Oncology Research and Treatment最新文献

Background: Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of hematologic malignancies, offering curative potential for patients with relapsed or refractory disease. However, the long-term survivorship of these patients is marked by unique challenges, particularly immune deficits and infectious complications, second primary malignancies (SPMs), and non-relapse mortality (NRM). Understanding and addressing these risks is paramount to improving patient outcomes and quality of life.

Summary: This review explores the incidence and risk factors for NRM and long-term complications following CAR T-cell therapy. Infections are the leading cause of NRM, accounting for over 50% of cases, driven by neutropenia, hypogammaglobulinemia, and impaired cellular immunity. SPMs, including secondary myeloid and T-cell malignancies, are increasingly recognized, prompting the FDA to issue a black box warning, although their direct link to CAR T cells remains disputed. While CAR T-cell-specific toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome contribute to morbidity, they represent only a minority of NRM cases. The management of these complications is critical as CAR T-cell therapy is being evaluated for broader use, including in earlier treatment lines and for non-malignant conditions like autoimmune diseases.

Key messages: CAR T-cell therapy has revolutionized cancer treatment, but survivorship is complicated by infections, SPMs, and ultimately endangered by NRM. Prophylactic strategies, close monitoring, and toxicity management strategies are key to improving long-term outcomes.

Introduction: The introduction of immune checkpoint inhibitors (CPIs) in oncology has improved the long-term perspectives of many patients and is bringing the quality of life (QoL) into focus as a treatment-relevant variable. In clinical routine, standardized and reliable tools for collecting, understanding, and utilizing QoL information are needed. In the current work, an interdisciplinary consensus on aspects of QoL in standard clinical practice has been put forth.

Methods: After independent, structured individual interviews with members of an interdisciplinary expert panel (n = 12), ten theses on QoL with particular consideration regarding CPI therapy were drafted. These formed the basis of a multistage, independent, anonymous, externally commented, qualitative Delphi process. During the period May - December 2022, the panel developed interdisciplinary consensus recommendations for recording QoL and its role in decision-making in everyday care.

Results: Out of ten theses, five recommendations arranged into three subject areas were agreed upon. QoL is considered a multifactorial and dynamic parameter that goes far beyond treatment-associated side effects. Mindful communication with the patient is considered the basis for QoL assessment and QoL modification. In everyday clinical practice, QoL should be documented and assessed in a structured, regular, and individualized way, thereby providing a basis for decisions on treatment options.

Conclusion: The individual QoL of cancer patients should be assessed before and throughout therapy. Especially for long-term responders of CPI therapy and in the adjuvant setting, QoL appears to be treatment relevant. The recommendations based on the Delphi method provide practical assistance.

Introduction: Cancer-associated venous thromboembolism (CAT) is a frequent and medical relevant problem. Guidelines recommend treatment with low molecular weight heparins (LMWH) or direct oral factor-Xa inhibitors as rivaroxaban for ≥3 months. Patient's preference and convenience is an important factor to guide treatment decision and to support treatment adherence. No data are available so far about patient-reported outcome in CAT.

Methods: CONKO-011/AIO-SUP-0115/ass. was an open-label, prospective, multicenter German phase III trial for cancer patients with newly diagnosed venous thromboembolism (VTE) randomized to rivaroxaban (Riva) or site-specific LMWH. Primary endpoint was patient-reported treatment satisfaction, measured by the Anti-Clot Treatment Scale (ACTS). The 12-item ACTS Burdens scale (primary endpoint after 4 weeks) and the 3-item ACTS Benefits scale were analyzed at 4, 8 and 12 weeks. Secondary endpoints included recurrent VTE, major/clinically relevant bleeding, safety, compliance, overall mortality at 3 and 6 months, quality of life measured by the Treatment Satisfaction Questionnaire for Medication II (TSQM II) and Spitzer Index.

Results: Between 03/2016 and 06/2019, 247 (123 Riva/124 LMWH) patients were randomized. Mean ACTS Burdens scores after 4 weeks were 52.8 versus 51.2 in favor of rivaroxaban (p = 0.019) with mean score differences ranging from 3.3 (week 8; p = 0.001) to 2.4 (week 12; p = 0.006). The treatment effect of ACTS burden was consistent over treatment time (p < 0.001). More patients on LMWH requested to stop study treatment preterm (19.4% versus 11.1%).

Conclusion: Oral treatment with rivaroxaban led to an improvement in patient-reported treatment satisfaction, particularly in reducing anticoagulation-related burden, resulting in less patient-requested treatment stops.

Introduction: In urological oncology, the physical and psychological effects of cancer and its treatment post-discharge highlight the importance of follow-up psycho-oncology consultations. This study examines their utilisation and identifies predictors in urological cancer patients after inpatient care.

Methods: A prospective, single-centre clinical observational study was conducted. Inpatients with urological cancer and ≥5 points on the Distress Thermometer and/or request for psycho-oncological support were recruited, offered an initial psycho-oncology consultation, and can attend up to five online or on-site appointments within 3 months of discharge. The following variables were collected: socio-demographics, psycho-oncological baseline documentation (PO-BADO), psychosocial distress (Distress Thermometer with problem list), anxiety and depressive symptoms (GAD-2 and PHQ-2), and performance status (ECOG).

Results: A total of 501 patients were screened, 139 were included, and 108 were analysed. Twenty five patients used psycho-oncological follow-up care (n = 16 online). The final hierarchical model predicting the use of follow-up psycho-oncological support included the two predictors: age (OR 0.93, 95% CI 0.90-0.96) and anxiety (OR 1.60, 95% CI 1.11-2.44).

Conclusion: Nearly 1 in 4 urological cancer patients use follow-up psycho-oncology consultations, mostly online. Predictors for this usage are younger age and higher levels of anxiety. To improve care, (1) online services reduce barriers; (2) older patients require support with these services; and (3) screening specifically for depression is crucial to ensure that follow-up appointments are scheduled as a mandatory part of hospitalisation.

Introduction: In urological oncology, the physical and psychological effects of cancer and its treatment post-discharge highlight the importance of follow-up psycho-oncology consultations. This study examines their utilisation and identifies predictors in urological cancer patients after inpatient care.

Methods: A prospective, single-centre clinical observational study was conducted. Inpatients with urological cancer and ≥5 points on the Distress Thermometer and/or request for psycho-oncological support were recruited, offered an initial psycho-oncology consultation, and can attend up to five online or on-site appointments within 3 months of discharge. The following variables were collected: socio-demographics, psycho-oncological baseline documentation (PO-BADO), psychosocial distress (Distress Thermometer with problem list), anxiety and depressive symptoms (GAD-2 and PHQ-2), and performance status (ECOG).

Results: A total of 501 patients were screened, 139 were included, and 108 were analysed. Twenty five patients used psycho-oncological follow-up care (n = 16 online). The final hierarchical model predi

Introduction: Standard treatments for intermediate-stage hepatocellular carcinoma (HCC), such as transarterial chemoembolization (TACE), offer limited efficacy, necessitating the exploration of additional therapeutic strategies. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown potential to enhance HCC outcomes when combined with TACE. This meta-analysis aimed to evaluate safety and efficacy of TACE, TKIs, and ICIs (TACE + T + I) combination compared to TACE with TKIs alone (TACE + T) in patients with HCC.

Methods: A systematic search was performed in "PubMed," "Google Scholar," "Cochrane Library," "Web of Science," "Scopus," and "Embase" databases on November 1, 2024. Studies involving patients with HCC comparing TACE + T + I versus TACE + T were included. Efficacy outcomes including objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were extracted. Meta-analysis was conducted using RevMan 5.4.

Results: Seventeen studies were included for analysis. Pooled analysis showed a marked improvement in ORR (risk ratio [RR] = 1.57, 95% CI: 1.36-1.80, p < 0.00001) and DCR (RR = 1.13, 95% CI: 1.06-1.20, p = 0.0004) for TACE + T + I regimen over TACE + T. TACE + T + I group also showed a marked benefit in OS (hazard ratio [HR] = 0.37, 95% CI: 0.29-0.48, p < 0.0001) and PFS (HR = 0.44, 95% CI: 0.36-0.53, p < 0.0001). No differences in adverse events were detected between the two groups, indicating comparable tolerability.

Conclusion: The findings suggest that the addition of ICIs to TACE and TKI therapy offers substantial efficacy benefits without increasing toxicity for HCC patients. This combination therapy shows potential to improve DCR, ORR, PFS, and OS, underscoring the value of immunotherapy in enhancing outcomes in HCC. However, further randomized trials with standardized treatment protocols are needed to confirm these results and inform clinical guidelines.

Introduction: The distribution of muscle and adipose tissues masses physiologically follow sex-specific patterns. On the other hand, the clinical and biological consequences of pathologic body composition, i.e., sarcopenia or obesity, also depend on tissue distribution patterns. Although obesity-associated inflammation has been correlated with survival benefits of cancer patients undergoing immune checkpoint inhibition (ICI) therapy, detailed and sex-specific body composition analyses are widely missing. Here, we prospectively analyzed body composition and serum parameters of inflammation and protein metabolism in patients with advanced melanoma before and 3 months after initiation of ICI therapy.

Methods: Between 2016 and 2018, consecutive patients with advanced cutaneous melanoma were recruited into the study at our cancer center (Skin Cancer Center, CIO, University Hospital Cologne, Germany). Blood samples and body composition based on bioelectrical impedance analysis (BIA) were assessed before ICI therapy initiation (T1) and after 3 months (T2). Correlation of blood parameters with body composition as well as progression-free (PFS) and overall survival (OS) was analyzed in sex-specific subgroups.

Results: From a total of 54 patients, 25 were women and 29 were men. In women, a high muscle mass at T1 was the strongest marker for longer PFS (HR 0.84; 95% CI: 0.74-0.98; p = 0.024), while in men (n = 29), high phase angle values at T1 correlated with significantly longer PFS (HR 0.48; 95% CI: 0.26-0.90; p = 0.023). Regarding OS, muscle mass status at T1 remained the strongest predictor for longer survival in women (HR 0.85; 95% CI: 0.72-0.99; p = 0.033), while in men, increased leukocyte blood counts at T1 were associated with the poorest OS (HR 1.36; 95% CI: 1.14-1.62; p = 0.001). Inflammation and the immuno-nutritional score mGPS correlated with body composition parameters in a sex-specific manner. However, we did not observe an impact of dynamic changes between T1 and T2 in all analyzed parameters.

Conclusion: Our data suggest that BIA-derived markers are associated with the prognosis of melanoma patients undergoing ICI therapy in a sex-specific manner. Selected body composition parameters correlate differently with blood markers of inflammation and protein metabolism in men and women. If validated in larger trials, these assessments might improve individualized supportive care and clinical risk stratification.