requires both innate and adaptive immunity. MDSCs inhibit both types of immunity and are immunosuppressive, particularly for T cells. However, the effect of anti-neu antibodies on MDSCs remains unclear.

Methods: HER2+ TUBO tumor-bearing mice were treated with an anti-neu antibody or a control. MDSC populations were analyzed via flow cytometry, and immunosuppressive function was analyzed by a suppression assay. Tumors were analyzed using an RT2-PCR array and RT-PCR for gene expression related to MDSC activation, migration, and function. Additional mice received combination therapy with 5-FU or zoledronic acid to assess enhanced MDSC inhibition and changes in MDSC and tumor-associated macrophage (TAM) populations.

Results: The number of MDSCs decreased within 3 days after anti-neu antibody treatment in the tumor and spleen, with the number of tumor MDSCs declining 1 day earlier. The number of monocytic MDSCs was significantly reduced in both tissues (p > 0.05). Anti-neu antibodies also reduced MDSC immunosuppressive activity. Gene expression analysis revealed decreased levels of IL-1β, VEGF, and CX3CL1, which are linked to MDSC activation and migration. The level of the immunosuppressive factor indoleamine 2,3-dioxygenase was also reduced. Compared with treatment with the antibody alone, combination therapy with 5-FU further suppressed the number of MDSCs and TAMs, resulting in better tumor suppression.

Conclusions: Tumor suppression by anti-neu antibodies is associated with a reduction in MDSCs via the inhibition of key MDSC-related factors. MDSCs may be therapeutic targets for increasing Herceptin efficacy in patients with breast cancer.

Introduction: The high incidence of breast cancer combined with the growing number of innovative and complex treatment options, such as oral tumor therapies, is increasingly shifting oncological care to the outpatient sector. This development is placing substantial capacity burdens on office-based providers. Evidence suggests that the use of "treatment navigators" - qualified nonphysician personnel tasked with coordination and support - can improve efficiency and reduce workload for physicians. This study aimed to assess the economic effects of task delegation in the German outpatient breast cancer from the healthcare provider´s perspective.

Methods: The study followed a three-step approach: (1) identification, (2) quantification, and (3) evaluation of resources. For (1), a micro-costing-based process analysis was conducted to capture resource use in outpatient breast cancer care. Relevant services were identified via literature review. For (2), the (a) duration of individual services and (b) delegation potential were quantified through structured interviews with physicians in hematology, oncology, and gynecological oncology. In (3), personnel costs were calculated using the currently applicable wages for physician and defined in the German Uniform Evaluation Standard (EBM) and analogously for medical assistants. Based on service durations and delegation opportunities, potential cost and time savings per case study were estimated.

Results: Eleven service categories comprising 40 individual tasks were identified in step 1. Four expert interviews were conducted in step 2. Full delegation (100%) was consistently reported for the performance of electrocardiograms, laboratory diagnostics, and the administration of medications. In contrast, delegation rates varied widely for tasks such as patient monitoring (0-100%), detailed medical history (0-90%), and documentation (0-87%). The highest time and cost-saving potentials were observed in the categories of patient counseling (up to 22.5 EUR or 45 min), monitoring (up to 51.75 EUR or 95.5 min), supportive measures (up to 39 EUR or 78 min), and disease management program consultations (up to 46.82 EUR or 93.6 min).

Conclusion: These findings highlight significant heterogeneity in delegation practices and efficiency gains across outpatient oncology and gynecology practices, reflecting structural differences in practice organization and staff qualification. Legal and financial frameworks in Germany support structured delegation, yet practical implementation remains inconsistent. Delegation to treatment navigators offers significant potential to improve efficiency and patient-centered care, particularly in light of rising case numbers and the growing relevance of oral tumor therapies. However, further research is needed to validate these findings and support broader implementation.

Introduction: Precise prediction of pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) in rectal cancer may identify candidates for non-operative management. The optimal selection of diagnostic tools is, therefore, of major clinical importance.

Methods: Clinical, laboratory, endoscopic, and radiological data of patients with rectal cancer treated with nCRT and surgery at an academic medical center from 2010 to 2020 were retrospectively collected. Pre- and post-nCRT magnetic resonance imaging (MRI) was reviewed with a structured report template and assessed by magnetic resonance imaging tumor regression grade (mrTRG). Two senior radiologists reviewed mrTRG independently to determine the inter-reader agreement. Univariate logistic regression was applied to identify parameters that predict pCR. A multivariate prediction model was developed using L1-penalized logistic regression, with performance assessed by area under the curve (AUC) in the total cohort (apparent AUC) and by cross-validation (CV-AUC).

Results: A total of 261 patients were identified, of whom 36 achieved pCR. Univariate analysis showed a significant correlation between post-nCRT features with pCR, including radiological T-stage (odds ratio [OR] 0.05 [0.02-0.15], p < 0.001), mrTRG (OR 0.13 [0.05-0.31], p < 0.001), and endoscopic response (OR 0.17 [0.05-0.54], p = 0.032). Of those, mrTRG showed the highest AUC of 0.77 with a substantial inter-reader agreement (kappa = 0.71, 95% confidence interval: 0.61-0.81). The multivariate predictive model selected eight pre- and post-nCRT parameters with an apparent AUC of 0.84 and a CV-AUC of 0.73.

Conclusion: Therapy response assessed by MRI, particularly by mrTRG, strongly predicted pCR. Therefore, mrTRG should be implemented in routine assessment of rectal cancer treated by nCRT.

Background: Ovarian cancer is a prevalent and highly lethal gynaecological cancer. Among its various subtypes, epithelial ovarian cancer predominates, comprising ten distinct subtypes and contributing significantly to the overall burden of ovarian malignancies. Concurrently, endometriosis, characterized by the ectopic growth of endometrial tissue within the pelvis, affects a substantial number of women of reproductive age.

Summary: Notably, atypical endometriosis serves as the precursor lesion to endometriosis-associated ovarian cancer, with endometrioid and clear-cell ovarian cancers being the most common prevalent histologic subtypes in this context. These exhibit a more favourable prognosis compared to ovarian cancers unrelated to endometriosis. The progression from endometriosis to atypical endometriosis and ultimately to ovarian cancer is influenced by multiple factors, including mutations in tumour suppressor genes and oncogenes, hyperestrogenism, ovarian inflammation resulting from cyclical bleeding of the ectopic endometrium, and oxidative stress from accumulated iron of ruptured erythrocytes. Conventional treatment for endometriosis-associated ovarian cancer involves macroscopic resection of the tumour combined with chemotherapy. The emergence of targeted therapies including immunotherapy has notably improved outcomes, particularly in cases of chemotherapy-resistant tumours. Despite these advancements, management poses numerous challenges, necessitating the development of more effective treatments.

Key message: The current review provides an overview of our current knowledge regarding the intricate relationship between ovarian cancer and endometriosis, illuminating the multifaceted aspects of their interplay and underscoring the imperative for continued research in this field.