Fudan University Shanghai Cancer Center Research Articles

Impact of a Quantitative Early Activity Program on Gastrointestinal Function Following Laparoscopic Pancreaticoduodenectomy: A Single-Center Retrospective Analysis.

The objective of this study is to assess the impact of a quantitative early activity program, integrated into the Enhanced Recovery After Surgery (ERAS) protocol on gastrointestinal function in patients undergoing laparoscopic pancreatoduodenectomy (LPD). Perioperative data from 203 patients who underwent LPD at the Department of Comprehensive Treatment of Pancreatic Cancer, Fudan University Shanghai Cancer Center, between January 2021 and December 2022 were analyzed retrospectively. The patients were categorized into 2 groups based on their nursing plans. Group A received the standard perioperative ERAS nursing plan, while group B followed the ERAS plan supplemented with a quantitative early activity program. We assessed postoperative outcomes including bowel sound recovery time, time to first anal exhaust, time to first mobilization, activity compliance 1-week postsurgery, and incidence of postoperative breakthrough pain. We compared several postoperative metrics between group A and group B. Specifically, the time to bowel sound recovery was 62.39±17.89 hours in group A versus 56.45±22.85 hours in group B. The time to first anal exhaust was 78.88±71.99 hours in group A compared with 63.62±24.73 hours in group B. The time to first mobilization was 56.98±18.66 hours in group A versus 49.85±20.48 hours in group B. In addition, activity compliance 1-week postsurgery and the incidence of postoperative breakthrough pain (1.55±2.01 times in group A vs. 0.94±1.16 times in group B) were also compared. All these differences were statistically significant (P<0.05). Conversely, the incidence of postoperative complications and the length of hospital stay (11.20±5.69d in group A vs. 12.47±6.67d in group B) did not reveal any significant differences (P>0.05). The quantitative early activity program for LPD, based on the ERAS protocol, enhances the adherence to postoperative activity and decreases the incidence of breakthrough pain, thereby facilitating gastrointestinal function recovery in patients. This approach merits clinical adoption.

Protocol for a multicentre, prospective, open-label, randomised controlled trial to compare PROs and safety outcomes between preoperative and postmastectomy radiotherapy in locally advanced breast cancer patients with immediate reconstruction via a deep inferior epigastric perforator flap (CAPPELLA) in China

IntroductionDespite its therapeutic advantages, postmastectomy radiotherapy (PMRT) increases the risk of complications and often leads to poor cosmesis in women undergoing breast reconstruction. Preoperative radiotherapy followed by skin-sparing mastectomy and...

Prevalence of Insomnia and Related Factors Among Cancer Outpatients in China.

The incidence of insomnia in cancer patients is significantly higher than in the general population. Chronic insomnia imposes pronounced physical and psychological burdens on cancer patients, affecting their quality of life and survival rate. This study aims to investigate insomnia in cancer patients and further analyze potentially related factors. Oncology outpatients treated at Fudan University Shanghai Cancer Center were consecutively recruited. Demographic information and clinical features, such as type of cancer and treatment status, were collected. Insomnia was assessed using the Insomnia Severity Index (ISI). A total of 146 patients participated in the study, with the majority suffering from breast tumors (40.4%), gastrointestinal tract tumors (18.5%), and endocrine tumors (5.8%). Among these patients, 25 (17.1%) did not report insomnia, 69 (47.3%) had subclinical insomnia, and 52 (35.6%) reached the level of clinical insomnia. Older patients aged 41-50 years (Estimate = -3.49, 95% CI, -6.99 to 0.00, p = 0.05) and those with higher education levels (Estimate = -2.72, 95% CI, -4.88 to -0.55, p = 0.01) were less likely to have higher ISI total scores. In contrast, undergoing chemotherapy (Estimate = 3.86, 95% CI, 0.53 to 7.19, p = 0.02) was associated with higher ISI total scores. Gender, age, education, treatment modalities correlated with ISI subitem scores. The prevalence of insomnia is higher in oncology patients and is associated with gender, age, education, tumor type, and treatment modality. Screening and interventions for insomnia should be emphasized in the whole-course management of oncology patients.

Psychological distress in biliary tract malignancy patients: influencing factors and development of a predictive nomogram model.

This study aims to investigate the psychological distress and its influencing factors in patients with biliary tract malignant tumors, alongside the development of a predictive model. A total of 219 patients diagnosed with biliary tract malignant tumors who were admitted to the Department of Liver Surgery at Fudan University Shanghai Cancer Center from July 2021 to May 2023, were selected using a convenience sampling method. Research tools involve psychological distress management screening tools, a demographic questionnaire, self-rating anxiety and depression scales, and the Chinese version of the Memorial Symptom Assessment Scale. Bootstrap method was utilized for repeated sampling to identify relevant factors influencing psychological distress in biliary tract cancer patients. The R software was employed to create a nomogram model, and the model's accuracy and predictive performance were assessed using the receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test. The average score of psychological distress among the 219 patients was (3.91 ± 2.44), with a psychological distress detection rate of 54.8%. Regression model results indicated that factors such as the presence of distant metastasis, comorbidity with other major diseases, poor sleep quality, anxiety, and severity of anxiety and depression were the primary influencers of psychological distress. The detection rate of psychological distress in patients with biliary tract malignant tumors is notably high. The predictive model constructed in this study exhibits good predictive efficacy and clinical value, providing valuable reference for healthcare professionals in developing targeted intervention strategies.

Psychological Stress and Its Correlations to Patients with Acute Lymphedema After Breast Cancer Surgery.

Lymphedema and psychological distress, including anxiety and depression, are common in breast cancer patients post-surgery. This study aimed to assess the incidence and determinants of anxiety and depression in patients with acute lymphedema (ALE) following breast cancer surgery. A retrospective study was conducted on 1613 breast cancer patients who underwent surgery at Fudan University Shanghai Cancer Center in 2018. ALE was defined as lymphatic fluid accumulation causing limb swelling and was classified by the difference in arm circumference. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS) at discharge. Descriptive statistics and logistic regression were used to identify psychological distress-related factors. Among the 1613 patients, 363 (22.5%) had ALE. Anxiety was observed in 31% and depression in 21% of patients. ALE significantly impacted anxiety in the multivariate analysis (OR = 1.57, 95% CI: [1.04-2.38], P = 0.033). Multivariate analysis of ALE patients showed that longer hospital stays (OR = 0.51, 95% CI: [0.30-0.88], P = 0.017) and invasive disease (OR = 0.39, 95% CI: [0.19-0.78], P = 0.008) were associated with reduced anxiety; while lymph-vessel invasive disease was associated with increased anxiety (OR = 5.97, 95% CI: [1.15-30.97], P = 0.034). ALE had no significant impact on depression in the multivariate analysis. However, menopause (OR = 0.72, 95% CI: [0.56-0.94], P = 0.014) and longer hospitalization (OR = 1.30, 95% CI: [1.00-1.68], P = 0.047) influenced depression in all patients. In the ALE group, lymph node surgery was the only significant factor for depression (OR = 8.67, 95% CI: [1.56-48.23], P = 0.014) in the multivariate analysis. Psychological stress, influenced by both surgical factors and emotional states, is associated with ALE development. Addressing both psychological and surgical factors is crucial for improving outcomes and quality of life in post-surgery breast cancer patients.

Elevated CA19-9 within the normal range suggests poorer prognosis in stage II CRC: A retrospective analysis of a large sample in a single center.

Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range. This retrospective study scrutinized 2,167 cases of stage II CRC verified by pathology after surgery at the Fudan University Shanghai Cancer Center. Using R software to calculate the optimal critical value to compare the clinical and pathological characteristics and prognosis of different levels of tumor markers. The survival and regression modeling strategies packages of R software drew the nomograms. Utilizing R software, the optimal critical value of CA19-9 was determined as 12.12 U/mL and that of CEA as 1.89 U/mL. Kaplan-Meier survival analysis unveiled that, within the normal range, higher levels of CEA were linked to poorer overall survival (OS) [HR = 1.829 (1.280, 2.989), P = 0.0033] and disease-free survival (DFS) [HR = 1.472 (1.114, 1.944), P = 0.0444]. Similarly, heightened levels of CA19-9 also indicated inferior OS [HR = 1.750 (1.203, 2.455), P = 0.0076] and DFS [HR = 1.361 (1.098, 1.686), P = 0.0049]. Furthermore, multivariate analysis identified CA19-9 as an independent risk factor for OS (HR = 1.49,95% CI: 1.086-2.045, P = 0.014) and DFS (HR = 1.327,95% CI: 1.070-1.647, P = 0.01), while the impact of CEA on OS and DFS was not statistically significant. A nomogram constructed based on the Cox regression model can effectively evaluate the prognosis of CRC patients. Although within the normal range, elevated CA19-9 was associated with an inferior prognosis, chemotherapy decisions of different intensities can be adjusted based on nomograms. This work will contribute to standardizing the diagnosis and treatment of stage II CRC and provide clinicians with essential insights for chemotherapy decisions.

A study on the effect of clinical intervention of evidence-based nursing measures on complications in patients after breast-conserving surgery.

Breast-conserving surgery is an important treatment for breast cancer, which not only eradicates the disease, but also protects the integrity of the breast, however, postoperative nausea and vomiting often bother patients. This study examines the effects of evidence-based nursing practices on nausea and vomiting in patients after breast-conserving surgery, with the aim of providing new perspectives for clinical nursing practice. One hundred and sixty patients who underwent breast-conserving surgery from January 2023 to December 2023 in Fudan University Shanghai Cancer Center were enrolled. The patients were divided into an intervention group (evidence-based nursing group) and a control group (conventional nursing group) using the random number table method, both groups comprised 80 patients. The control group used conventional nursing methods, and the intervention group added evidence-based nursing intervention on this basis. Comparative analysis focused on the incidence of nausea and vomiting, quality of life metrics, and postoperative satisfaction. In the intervention group, notably lower incidence rates of postoperative nausea and vomiting were observed compared to the control group within both the 0-24 hour and 24-48-hour postoperative periods (P< 0.05). Furthermore, the intervention group exhibited significantly higher scores across all five dimensions as well as the overall score of the FACT-B scale in comparison to the control group (P< 0.05), accompanied by heightened satisfaction with the nursing staff. This study demonstrated the positive clinical intervention effects of evidence-based nursing measures and emphasized their importance in improving postoperative nausea and vomiting and quality of life. Future studies are expected to incorporate evidence-based nursing practices into nursing care to improve patient recovery and overall quality of care.

Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. The study included 15489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset gastric cancer: A retrospective cohort study

IntroductionThis study investigates the differences between early-onset gastric carcinoma (EOGC) and late-onset gastric carcinoma (LOGC) by examining trends, demographics, clinical and molecular features, treatments, and outcomes at a leading cancer center in China. ObjectivesTo delineate the distinctions between EOGC and LOGC in terms of patient characteristics, disease progression, and treatment outcomes, and to suggest appropriate screening strategies. MethodsWe analyzed 18,877 gastric carcinoma cases treated at Fudan University Shanghai Cancer Center (FUSCC) from 2000 to 2022. Descriptive statistics were performed using IBM SPSS. Survival rates were assessed via the Kaplan-Meier method and log-rank test, while COX regression analysis identified factors affecting disease-free survival (DFS) and overall survival (OS). ResultsThe average age of gastric cancer diagnosis has increased slightly since 2000, with a steady rise in both EOGC and LOGC cases, though EOGC’s proportion has slightly decreased. EOGC had a higher proportion of female patients and was more common in the gastric body and antrum pylorus. EOGC cases showed lower levels of cancer biomarkers, HER2 expression, vascular and lymphatic invasion, and lower differentiation and invasion depth. They also exhibited more advanced N and TNM staging, Borrmann IV type, and low adhesive carcinoma. EOGC underwent more extensive D2 lymphadenectomy and neoadjuvant chemotherapy. There were no significant differences in Claudin18.2 and MMR protein status between EOGC and LOGC. EOGC had higher rates of ovarian and peritoneal metastases, with a better early prognosis but faster late-stage progression. ConclusionEOGC and LOGC cases have increased over the past two decades. EOGC presents unique clinical and pathological features, requiring thorough surgical treatment and has a better early prognosis but more rapid late-stage progression. Enhanced screening for younger adults is recommended to address the rising EOGC trend.

LINC01764 promotes colorectal cancer cells proliferation, metastasis, and 5-fluorouracil resistance by regulating glucose and glutamine metabolism via promoting c-MYC translation.

Few biomarkers are available for predicting chemotherapeutic response and prognosis in colorectal cancer (CRC). Long-noncoding RNAs (lncRNAs) are essential for CRC development and growth. Therefore, studying lncRNAs may reveal potential predictors of chemotherapy response and prognosis in CRC. LINC01764 was analyzed using datasets from Fudan University Shanghai Cancer Center's advanced CRC patients' RNA-seq and The Cancer Genome Atlas datasets. Gene set enrichment analysis was employed to detect related pathways. Cotransfection experiments, RNA pulldown assays, RNA-binding protein immunoprecipitation, protein synthesis activity, and dual-luciferase reporter assays were performed to determine interactions among LINC01764, hnRNPK, and c-MYC. High LINC01764 expression correlates with metastasis, a poor response to FOLFOX/XELOX chemotherapy, and a poor prognosis in CRC. LINC01764 enhance glycolysis and glutamine metabolism to promote CRC cells proliferation, metastasis, and 5-fluorouracil (5-FU) resistance. LINC01764 specifically binds to hnRNPK, facilitating its interaction with c-MYC mRNA and promoting internal ribosome entry site (IRES)-dependent translation of c-MYC, thereby exerting oncogenic effects. LINC01764 induced 5-FU chemoresistance by upregulating the c-MYC, glucose, and glutamine metabolism pathways, which downregulated UPP1, crucial for activating 5-FU. Conclusively, LINC01764 promotes CRC progression and 5-FU resistance through hnRNPK-mediated-c-MYC IRES-dependent translational regulation, which suggests its potential as a predictor of CRC chemotherapy response and prognosis.

Thyroid-stimulating hormone suppression in low-risk papillary thyroid cancer: a large-scale retrospective analysis of real-world data

Over 500,000 new cases are diagnosed with papillary thyroid cancer (PTC) globally per year, of whom the vast majority are in the low-risk stratification. Although thyroid-stimulating hormone (TSH) suppression is traditionally recommended for all postoperative PTCs in current guidelines, its necessity remains highly controversial in low-risk patients. Since relevant recommendations in current guidelines are still empirical, we aim to provide a direct, large-scale, real-world evidence. This large-scale real-world retrospective study included 11,140 low-risk PTC patients from two Chinese large-volume centers (Fudan University Shanghai Cancer Center [FUSCC] and Cancer Hospital of Chinese Academy of Medical Sciences [CH-CAMS]) treated from January 1, 2000 to June 30, 2022. The mean TSH level was calculated based on postoperative serum TSH values during follow-up. The primary outcome was the association between postoperative TSH level and structural recurrence assessed by Kaplan-Meier, log-rank, multivariate Cox regression analyses and equivalence testing by Two One-Sided Tests (TOST) procedure. Propensity score matching (PSM) was used to adjust for confounders among groups. A total of 11,140 patients with low-risk PTC were included with a median follow-up of 70 months. Based on the mean TSH level, we classified these patients into ≤0.5 (n=1,504, 13.5%), (0.5-1] (n=4,336, 38.9%), (1-2] (n=4,285, 38.5%), (2-3] (n=704, 6.3%) and >3 (n=311, 2.8%) mU/L groups. After PSM adjusting for age, sex, T and N stage, 8991 patients were included in further analysis, for whom the log-rank analyses showed no significant differences between any two groups (all P>0.05) in recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS), and suppressed TSH was not associated with tumor recurrence in the multivariate Cox analysis (TSH > 2 group vs TSH ≤ 2 group: HR=1.30, 95% CI=0.85-2.01, P=0.23). Furthermore, the TOST equivalence tests showed that tumor recurrence status of any two TSH groups were statistically comparable (all Bonferroni-corrected P values<0.005). Subgroup multivariate analyses showed that TSH level did not impact tumor recurrence regardless of age, tumor size, lymph node metastasis, multifocality, surgical extent, biochemical evidence. Our results suggested that postoperative TSH level was not associated with tumor recurrence in patients with low-risk PTC, for whom deliberate TSH suppression may be exempted to avoid potential secondary complications. Maintaining a TSH level within the normal range may be safe for these patients. The study was supported by the National Natural Science Foundation of China (82072951 to Y.W.; 82373008 to X.S.), Shanghai Hospital Development Center (SHDC2020CR6003-001 to Y.W., SHDC2024CRI087 to Y.-J.W.), the Science and Technology Commission of Shanghai Municipality (22Y21900100/23DZ2305600 to Y.W.; 23ZR1412000 to X.S.), the Shanghai Anticancer Association Foundation (SACA-AX202213 to Yu Wang), Shanghai Municipal Health Commission and Shanghai Medicine and Health Development Foundation (WJWRC202302 to X.S.).

SWItch/Sucrose Nonfermentable complex-deficient pulmonary neoplasms: clinicopathologic characteristics and outcomes to radiotherapy and immunotherapy.

The SWItch/Sucrose Nonfermentable (SWI/SNF) complex, a multi-subunit chromatin remodeler, is linked to aggressive tumors when deficient. Accurate identification of SWI/SNF expression status is crucial for tailoring targeted therapies. Previous studies on the efficacy of immunotherapy for SWI/SNF-deficient (SWI/SNF-d) pulmonary tumors primarily focus on non-small cell lung cancer (NSCLC), with limited data on other modalities like radiotherapy. This study aims to analyze the clinicopathological characteristics and prognostic factors of SWI/SNF-d pulmonary neoplasms, including NSCLC and undifferentiated tumors, and to evaluate the effectiveness of radiotherapy and immunotherapy, providing a foundation for improved treatment strategies and prognostic assessments. Patient data on SWI/SNF-d pulmonary neoplasms were collected from Fudan University Shanghai Cancer Center, assessing ARID1A, SMARCA2, SMARCA4, and SMARCB1 subunit expression via immunohistochemistry, with retrospective analysis of survival and treatment results. The study analyzed 101 SWI/SNF-d pulmonary neoplasms from 675 SWI/SNF-d cancer patients (January 2017 to August 2023), mostly male smokers, showing high malignancy. Clinicopathologic features were consistent across patients with various SWI/SNF subunit deficiencies. TP53 was the most common co-mutated gene (71%), followed by STK11, CDKN2A, KRAS, APC, and EGFR. Key prognostic factors for overall survival (OS) were distant metastasis, radiotherapy, and immunotherapy. Immunotherapy improved 3-year OS rates from 20.8% to 68.4% (P<0.001). KRAS-mutated patients on immunotherapy showed a lower 1-year survival rate (60.0% vs. 83.1%, P=0.08). Radiotherapy increased 3-year OS rates to 61.7% from 30.7% (P=0.012). Of 38 patients treated with immunotherapy, 16 benefited from radiotherapy [median OS: 31.4 months vs. not estimable (NE), P=0.045], with an average 17.2 days between radiotherapy and immunotherapy. SWI/SNF-d pulmonary neoplasms, whether with multiple or single subunit losses, exhibit similar clinicopathological characteristics. Radiotherapy and immunotherapy are effective treatments for these patients, and the combination of radiotherapy with immunotherapy may offer synergistic effects.

MR radiomics unveils neoadjuvant chemo-responsiveness with insights into selective treatment de-intensification in HPV-positive oropharyngeal carcinoma

BackgroundAccurate prediction of neoadjuvant chemotherapy (NAC) response allows for NAC-guided personalized treatment de-intensification in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). In this study, we aimed to apply baseline MR radiomic features to predict NAC response to help select NAC-guided de-intensification candidates, and to explore biological underpinnings of response-oriented radiomics. MethodsPre-treatment MR images and clinical data of 131 patients with HPV-positive OPSCC were retrieved from Fudan University Shanghai Cancer Center. Patients were divided into training cohort (n = 47), validation cohort 1 (n = 49) from NAC response-adapted de-intensification trial (IChoice-01, NCT04012502) and real-world validation cohort 2 (n = 35). NAC prediction model using linear support vector machine (SVM) was built and validated. Subsequent nomograms combined radiomics and clinical characteristics were established to predict survival outcomes. RNA-seq and proteomic data were compared to interpret the molecular features underlying radiomic signatures with differential NAC response. FindingsFor NAC response prediction, the fusion model with both oropharyngeal and nodal signatures achieved encouraging performance to predict good responders in the training cohort (AUC 0·89, 95% CI, 0·79-0·95) and validation cohort 1 (AUC 0·71, 95% CI, 0·59-0·83). For prognosis prediction, radiomics-based nomograms exhibited satisfactory discriminative ability between low-risk and high-risk patients (PFS, C-index 0·85, 0·76 and 0·83; OS, C-index 0·79, 0·76 and 0·87, respectively) in three cohorts. Expression analysis unveiled NAC poor responders had predominantly enhanced keratinization while good responders were featured by upregulated immune response and oxidative stress. InterpretationThe MR-based radiomic models and prognostic models efficiently discriminate among patients with different NAC response and survival risk, which help candidate selection in HPV-positive OPSCC with regard to personalized treatment de-intensification.

Clinical characteristics and genomic profiling of outpatients with endometrial cancer at a Chinese tertiary cancer center

ObjectiveEndometrial cancer is stepping into the era of precision therapy. Genomic test is recommended for newly diagnostic patients. However, outpatients displayed more complex characteristics. Here, we elucidated the clinical characteristics and genomic profiling of outpatients with endometrial cancer at our institution.MethodsBetween 2018 and 2023, 68 endometrial cancer received genomic tests at outpatient department of Fudan University Shanghai Cancer Center. Data, including age, pathological histology, FIGO stage and treatment strategy were collected. Germline mutations, molecular subtypes and other somatic mutations were also summarized.ResultsOverall, 72.1% (49/68) of patients receive genomic tests at primary diagnosis, while 27.9% (19/68) of patients received tests at recurrence. Nine patients had deleterious germline mutations, including BRCA1(2), MLH1(1), MSH2(2, including one with co-mutation of RAD50), MSH6(2), FANCA(1), MUTYH(1). Molecular subtypes were recognized among 62 patients, as POLE super-mutation(4, 6.5%), MSI-H(7, 11.3%), CN-Low(36, 58.1%) and CN-High(15, 24.2%). Ten patients received anti-PD1 monotherapy or in combination with chemotherapy or anti-angiogenic therapy, with the duration of disease control of 1 to 35 months. The ORR rate was 30%, and six patients had stable disease. The median (range) follow-up time was 18(2–160) months. 23(33.8%) relapses were recorded, and CN-High subtype displayed worst PFS compared with other subtypes (P < 0.01). 6 deaths were reported including 2(5.6%) of CN-Low and 4(26.7%) of CN-High.ConclusionOutpatients department gathered a considerable proportion of recurrent patients with complex genomic features. Patients with worse prognosis could be well studied, and anti-PD1 therapy was a promising salvage therapy in the real world.

Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial

BackgroundThe combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer.MethodsThis single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle.ResultsBetween January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred.ConclusionsCamrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.Trial registrationThis trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.

PD-L1 expression and tumor-infiltrating lymphocytes: Correlations and prognostic values in Chinese triple-negative breast cancer patients with different molecular subtyping

ObjectiveTo investigate the correlation between programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) and evaluate the prognostic value of PD-L1 and TILs in Chinese triple-negative breast cancer (TNBC) patients with different molecular subtype MethodsThis retrospective study was conducted at 2020. Specifically, the pre-chemotherapy clinical data and non-stained tissue blocks of 465 TNBC patients visited the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014 were collected, with their blocks sliced and stained using PD-L1(SP142), and the outcome of subsequent chemotherapy obtained in 2020. The relapse-free survival (RFS) of the study population was calculated. The baseline PD-L1 expression status correlations with TILs and molecular subtypes were assessed using Spearman’s rank correlation analysis and the Kruskal-Wallis test. Kaplan-Meier survival analyses were undertaken to evaluate the prognosis value of TILs and PD-L1 expression. ResultsPD-L1 expression status on IC was moderately and positively correlated with stromal tumor-infiltrating lymphocytes (sTILs) (rs = 0.502, P <0.001) and iTILs (rs = 0.410, P < 0.001), respectively. PD-L1 expression status and TILs showed significant differences among molecular subtypes (P < 0.001), with the highest proportion of PD-L1+ and high TILs patients observed in the immunomodulatory (IM) subtype. TILs were significantly associated with RFS. Moreover, sTILs could act as an independent predictor of RFS (RR 0.953, 95 % CI 0.920 ∼ 0.987, P = 0.007), while PD-L1 expression status did not show the same prognostic significance. ConclusionsThe incorporation of pre-treatment TILs and PD-L1 expression status as valuable tools for optimizing patient selection for immunotherapy and managing the risks associated with chemotherapy in Chinese TNBC patients. Data availabilityThe data sets generated and analyzed during the current study are available from the corresponding author.

Identification of new subtypes of breast cancer based on vasculogenic mimicry related genes and a new model for predicting the prognosis of breast cancer

Breast cancer is a malignant tumor that poses a serious threat to women's health, and vasculogenic mimicry (VM) is strongly associated with bad prognosis in breast cancer. However, the relationship between VM and immune infiltration in breast cancer and the underlying mechanisms have not been fully studied. On the basis of the Cancer Genome Atlas (TCGA), Fudan University Shanghai Cancer Center (FUSCC) database, GSCALite database, and gene set enrichment analysis (GSEA) datasets, we investigated the potential involvement of VM-related genes in the development and progression of breast cancer. We analyzed the differential expression, mutation status, methylation status, drug sensitivity, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoints, tumor microenvironment (TME), and immune cell infiltration levels associated with VM-related genes in breast cancer. We created two VM subclusters out of breast cancer patients using consensus clustering, and discovered that patients in Cluster 1 had better survival outcomes compared to those in Cluster 2. The infiltration levels of T cells CD4 memory resting and T cells CD8 were higher in Cluster 1, indicating an immune-active state in this cluster. Additionally, we selected three prognostic genes (LAMC2, PIK3CA, and TFPI2) using Lasso, univariate, and multivariate Cox regression and constructed a risk model, which was validated in an external dataset. The prognosis of patients is strongly correlated with aberrant expression of VM-related genes, which advances our knowledge of the tumor immune milieu and enables us to identify previously unidentified breast cancer subtypes. This could direct more potent immunotherapy approaches.

A novel model for predicting postoperative liver metastasis in R0 resected pancreatic neuroendocrine tumors: integrating computational pathology and deep learning-radiomics

BackgroundPostoperative liver metastasis significantly impacts the prognosis of pancreatic neuroendocrine tumor (panNET) patients after R0 resection. Combining computational pathology and deep learning radiomics can enhance the detection of postoperative liver metastasis in panNET patients.MethodsClinical data, pathology slides, and radiographic images were collected from 163 panNET patients post-R0 resection at Fudan University Shanghai Cancer Center (FUSCC) and FUSCC Pathology Consultation Center. Digital image analysis and deep learning identified liver metastasis-related features in Ki67-stained whole slide images (WSIs) and enhanced CT scans to create a nomogram. The model’s performance was validated in both internal and external test cohorts.ResultsMultivariate logistic regression identified nerve infiltration as an independent risk factor for liver metastasis (p < 0.05). The Pathomics score, which was based on a hotspot and the heterogeneous distribution of Ki67 staining, showed improved predictive accuracy for liver metastasis (AUC = 0.799). The deep learning-radiomics (DLR) score achieved an AUC of 0.875. The integrated nomogram, which combines clinical, pathological, and imaging features, demonstrated outstanding performance, with an AUC of 0.985 in the training cohort and 0.961 in the validation cohort. High-risk group had a median recurrence-free survival of 28.5 months compared to 34.7 months for the low-risk group, showing significant correlation with prognosis (p < 0.05).ConclusionA new predictive model that integrates computational pathologic scores and deep learning-radiomics can better predict postoperative liver metastasis in panNET patients, aiding clinicians in developing personalized treatments.

Approaches for Lynch syndrome screening and characteristics of subtypes with mismatch repair deficiency in patients with colorectal carcinoma.

To evaluate different Lynch syndrome (LS) screening approaches and establish an efficient and sensitive strategy are critical for clinical practice. In total, 583 patients with colorectal carcinoma (CRC) at Fudan University Shanghai Cancer Center were enrolled. Patient samples were examined by immunohistochemistry (IHC) and next-generation sequencing (NGS), and MLH1 promoter hypermethylation (MPH) was detected in MLH1-deficient cases. Germline genetic testing was performed in cases with deleterious variants and large genomic rearrangements (LGRs) of tumor MMR genes were detected in cases with dMMR or MSI-H cases with no MMR germline variants. Our results showed that triage with IHC and followed by BRAF/MLH1 methylation testing (Strategy 1) identified 93.3% (70/75) of LS cases. IHC followed by germline NGS (Strategy 2) or direct tumor NGS (Strategy 3) both identified 98.7% (74/75) of LS cases. The proportion of LGRs in LS cases was 16.0% (12/75), while 84.0% (63/75) showed SNV/Indel. The average cost per patient was ¥6010.81, ¥6058.48, and ¥8029.98 for Strategy 1, Strategy 2 and Strategy 3, respectively. The average time spent on different strategies was 4.74 days (Strategy 1), 4.89 days (Strategy 2), and 14.50 days (Strategy 3) per patient, respectively. LS and Lynch-like syndrome (LLS) were associated with an earlier onset age than MPH. In conclusion, we compared different workflows for LS screening and IHC plus germline NGS is recommended for LS screening when taking sensitivity, time, and cost into account. Moreover, multiplex ligation-dependent probe amplification made up for the shortcoming of NGS and should be incorporated into routine screening.

A preoperative radiogenomic model based on quantitative heterogeneity for predicting outcomes in triple-negative breast cancer patients who underwent neoadjuvant chemotherapy

BackgroundTriple-negative breast cancer (TNBC) is highly heterogeneous, resulting in different responses to neoadjuvant chemotherapy (NAC) and prognoses among patients. This study sought to characterize the heterogeneity of TNBC on MRI and develop a radiogenomic model for predicting both pathological complete response (pCR) and prognosis.Materials and methodsIn this retrospective study, TNBC patients who underwent neoadjuvant chemotherapy at Fudan University Shanghai Cancer Center were enrolled as the radiomic development cohort (n = 315); among these patients, those whose genetic data were available were enrolled as the radiogenomic development cohort (n = 98). The study population of the two cohorts was randomly divided into a training set and a validation set at a ratio of 7:3. The external validation cohort (n = 77) included patients from the DUKE and I-SPY 1 databases. Spatial heterogeneity was characterized using features from the intratumoral subregions and peritumoral region. Hemodynamic heterogeneity was characterized by kinetic features from the tumor body. Three radiomics models were developed by logistic regression after selecting features. Model 1 included subregional and peritumoral features, Model 2 included kinetic features, and Model 3 integrated the features of Model 1 and Model 2. Two fusion models were developed by further integrating pathological and genomic features (PRM: pathology-radiomics model; GPRM: genomics-pathology-radiomics model). Model performance was assessed with the AUC and decision curve analysis. Prognostic implications were assessed with Kaplan‒Meier curves and multivariate Cox regression.ResultsAmong the radiomic models, the multiregional model representing multiscale heterogeneity (Model 3) exhibited better pCR prediction, with AUCs of 0.87, 0.79, and 0.78 in the training, internal validation, and external validation sets, respectively. The GPRM showed the best performance for predicting pCR in the training (AUC = 0.97, P = 0.015) and validation sets (AUC = 0.93, P = 0.019). Model 3, PRM and GPRM could stratify patients by disease-free survival, and a predicted nonpCR was associated with poor prognosis (P = 0.034, 0.001 and 0.019, respectively).ConclusionMultiscale heterogeneity characterized by DCE-MRI could effectively predict the pCR and prognosis of TNBC patients. The radiogenomic model could serve as a valuable biomarker to improve the prediction performance.