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Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with a predisposition to a variety of cancers. Previous studies that have evaluated the cancer spectrum and risk of this rare disease have primarily been based on small data sets or heterogeneous cohorts from different countries. Here, we report the results of a large homogeneous cohort of Chinese PJS patients who were followed prospectively from 2006 to July 2021, and clinical data before 2006 were retrospectively collected. A total of 412 PJS patients (56.55% males) from 208 families were enrolled, contributing 12,798 person-years of follow-up. A total of 113 cancers were diagnosed in 109 patients (26.46%). The median age at the first cancer diagnosis was 40 years. In particular, patients born after the 1980s were diagnosed with cancer at an earlier median age of 30.5 years. The cumulative cancer risk was sharply increased to 30.9% at age 40 years; this high cancer risk age was 10 years earlier than that reported in previous Western studies, and increased to 76.2% at an age of 60 years. The most common cancer was gastrointestinal (GI) cancer (64.6%), in which colorectal cancer constituted a significantly larger proportional distribution (32.74%), when compared with previous investigations (11.1%−20.83%). There was some evidence that overrepresentation point variants in domain XI of STK11 may be associated with GI cancers. Furthermore, the incidences of gynecological and lung cancers were second only to that of GI cancer in this cohort. These results may provide novel insight for justifying surveillance to detect cancers at an earlier phase to improve clinical outcomes. Furthermore, the potential STK11 genotype-phenotype association could be the basis for future genetic counseling.

BackgroundTislelizumab combined with radiotherapy as a salvage treatment for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC) is not reported. This study aimed to describe a protocol to evaluate the safety and efficacy of multisite radiotherapy combined with tislelizumab as a salvage therapy for mCRPC in patients who had at least one second-line treatment failure.MethodsThe study included patients with mCRPC who had at least one lesion suitable for radiotherapy and failed androgen deprivation therapy (ADT), followed by at least one novel second-line endocrine therapy. All patients received tislelizumab monotherapy induction therapy for two cycles, then combined with multisite radiotherapy for one cycle, followed by tislelizumab maintenance therapy, until either disease progressed or the patient developed unacceptable toxicity. Radiation methods and lesions were individually selected according to the specified protocol. Primary endpoints included safety and objective response rate. Secondary endpoints included prostate-specific antigen (PSA) response rate, disease control rate, overall survival, radiographic progression-free survival (rPFS), and biochemical progression-free survival (bPFS). Furthermore, the exploratory endpoints included the identification of the predictive biomarkers and exploration of the correlation between biomarkers and the tumor response to the combined regimen.DiscussionThis study included three treatment stages to evaluate the efficacy of immunotherapy and the combination of immunotherapy and radiotherapy for patients with mCRPC who have had at least second-line treatment failure. Additionally, radiation-related and immune-related early and late toxicities were determined, respectively. Furthermore, the study also aimed to identify the predictive biomarkers associated with immunotherapy for treating mCRPC.Trial Registrationhttps://www.chictr.org.cn/showproj.aspx?proj=126359, identifier ChiCTR2100046212.

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

BackgroundSignet ring cell containing gastric cancer (SRCGC) is a rare subtype of gastric cancer, and its adjuvant therapy is based on general gastric cancer. However, the effectiveness of radiotherapy for those SRCGC patients remains unknown.PurposeThe purpose of the study was to analyze whether the addition of radiotherapy to adjuvant chemotherapy (CT) can benefit survival in resected SRCGC patients.MethodsPatients with SRCGC, who underwent D2 gastrectomy followed by adjuvant chemotherapy or chemoradiotherapy (CRT), were retrospectively collected. According to the proportion of signet ring cells, patients were histologically classified as pure SRCGC (pSRCGC) containing 100% of signet ring cells, mixed SRCGC (mSRCGC) containing >50% of signet ring cells, and contaminated SRCGC (cSRCGC) containing

ObjectivesTo develop and validate predictive nomograms of cancer specific survival (CSS) and overall survival (OS) for synchronous colon cancer with liver metastasis (SCLM) patients.MethodsPatients with pathologically diagnosed colon cancer with liver metastasis were retrieved from the SEER database between 2010 and 2015. Only SCLM patients were included. Univariate and multivariate cox regression analyses were conducted to identify the potential predictors of patients’ survival outcomes. The selected variables were integrated to create predictive nomograms via R tools. Furthermore, the concordance index Harrell’s C statistic (C-index) was calculated to describe the discrimination of nomograms. Calibration (1000 bootstrap resamples) curves were plotted to compare the predictions of nomograms with the observed outcomes. Decision curve analysis (DCA) and clinical impact curves were performed to evaluate the clinical effects of nomograms.ResultsA total of 22,378 SCLM patients were included. The median time of OS and CSS was 13 and 17 months, respectively. The 1-, 2-, and 3-year rate of OS was 50.6, 28.1, and 14.8%, respectively. While the 1-, 2-, and 3-year rate of CSS was 58.7, 36.8, and 22.5%, respectively. SCLM patients with increased age, left primary tumor location, AJCC IVb stage, and no chemotherapy were associated with an obviously reduced OS and CSS. Variables including age, histological grade, T/N/M stage, tumor size, bone/lung metastasis, CEA, surgery of primary site, and chemotherapy were closely related to the prognoses of SCLM patients. Nomograms of OS and CSS were built and displayed online for convenient utilization. The C-index of OS and CSS monograms were 0.74 and 0.73, respectively, indicating relatively good discrimination of the nomograms. The calibration curves suggested a good agreement between the actual observation and the nomogram prediction. DCAs and clinical impact curves reflected favorable potential clinical effects of predictive nomograms.ConclusionChemotherapy, surgery of primary site, and age were important independent risk factors for the CSS and OS of SCLM patients. We built and validated two reliable nomograms of OS and CSS to predict the prognoses of SCLM patients, which can be accessed online at (https://predictive-tool.shinyapps.io/CSS-DynNomapp/; https://predictive-tool.shinyapps.io/OS-DynNomapp/).

Human epidermal growth factor receptor 2 (HER2) has been verified as a valuable biomarker and treatment target in metastatic colorectal cancer (mCRC). Pyrotinib, a novel irreversible HER2/epidermal growth factor receptor (EGFR) dual tyrosine kinase inhibitor, can efficiently inhibit the proliferation of HER2-positive cancer cells in many tumors. We report a case of a 40-year-old woman with both HER2- and EGFR-amplified metastatic colon cancer, who developed refractory disease resistant to multiline therapies (including trastuzumab with lapatinib) but achieved a remarkable response after pyrotinib treatment. For patients with HER2-positive mCRC, who have developed resistance to trastuzumab and lapatinib, pyrotinib is a promising new candidate, which can be used as salvage therapy.

ObjectiveTo review our single-institution experience in the surgical management of foramen magnum tumors via a far-lateral approach using an oblique straight incision.MethodsFrom October 2023 to January 2024, four cases of tumors in the foramen magnum area treated at the Capital Medical University-affiliated XuanWu hospital neurosurgery department were involved in this study. All cases were managed with a far-lateral approach using an oblique straight incision. We retrospectively reviewed the clinical and imaging data, as well as the surgical strategies employed.ResultsThree cases of foramen magnum meningiomas and one case of glioma of the ventral medulla. All cases underwent a far-lateral approach using an oblique straight incision; all cases had a gross total resection, and the wounds healed well without cerebral fluid leakage or scalp hydrops. Except for one case of right foramen magnum meningioma, which had dysphagia and pneumothorax, the other cases were without any postoperative complications.ConclusionA far-lateral approach using an oblique straight incision can preserve muscle integrity and minimize subcutaneous exposure, allowing for complete anatomical reduction of muscles. This craniectomy method is simple and replicable, making it worthy of further clinical practice.

The occurrence and development of cancer are closely related to the immune escape of tumor cells and immune tolerance. Unlike previous surgical, chemotherapy, radiotherapy and targeted therapy, tumor immunotherapy is a therapeutic strategy that uses various means to stimulate and enhance the immune function of the body, and ultimately achieves the goal of controlling tumor cells.With the in-depth understanding of tumor immune escape mechanism and tumor microenvironment, and the in-depth study of tumor immunotherapy, immune checkpoint inhibitors represented by Programmed Death 1/Programmed cell Death-Ligand 1(PD-1/PD-L1) inhibitors are becoming increasingly significant in cancer medication treatment. employ a variety of ways to avoid detection by the immune system, a single strategy is not more effective in overcoming tumor immune evasion and metastasis. Combining different immune agents or other drugs can effectively address situations where immunotherapy is not efficacious, thereby increasing the chances of success and alternative access to alternative immunotherapy. Immune combination therapies for cancer have become a hot topic in cancer treatment today. In this paper, several combination therapeutic modalities of PD1/PD-L1 inhibitors are systematically reviewed. Finally, an analysis and outlook are provided in the context of the recent advances in combination therapy with PD1/PD-L1 inhibitors and the pressing issues in this field.

Gliomas exhibit high intra-tumoral histological and molecular heterogeneity. Introducing stereotactic biopsy, we achieved a superior molecular analysis of glioma using O-(2-18F-fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI). Patients underwent simultaneous DWI and FET-PET scans. Correlations between biopsy-derived tumor tissue values, such as the tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC)/exponential ADC (eADC) and histopathological diagnoses and those between relevant genes and TBR and ADC values were determined. Tumor regions with human telomerase reverse transcriptase (hTERT) mutation had higher TBR and lower ADC values. Tumor protein P53 mutation correlated with lower TBR and higher ADC values. α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX) correlated with higher ADC values. 1p/19q codeletion and epidermal growth factor receptor (EGFR) mutations correlated with lower ADC values. Isocitrate dehydrogenase 1 (IDH1) mutations correlated with higher TBRmean values. No correlation existed between TBRmax/TBRmean/ADC/eADC values and phosphatase and tensin homolog mutations (PTEN) or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Furthermore, TBR/ADC combination had a higher diagnostic accuracy than each single imaging method for high-grade and IDH1-, hTERT-, and EGFR-mutated gliomas. This is the first study establishing the accurate diagnostic criteria for glioma based on FET-PET and DWI.

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 03423992

The metabolic reprogramming of cancer tissue has higher metabolic activity than surrounding tissues. At the same time, the local infiltration of immunosuppressive cells is also significantly increased, resulting in a significant decrease in tumor immunity. During the progression of cancer cells, immunosuppressive tumor microenvironment is formed around the tumor due to their metabolic reprogramming. In addition, it is the changes in metabolic patterns that make tumor cells resistant to certain drugs, impeding cancer treatment. This article reviews the mechanisms of immune escape caused by metabolic reprogramming, and aims to provide new ideas for clinical tumor immunotherapy combined with metabolic intervention for tumor treatment.

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

Background and PurposeWe investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC.Materials and MethodsThis was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan–Meier method and compared by the log-rank test.ResultsPatients were classified into three groups: HER2-negative (HER2−; n = 547), HER2-positve with trastuzumab (HER2+ + T; n = 136), and HER2-positive without trastuzumab (HER2+ − T; n = 110). The HER2+ + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2+ − T group (P .05). Different annual LRR patterns was found among groups according to HR status.ConclusionTrastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC.

PurposeTo investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer.Patients and MethodsWe retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat.ResultsThe median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes.ConclusionFor women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes.