Sun Yat-sen University Cancer Center Research Articles

Plasma ofCS-modified CD44 predicts the survival of patients with lung cancer.

Plasma levels of oncofetal chondroitin sulfate (ofCS)-modified CD44 have emerged as a promising biomarker for multi-cancer detection. Here, we explored its potential to predict the survival of patients with lung cancer. A prospective observational cohort was conducted involving 274 newly diagnosed patients with lung cancer at the Sun Yat-sen University Cancer Center from 2013 to 2015. The plasma levels of ofCS-modified CD44 were measured, and Cox regression analysis was performed to assess the association between plasma-modified CD44 levels and overall survival (OS) as well as other prognostic outcomes. Prognostic nomograms were constructed based on plasma ofCS-modified CD44 levels to predict survival outcomes for patients with lung cancer. Patients with high expression ofCS-modified CD44 exhibited significantly worse outcomes in terms of OS (HR = 1.61, 95%CI = 1.13-2.29, p = 0.009) and progression-free survival (PFS). These findings were consistent across various analyses. The concordance index of the prognostic nomogram for predicting OS in both the training set and validation set were 0.723 and 0.737, respectively. Additionally, time-dependent receiver operating characteristic (ROC) curves showed that the nomogram could serve as a useful tool for predicting OS in patients with lung cancer. Plasma ofCS-modified CD44 may serve as an independent prognosis marker for patients with lung cancer. Further validation of its predictive value could enhance prognostic assessment and guide personalized treatment strategies for patients with lung cancer.

Optimal therapeutic strategies for hepatic metachronous oligometastatic nasopharyngeal carcinoma: Insights from a retrospective study.

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.

UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive tumor with extremely poor prognosis due to the low resection rate, high recurrence rate and drug resistance. Uridine-cytidine kinase 2 (UCK2) is proved to promote progression and drug resistance of various carcinomas by regulating pyrimidine metabolism. However, the role of UCK2 in progression and drug resistance of iCCA was largely unclear. Gene expression matrices were obtained from public database and were verified by qRT-PCR using tumor sample from Sun Yat-sen University Cancer Center. Knockdown and overexpression of UCK2 were used to evaluate the effects of UCK2 on carcinogenesis and cisplatin response in iCCA. CCK8-kit assays and plate clone formation assays were performed to detect the effect of UCK2 on proliferative activity of tumor cells. Western blotting was performed to investigate protein level of UCK2 and the relevant biomarkers of PI3K/AKT/mTOR/autophagic axis. Cell migration and invasion were assessed by using wound-healing and transwell assays. UCK2 expression was detected elevated in iCCA tissues compared with adjacent normal tissues. Biologically, overexpression of UCK2 can promote proliferation of iCCA cells, and desensitizes iCCA to cisplatin in both in vivo and in vitro models. Mechanistically, UCK2 promote iCCA progression and cisplatin resistance through inhibition of autophagy by activating the PI3K/AKT/mTOR signaling pathway. Clinically, higher UCK2 expression in iCCA tumor was associated with aggressive tumor features, poorer survival and lower sensitivity of chemotherapy. UCK2 promotes iCCA progression and desensitizes cisplatin treatment by regulating PI3K/AKT/mTOR/autophagic axis. UCK2 exhibited potential as a biomarker in predicting prognosis and drug sensitivity of iCCA patients.

Peripheral hemoglobin to albumin ratio predicts prognosis in patients with nasopharyngeal carcinoma underwent concurrent chemoradiotherapy

BackgroundRecently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT).MethodsThis retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed.ResultsIn both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679–0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448–0.770].ConclusionThe HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.

Detailed pathological characteristics and survival prognosis of patients with penile cancer from a high-capacity tertiary referral centre over a 20-year period.

120 Background: Penile cancer is a rare cancer that affects 0.1-1 per 100,000 men in developed countries. However, data on this cancer in developing countries, particularly in Asian populations, are lacking. A retrospective study is needed to determine the characteristics of penile cancer patients, tumor-related treatments, and prognosis. The objective of our study was to present statistical results that are applicable to an Asian population under the most recent staging system. Additionally, we aimed to report on the pathological characteristics and prognosis of a large sample of patients with penile cancer who underwent long-term follow-up with the standard extent of radical dissection. Methods: This study retrospectively analyzed clinical and pathological data from 1017 patients who were diagnosed with penile cancer at Sun Yat-sen University Cancer Center between October 2001 and October 2023. The primary study endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Survival curves were plotted using the Kaplan‒Meier method, and differences were compared using the log-rank test. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with tumor survival. Results: The average follow-up time was 50 months (range: 0.6-232.8 months). The 5- and 10-year OS rates were 67.3% and 62.7%, respectively, and the 5- and 10-year PFS rates were 63.9% and 61.1%, respectively. After excluding 127 Tx patients and 23 TIS stage patients, the 10-year OS rates of pTa stage (29 patients), pT1 (305 patients), pT2 stage (217 patients), pT3 stage (271 patients), and pT4 stage (45 patients) patients were 96.3%, 80.1%, 61.7%, 55.4%, and 14.2%, respectively. A total of 690 patients underwent standard lymph node dissection. The 10-year OS rates of pN0 (376 patients), pN1 (111 patients), pN2 (78 patients), and pN3 (125 patients) patients were 92.7%, 62.5%, 48.1% and 31.3%, respectively. The results of the multifactorial analysis revealed that T stage (T4 stage versus Ta-T1 stage: HR=2.38, 95% CI: 1.00~5.66, P=0.05), pathological grade (G3~4 grade versus G1~2 grade: HR=1.63, 95% CI: 1.05~2.53, P=0.027), N stage (pN+ versus pN0: HR=14.11, 95% CI: 7.83~25.43, P<0.001), and white blood cell count (WBC>8.5: HR=1.71, 95% CI: 1.17~2.51, P=0.006) were independent prognostic factors in penile cancer patients. Conclusions: Patients with penile cancer had better long-term OS after standard lymph node dissection. The adverse factors were T stage, pathological grade, extent of lymph node metastasis, and preoperative WBC count. Identifying high-risk patients through preoperative evaluation can improve long-term survival rates. Radical lymph node dissection in the early stage has more curative value, and adjuvant therapy should be provided in patients with advanced-stage disease after surgery.

Impact of acute therapeutic toxicities on anxiety during radiotherapy among Chinese patients with newly diagnosed nonmetastatic head and neck cancer: A cross-sectional study.

147 Background: Head and neck cancer (HNC) poses a significant threat to both psychological and physical health. This study aimed to depict the anxiety status of Chinese newly diagnosed nonmetastatic HNC patients during radiotherapy (RT) and to examine predictors of anxiety symptoms. Methods: Newly diagnosed nonmetastatic HNC patients who received RT at the Radiation Therapy Center of Sun Yat-sen University Cancer Center from August 23,2023 to August 24,2023 were recruited into this study. Using Zung Self-Rating Anxiety Scale (Zung SAS) to screen anxiety. Twenty-four common acute therapeutic toxicities (18 patient-reported and 6 clinician-rated) were assessed according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-HN35) and Common Terminology Criteria for Adverse Events, fifth version (CTCAE V5.0). Chi-square ( χ2) test and multivariate binary logistic regression stepwise forward selection: likelihood ratio (LR) method were applied to identify factors associated with anxiety. Results: A total of 457 patients were included ultimately. Up to 29.10% of the patients showed varying degrees of anxiety and the average SAS standardized score was 45.66 ± 8.83. Chi-square test manifested that sex, annual household income, fatigue, anorexia, nausea, vomit, pain, dysphagia, sense problems (smell and taste), speech problems, trouble in social eating, trouble in social contact, sexual frustration, teeth problems, difficulty in opening mouth, xerostomia, sticky saliva, coughing, feeling ill, use of analgesics, use of nutritional supplements and weight loss were related to anxiety ( p < 0.05). But multivariate logistic regression only demonstrated fatigue (OR = 3.696, 95% CI = 2.096-6.519), speech problems (OR = 3.247, 95% CI = 1.554-6.783), sexual frustration (OR = 2.029, 95% CI = 1.232-3.341), nausea (OR = 3.075, 95% CI = 1.807-5.234), feeling ill (OR = 2.283, 95% CI = 1.215-4.291), use of nutritional supplements (OR = 1.930, 95% CI = 1.136-3.280) and difficulty in opening mouth (OR = 3.007, 95% CI = 1.081-8.363) as independent predictive factors of anxiety. Conclusions: The Chinese newly diagnosed nonmetastatic HNC patients suffered greatly from anxiety during RT. This study identified the predictive contribution of sociodemographic and clinical characteristics and 24 common acute therapeutic toxicities to the vulnerability to anxiety, which can provide evidence and reference for medical staff to carry out psychological intervention.

Prognostic and immunological significance of tertiary lymphoid structures in nasopharyngeal carcinoma.

220 Background: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues found in non-lymphoid organs, characterized by the presence of CD20+ B cell follicles adjacent to a T cell zone. Their presence has been associated with improved survival in various tumor types. However, the role of TLSs in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated the prognostic and immunological significance of TLSs in NPC patients. Methods: The investigation involved a discovery cohort (n = 145) comprising NPC patients diagnosed at Sun Yat-sen University Cancer Center between July 2010 and December 2016, with pretreatment primary tumor samples collected. An independent validation cohort included 150 NPC patients with gene expression profiles, among whom Hematoxylin & Eosin (H&E)-stained slides were available for 95 patients. The primary endpoint of this study is overall survival, defined as the duration of time from diagnosis until death from any cause. The presence of TLSs was assessed on H&E and CD20-stained slides. Analyses of tumor-infiltrating immune cell subsets, differentially expressed genes, and BCR/TCR clonotypes were performed to explore the association between TLSs and the anti-tumor immune response. A molecular definition of TLSs was proposed and assessed for its prognostic value across multiple cohorts. Results: The presence of TLSs was independently associated with a favorable overall survival (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank p = 0.04), surpassing the significance of B cell density in multivariate analysis (HR, 0.83; 95% CI, 0.38-1.79, log-rank p = 0.63). These findings were corroborated in the independent validation cohort. TLSs positively correlated with multiple immune-related pathways and a higher proportion of functionally mature immune cells. Notably, the counts of BCR and TCR clonotypes showed a significant positive correlation with the TLSs score. We proposed a TLSs gene signature and demonstrated its prognostic relevance across multiple cohorts, including patients treated with immune checkpoint blockade. Conclusions: TLSs exhibit heightened immune activity and indicate improved survival outcomes in NPC patients. A TLSs gene signature was proposed and demonstrated its prognostic relevance across multiple cohorts, indicating potential guidance for treatment decisions in cancer.

Induction chemoimmunotherapy followed by radiotherapy in locally advanced head and neck squamous cell carcinoma: A real-world study.

131 Background: Patients with locally advanced head and neck squamous cell cancers (LAHNSCC) present poor prognosis despite multi-disciplinary comprehensive treatment, and novel treatment strategies are urgently needed. Recently, several phase II clinical trials reported encouraging pathological complete response rate of induction chemoimmunotherapy (IC+ICI) in LAHNSCC, suggesting potentially long-term survival benefits. Therefore, we conducted this real-world study to compare the efficacy of IC+ICI followed by radiotherapy (RT) versus induction chemotherapy (IC) followed by RT in LAHNSCC. Methods: We retrospectively included patients with LAHNSCC from Sun Yat-sen University Cancer center database treated with IC+ICI followed by RT or IC followed by RT between 1/2018-12/2021. Survival outcomes and adverse effects (AEs) were compared between the two groups. Results: A total of 262 patients were included: 128 (48.9%) in the IC+ICI group, and 134 (51.1%) in the IC group. Median age for the whole cohort was 60 (53–66) years, and the male-to-female ratio is 8.9:1. Most patients (84.4%) had stage IV disease. The median follow-up time was 26.7 (IQR 25.8-29.6) months. Marginally significant higher objective response rate (ORR) was observed in the IC+ICI group than that in the IC group (81.25% vs 72.39%, P=0.09). Patients in the IC+ICI group had significantly better results than those in the IC group in 2-year overall survival (OS; 88.9% vs. 71.5%, P<0.001), disease-free survival (DFS; 77.5% vs. 58.3%, P=0.005), locoregional relapse-free survival (LRRFS; 78.4% vs. 59.7%, P=0.009) and distant metastasis-free survival (DMFS; 87.5% vs. 64.6%, P<0.001). Multivariate analysis confirmed that combining immunotherapy in the induction stage was an independent prognostic factor for OS (HR 0.40, 95%CI 0.19-0.84), DFS (HR 0.45, 95%CI 0.28-0.72), LRRFS (HR 0.56, 95%CI 0.31-0.99), and DMFS (HR 0.37, 95%CI 0.19-0.73). The incidences of G3/4 AEs between the IC+ICI group and the IC group were comparable during the induction stage (6.25% vs 12.69%, P = 0.076) as well as the radiotherapy stage (14.06% vs 14.18%, P = 0.978). Conclusions: This study firstly reported that IC+ICI followed by RT was superior to IC followed by RT in long-term survival outcome in LAHNSCC.

Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer

BackgroundLARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection.MethodsSequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome.ResultsOur study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer.ConclusionsOur study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Transoral Robotic Surgery and Human Papillomavirus Infection: Impact on Oropharyngeal Cancer Prognosis.

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study

BackgroundThe hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms.MethodsClinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan–Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms.ResultsA total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405–0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538–0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS.ConclusionPreoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.

The conditional recurrence-free survival after R0 hepatectomy for locally advanced intrahepatic cholangiocarcinoma: A competing risk analysis based on inflammation-nutritional status

BackgroundConditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method. MethodsWe extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators. ResultsConsidering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set. ConclusionsConditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.

Molecular characteristics of patients with colorectal signet-ring cell carcinoma with different ABO blood groups

BackgroundColorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. MethodsA retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. ResultsThe blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. ConclusionsOur study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

Financial toxicity, coping strategies, and quality of life among Chinese patients with hematologic malignancies: a cross-sectional study.

Financial toxicity is used to describe the financial hardship experienced by cancer patients. Financial toxicity may cause negative consequences to patients, whereas little is known in Chinese context. This study aimed to explore the level of financial toxicity, coping strategies, and quality of life among Chinese patients with hematologic malignancies. We conducted a prospective, observational study among 274 Chinese patients with hematologic malignancies from November 2021 to August 2022 in Sun Yat-sen University Cancer Center. Clinical data were extracted from electronic clinical records. Data on financial toxicity, coping strategies, and quality of life were collected using PRO measures. Chi-square or independent t test and multivariate logistic regression were performed to explore the associated factors of financial toxicity and quality of life, respectively. Effects of financial toxicity on coping strategies were examined using Chi-square. The mean age of the participants was 50.2 (± 14.6) years. Male participants accounted for 57.3%. About half of the participants reported high financial toxicity. An average median of ¥200,000 on total medical expenditures since the diagnosis was reported. The average median monthly out-of-pocket health expenditure relating to cancer treatment was ¥20,000 (range ¥632-¥172,500) after reimbursement. Reduce daily living expenses (64.9%), borrowing money (55.7%), and choosing cheaper regimens (19.6%) were the commonly used strategies to cope with financial burden. Financial toxicity was negatively associated with quality of life (β = 0.071, P = 0.001). Financial toxicity was not uncommon in patients with hematological malignancies. Reducing daily living expenses, abandoning treatment sessions, and borrowing money were the strategies commonly adopted by participants to defray cancer costs. Additionally, participants with high level of financial toxicity tended to have worse quality of life. Therefore, actions from healthcare providers, policy-makers, and other stakeholders should be taken to help cancer patients mitigate their financial toxicity.

Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery

Objective: To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Results: Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion: The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study

PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Clinical characteristics, prognosis, and immunotherapy outcome in pediatric melanoma: Analysis from a large Chinese cohort.

10050 Background: Malignant melanoma in children and adolescents is rare, with limited data on Chinese populations.To assess the clinical characteristics, survival, prognostic factors, and the efficacy of immunotherapy in a real-world cohort of Chinese pediatric patients with melanoma. Methods: This is a retrospective, cohort study included pediatric melanoma patients between February, 2005 and May, 2021, with a median follow-up time of 76.7 months. Data analyses were conducted in May, 2023. This study enrolled patients from Sun Yat-sen University Cancer Center, the biggest cancer institution in South China for cancer prevention, diagnosis and treatment. Inclusion criteria for this study were as follows: 1) histopathologically confirmed diagnosis of melanoma; 2) Age ≤18 year; 3) with complete clinical data on sex, age, histopathological features, etc. The exclusion criteria was secondary malignant melanoma. Main outcomes and measures were patient’s OS and EFS. Results: 43 patients were enrolled, with median age of 138.9 (range 13.1-215.0) months, including 30 cutaneous melanoma, 7 meningeal melanoma, 5 mucosal melanoma, and 1 uveal melanoma. The frequency of BRAF V600E mutation was 16.7% (4/24). Mismatch repair proteins were normally expressed (7/7), and the positive rate of programmed cell death ligand 1 expression was 55.6% (5/9). The event-free survival and overall survival of cutaneous, mucosal and meningeal melanoma were 46.7±9.1% vs 75.0±21.7% vs 16.7±15.2% ( P = 0.010), 65.5±8.9% vs 75.0±21.7% vs 16.7±15.2% (P&lt; 0.001), respectively. Survival of cutaneous melanoma were associated with pathological type, ulceration, Clark level, disease spread, sentinel lymph node status, tumor stage and Ki-67 expression. 5 of 9 patients who were treated with PD-1 inhibitors (5 with PD-1 inhibitors alone, 3 with PD-1 inhibitors plus angiogenesis inhibitors, 1 with combination of anti-PD1, anti-angiogenic inhibitors plus chemotherapy) were evaluable with the overall response rate of 20%. The most common immune-related adverse event was hypothyroidism. Conclusions: This is the largest real-world study in pediatric melanoma patients in Asia. The prognosis of mucosal melanoma was favorable, followed by cutaneous melanoma, and meningeal melanoma had the worst prognosis. PD-1 antibody combined with angiogenesis inhibitors maybe a promising choice in pediatric melanoma.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio and wide clinical application are needed. Based on public data sets, the Chemotherapy Cohort and the Immunotherapy Cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, single-sample gene set enrichment analysis (ssGSEA), stemness index calculation, immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful to predict the prognosis of GC patients, the degree of chemotherapy resistance and the efficacy of immunotherapy.

Temporal dynamics and prognostic significance of cancer free status in patients with intermediate stage hepatocellular carcinoma: A multicenter cohort study.

e16236 Background: A proportion of patients with intermediate stage hepatocellular carcinoma (HCC) can achieve cancer free status (CFS) during treatment, the prognostic value of CFS across the period of dynamic surveillance and treatment remained unknown. Methods: This longitudinal cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007 to May 31, 2019. The data from Sun Yat-sen University Cancer Center served as the derivation cohort and other centers as testing cohort. The time-series data were converted into data of time slices, with an interval of three months. Image CFS is defined as patients with no evidence of disease based on imaging exams after treatment and Image-Bio CFS is defined as achievement of Image CFS, together with normal AFP level. Based on the dynamic changes of disease during treatment, patients at specific time slice were classified into either “Arrive”, “Maintain”, or “Not reached” CFS subgroups. The correlations between CFS subgroups and overall survival (OS) were determined by Cox regression. Results: A total of 945 (42.2%) and 741 (33.1%) patients in derivation cohort reached Image CFS and Image-Bio CFS during treatment, respectively. The corresponding rates for Image CFS and Image-Bio CFS in testing cohort were 155 (37.4%) and 130 (31.4%), respectively. Maintaining Image CFS or Image-Bio CFS, rather than just arrive Image CFS or Image-Bio CFS, had stable predictive value for improved OS across different time slices. The merged Hazard ratio of Maintain Image-Bio CFS was 0.23 (95%CI, 0.20-0.25, P &lt; 0.001). The patients achieved Image-Bio CFS could be further classified into three subgroups with differential prognosis based on duration of CFS (≤ 4.5months; 4.5-18.0 months; &gt; 18.0 months). Maintaining Image-Bio CFS for more than 18.0 months predicted long term survival (5-year OS: 91.2% in derivation cohort, 94.7% in testing cohort). Conclusions: Maintaining CFS, rather than just arrive CFS, is a key marker of favorable survival during dynamic management of intermediate stage HCC. A duration of Image-Biochemical CFS for more than eighteen months predicts long-term survival.

Comparing the mutation profiles of primary HER2-positive breast cancers in patients with and without brain metastases.

e13018 Background: Brain metastasis is a frequent and devastating event of HER2-positive breast cancer. Identifying the driver genes of brain metastasis is important for the prevention and treatment of brain metastasis. In this study, we compared the gene mutation profiles of primary breast cancers between patients with and without brain metastases, aiming to identify new candidate genes associated with brain metastases. Methods: HER2-positive and lymph node-positive early breast cancers of 21 patients who eventually developed brain metastases (BM group) and 27 patients without any metastasis (NM group) at a minimum 5-year follow-up were retrieved from the Sun Yat-sen University Cancer Center. Whole-exome sequencing was performed on primary breast cancers (FFPE) and matched normal breast tissues or peripheral blood. Mutect2 was used to detect somatic mutations, and Fisher’s exact test was used to identify genes mutated at different frequencies in the BM and NM groups. The mRNA expression changes of genes mutated at higher frequencies in the BM group were further analyzed in 16-pair matched HER2-positive primary breast cancers and brain metastases using the public dataset (1). Results: The BM and NM groups exhibited similar TP53 (33.3% vs. 55.6%, p=0.15) and PIK3CA (23.8% vs. 25.9%, p=1) mutation rates. The mutation rates of AP3B1 (38.1% vs. 3.7%), DHTKD1 (23.8% vs. 0), ERCC6L2 (38.1% vs. 7.4%), DNAH5 (33.3% vs. 3.7%), ZNF207 (33.3% vs. 7.4%), SPATA31E1 (19.0% vs. 0), FAM111B (19.0% vs. 0), ATG3 (19.0% vs. 0), CDK14 (19.0% vs. 0), TUT4 (19.0% vs. 0), CCNB3 (19.0% vs. 0), MGA (19.0% vs. 0), CLCA1 (28.6% vs. 3.7%), BBS7 (28.5% vs. 3.7%) and GABRG1 (38.1% vs. 11.1%) were significantly (p&lt;0.05) higher in the BM group than in the NM group. Among these genes, CDK14 and TUT4 were significantly downregulated, and ZNF207 and FAM111B were significantly upregulated in brain metastases compared to their matched primary breast cancers. Conclusions: We identified several genes with higher mutation rates in primary breast cancer of patients who eventually developed brain metastases. These genes warrant further investigation in the development of brain metastases in HER2-positive breast cancer. 1. Cosgrove et al. NC 2022.