Journal of the National Cancer Center最新文献

“Screening” is a search for preclinical, asymptomatic disease, including cancer. Widespread cancer screening has led to large increases in early-stage cancers and pre-cancers. Ubiquitous public messages emphasize the potential benefits to screening for these lesions based on the underlying assumption that treating cancer at early stages before spread to other organs should make it easier to treat and cure, using more tolerable interventions. The intuition is so strong that public campaigns are sometimes launched without conducting definitive trials directly comparing screening to usual care. An effective cancer screening test should not only increase the incidence of early-stage preclinical disease but should also decrease the incidence of advanced and metastatic cancer, as well as a subsequent decrease in cancer-related mortality. Otherwise, screening efforts may be uncovering a reservoir of non-progressive and very slowly progressive lesions that were not destined to cause symptoms or suffering during the person's remaining natural lifespan: a phenomenon known as “overdiagnosis.” We provide here a qualitative review of cancer overdiagnosis and discuss specific examples due to extensive population-based screening, including neuroblastoma, prostate cancer, thyroid cancer, lung cancer, melanoma, and breast cancer. The harms of unnecessary diagnosis and cancer therapy call for a balanced presentation to people considering undergoing screening, even with a test of accepted benefit, with a goal of informed decision-making. We also discuss proposed strategies to mitigate the adverse sequelae of overdiagnosis.

Immune checkpoint inhibitor-based immunotherapy has revolutionized the treatment approach of non-small cell lung cancer (NSCLC). Monoclonal antibodies against programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) are widely used in clinical practice, but other antibodies that can circumvent innate and acquired resistance are bound to undergo preclinical and clinical studies. However, tumor cells can develop and facilitate the tolerogenic nature of the tumor microenvironment (TME), resulting in tumor progression. Therefore, the immune escape mechanisms exploited by growing lung cancer involve a fine interplay between all actors in the TME. A better understanding of the molecular biology of lung cancer and the cellular/molecular mechanisms involved in the crosstalk between lung cancer cells and immune cells in the TME could identify novel therapeutic weapons in the old war against lung cancer. This article discusses the role of TME in the progression of lung cancer and pinpoints possible advances and challenges of immunotherapy for NSCLC.

Hepatocellular carcinoma (HCC) is a common malignancy with high mortality rates. While surgery can be curative in early-stage disease, 80% of patients cannot undergo surgical resection. Stereotactic body radiotherapy (SBRT), an emerging, non-invasive, precision treatment, has shown promising results across various stages of HCC and has thus been adopted in practice to varying degrees around the world. This article aims to review current guideline recommendations on SBRT, clinical evidence, and outcome comparisons with other local treatment modalities. Attempts are also made to compare the differences in clinical trials between Asian and Western countries.

Background

Breast cancer survivors with psychological problems have higher mortality than those without. Therefore, it is important to monitor and manage their psychological status. This study mainly aimed to dynamically estimate the prevalence of anxiety and depression and to clarify the factors associated with anxiety and depression of patients undergoing adjuvant chemotherapy. The secondary objective was to investigate the relationship between depression and anxiety and quality of life (QOL) in Chinese early-stage breast cancer patients.

Methods

In a prospective observational single-center cohort study with early-stage breast cancer patients (n = 290), depression and anxiety severity, QOL, and social support were measured using the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) scale, and the Chinese version of the Social Support Rating Scale (SSRS), respectively. Canonical correlations were applied to identify correlates between anxiety and depression and demographic and clinical variables. One-way repeated measure analysis of covariance (RMANCOVA) was used to analyze dynamic changes in anxiety, depression, and QOL. Relationships between anxiety and depression and QOL were analyzed using two-way RMANCOVA.

Results

The overall anxiety and depression prevalence rates were 35.2% and 44.1%, respectively. Age (P = 0.042), surgical method (P = 0.009), social support (P = 0.001), and breast cancer family history (P = 0.045) were significantly associated with depression. The number of children (P = 0.048) was significantly associated with anxiety. FACT-B scores differed between anxiety and depression and nonanxiety and depression groups, and patients with higher HADS depression and anxiety scores had lower FACT-B scores during chemotherapy (P < 0.001).

Conclusions

We observed dynamic changes in anxiety and depression and QOL and associated factors of anxiety and depression. These findings can provide guidance for psychological monitoring and support for breast cancer patients during the postoperative chemotherapy period.

Background

The genomic background affects the occurrence and metastasis of cancers, including clear cell renal cell carcinoma (ccRCC). However, reports focusing on the prognostic mutational signature of Chinese ccRCC are lacking.

Methods

Overall, 929 patients, including a training cohort with Chinese patients (n = 201), a testing cohort with Caucasian patients (n = 274), and a validation cohort (n = 454) were analyzed for the genomic landscape of ccRCC. Then, machine-learning algorithms were used to identify and evaluate the genomic mutational signature (GMS) in ccRCC. Analyses for prognosis, immune microenvironment, association with independent clinicopathological features, and predictive responses for immune checkpoint therapies (ICTs) were performed.

Results

The DNA variation data of 929 patients with ccRCC suggested markedly differential genomic mutational frequency of the most frequent genes, such as VHL, PBRM1, BAP1, SETD2, and KDM5C between the Chinese and Caucasian populations. PBRM1 showed significant co-occurrence with VHL and SETD2. We then successfully identified a seven-gene mutational signature (GMS^Mut) that included mutations in FBN1, SHPRH, CELSR1, COL6A6, DST, ABCA13, and BAP1. The GMS^Mut significantly predicted progressive progression (P < 0.0001, HR = 2.81) and poor prognosis (P < 0.0001, HR = 3.89) in the Chinese training cohort. Moreover, ccRCC patients with the GMS^Mut had poor survival rates in the testing cohort (P = 0.020) and poor outcomes were predicted for those treated with ICTs in the validation cohort (P = 0.036). Interestingly, a favorable clinical response to ICTs, elevated expression of immune checkpoints, and increased abundance of tumor-infiltrated lymphocytes, specifically CD8⁺ T cells, Tregs, and macrophages, were observed in the GMS^Mut cluster.

Conclusions

This study described the pro-tumorigenic GMS^Mut cluster that improved the prognostic accuracy in Chinese patients with ccRCC. Our discovery of the novel independent prognostic signature highlights the relationship between tumor phenotype and genomic mutational characteristics of ccRCC.

Background

The SPF10 LiPA-25 system for human papillomavirus (HPV) detection with high analytical performance is widely used in HPV vaccine clinical trials. To develop and evaluate more valent HPV vaccines, other comparable methods with simpler operations are needed.

Methods

The performance of the LiPA-25 against that of other 7 assays, including 4 systems based on reverse hybridization (Bohui-24, Yaneng-23, Tellgen-27, and Hybribio-16) and 3 real-time polymerase chain reaction (PCR) assays (Hybribio-23, Bioperfectus-21, and Sansure-26), was evaluated in selected 1726 cervical swab and 56 biopsy samples. A total of 15 HPV genotypes (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) were considered for comparison for each HPV type.

Results

Among the swab samples, compared to LiPA-25, compatible genotypes were observed in 94.1% of samples for Hybribio-23, 92.8% for Yaneng-23, 92.6% for Bioperfectus-21, 92.4% for Hybribio-16, 91.3% for Sansure-26, 89.7% for Bohui-24, and 88.0% for Tellgen-27. The highest overall agreement of the 15 HPV genotypes combined was noted for Hybribio-23 (κ = 0.879, McNemar's test: P = 0.136), followed closely by Hybribio-16 (κ = 0.877, P< 0.001), Yaneng-23 (κ = 0.871, P < 0.001), Bioperfectus-21 (κ = 0.848, P < 0.001), Bohui-24 (κ = 0.847, P < 0.001), Tellgen-27 (κ = 0.831, P < 0.001), and Sansure-26 (κ = 0.826, P < 0.001). Additionally, these systems were also highly consistent with LiPA-25 for biopsy specimens (all, κ > 0.897).

Conclusions

The levels of agreement for the detection of 15 HPV types between other 7 assays and LiPA-25 were all good, and Hybribio-23 was most comparable to LiPA-25. The testing operation of HPV genotyping should also be considered for vaccine and epidemiological studies.

Liver metastases occur commonly in many solid malignancies. With advances in systemic therapies and increased life expectancy, the role of using local therapies in oligo-metastases is rapidly increasing. Stereotactic body radiotherapy (SBRT) is an emerging precision therapy that is being used more frequently in the treatment for unresectable liver metastases. This review focuses on the role of SBRT for liver metastases, principles of treatment, clinical outcomes, toxicity, and optimal patient selection.