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 non-relapse mortality 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 CRS and ICANS 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 INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated. Methods The prospective, multicenter, multi-cohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany. The primary endpoint was the clinical benefit rate (CBR) in patients with measurable disease according to RECIST v1.1. Secondary endpoints were overall response rate (ORR), progression free survival (PFS), overall survival (OS), safety and quality of life. Data were analyzed with descriptive statistics. Results Between 2016 and 2018, 388 patients were enrolled at 64 German sites. Among patients with measurable disease treated with PAL in 1L (n=157), the CBR was 63.7% (100/157). Among all patients treated with PAL 1L (n=219), PFS was 20.1 months (95% CI 14.6 - 24.0) and OS was 40.9 months (95% CI 35.1-49.2). The most common grade 3/4 adverse event was neutropenia (33.4% n=77). There were no treatment-related deaths. Conclusion The INGE-B trial demonstrated good efficacy and tolerability of PAL with letrozole (1L) or fulvestrant (first and later line) in accordance with the PALOMA-trials. In addition, the so far lacking proof of efficacy and safety of PAL in combination with anastrozole or exemestane in 1L and with letrozole in later line was provided by INGE-B.

Introduction: Men are generally more susceptible to bacterial infections than women. Central venous catheters (CVCs), often used to administer systemic treatment in patients with cancer, are an important source of infection. However, little is known about sex-specific differences of CVC-related bloodstream infections (CRBSIs) in patients with cancer. This study aimed to compare CRBSIs in men vs. women in a large cohort of patients with cancer.

Methods: Data were derived from the SECRECY registry including non-selected patients with centrally inserted non-tunneled internal jugular or subclavian vein CVCs in 10 hematology and oncology sites in Germany. Only CRBSIs classified as definite CRBSI (dCRBSI) or probable CRBSI were included, and the combination of both was summarized as dpCRBSI. CVCs were matched 1:1 for underlying disease, anatomic site of CVC insertion, type of CVC dressing, antimicrobial coated CVC, complicated CVC insertion and CVC in situ time by propensity score matching (PSM). Endpoints were CRBSI rates and incidences in CVCs inserted in men vs. women.

Results: A total of 5075 CVCs registered from March 2013 to March 2024 were included in the analysis, of which 3024 comprises the PSM cohort. 1512 (50.0%) CVCs were inserted in men. Underlying diseases mainly were hematological malignancies (96.4%). While there was no statistically significant difference between men and women in the dCRBSI rate (5.4% vs. 4.1%; p=0.12) and the dCRBSI incidence (3.8 vs. 2.9/1000 CVC days; p=0.11), the rate of dpCRBSI (9.9% vs. 6.7%; p=0.002) and the dpCRBSI incidence (7.0 vs. 4.7/1000 CVC days; p=0.002) were significantly higher in men vs. women. The proportion of coagulase-negative staphylococci as causative agent of both dCRBSI and dpCRBSI was higher in men than in women (58.8% vs. 41.2%; p=0.07, and 61.5% vs. 38.5%; p=0.002, respectively). A multivariable regression revealed neutropenia as an independent risk factor for dCRBSI and male sex as risk factor for dCRBSI and dpCRBSI.

Conclusion: In patients with hematological malignancies, men have a higher risk of CRBSI than women. This finding may be attributed to the high number of jugular vein inserted CVCs which in men may be associated with higher rates of skin colonization than in women. Special preventive measures such as earlier removal of CVCs in men may be studied in future.

Introduction Cancer-related malnutrition is a highly prevalent, yet often overlooked concern in clinical practice. Although cancer-related management guidelines recommend standardized nutritional care, its implementation is scarce. The aim of this study was to investigate the prevalence of malnutrition and the medical need for nutrition counseling in cancer patients employing a novel standardized nutritional management program (containing malnutrition risk screening, nutritional assessment and counseling). Furthermore, differences of malnutrition parameters in different cancer patient cohorts were examined. Methods Cancer patients were screened for malnutrition using the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) on the first day of their inpatient admission to the internal oncology or hematology wards. PG-SGA total score and classification into the three PG-SGA nutrition stages (A, B, C) were used to determine nutritional status. In case of a positive screening, nutritional assessment and individualized counseling by a nutritionist followed. For group comparisons, patients were divided into different groups (e.g., age, gender, tumor entity) and were evaluated accordingly. Results A total of 1,100 inpatients were included. 56.8 % of the patients had suspected or already existing malnutrition. The most common nutrition impact symptom was loss of appetite (26.7 %), followed by fatigue (16.5 %) and pain (16.0 %). Female (p < 0.001), elderly (p < 0.001) and patients with upper gastrointestinal tract tumors (p < 0.001) showed an unfavorable nutritional status and higher need for counseling. Despite suffering from malnutrition, patients had Body Mass Indices within the upper end of the normal range. Conclusion This study shows a high prevalence of malnutrition in hospitalized cancer patients and highlights the need for a standardized nutritional management in the clinical setting. Therefore, it is recommended to provide a malnutrition risk screening for all cancer patients and a following adequate assessment and personalized nutritional care if needed.

Background: 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 up to five online or on-site appointments within three 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 & PHQ-2), and performance status (ECOG).

Results: A total of 501 patients were screened, 139 were included, and 108 were analysed. 25 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).

Discussion: Nearly one in four 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: While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aimed to assess the impact of the Geriatric-8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients.

Methods: Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45-66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients.

Results: In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months, respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p = 0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6-48.4) and 19 months (95% CI, 0-39.4), respectively (p = 0.832). The median overall survival (OS) was 38 months (95% CI, 23.8-52.2) in geriatric patients, while it was not reached in younger patients (p = 0.745). There was no significant difference between the two groups. The pretreatment and post-treatment G8 values of the geriatric patients were 9.25 (6-13.5) and 9.5 (6-14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 months vs. 11 months, p = 0.001) and OS (median 85 months vs. 14 months, p = 0.001) compared to those with unchanged or decreased G8 scores.

Conclusion: Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value.

Background: Lung cancer is a major contributor to cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are currently viewed as the established first-line therapy for patients with advanced NSCLC with EGFR mutations.

Summary: The potential predictive value of the quantitative abundance of epidermal growth factor receptor (EGFR) mutations in the treatment of NSCLC is widely recognized and regarded as a significant indicator. The definition of mutation abundance in the EGFR gene in most current studies is mainly calculated based on the ratio of mutation to wild-type gene copy number or based on the ratio of allele number; for example, variant allele frequency is the ratio of the number of mutant alleles to the total number of alleles at a particular locus. Results of the included primary studies are as follows. (1) Significant association between EGFR mutation abundance and progression-free survival (PFS): median PFS was significantly longer in the high abundance group (11.0 months, 95% CI: 9.7-12.3 months) than in the low abundance group (5.3 months, 95% CI: 3.6-7.0 months) in the study by Liu et al. High mutation abundance (HR: 0.77, 95% CI: 0.66-0.82, p = 0.037) was an independent prognostic determinant of PFS in the study by Wang et al. Among patients receiving EGFR-TKI as first-line therapy, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 months vs. 8.7 months, p = 0.002). EGFR mutation abundance ≥30% was an independent risk factor for PFS (HR: 1.64, 95% CI: 1.17-2.31). (2) Significant association between EGFR mutation abundance and overall survival (OS): the median OS in the high abundance group in the study by Liu et al. was 20.9 months (95% CI: 18.3-23.5 months), while that in the low abundance group was 13.0 months (95% CI: 10.0 months) (95% CI: 10.3-15.7 months); longer OS was independently associated with high mutation abundance (HR: 0.62, 95% CI: 0.50-0.79, p = 0.027).

Key messages: The objective of this article was to conduct a comprehensive examination and analysis of the association between the abundance of EGFR mutations in NSCLC and the effectiveness of treatment with TKIs while also considering the development of drug resistance.