Clinical & Translational Oncology最新文献

Background and objective: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy against various cancers in clinical practice. However, ICIs can cause immune checkpoint inhibitor-associated pancreatic injury, often leading to drug withdrawal, and then patients must go to specialized treatment. The patients, their primary tumors are sensitive to ICIs therapy, may experience treatment delays due to such adverse reactions. Therefore, there is a need for systematic clinical researches on immune-related pancreatic toxicity to provide a clinical basis for its prevention and treatment.

Methods: This study involved the collection of data from patients treated with ICIs and addressed pancreatic injury with preemptive treatment before continuing ICIs therapy. Then, we also statistically analyzed the incidence of pancreatic injury in patients with different courses and combined treatment, and the success rate of rechallenge treatment.

Results: The study included 62 patients, with 33.9% (21/62) experiencing varying degrees of pancreatic injury. Patients with pancreatic injury, 10 cases evolved into pancreatitis, representing 47.6% (10/21) in the pancreatic injury subgroup and 16.1% (10/62) of the total patient cohort. Preemptive treatment was administered to 47.6% (10/21) of patients with pancreatitis, the effective rate was 100%. Among these patients, 70% (7/10) underwent successful rechallenge with ICIs. The occurrence of pancreatic injury was positively correlated with the treatment duration (P < 0.05) but showed no significant correlation with combination therapies (P > 0.05).

Conclusion: The likelihood of pancreatic injury increased with longer treatment durations with ICIs; no significant association was found between the incidence of ICIs-related pancreatic damage and combination therapies. Preemptive treatment for immune-related pancreatitis is feasible, allowing some patients to successfully undergo rechallenge with ICIs therapy.

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here.

Methods/patients: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life.

Results: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being.

Conclusions: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.

Background: Few studies have been designed to predict the survival of Chinese patients initially diagnosed with metastatic gastric cancer (mGC). Therefore, the objective of this study was to construct and validate a new nomogram model to predict cancer-specific survival (CSS) in Chinese patients.

Methods: We collected 328 patients with mGC from Northern Jiangsu People's Hospital as the training cohort and 60 patients from Xinyuan County People's Hospital as the external validation cohort. Multivariate Cox regression was used to identify risk factors, and a nomogram was created to predict CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), the calibration curve, and the decision curve analysis (DCA) in the training cohort and the validation cohort.

Results: Multivariate Cox regression identified differentiation grade (P < 0.001), T-stage (P < 0.05), N-stage (P < 0.001), surgery (P < 0.05), and chemotherapy (P < 0.001) as independent predictors of CSS. Nomogram of chemotherapy regimens and cycles was also designed by us for the prediction of mGC. Thus, these factors are integrated into the nomogram model: the C-index value was 0.72 (95% CI 0.70-0.85) for the nomogram model and 0.82 (95% CI 0.79-0.89) and 0.73 (95% CI 0.70-0.86) for the internal and external validation cohorts, respectively. Calibration curves and DCA also demonstrated adequate fit and ideal net benefit in prediction and clinical applications.

Conclusions: We established a practical nomogram to predict CSS in Chinese patients initially diagnosed with mGC. Nomograms can be used to individualize survival predictions and guide clinicians in making therapeutic decisions.

Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.

Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset. Comprehensive analysis was performed to investigate the molecular and immune features of APMGS subgroups.

Results: The APMGS constructed by StepCox [both] + Ridge method achieved the highest C-index and area under curve (AUC) at 3 years and were thus adopted as the final model. Low-APMGS patients exhibited superior overall survival compared with high-APMGS patients in both TCGA and GEO cohorts. Subsequent analysis confirmed that a low APMGS was associated with immune response-related pathways; low TP53 mutation rate and low tumor mutation burden (TMB); a less aggressive phenotype; high infiltration of activated CD4⁺ memory T cells, CD8⁺ T cells, follicular helper T cells, and Tregs; active immunity; and higher sensitivity to chemotherapeutic and targeted agents. In contrast, a high APMGS linked to proteasome and protein export pathways; high TP53 mutation rate and high TMB; a more aggressive phenotype; high infiltration of M0 macrophages and eosinophils; suppressed immunity; and lower sensitivity to chemotherapeutic and targeted agents.

Conclusions: Our findings suggest that APMGS has potential to predict the prognosis, and molecular and immune characteristics of HNSCC, and may also serve as an indicator for immunotherapy benefit.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitors of T cell activation and function. With the widespread use of ICIs in cancer therapy, immune-related adverse events (irAEs) have gradually emerged as urgent clinical issues. Tumors not only exhibit high heterogeneity, and their response to ICIs varies, with "hot" tumors showing better anti-tumor effects but also a higher susceptibility to irAEs. The manifestation of irAEs displays a tumor-heterogeneous pattern, correlating with the tumor type in terms of the affected organs, incidence, median onset time, and severity. Understanding the mechanisms underlying the pathogenic patterns of irAEs can provide novel insights into the prevention and management of irAEs, guide the development of biomarkers, and contribute to a deeper understanding of the toxicological characteristics of ICIs. In this review, we explore the impact of tumor type on the therapeutic efficacy of ICIs and further elucidate how these tumor types influence the occurrence of irAEs. Finally, we assess key candidate biomarkers and their relevance to proposed irAE mechanisms. This paper also outlines management strategies for patients with various types of tumors, based on their disease patterns.

Background: Granulosa cell ovarian tumors (GCTs) are a rare neoplasia characterized by a pathognomonic mutation in the FOXL2 gene. In vitro studies have demonstrated an overactivation of hormone activity due to this alteration. Thus, we aimed to determine the activity of orteronel, a CYP17 inhibitor, in advanced disease.

Methods: We designed a multicentric open-label phase II clinical trial. Eligible patients were adult woman with advanced or unresectable GCTs. Primary objective was clinical benefit rate, defined as the average of patients with radiological response plus stable disease longer than 6 months.

Results: From October 1, 2014 to May 20, 2016, ten patients were included in six participating institutions members of the GETTHI group. The study was terminated early due to a low recruitment rate. Up to 40% (CI 95% [9.6-70.4%]) cases presented a disease stabilization longer than 6 months and two of them, longer than 12 months. One patient continued on treatment at database closure 29 months after inclusion in the trial. No patient reached partial or complete response by RECIST criteria on the independent radiological review. The drug was well tolerated with nausea as the only grade 3 adverse event in one case.

Conclusion: Low accrual led to an early interruption of the study. However, orteronel achieved a promising clinical benefit rate that supports further development of new hormonotherapies in this tumor.

Clinicaltrials:

Gov identifier: NCT02101684.

Purpose: Previous studies that evaluated the influence of melatonin supplementation on cancer-related fatigue (CRF) revealed inconsistent results. The present meta-analysis was performed to systematically evaluate the influence of melatonin on the severity of fatigue in patients with cancer.

Methods: Relevant randomized controlled trials (RCTs) were acquired by conducting a comprehensive search in the PubMed, Embase, and Cochrane Library databases. Only RCTs published as full-length English-language articles were included. A random-effects model was utilized to combine the findings by incorporating its potential influence.

Results: Nine RCTs were included for the meta-analysis. Compared to the placebo, melatonin supplementation improved the symptoms of fatigue of these patients (standardized mean difference [SMD]: -0.23, 95% confidence interval [CI]: -0.44 to -0.01, p = 0.04, I² = 53%). The univariate analysis suggested that the treatment duration was significantly correlated with the improvement of melatonin supplementation on CRF (coefficient =  -0.0063, p = 0.02), which largely explains the source of heterogeneity (adjusted R² = 83.7%). The subgroup analysis revealed significantly improved fatigue in studies with treatment durations of ≥13 weeks, but not in studies with treatment durations of <13 weeks (SMD: -0.38 vs. 0.06, p for subgroup difference = 0.02). The further subgroup analysis suggested that the results were not significantly influenced by the type of cancer, status (advanced cancer or overall cancer), sample size, treatment (active anticancer treatment or palliative care only), dose of melatonin, or scale for evaluating fatigue symptoms.

Conclusions: Melatonin supplementation may relieve CRF, especially for intervention durations of ≥13 weeks.

The pan-cancer and multi-omics approach is motivated by the genetic and molecular complexity inherent in the varied types of cancer. This method presents itself as a crucial resource for advancing early diagnosis, defining prognoses and identifying treatments that share common bases between different forms of tumors. The aim of this article is to explore pan-cancer analysis in conjunction with multi-omics strategies, evaluating laboratory, computational, clinical procedures and their consequences, as well as examining the tumor microenvironment, epigenetics and future directions of these technologies in patient management. To this end, a literature review was conducted using PUBMED, resulting in the selection of 260 articles, of which 81 were carefully chosen to support this analysis. The pan-cancer methodology is applied to the study of this microenvironment with the aim of investigating its common characteristics through multiomics data. The development of new therapies depends on understanding the oncogenic pathways associated with different cancers. Thus, the integration of multi-omics and pan-cancer analyzes offers an innovative perspective in the search for new control points, metabolic pathways and markers, in addition to facilitating the identification of patterns common to multiple cancer types, allowing the development of targeted treatments. In this way, the convergence of multiomics and clinical approaches promotes a broad view of cancer biology, leading to more effective and personalized therapies.

Adipocytes represent a significant proportion of breast tissue, comprising between 3.7 and 37% of stromal tissue. They play a pivotal role in metabolic regulation, energy supply, metabolic regulation, support effects, and cytokine release within the breast. In breast cancer (BC) tissue, adipocytes engage in intricate crosstalk with BC cells, playing a key role in tumor proliferation, invasion, metastasis formation, and metabolic remodeling. This is due to the provision of hormones, adipokines, and fatty acids to tumor cells by the adipocytes. With the initiation of metastatic outgrowth of BC, the peritumoral adipose tissue exhibits abundant and intricate changes based on its original construction and function, which convert it into a tumor-associated adipose tissue microenvironment (TAAME). It includes some specific adipocytes: adipose-derived stem cells (ASCs), cancer-associated adipocytes (CAAs), adipocyte-derived fibroblasts (ADFs), etc. From a mechanistic standpoint, specific adipocytes can facilitate the proliferation, invasion, metastasis, and angiogenesis of BC cells by secreting a multitude of cytokines (IL-6) and adipokines (leptin), which collectively create an environment conducive to BC progression. It is of paramount importance to recognize the TAAME as a crucial target for the diagnosis, treatment, and drug resistance of BC. Consequently, the review presents an overview of the characteristics and interactions of specific adipocytes within TAAME cell populations. This will facilitate the development of more effective personalized therapies against BC progression, relapse, and metastasis.

Purpose: The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain.

Methods: This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined.

Results: 46% PSC patients harbored KRAS mutation and 23% harbored EGFR mutation. Univariable analysis identified type and cTNM stage as significant predictor of PFS (type: HR 0.216; 95% CI 0.133-0.349; P < 0.001, cTNM stage: HR 0.483; 95% CI 0.269-0.846; P = 0.014) and OS (type: HR 0.269; 95% CI 0.156-0.465; P < 0.001, cTNM stage: HR 0.435; 95% CI 0.219-0.865; P = 0.018). Multivariable analysis confirmed sex, type and cTNM stage as independent predictors of PFS (sex: HR 2.026; 95%CI 1.027-3.996; P = 0.042; type: HR0.140; 95% CI 0.083-0.238; P < 0.001, cTNM stage: HR0.305; 95% CI 0.165-0.564; P < 0.001) and OS (type: HR0.231; 95% CI 0.132-0.404; P < 0.001, cTNM stage: HR 0.394; 95% CI 0.194-0.797; P = 0.010). Significant differences in PFS (P < 0.0001) and OS (P = 0.022) were observed between PSC and LUAD, and for PC compared with SCC (PFS: P = 0.00036, OS: P = 0.0053). Additionally, PSC patients treated with immunotherapy showed significantly better OS (P = 0.0019) compared with those treated without immunotherapy.

Conclusions: PSC exhibits high KRAS and EGFR mutation rates, and spindle cell carcinoma has a worse prognosis. Immunotherapy shows potential as a treatment for advanced PSC.