Special issue “The advance of solid tumor research in China”: 68Ga-PSMA-11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of ⁶⁸Ga-prostate specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) in the detection of primary and metastatic lesions in such patients. We retrospectively analyzed 50 RCC patients who underwent ⁶⁸Ga-PSMA-11 PET/CT from November 2017 to December 2020. We observed a higher median accuracy and tumor-to-background maximum standard uptake value (SUV_max) ratio (TBR) of ⁶⁸Ga-PSMA-11 PET/CT in clear cell RCC (ccRCC; 96.57% and 6.00, respectively) than in non-clear cell RCC (ncRCC; 82.05% and 2.99, respectively). The accuracies in detecting lesions in the renal region, bone, lymph nodes and lungs in ccRCC were 100.00%, 95.00%, 98.08% and 75.00%, respectively, and those in the renal region, bone and lymph nodes in ncRCC were 100.00%, 86.67% and 36.36%, respectively. The median TBRs of the lesions from the above locations were 0.38, 10.96, 6.69 and 13.71, respectively, in ccRCC and 0.13, 4.02 and 0.73, respectively, in ncRCC. The PSMA score evaluated with immunohistochemistry was correlated with the SUV_max (P = .046) in RCC. Higher PSMA scores were observed in ccRCC than in ncRCC (P = .031). ⁶⁸Ga-PSMA-11 PET/CT resulted in changes in clinical management in 12.9% (4/31) of cases because of the discovery of new metastases not detected with conventional imaging. These results indicate that ⁶⁸Ga-PSMA-11 PET/CT is a promising method for the detection of metastatic lesions in ccRCC, especially for those in the bone and lymph nodes.     

Special issue “The advance of solid tumor research in China”: Prediction of Sunitinib efficacy using computed tomography in patients with pancreatic neuroendocrine tumors

Clinically effective methods to predict the efficacy of sunitinib, for patients with metastatic or locally advanced pancreatic neuroendocrine tumors (panNET) are scarce, making precision treatment difficult. This study aimed to develop and validate a computed tomography (CT)-based method to predict the efficacy of sunitinib in patients with panNET. Pretreatment CT images of 171 lesions from 38 patients with panNET were included. CT value ratio (CT value of tumor/CT value of abdominal aorta from the same patient) and radiomics features were extracted for model development. Receiver operating curve (ROC) with area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the proposed model. Tumor shrinkage of >10% at first follow-up after sunitinib treatment was significantly associated with longer progression-free survival (PFS; P < .001) and was used as the major treatment outcome. The CT value ratio could predict tumor shrinkage with AUC of 0.759 (95% confidence interval [CI], 0.685-0.833). We then developed a radiomics signature, which showed significantly higher AUC in training (0.915; 95% CI, 0.866-0.964) and validation (0.770; 95% CI, 0.584-0.956) sets than CT value ratio. DCA also confirmed the clinical utility of the model. Subgroup analysis showed that this radiomics signature had a high accuracy in predicting tumor shrinkage both for primary and metastatic tumors, and for treatment-naive and pretreated tumors. Survival analysis showed that radiomics signature correlated with PFS (P = .020). The proposed radiomics-based model accurately predicted tumor shrinkage and PFS in patients with panNET receiving sunitinib and may help select patients suitable for sunitinib treatment.     

Special issue “The advance of solid tumor research in China”: Real-world clinical outcomes of alectinib for advanced nonsmall-cell lung cancer patients with ALK fusion in China

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced nonsmall-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that “crizotinib pretreatment”, “liver metastasis” and “TP53 co-mutation” were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice.     

Special issue “The advance of solid tumor research in China”: Participants with a family history of cancer have a higher participation rate in low-dose computed tomography for lung cancer screening

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.     

Special issue “The advance of solid tumor research in China”: Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3β/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment.     

Special issue “The advance of solid tumor research in China”: Prognosis prediction for stage II colorectal cancer by fusing computed tomography radiomics and deep-learning features of primary lesions and peripheral lymph nodes

Currently, the prognosis assessment of stage II colorectal cancer (CRC) remains a difficult clinical problem; therefore, more accurate prognostic predictors must be developed. In our study, we developed a prognostic prediction model for stage II CRC by fusing radiomics and deep-learning (DL) features of primary lesions and peripheral lymph nodes (LNs) in computed tomography (CT) scans. First, two CT radiomics models were built using primary lesion and LN image features. Subsequently, an information fusion method was used to build a fusion radiomics model by combining the tumor and LN image features. Furthermore, a transfer learning method was applied to build a deep convolutional neural network (CNN) model. Finally, the prediction scores generated by the radiomics and CNN models were fused to improve the prognosis prediction performance. The disease-free survival (DFS) and overall survival (OS) prediction areas under the curves (AUCs) generated by the fusion model improved to 0.76 ± 0.08 and 0.91 ± 0.05, respectively. These were significantly higher than the AUCs generated by the models using the individual CT radiomics and deep image features. Applying the survival analysis method, the DFS and OS fusion models yielded concordance index (C-index) values of 0.73 and 0.9, respectively. Hence, the combined model exhibited good predictive efficacy; therefore, it could be used for the accurate assessment of the prognosis of stage II CRC patients. Moreover, it could be used to screen out high-risk patients with poor prognoses, and assist in the formulation of clinical treatment decisions in a timely manner to achieve precision medicine.