Oncology最新文献

Introduction: Non small cell lung cancer (NSCLC) patients with poor Eastern Cooperative Oncology Group Performance Status (ECOG PS >2) represent a challenging subset of patients. Best supportive care (BSC) has been the standard of care as per NCCN guidelines in this cohort; however immune checkpoint inhibitors have a potential of offering better tolerance and survival benefits. This study aimed to compare outcomes of immunotherapy versus BSC in NSCLC patients with PS>2.

Methods: This is a retrospective analysis of NSCLC patients who have progressed on initial lines of therapy and had ECOG PS 3 or 4. A propensity score matching was conducted between the two groups- those who received immune checkpoint inhibitors (nivolumab group) and those who were managed with BSC (BSC group) using the variables of age, sex, smoking status, stage and tumor type. The final study cohort included 39 patients in nivolumab arm and 21 in BSC arm. Baseline demographics, treatment responses, overall survival (OS), and adverse events were compared.

Results: Most patients were males (81.7%), smokers (85%), and had stage IV disease (75%), and squamous histology (70%). PDL1 status was unknown in 53.3%. All patients had initially received platinum-based-doublet chemotherapy. Compared to the nivolumab group, the BSC group had a higher proportion of ECOG 4 patients (80.9% vs 35.9%, p<0.001), while more nivolumab patients had PDL1 levels of 1-49% (30.8% vs 14.3%, p=0.003). Median progression-free survival in the nivolumab group was 18-weeks, with 25.6% remaining progression-free at data cutoff. Median OS was significantly longer with nivolumab: 29-weeks (95% CI: 11.3-46.7) versus 8-weeks (95% CI: 3.5-12.5; p<0.001) with adjusted-hazard-ratio of 0.243 (95% CI: 0.106-0.56; p<0.001). In the nivolumab group, 23.1% had partial-responses, and 41% showed at least one-point improvement in PS (4.8% in the BSC group).

Conclusion: Immunotherapy demonstrated superior survival outcomes and acceptable tolerability profile than BSC in NSCLC patients with PS >2.

Introduction: Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). Antibiotics (ATBs) usage has risen among such patients, yet its relationship with CIP remains uncertain. We investigated the association between ATB exposure and CIP development in lung cancer patients treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors.

Methods: We retrospectively collected clinical data of lung cancer patients who received PD-1/PD-L1 inhibitors for the first time, according to predefined eligibility criteria. ATB exposure was defined as receipt of ATBs within 3 months before ICIs initiation, or within 3 months after ICI initiation but before CIP onset. Patients with ATB exposure were further stratified by timing relative to ICIs initiation and CIP onset (pre-ICIs only, post-ICIs only, or both). CIP was adjudicated by two oncologists and three thoracic radiologists on the basis of clinical symptoms, imaging findings, and laboratory/microbiological testing to exclude alternative etiologies, including infection. Associations between ATB exposure and CIP risk were evaluated using Fine-Gray competing-risk regression models.

Results: Among 998 patients, 233 (23.3%) had ATB exposure and 142 (14.2%) developed CIP, with a median onset of 82 days (range, 9 to 552). After multivariable adjustment, ATB exposure was associated with a higher risk of CIP (subdistribution hazard ratio [sHR] = 9.05, 95% CI 6.32 to 12.94, p < 0.001). The magnitude of association increased with CIP severity (mild to severe), with sHRs of 5.81, 11.40, and 12.46, respectively. Broad-spectrum ATBs (sHR = 7.27, 95% CI 5.19 to 10.17, p < 0.001) and oral administration (sHR = 7.06, 95% CI 5.07 to 9.84, p < 0.001) were associated with greater CIP risk than narrow-spectrum agents and intravenous administration, respectively. Patients exposed to ATBs exclusively after ICI initiation had the highest CIP risk (sHR = 11.19, 95% CI 6.92 to 18.09, p < 0.001). Prophylactic ATB use was associated with worse outcomes among patients with CIP (adjusted p = 0.014).

Conclusion: In lung cancer patients treated with anti-PD-1/PD-L1 therapy, ATB exposure was associated with a substantially increased risk of CIP. ATB use, particularly broad-spectrum and orally administered regimens, should be carefully evaluated, and ICI-treated patients receiving ATBs warrant close monitoring. In patients with established CIP, routine prophylactic ATB therapy should be used judiciously given its association with worse outcomes.

Introduction: Radiotherapy is a cornerstone of laryngeal cancer treatment. MRE11, a key component of the MRN complex, and the ATM protein are important elements of DNA repair. This study examines the impact of MRE11 and ATM on treatment outcomes in laryngeal cancer patients treated at Bulovka University Hospital in Prague.

Methods: This retrospective study included 108 patients with laryngeal cancer treated with radiotherapy. Immunohistochemical analysis of pre-treatment biopsy samples was performed to evaluate MRE11 and ATM expression and statistically estimate the impact on treatment outcomes.

Results: Statistically significant differences were found in subgroups of patients according to the IHC positivity of at least one of these two proteins. A statistically significant association was confirmed between immunohistochemical positivity for MRE11 or ATM protein (at least one of them) and better overall survival (p<0.001). IHC negativity for both proteins was found only in patients in clinical stage IV (p<0.001) with the shortest overall survival confirmed in this subgroup of patients.

Conclusion: High immunohistochemical expression of MRE11 and ATM proteins was associated with earlier clinical stages and better treatment outcomes in laryngeal carcinoma, particularly when both proteins were elevated. The results point to the potential of MRE11 and ATM as predictors of treatment response, but more extensive molecular and clinical research would be needed to gain a more detailed insight.

Background Primary head and neck mucosa-associated lymphoid tissue lymphoma (HN-MALT) is a rare B-cell lymphoma whose epidemiology, clinical features, and treatment strategies remain unclear. Methods We conducted a retrospective analysis of HN-MALT data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2021) and compared the incidence and mortality rates among age groups. Kaplan-Meier was used to determine the overall survival (OS) and lymphoma-specific survival (LSS). Prognostic factors were identified using univariate and multivariate Cox regression models. Results In a cohort of 2,517 patients, the annual incidence rate of HN-MALT in patients ≥ 60 years old was higher than that in those < 60 years old, with an increasing trend in overall mortality over time. Multivariable Cox analysis identified that male, age ≥ 60 years, being divorced/separated/widowed, and having a second malignant neoplasm (SMN) were associated with poorer OS and LSS. Additionally, not receiving radiotherapy was identified as a risk factor for poorer OS, whereas not undergoing surgical treatment was associated with decreased LSS. Notably, subgroup analyses demonstrated that the combination of surgery and radiotherapy consistently yielded superior survival outcomes across key patient strata. It significantly improved OS compared to radiotherapy alone in males, females, patients aged ≥ 60, and married patients, regardless of SMN status. Most strikingly, this combined modality led to a pronounced improvement in LSS, particularly among patients aged ≥ 60 (males: HR = 0.221; females: HR = 0.447) and those categorized by marital status (married: HR = 0.379; divorced/separated/widowed: HR = 0.338), as well as in patients with or without SMN. Kaplan-Meier analyses confirmed that surgery combined with radiotherapy improved OS and LSS compared to radiotherapy alone in certain subgroups of patients with HN-MALT. Conclusions HN-MALT has unique clinical and pathological characteristics; surgery combined with radiotherapy can improve OS and LSS.

Hepatitis B virus (HBV) infection is a significant risk factor for hepatocellular carcinoma (HCC). During the infection, HBV DNA integrates into the host genome, promoting hepatocarcinogenesis through both gene-dependent and gene-independent mechanisms. It can activate oncogenic gene transcription or produce chimeric and novel proteins that contribute to tumorigenesis. On the other hand, it also compromises genomic stability on a large scale. Furthermore, HBV integration can alter the liver microenvironment, fostering conditions conducive to tumor development. HCC remains one of the most challenging cancers to treat, primarily due to the incomplete understanding of HCC, inadequate diagnostic and prognostic strategies, and limited effective therapeutic options. Liquid biopsy represents a significant advancement in oncology, offering a non-invasive tool for cancer detection and management. HBV integration detection through liquid biopsy serves as a promising strategy for managing HBV-associated HCC. Importantly, it exhibits preferential patterns that differentiate HCC from chronic hepatitis or cirrhosis patients, making it a potential biomarker for HCC diagnosis. Moreover, the quantification of HBV-host chimeric reads in the bloodstream can indicate the presence of residual tumor cells post-surgery, serving as a promising biomarker for the screening of HCC recurrence. HBV integration additionally contributes to the production of HBV surface antigen (HBsAg), which is crucial for achieving a functional cure for HBV infection and influences the efficacy of antiviral treatments. Overall, HBV integration plays a pivotal role in hepatocarcinogenesis, and its detection via liquid biopsy will greatly enhance the clinical management of HBV-associated HCC.

Purpose In studies, weight loss is strongly associated with outcomes in metastatic non-squamous cell lung cancer (mNSCLC). This work examines weight variations in first-line treatment, exploring their mechanisms based on treatment type, age, sex, weight loss and excess weight before treatment. Methods A retrospective analysis was conducted on patients undergoing first-line treatment. Weight was recorded at four points: before treatment (Wbe), day one of treatment (Wd1), three months into immune checkpoint inhibitors (ICIs) treatment or maintenance (W3mo), and at progression diagnosis (Wpro). Results Among patients (n=198), 47% received chemotherapy (CT) with ICIs, 26% CT alone, and 27% ICIs alone. At Wd1, 32% were overweight/obese (Body mass index kg/m2) (BMI ≥25). Weight loss ≥ 5% before treatment was observed in 37%. Mean (SD) weight variations between Wd1 and W3mo were -1.1% (4.6) (CT), -0.2% (7.1) (CT+ICIs), and +0.4% (7.7) (ICIs alone) (P = 0.52). Patients older than 70 compared to ≤70 lost more weight between Wd1 and Wpro (-4.7% vs. -0.4%) (P = 0.019). Patients with pre-treatment weight loss ≥ 5% compared to those without weight loss stabilized or gained weight during treatment (+2.1% vs. -1.5%) (P = 0.009). Patients with BMI ≥25 lost more weight during treatment than those with BMI <25 (-1.4% vs. +0.8%) (P = 0.024). Conclusion Weight variations did not differ significantly across treatment types. Older patients are nutritionally more vulnerable. Pre-treatment significant weight loss ≥ 5% patients stabilized or gained weight during treatment, unlike those without initial weight loss. Pre-treatment weight loss in first-line mNSCLC supports, rather than contraindicates, cancer therapy. Higher BMI was associated with greater weight loss during treatment.

Introduction: Blood-based inflammatory and nutritional biomarkers have been crucial prognostic indicators in various malignancies. This study aimed to investigate the association of preoperative biomarkers with postoperative outcome in patients with non-metastatic bladder cancer (clinical stage ≤IIIb) who underwent radical cystectomy (RC).

Methods: This study retrospectively analyzed data, including preoperative albumin-to-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein-to-albumin ratio (CAR), of 235 patients with non-metastatic bladder cancer who underwent RC at 10 Kitasato University-affiliated hospitals between 2002 and 2023.

Results: Survival analyses revealed the significant association of low AGR with poorer 5-year disease-free survival (DFS) (31% vs. 64%, p < 0.001) and overall survival (OS) (44% vs. 70%, p < 0.001). High NLR correlated with DFS (53% vs. 72%, p = 0.008) and OS (59% vs. 79%, p = 0.009), whereas high CAR was significant only for OS (39% vs. 60%, p = 0.001). Multivariable analysis demonstrated that low AGR was significantly associated with poorer DFS (hazard ratio [HR]: 1.75; 95% confidence interval [CI] : 1.02-2.98; p = 0.041) and OS (HR: 1.83; 95% CI: 1.04-3.22; p = 0.037).

Conclusion: Preoperative blood-based biomarkers may help identify patients at high risk of non-metastatic bladder cancer after RC. In particular, AGR provides a simple, inexpensive, and widely applicable tool for risk stratification and treatment planning.

The success of modern chemotherapy in overall survival of patients with advanced stages of osteosarcoma and soft tissue sarcoma has reached a plateau. Therefore a deeper understanding of molecular mechanisms behind deregulated apoptosis in sarcoma is essential for the cure of patients with advanced stages of osteosarcoma and soft tissue sarcoma. Lifeguard (LFG) is a member of the Bax Inhibitor-1 (BI-1) protein family and has anti-apoptotic effects by inhibiting Fas-mediated cell death signaling. Although LFG has been proven to be expressed in several breast cancer tissues, the expression and function of LFG regarding apoptosis in different subtypes of sarcoma remains unclear. In the present study, the expression of LFG in osteosarcoma (50 samples), chondrosarcoma (28 samples) and soft tissue sarcoma (total 55 samples) with different tumor stages for each sarcoma subtype were analyzed. For each subtype, clinical TNM-classification and pathological grading were determined and compared to healthy corresponding tissues. Soft tissue sarcoma subtypes included liposarcoma, dermatofibrosarcoma, angiosarcoma, leiomyosarcoma, malignant schwannoma and synovial cell sarcoma. In this study, significantly higher expressions of anti-apoptotic LFG protein in osteosarcoma, chondrosarcoma and many different subtypes of soft tissue sarcoma were found, compared to corresponding healthy tissues. More importantly a positive correlation between LFG expression and tumor stage for osteosarcoma and chondrosarcoma was found. In conclusion, LFG protein might play an important role in inhibition of Fas-mediated apoptosis in osteosarcoma cells, with possible potential for targeted tumor therapy in osteosarcoma.

Introduction: Atezolizumab-bevacizumab (AB) and durvalumab-tremelimumab (DT) combination therapies are widely used for the treatment of unresectable hepatocellular carcinoma (u-HCC). However, the optimal predictors of the therapeutic response remain unclear. Interferon-γ-induced protein-10 (IP-10) levels are considered potential biomarkers in immunotherapy for u-HCC and other cancers. To our knowledge, this study is the first to analyze the relationship between blood IP-10 levels and therapeutic response in patients with u-HCC receiving AB or DT.

Methods: This retrospective cohort included 106 patients who received immunotherapy for u-HCC. In these patients, IP-10 levels were quantified through enzyme-linked immunosorbent assay using stored plasma samples at baseline and after induction, and the ratio of postinduction to baseline IP-10 levels was calculated.

Results: The initial therapeutic responses were partial response (PR), stable disease (SD), and progressive disease (PD) rates of 42%, 28%, and 30%, respectively. The best responses were complete response, PR, SD, and PD of 3%, 43%, 26%, and 28%, respectively. Baseline IP-10 levels in the PR group as the initial therapeutic response were higher than those in the SD/PD group (p = 0.0067). Using receiver operating characteristic curve analysis, patients with a baseline IP-10 level >150 pg/mL showed a higher response rate than those with not high levels (62% vs. 26%, p < 0.001). Moreover, the non-PD group, showing the best response, exhibited a lower IP-10 ratio before response evaluation than the PD group (p = 0.015). Achieving an IP-10 ratio <1 was independently associated with longer progression-free survival (hazard ratio 1.9, p = 0.022).

Conclusion: IP-10 levels may be useful predictors of therapeutic response in patients receiving AB or DT therapy.