Journal of the National Cancer Center最新文献

Background

The target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC.

Methods

All ES-SCLC patients without initial brain metastases who completed ≥ 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT.

Results

A total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9–39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1–11.2 months) and 16.2 months (IQR, 9.9–24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without synchronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12–0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13–1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred.

Conclusion

Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly improve local control in ES-SCLC.

Esophageal cancer (EC) is particularly common in China. With the continuing progress of multi-disciplinary therapy including early screening, minimally invasive techniques, radiotherapy and chemotherapy, the 5-year survival of EC has been improved in China. However, there are considerable disparities in the diagnosis and treatment quality among different regions. The Esophageal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) considers a set of authoritative quality control standards as an opportunity to eliminate the disparities and improve the overall survival and quality of life of EC. To further promote the quality control for standardized diagnosis and treatment of EC, the National Cancer Center commissioned the Esophageal Cancer Quality Control Expert Committee to draft and formulate the Chinese Quality Control Indices for Standardized Diagnosis and Treatment of Esophageal Cancer (2022 edition). The Indices includes 21 items that cover all key areas in the diagnosis and treatment of esophageal cancer, such as medical oncology, radiation oncology, endoscopy, and pathology.

Background

Human epidermal growth factor receptor 2 (HER2) overexpression is related to anti-HER2 therapy in many tumors. RC48- antibody-drug conjugate (ADC) has shown promising efficacy in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC). The characteristic expression and scoring systems of HER2 are nonexistent in UC. We aimed to explore HER2 status and its correlation with the efficacy of HER2-targeting ADC therapy in UC.

Methods

A total of 137 and 43 patients were enrolled in cohort 1 and cohort 2, respectively, from March 2009 to December 2018. The patients in cohort 2 were enrolled in a phase II study of RC48-ADC. UC samples were tested for HER2 status using immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The 2018 ASCO/CAP HER2 scoring system was adopted and modified to score HER2 expression in UC.

Results

The HER2-positive (IHC 2+ or 3+) rate was 24.1% (33/137). In HER2 IHC 2+ or 3+ patients, the HER2 gene amplification rate was 31% (13/42). The objective response rates (ORRs) in RC48-ADC-treated patients with IHC 3+, IHC 2+ and FISH+, IHC 2+ and FISH- were 58.8%, 66.7% and 40%, respectively. The ORR showed a trend toward a better benefit for RC48-ADC therapy in patients with HER2 amplification than in those without amplification (61.5% vs. 44.8%, P = 0.059). The heterogeneity of HER2 expression in the primary tumor was 55.5% (15/27), and the ORR was not significantly different between patients with tumor heterogeneity and homogeneity.

Conclusions

IHC testing should be performed to assess the HER2 status before the initiation of HER2-ADC therapy. There was a trend toward a better benefit for patients with HER2 amplification, and tumor heterogeneity did not influence the drug efficacy.

For many cancers a primary cause of poor survival is that they are detected at a late stage when therapies are less effective. Although screening methods exist to detect some types of cancer at an early stage, there are currently no effective methods to screen for most types of cancer. Biomarkers have the potential to improve detection of early-stage cancers, risk stratification, and prediction of which pre-cancerous lesions are likely to progress and to make screening tests less invasive. Although thousands of research articles on biomarkers for early detection are published every year, few of these biomarkers have been validated and shown to be clinically useful. This reflects both the inherent difficulty in detecting early-stage cancers and a disconnect between the process of discovering biomarkers and their use in the clinic. To overcome this limitation the US National Cancer Institute created the Early Detection Research Network. It is a highly collaborative program that brings together biomarker discoverers, assay developers, and clinicians. It provides an infrastructure that is essential for developing and validating biomarkers and imaging methods for early cancer detection and has successfully completed several multicenter validation studies.

With the advancement of anticancer therapy, there is increasing interest in understanding the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) play a pivotal role in the TME and have been the focus of much research in recent years. CAFs play an active role in cancer progression through complex interactions with other cells in the TME, releasing regulatory factors, synthesizing and remodeling the extracellular matrix. However, research on the role of CAFs in renal cell carcinoma (RCC) is still in its nascent stages. Here, we describe the origins and subgroups of CAFs, the roles of CAFs in the development and progression of RCC, the impact of CAFs on RCC prognosis, and the potential of CAFs as treatment targets in RCC. By analyzing CAF subsets, biomarkers, and targeted therapies, we present the significance and contribution of CAFs in RCC research. Furthermore, we highlight the distinct contribution of CAFs in advanced RCC through horizontal comparison with other cancers. This paper provides a comprehensive perspective of recent and foundational studies on the role of CAFs in RCC and other types of cancers and new insights for further study of CAFs in RCC.

Modern day survivorship from childhood malignancies is estimated to be over 80%. However, central nervous system tumors remain the leading cause of cancer mortality in children and is the most common solid tumor in this population. Improved survivorship is, in part, a result of improved multidisciplinary care, often with a combination of surgery, radiation therapy, and systemic therapy. With improved survival, long term effects of treatment and quality of life impacts have been recognized and pose a challenge to maximize the therapeutic ratio of treatment. It has been increasingly more apparent that precise risk stratification, such as with the inclusion of molecular classification, is instrumental in efforts to tailor radiotherapy for appropriate treatment, generally towards de-intensification for this vulnerable patient population. In addition, advances in radiotherapy techniques have allowed greater conformality and accuracy of treatment for those who do require radiotherapy for tumor control. Ongoing efforts to tailor radiotherapy, including de-escalation, omission, or intensification of radiotherapy, continue to improve as increasing insight into tumor heterogeneity is recognized, coupled with advances in precision medicine employing novel molecularly-targeted therapeutics.

Objective

To deliver a comprehensive picture of the landscape and changing trend of trials and approvals on targeted anticancer drugs in China from 2012 to 2021.

Methods

Trials, investigated products, and listed drugs were acquired from national databases. The status quo, changing trend of absolute number, and proportion of targeted trials, products, and drugs, as well as the corresponding difference between domestic and foreign companies were analyzed.

Results

A total of 2,632 trials on 1,167 targeted antitumor drugs were identified, accounting for 81.5% of all registered trials. The number and proportion of trials on targeted drugs increased steadily, with an average growth rate of 36.0% and 6.2%, respectively. A similar growth trend was observed in the number (33.7%) and proportion (13.8%) of targeted drugs. Targeted drugs and trials owned by domestic companies accounted for a higher proportion than that by foreign companies (80.5% vs. 19.5%; 83.2% vs. 16.8%, respectively), and the growing trend for both targeted drugs (13.8% vs. 5.7%) and trials (13.8% vs. 33.7%) owned by domestic companies was faster. The proportion of targeted drug trials (80.5% vs. 85.6%) and multicenter trials (6.0% vs. 69.9%) initiated by domestic companies was lower than that by foreign companies, with the gap gradually narrowing. Among the identified 18 targets of the 126 immune drugs under development, only one globally new target was found.

Conclusions

Research and development of targeted antitumor drugs in China are booming and advancing rapidly, and domestic enterprises have become the pillar. Encouraging genomics activities and establishing incentives and public–private collaboration frameworks are crucial for innovation-oriented drug development in China.

Objectives

To investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients.

Methods

In this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon–Mann–Whitney test. Overall survival (OS) was estimated using the Kaplan–Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS.

Results

The data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70–3.47]; P < 0.001) or three-dimensional radiotherapy (3DRT; HR, 1.45 [95% CI, 1.14–1.84]; P = 0.003) had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO. Of the 716 (23.4%) long-term survivors who completed the HRQL questionnaire, nearly 70% patients were still able to swallow normally or almost normally, and >80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life.

Conclusions

This large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Background

Whether minimally invasive esophagectomy (MIE) is superior to open esophagectomy (OE) in the treatment of esophageal squamous cell carcinoma (ESCC) is still uncertain. Therefore, this multicenter prospective study aimed to compare MIE with OE in postoperative parameters and long-term survival.

Methods

All hospitalized patients with cT1b-3N0–1M0 thoracic ESCC treated by MIE or OE were enrolled from 19 selected centers from April 1, 2015 to December 31, 2018. The propensity score matching (PSM) was performed to minimize the selection bias. The basic clinicopathological characteristics and 3-year overall survival (OS) as well as disease-free survival (DFS) of two groups were compared by R version 3.6.2.

Results

MIE were performed in 1,387 patients and OE in 335 patients. 335 cases in each group were finally matched by PSM, and no significant differences in the essential demographic characteristics were observed between the MIE and OE groups after PSM. Compared with OE, MIE had significantly less intraoperative bleeding, less total drainage volume, shorter postoperative hospital stay, and harvested significantly more lymph nodes (LNs) (all P < 0.001). There were no significant differences in the major postoperative complications and death rates between MIE and OE. The 3-year OS and DFS were 77.0% and 68.1% in the MIE group versus 69.3% and 60.9% in the OE group (OS: P = 0.03; DFS: P = 0.09), and the rates were 75.1% and 66.5% in the MIE group versus 66.9% and 58.6% in the OE group for stage cII patients (OS: P = 0.04, DFS: P = 0.09), respectively.

Conclusions

Compared with OE, MIE is a safe and effective treatment approach with similar mortality and morbidity. It has the advantages in harvesting more LNs, improving postoperative recovery and survival of stage cII ESCC patients.