2023年 · 第01卷第01期

Background: Postoperative radiotherapy after conservative surgery for patients with breast cancer usually includes focal over-irradiation (boost) to the surgical bed (SB). Irradiation planning using computed tomography (CT) is difficult in many cases because of insufficient intrinsic soft tissue contrast. To ensure appropriate radiation to the tumor, large boost volumes are delineated, resulting in a higher dose to the normal tissue. Magnetic resonance imaging (MRI) provides superior soft tissue contrast than CT and can better differentiate between normal tissue and the SB. However, for SB delineation CT images alone remain the pathway followed in patients undergoing breast irradiation. This study aimed to evaluate the potential advantages in boost dosimetry by using MRI and CT as pre-treatment imaging. Methods: Eighteen boost volumes were drawn on CT and MRI and elastically co-registered using commercial image registration software. The radiotherapy treatment plan was optimized using the CT volumes as the baseline. The dose distributions of the target volumes on CT and MRI were compared using dose-volume histogram cutoff points. Results: The radiation volumes to the SB varied considerably between CT and MRI (conformity index between 0.24 and 0.67). The differences between the MRI and CT boost doses in terms of the volume receiving 98% of the prescribed dose (V98%) varied between 10% and 30%. Smaller differences in the V98% were observed when the boost volumes were delineated using MRI. Conclusion: Using MRI to delineate the volume of the SB may increase the accuracy of boost dosimetry.

Background: Small cell lung cancer (SCLC) is a highly malignant and aggressive neuroendocrine tumor. With the rise of immunotherapy, it has provided a new direction for SCLC. However, due to the lack of prognostic biomarkers, the median overall survival of SCLC is still to be improved. This study aimed to explore novel biomarkers and tumor-infiltrating immune cell characteristics that may serve as potential diagnostic and prognostic markers in SCLC. Methods: Gene expression profiles from patients with SCLC were downloaded from the Gene Expression Omnibus (GEO) database, and tumor microenvironment (TME) infiltration profile data were obtained using CIBERSORT. The robust rank aggregation (RRA) method was utilized to integrate three SCLC microarray datasets downloaded from the GEO database and identify robust differentially expressed genes (DEGs) between normal and tumor tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the functions of the robust DEGs. Subsequently, protein-protein interaction networks and key modules were constructed by Cytoscape, and hub genes were selected from the whole network using the plugin cytoHubba. Survival analysis of hub genes was performed by Kaplan-Meier plotter in 18 patients with extensive-stage SCLC. Results: A total of 312 robust DEGs, including 55 upregulated and 257 downregulated genes, were screened from 129 SCLC tissue samples and 44 normal tissue samples. GO and KEGG enrichment analyses revealed that the robust DEGs were predominantly involved in human T-cell leukemia virus 1 infection, focal adhesion, complement and coagulation cascades, tumor necrosis factor (TNF) signaling pathway, and ECM-receptor interaction, which are closely associated with the development and progression of SCLC. Subsequently, three DEGs modules and six hub genes (ITGA10, DUSP12, PTGS2, FOS, TGFBR2, and ICAM1) were identified through screening with the Cytoscape plugins MCODE and cytoHubba, respectively. Immune cell infiltration analysis by the CIBERSORT algorithm revealed that resting memory CD4+ T cells were the predominant infiltrating immune cells in SCLC. In addition, Kaplan-Meier plotter revealed that the gene prostaglandin-endoperoxide synthase 2 (PTGS2) was a potential prognostic biomarker of SCLC. Conclusions: Hub genes and tumor-infiltrating immune cells may be the molecular mechanisms underlying the development of SCLC, and this finding could contribute to the formulation of individualized immunotherapy strategies for SCLC.

Background: Several prognostic biomarkers have been validated for acute myeloid leukemia (AML), a heterogeneous hematopoietic malignancy. However, the factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in real-world patients with AML have not been well defined. Methods: This study examined clinical and mutational data of 246 patients with newly diagnosed AML who received the traditional "3 + 7" regimen in PLA General Hospital from January 2008 to August 2020. Factors associated with CIR and LFS in patients newly diagnosed with AML were analyzed using next-generation sequencing. Results: Additional sex combs-like 1 (ASXL1) and Serine/arginine-rich splicing factor 2 (SRSF2) mutations were found to be associated with an increased risk of CIR and a reduced LFS in univariate analysis, while only SRSF2 mutations were associated with these factors in the multivariate analysis. Hyperleukocytosis maintained an independent effect on LFS in the multivariate analysis. Hematopoietic stem cell transplantation conferred a significant prognostic benefit on both CIR and LFS in our cohort. Furthermore, we validated the risk classification of patients with AML receiving traditional induction regimens across a broad age range. Based on next-generation sequencing results, we concluded that SRSF2 mutations were predictive of an increased risk of relapse, inferior LFS rates, and non-relapse mortality in patients with newly diagnosed AML. Conclusion: These findings indicate that patients with SRSF2 mutations might not benefit from the conventional "3 + 7" regimen. Our results may help in developing molecular stratification strategies and could guide treatment decisions for patients with newly diagnosed AML.

Background: Rituximab combined with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) regimen has improved the survival of diffuse large B-cell lymphoma (DLBCL) patients worldwide, compared with CHOP alone. Several limitations were seen in previous studies of Chinese DLBCL patients treated with R-CHOP or R-CHOP-like regimens. This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment. Methods: Clinical data were collected from DLBCL patients who received frontline R-CHOP or R-CHOP-like regimens at the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS) between January 1, 2005, and December 31, 2018. The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis of progression-free survival (PFS) and overall survival (OS) was performed using Cox proportional hazard regression. Results: Overall, 1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study. As of April 30, 2022, the median follow-up period for the CHCAMS group was 87.3 (range: 0.5-195.4) months. For the CHCAMS group, the 5-year PFS and OS rates were 61.7% (95% confidence interval [CI]: 58.8-64.7%) and 70.6% (95% CI: 67.8-73.4%), respectively. For the SEER group, the 5-year OS rate was 66.5% (95% CI: 65.0-68.0%), which was inferior to that of the CHCAMS group (P < 0.001). After adjusting for clinical factors and treatment, no significant difference was observed in the OS between the CHCAMS and SEER groups (P= 0.867). In the CHCAMS group, multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score ≥2, presence of B symptoms, Ann Arbor stage III-IV, elevated serum β2-microglobulin levels, and bulky mass were independent adverse prognostic factors affecting PFS and OS (P < 0.05). Additionally, patients aged over 60 years, elevated lactate dehydrogenase levels, and more than two extranodal sites were independent adverse prognostic factors for OS (P < 0.05). Local radiotherapy was significantly associated with better PFS (P < 0.001) and OS (P = 0.001). Conclusion: After adjusting for clinical and treatment-related factors, no significant difference was observed in the 5-year OS rate between Chinese DLBCL patients treated with standard first-line treatment and those from the SEER database.

Background: Freehand transperineal prostate biopsy (TPPBx) using a coaxial needle technique offers an alternative to probe-mounted freehand or template-guided techniques in the diagnosis of prostate cancer (PCa). It only requires the same equipment used for transrectal ultrasound-guided (TRUS) biopsy. Our study is the first in Malaysia to report this experience and its outcomes. We aim to determine PCa detection rate and pain tolerability of freehand TPPBx utilizing a coaxial needle under local anesthesia (LA). Methods: Institutional review board approval was obtained from National Medical Research Register (NMRR ID-21-02052-VIL). We retrospectively reviewed the medical records of patients who underwent TPPBx between August 2020 and April 2022. Records were reviewed for patients’ characteristics, prostate volume, prostate-specific antigen (PSA) results, biopsy results and pain tolerability. Data was analyzed to determine PCa and clinically significant prostate cancer (csPCa) detection rate. LA was achieved using perineal skin infiltration and a periprostatic nerve block. The commonly used standard side-firing transrectal ultrasound with its Prostate Biplane Transducer was used as an imaging guide. The principles of the Ginsburg protocol were followed. Pain tolerability was assessed using a visual analog scale. Results: A total of 55 patients with elevated PSA levels underwent freehand TPPBx under LA. The mean age was 67.3 years, the median PSA was 14.2 ng/mL, and the median PSA density (PSAD) was 0.33 ng/mL/cc. The optimal PSAD cutoff for predicting csPCa was 0.35 ng/mL/cc (area under the curve [AUC], 0.792; sensitivity, 87.5%; specificity, 69.2%). PCa was detected in 24 patients (43.6%), of whom 16 (29.1%) had csPCa. The median pain scores during LA infiltration and biopsy were four and two, respectively, which were significant different (P < 0.05). TPPBx exhibited an infection rate of zero. Conclusion: The PCa detection rate and patient tolerability of freehand TPPBx using a coaxial needle are similar to those of a contemporary published series. The use of existing equipment that is used for TRUS biopsy allows for widespread use and transition from TRUS biopsy.

Background: Autologous hematopoietic stem cell (HSC) transplantation remains the recommended treatment for eligible patients with multiple myeloma (MM). Increasing the number of transplanted CD34+ cells shorten the time to hematopoietic reconstitution and increases the overall survival of patients. With the harvest of a sufficient CD34+ cell number being crucial, this study aimed to predict the factors that affect stem cell collection. Methods: We conducted a retrospective study of 110 patients who were newly diagnosed with MM and underwent autologous HSC collection at Beijing Jishuitan Hospital between March 2016 and July 2022. Multiple factors were analyzed using the Mann-Whitney U tests for between-group comparisons. Differences were considered statistically significant at P < 0.05. Results: We found that patient age affected stem cell collection significantly; for patients younger than 55 years, the number of CD34+ cells harvested may be ≥ 2 × 106/L, is unlikely to reach 5 × 106/L. Platelet count at initial mobilization was a predictor of the number of CD34+ cells collected. Collection may fail when the platelet count at initial mobilization is below 177 × 109/L and may be excellent when it is higher than 199 × 109/L. Conclusions: This finding could guide us to predict the approximate number of CD34+ cells collected in advance during autologous transplant mobilization for MM and to decide in advance whether to apply plerixafor to improve the number of HSCs collected.

Background: A hepatic adverse event (HAE) is defined as a liver injury that occurs following immune checkpoint inhibitor (ICI) administration in oncology Patients. Immune-mediated hepatotoxicity (IMH) is a type of HAE directly caused by ICI and is associated with immune system hyperactivation. HAE incidence varies across different clinical studies. This study aimed to explore the risk factors of HAE and establish a personalized IMH treatment strategy. Methods: Randomized controlled trials (RCTs) on ICIs and case reports related to IMH were collected and summarized separately. Meta-analysis was performed using Review Manager (version 5.0), whereas correlation analysis and linear regression were performed using SPSS (version 24.0) to evaluate any correlations between the two variables. Results: Overall, 36 RCTs containing 18,515 patients and 39 case reports met our inclusion criteria. The ICI administration increased the HAE risk (risk ratio [RR] = 1.40) as well as severe HAE (RR = 2.55). The overall HAE incidence and severe incidence were about 15.3% and 4.3%, respectively. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors have a higher incidence of HAE than programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. Finally, we found a positive correlation between the onset time of IMH and the recovery time of liver injury. Conclusions: ICI administration increased the incidence risk of HAE, especially in patients treated with CTLA-4 inhibitors. Regarding IMH treatment, the glucocorticoid dosage must be individually reduced according to the severity and onset time of HAE.

Small cell lung cancer (SCLC) is a highly aggressive tumor type for which limited therapeutic progress has been made. Platinum-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment, but most patients with SCLC acquire therapeutic resistance. Given the need for more effective therapies, better elucidation of the molecular pathogenesis of SCLC is imperative. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid tumors. This pathway is an important regulator of cancer cell glucose metabolism, and its activation probably effects radioresistance by influencing bioenergetic processes in SCLC. Glucose metabolism has three main branches—aerobic glycolysis, oxidative phosphorylation, and the pentose phosphate pathway—involved in radioresistance. The interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1 (HIF-1) signaling. The PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radio-resistance, including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate pathway. This review summarizes our understanding of links among the PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.

Even today, lung cancer remains one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Throughout the past decades, remarkable advances have been made in the research and development of anti-lung cancer drugs in China. Since the first registered Chinese clinical trial on May 2, 2006, many potent anti-lung cancer drugs have been developed and approved by the China Food and Drug Administration and the National Medical Product Administration of China. Among them, the most advance were observed in the development of targeted agents and immunotherapeutic agents such as epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) icotinib, aumolertinib, and furmonertinib, anaplastic lymphoma kinase (ALK)-TKI ensartinib, programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) camrelizumab, sintilimab, and tislelizumab, and programmed cell death-ligand 1 (PD-L1) mAb sugemalimab, which have made huge breakthrough in recent years. Some other investigational innovative drug also demonstrated promising efficacy and acceptable safety profiles. Results from clinical studies on these China innovative drugs have led to changes in clinical practice guidelines and considerably improved the outcomes for patients with lung cancer. Thus, in this review, we aim to provide further insight into the clinical development and achievement of China innovative anti-lung cancer drugs.

The adaptive arm of the immune system is crucial for appropriate antitumor immune responses. It is generally accepted that clusters of differentiation 4+ (CD4+) T cells, which mediate T helper (Th) 1 immunity (type 1 immunity), are the primary Th cell subtype associated with tumor elimination. In this review, we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans, with a focus on Th2 cells. The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the (1) site of tumor development, (2) tumor properties (i. e., tumor metabolism and cytokine receptor expression), and (3) type of immune response that the tumor initially escaped. Therefore, we discuss how low-tolerance organs, such as lungs and brains, might benefit from a less tissue-destructive immune response mediated by Th2 cells. In addition, Th2 cells antitumor effects can be independent of CD8+ T cells, which would circumvent some of the immune escape mechanisms that tumor cells possess, like low expression of major histocompatibility-I (MHC-I). Finally, this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.