Journal of the National Cancer Center最新文献

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.

Background

Radiotherapy following primary operation is strongly recommended for salivary gland carcinomas (SGCs) with adverse features. The interval between surgery and the initiation of radiotherapy (SRT) varied and a prolonged SRT may cause failure of cancer treatment. However, the association of SRT with survival is unclear in major SGCs.

Methods

This retrospective study included a total of 346 patients who underwent radiotherapy after the primary operation from Fudan University Shanghai Cancer Center from 2005 to 2020. The best cutoff value of the SRT was determined by the maximum log-rank statistic method. The primary endpoint of the study was overall survival (OS). Correlations between variables and OS were conducted by the univariable analysis using the Log-rank method, and a multivariate Cox proportional hazards regression was performed to identify the independent prognostic factors associated with OS. The estimated survival rates were captured using the Kaplan-Meier method.

Results

With a median follow-up time of 70.31 months, the estimated 5-year OS, LRFS, and DMFS were 83.3%, 80.1%, and 75.9%, respectively. The cutoff value for SRT was 8.5 weeks, while age, T stage, N stage, perineural invasion (PNI), pathological aggression, chemotherapy, and SRT were associated with OS in the univariable analysis. The Cox regression analysis demonstrated that older age (P < 0.001), T3-4 tumors (P = 0.007), positive N stage (P < 0.001), pathological aggression (P = 0.014), and longer SRT (P = 0.009) were independent prognostic factors for major SGCs. Using the stratification model, we observed that delay in the SRT was associated with worse OS (P = 0.006) in the high-risk group, whereas no significant difference was observed in the low-risk subgroup (P = 0.61).

Conclusions

The delay in the initiation of postoperative radiotherapy may be a prognostic factor for patients with major SGCs. It was suggested that radiotherapy should be delivered within 8.5 weeks following the operation, especially for patients with ≥2 risk factors, including older age, high pathological aggression, T3-4 tumors, and positive N stage.

Background

Updated systematic statistics on lung cancer are the underpinning cornerstones for formulating prevention and control strategies for the disease. The incidence and mortality data of lung cancer in China in 2016 were estimated, and also used to analyze the temporal trends of lung cancer from 2000 up to 2016 in this study.

Methods

The burden of lung cancer in China in 2016 was estimated using data from 487 cancer registries, which were abstracted from the database of the National Cancer Center of China (NCC). The temporal trends were estimated with the data of 2000 to 2016 from 22 cancer registries.

Results

About 828,100 new lung cancer cases and 657,000 lung cancer deaths were estimated in China in 2016. The crude incidence and mortality rates in the eastern region were the highest nationwide. The incidence and mortality of lung cancer increased with age, and most of the new cases occurred in the age group of over 60 years. The age-standardized incidence increased by about 0.8% per year during 2000 to 2016, especially in woman, whose annual increase rate reached 2.1%. The age-standardized mortality rate decreased by about 0.6% per year, with a decrease of 1.3% per year in urban areas and an increase of 2.3% per year in rural areas. The numbers of new cases and deaths increased by 162.6% and 123.6%, respectively, during 2000 to 2016, which can be explained mainly by the change of the age structure.

Conclusions

The burden of lung cancer is serious in China, and increased especially rapidly for women in rural areas. The disease is expected to threaten the lives of more people in the future due to factors such as aging and population growth. Lung cancer prevention and control strategies and resources should be leveraged toward women and rural areas in the future.

Objective

The postoperative survival rates of patients with gastric cancer at different stages treated at the National Cancer Center (NCC) of China have not been reported. Therefore, we evaluated the survival of patients with gastric cancer who underwent surgery at the NCC from 2011 to 2018 to provide baseline information for further studies.

Methods

We identified 7,301 patients with primary gastric carcinoma who underwent surgery at the NCC between January 2011 and May 2018; among these, 5,008 patients were enrolled in this study. Follow up was completed on April 30, 2020. We analyzed the 5-year survival according to the stage, sex, age, and other clinicopathological features.

Results

Five-year survival rates of patients with pTNM stages IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV treated at the NCC were 94.9%, 91.8%, 86.5%, 76.1%, 61.1%, 44.2%, 29.7%, and 8.1%, respectively, which were similar to those reported in Japan during the same period. Five-year survival rates of patients with ypTNM stages I, II, III, and IV were 93.1%, 63.2%, 27.2%, and 0.0%, respectively. In multivariable analysis, age, signet ring cell carcinoma, adjuvant chemotherapy, and degree of differentiation were revealed as important prognostic factors.

Conclusion

The survival rates of patients with gastric cancer treated at the NCC have been significantly improved, reaching the levels of Japan in the same period.

Several guidelines including radiotherapy recommendations exist worldwide for the treatment of small cell lung cancer (SCLC). To evaluate the differences in radiotherapy recommendations we conducted a systematic review. PubMed and the sites of medical societies were searched for SCLC guidelines published in either English, Chinese, or Dutch. This was limited to January 2018 till February 2021 to only include up-to-date recommendations. Data was extracted and compared regarding the guideline's development method and radiotherapy recommendations. Eleven guidelines were identified (PubMed n=4, societies n=7) from Spain (n=1), Canada (n=1), America (n=3), United Kingdom (n=1), the Netherlands (n=1), and China (n=3), respectively. Nine guidelines assessed the strength of evidence (SOE) and specified the strength of recommendation (SOR), although methods were different. The major radiotherapy recommendations are similar although differences exist in thoracic radiotherapy (TRT) dose, time, and volume. Controversial areas are TRT in resected stage I-IIA (pN1), prophylactic cranial irradiation (PCI) in resected as well as unresected stage I-IIA, stereotactic body radiation therapy (SBRT) in unresected stage I-IIA, PCI time, and PCI versus magnetic resonance imaging (MRI) surveillance in stage IV. The existence of several overlapping guidelines for SCLC treatment indicates that guideline development is (unnecessarily) repeated by different organizations or societies. Improvement could be made by better international collaboration to avoid duplicating unnecessary work, which would spare a lot of time and resources. Efforts should be made to work together on controversial or unknown fields.