Sun Yat-sen University Cancer Center Research Articles

Evaluation and analysis of risk factors of hearing impairment for nasopharyngeal carcinoma treated using intensity-modulated radiotherapy

BackgroundTreating nasopharyngeal carcinoma (NPC) with radiotherapy frequently causes hearing impairment (HI). HI risk data haven’t been evaluated quantitatively. This study aimed to analyze the probability of HI and sever HI (SHI), develop a nomogram to quantify individual prediction, and provide dose limitation suggestions. Methods and materialsThis single-center, retrospective study was conducted based on 588 adolescents and young adults with non-metastatic NPC treated using intensity modulated radiation therapy (IMRT) at Sun Yat-sen University Cancer Center between 2010 and 2016. A least absolute shrinkage and selection operator (LASSO) logistic regression model and univariate analysis were used to screen potential risk factors. The concordance index and a calibration curve evaluated the nomogram models' predictive ability, with bootstrap resampling validation. ResultsWe analyzed 588 patients with NPC, with a median follow-up of 103.4 months. HI occurred in 39.5 % of patients, with 29.7 % experiencing SHI. Two factors were classified as precursors for HI (volume 45 Gy of the inner ear (IEV45) and volume 50 Gy of the internal auditory canal (IACV50)), and IACmin and IACV60 for SHI, respectively. Prognostic nomograms were developed to predict HI and SHI probabilities, showing excellent discriminative abilities (c-index values = 0.806 and 0.793, respectively). We also suggested IEV45 < 50 % and/or IACV50 < 40 % as rational dose limitations for HI, and IACmin < 44 Gy and/or the IACV60 < 40 % for SHI. ConclusionComprehensive analysis could predict the risk of HI and SHI in NPC after IMRT, proposing rational dose limitations and improving long-term quality of life.

Utility of peripheral blood macrophage factor Apo10 and TKTL1 as markers in distinguishing malignant from benign lung nodules: a protocol for a prospective cohort study in Southern China

IntroductionLung nodules are one of the most prevalent diseases. Medical imaging methods have a high false positive rate for distinguishing malignant nodules from benign nodules. Therefore, developing new technologies with...

Serum Creatinine and Amylase in Drain to Predict Pancreatic Fistula Risk after Pancreatoduodenectomy

Introduction: The identification of patients with low risk of clinically relevant postoperative pancreatic fistula (CR-POPF) and postoperative hemorrhage (PPH) can guide drain removal after pancreatoduodenectomy (PD). However, drain fluid amylase (DFA) ≤5,000 U/L on postoperative day (POD) 1 does not robustly predict the absence of CR-POPF. Methods: Consecutive patients undergoing PD at Sun Yat-sen University Cancer Center between July 2018 and October 2021 were analyzed. Recursive partitioning analysis was used to classify patients into groups with different risks of CR-POPF and PPH. Results: Among 288 consecutive patients included, 99 patients (34.38%) developed CR-POPF (86 grade B and 13 grade C). Patients with CR-POPF had increased levels of preoperative creatinine (CRE) and POD1 CRE. The combination of POD1 CRE (>104 μmol/L or not) and POD1 DFA (>5,000 U/L or not) stratified patients into subgroups with the maximum difference in CR-POPF risk. The CR-POPF rates were 17.82% (36/202) in group A (POD1 CRE ≤104 μmol/L and POD1 DFA ≤5,000 U/L), 53.33% (8/15) in group B (POD1 CRE >104 μmol/L and POD1 DFA ≤5,000 U/L), and 77.46% (55/71) in group C (POD1 DFA >5,000 U/L). The PPH rates were 1.98% (4/202), 20.00% (3/15), and 19.72% (14/71) in groups A, B, and C, respectively. Conclusion: Patients with POD1 DFA ≤5,000 U/L and POD1 CRE >104 μmol/L have a high risk of CR-POPF and may not benefit from early drain removal. Patients with POD1 DFA ≤5,000 U/L and POD1 CRE ≤104 μmol/L have low risk of CR-POPF and PPH.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study

BackgroundGenitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC).MethodsWe performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed.ResultsForty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84–21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08–0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism.ConclusionsAmong patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Evaluation of neoadjuvant chemotherapy combined with PD-1 inhibitors in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma: a comparative study of antitumor activity.

To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC) and compare its efficacy with neoadjuvant chemotherapy alone. We conducted a retrospective analysis using data from patients diagnosed with OPHSCC and treated at the Sun Yat-sen University Cancer Center between September 2012 and August 2022. We included patients who received neoadjuvant chemotherapy alone or combined with PD-1 inhibitors. We assessed the clinical response using the Response Evaluation Criteria in Solid Tumors and evaluated progression-free survival (PFS) and overall survival (OS). Preliminary results demonstrate that neoadjuvant chemoimmunotherapy exhibited robust antitumor activity in OPHSCC, with an impressive overall response rate (ORR) of 81.0%. Complete response and partial response rates were 14.9% and 65.9%, respectively. Notably, neoadjuvant chemoimmunotherapy demonstrated superior PFS and OS to neoadjuvant chemotherapy alone. The 1-year PFS rate was 80.7%, and the 2-year rate was 61.1%. Additionally, the 1-year OS rate reached 92.3%. Finally, a multivariate analysis identified the American Joint Committee on Cancer stage reduction post-treatment as a favorable predictor of PFS. Our results underscore the promising potential of neoadjuvant chemoimmunotherapy in enhancing antitumor activity in patients with OPHSCC. The robust ORR, along with improved PFS and OS, supports the utility of this combined approach. These results pave the way for further investigations to validate and refine the application of neoadjuvant chemoimmunotherapy in this challenging clinical context.

Development and validation of a sensitive LC–MS/MS method for the assay of four PARP inhibitors in human plasma and its application in ovarian cancer patients

PARP inhibitors have demonstrated marked efficacy in ovarian cancer patients with BRCA1/2 loss-of-function mutations. In this study, we established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method to simultaneously quantify the four frequently prescripted PARP inhibitors, namely niraparib, olaparib，fluzoparib, and pamiparib, in ovarian cancer. The mobile phase was 50 % methanol with 0.1 % formic acid at a flow rate of 0.3 mL/min, within 8 min run time. Four PARP inhibitors were separated on a Hypersil GOLD™ aQ C18 Polar Endcapped LC column (50 × 2.1 mm, 1.9 µm) at 35 ℃ and subjected to mass analysis using positive electro-spray ionization (ESI). The linear range of this method was 10–2000 ng/mL, 25–5000 ng/mL, and 50–10,000 ng/mL for niraparib, olaparib and fluzoparib, and pamiparib, respectively, with the correlation coefficients (r2) ≥ 0.99. Accuracies ranged from 93.12 %–110.71 and the inter- and intra-batch precisions were less than 15 % for all analytes in quality control samples. There was no significant matrix effect. Twenty-eight plasma samples were obtained from Sun Yat-sen University Cancer Center. The mean plasma concentrations (±SD) of niraparib and olaparib were 424.76 (±228.35) ng/mL and 1760.47 (±1739.69) ng/mL, respectively. The validated LC-MS/MS method allows the convient and efficient determination of four PARP inhibitors’ exposure levels in ovarian cancer patients.

Effect of Nanoknife Ablation Therapy in Patients with Pancreatic Cancer

This study was established to explore the therapeutic effect of nanoknife ablation in the treatment of pancreatic cancer with comprehensive perioperative nursing. The clinical data of 92 patients with pancreatic cancer who underwent nanoknife ablation surgery in The First Affiliated Hospital, Sun Yat-sen University and Sun Yat-sen University Cancer Center from January 2015 to December 2018 were retrospectively studied. These 92 patients were randomly and equally divided into a group with comprehensive perioperative nursing care and a group with routine nursing care. After the intervention period, the satisfaction with the nursing, serum albumin, total protein, and hemoglobin levels, length of hospital stay, and incidence of postoperative complications were compared between the two groups. Meanwhile, blood biochemical indicators and related immune indicators of 30 patients in the comprehensive nursing group were analyzed and compared between before and after the operation. Results: The hospitalization time of patients in the routine care group was significantly longer than that in the comprehensive care group (P &lt; 0.05). Meanwhile, the levels of albumin, total protein, and hemoglobin in the serum of patients in the comprehensive care group were significantly higher than those in the routine care group (P &lt; 0.05). All patients exhibited a certain increase in serum amylase level on the day after the operation, which then gradually decreased. There was no statistically significant difference in myocardial enzyme indexes at different time points before and after the operation. The glycoprotein antigen tumor markers carbohydrate antigen (CA)-19-9 and CA-242 increased on the 1st day after surgery, and gradually decreased thereafter. This study indicated that the safety of nanoknife ablation in patients with pancreatic cancer is relatively high. In addition, there is a clear clinical effect of comprehensive nursing care in the perioperative period, which can effectively improve the levels of albumin, total protein, and hemoglobin, shorten the hospitalization time, and reduce the incidence of postoperative complications. Such nursing care also relieved the tumor-related immunosuppression after surgery and significantly decreased the levels of tumor markers.

Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.

Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC.

Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality.

The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.

Definitive concurrent chemoradiotherapy with docetaxel plus cisplatin versus 5-fluorouracil plus cisplatin in patients with esophageal squamous cell carcinoma: long-term follow-up results of a phase II randomized controlled trial

BackgroundDefinitive radiotherapy plus concurrent chemotherapy has been a standard treatment for esophagus patients who are unfit to undergo surgery. However, there are a variety of concurrent chemotherapy regimens with varying efficacy. In this phase II prospective study, we compared the efficacy and toxicity of DP (docetaxel and cisplatin) and PF (cisplatin and 5-fluorouracil) regimens with concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC) and analyzed the 5-year overall survival (OS) and progression free survival (PFS). We also summarized the salvage treatments and late toxicities.MethodsWe enrolled 86 patients with clinical stage II-IVA from the Sun Yat-sen University Cancer Center. The patients were divided into two groups: PF group (41) and DP group (45). Statistics were analyzed using SPSS version 19.0.ResultsThe 5-year OS rates were 62.9% ± 7.6% in PF group, and 52.7% ± 7.5% in DP group (P = 0.131), respectively. The 5-year PFS rates were 43.9% ± 7.8% for PF group, and 40.0% ± 7.3% for DP group (P = 0.398), respectively. Sixteen patients in the DP group and thirteen in the PF group received salvage treatment. For those patients with local residual or local recurrent disease, the median survival time after salvage treatment was 13.5 months and the 1, 2, and 3-year survival rates were 79.0%, 50.3%, and 43.1%, respectively. For all patients, thirteen (15.1%) had Grade 2 late cardiac toxicities. One patient had Grade 2 pleural effusion and required diuretic. Most patients with pneumonia are mild, and only one patient in PF group had Grade 2 pneumonia. One patient in the DP group developed tracheoesophageal fistula.ConclusionsThe 5-year follow-up confirmed that definitive CCRT with the DP regimen did not improve the treatment response, OS, or PFS in patients with ESCC compared to the PF regimen. The PF regimen remains the standard regimen for definitive CCRT for patients with locally advanced ESCC. Long-term follow-up also suggested that appropriate and active salvage treatment has a survival benefit for some patients, and late cardiopulmonary toxicities should be noticed during follow-up.Trial registrationThe trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT 02969473, October 2010).

Response to programmed cell death protein 1 antibody in patients with Epstein–Barr virus-associated intrahepatic cholangiocarcinoma

AimEpstein–Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) has a distinct genomic profile and increased CD3+ and CD8+ T cells infiltration. However, the efficacy of immunotherapy in EBVaICC remains largely unknown. This study aimed to assess the efficacy of programmed cell death protein 1 (PD-1) antibody therapy in EBVaICC. MethodsPatients with metastatic biliary tract cancer (BTC) diagnosed at Sun Yat-sen University Cancer Center from January 2016 to December 2021 were identified. In situ hybridisation was performed to detect EBV. Overall survival (OS) and progression-free survival (PFS) were measured. ResultsA total of 698 patients with metastatic BTC were identified, of whom 39 (5.6%) had EBVaICC. Among the 136 patients who were not administered PD-1 antibody, the OS was similar between patients with EBVaICC and EBV-negative ICC (median OS 12.5 versus 9.5 months, respectively; P = 0.692). For the 205 patients who were administered PD-1 antibody, patients with EBVaICC had significantly longer OS than patients with EBV-negative ICC (median OS 24.9 versus 11.9 months, respectively; P = 0.004). Seventeen patients with EBVaICC were administered PD-1 antibody. Eight patients (47%) achieved a partial response, and 17 patients achieved disease control. The median PFS was 17.5 months. ConclusionsThis study identified a clinically actionable subset of patients with EBVaICC with a promising response to the PD-1 antibody.

P02.11.A INTEGRATED GENOMIC PROfiLING OF LONG-TERM GLIOBLASTOMA SURVIVORS

Abstract BACKGROUND Glioblastoma (GBM) is a fatal brain tumor, and few patients survive beyond 5 years. Therefore, a study of genomic alterations in GBM long-term survivors (LTS) is essential for insights into tumor biology and biomarker identification. MATERIAL AND METHODS In our study, we reviewed medical records from Sun Yat-sen University Cancer Center for GBM patients received initial surgery between the years 2000 and 2018. Thirty patients with GBM had an overall survival of more than 5 years. In addition to established prognostic factors such as radiochemotherapy and total surgical excision, we sought to identify genomic alterations associated with LTS by collecting surgically resected tumor tissues and normal blood controls from 13 GBM LTS (overall survival &amp;gt; 60 months) and 19 short-term survivors (STS, overall survival &amp;lt; 24 months). We performed whole exome sequencing and transcriptome sequencing on these samples. RESULTS Our findings revealed no significant differences in the composition of driver genes between the two groups. However, mutation signature analysis indicated that the proportion of mutation signature 19 was higher in the LTS than in the STS (P=0.059). Analysis of copy number variants showed that the longer survivors group had higher copy number variants at the chromosomal level (P=0.049). At the chromosome arm level, the proportion of 19p amplification and 19q amplification in the longer survivors group was significantly higher than in the short survival group (P=0.001/0.002). And in the TCGA GBM dataset, GBM patients with 19p amplification also had a better prognosis (log-rank P=0.04). CONCLUSION In conclusion, our study identified the proportion of mutation signature 19 and amplification of 19p as potential genomic alterations that could be used as prognostic biomarkers for GBM. This study could pave the way for new therapeutic approaches to this challenging disease.

P13.01.A POST-OPERATIVE MRI SYNTHESIS FROM PRE-OPERATIVE MRI AND POST-OPERATIVE CT USING CONDITIONAL GAN FOR THE ASSESSMENT OF DEGREE OF RESECTION

Abstract BACKGROUND Magnetic resonance imaging (MRI) is an essential part of assessing the extension of resection after craniotomy, allowing for accurate assessment of the brain. However, the application of MRI within 72 hours after surgery is limited, owing to its high cost, long time duration, and patients’ limited mobility. Besides, MRI excludes people with contraindications, including implantable electronic devices or artificial limbs, in which sceneries computerized tomography (CT) is the only available choice. To overcome these limitations, we investigated the use of a deep learning model for synthesizing post-operative MRI images. MATERIAL AND METHODS We aim to employ Cross-domain Correspondence Learning for Exemplar-based Image Translation Network (CoCosNet), an exemplar-based image translation model to synthesize T1 contrast-enhanced (T1ce) MRI images by combining post-operative T1ce and post-operative CT images. 233 cases were retrospectively collected at Sun Yat-sen University Cancer Center, who underwent complete MRI and CT scans. RESULTS After 200 epochs and a batch size of 10, CoCosNet achieved comparable results compared to other existing models, with objective indicators structural similarity index = 0.75, peak signal-to-noise ratio = 21.68, and mean absolute error = 0.007. Furthermore, assessments of the extent of resection between the true and synthesized T1ce images achieve great consistency. CONCLUSION Our study demonstrates the effectiveness of the CoCosNet deep learning model in synthesizing post-operative MRI images from pre-operative MRI and post-operative CT scans. Our quantitative analysis indicates that the synthesized images have comparable quality to real MRI images and are able to accurately assess the extent of resection. This approach has a promising future by providing a reliable alternative to traditional post-operative MRI.

Development and external validation of the multichannel deep learning model based on unenhanced CT for differentiating fat-poor angiomyolipoma from renal cell carcinoma: a two-center retrospective study.

There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC). This two-center retrospective study included 320 patients from the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU) and 132 patients from the Sun Yat-Sen University Cancer Center (SYSUCC). Data from patients at FAHSYSU were divided into a development dataset (n = 267) and a hold-out dataset (n = 53). The development dataset was used to obtain the optimal combination of CT modality and input channel. The hold-out dataset and SYSUCC dataset were used for independent internal and external validation, respectively. In the development phase, models trained on unenhanced CT images performed significantly better than those trained on enhanced CT images based on the fivefold cross-validation. The best patient-level performance, with an average area under the receiver operating characteristic curve (AUC) of 0.951 ± 0.026 (mean ± SD), was achieved using the "unenhanced CT and 7-channel" model, which was finally selected as the optimal model. In the independent internal and external validation, AUCs of 0.966 (95% CI 0.919-1.000) and 0.898 (95% CI 0.824-0.972), respectively, were obtained using the optimal model. In addition, the performance of this model was better on large tumors (≥ 40mm) in both internal and external validation. The promising results suggest that our multichannel deep learning classifier based on unenhanced whole-tumor CT images is a highly useful tool for differentiating fp-AML from RCC.

Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

Development and validation of a nomogram based on common biochemical indicators for survival prediction of children with high-risk neuroblastoma: A valuable tool for resource-limited hospitals

BackgroundDespite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of “ultra high-risk NB” is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years.MethodsOne hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC).ResultsThrough univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633—0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p < 0.001). AUC values of ROC curves for 3- and 5-year OS rates in the training set were 0.758 and 0.756, respectively. Moreover, based on the cut-point score (34 points) developed in training set, The model also showed good discrimination power with C-index of 0.773 (95%CI: 0.664—0.897) and powerful prognostic accuracy of AUC for 3- and 5-year OS rates being 0.825 and 0.826, respectively, in validation cohort.ConclusionsWe developed a simple-to-use nomogram based on common laboratory indicators to identify the subgroup of ultra high-risk NB before treatment, providing these children even from developing countries or regions access to intensified multimodal treatments earlier and thus improving their long-term outcome.

Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

Development and validation of web-based dynamic nomograms predictive of disease-free and overall survival in patients who underwent pneumonectomy for primary lung cancer.

The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram's discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610-0.724]) and 0.697 (95% CIs [0.649-0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

NEIM-03 A GRADUAL INTEGRATION MODEL BASED ON MRI TO PREDICT MOLECULAR PROFILES IN PATIENTS WITH GLIOMA

Abstract Glioma is the most common primary brain tumor. Molecular profiles, including IDH mutation, 1p/19q co-deletion, and MGMT promoter methylation, are highly correlated with the prognosis and clinical decision-making of glioma. To predict the molecular profiles from rough segmentation MRI, we developed and validated a gradual integration model. We proposed a multi-task pseudo-3D model based on rough segmented multiparametric MRI to predict molecular profiles. In this model, convolution along the depth axis was performed between convolution blocks. A total of 750 patients with glioma were retrospectively enrolled from Sun Yatsen University Cancer Center(n=576) and The Cancer Imaging Archive(n=167) to validate the performance of the framework. The model was developed and validated on the local dataset and tested on an independent external (TCIA) test set. For IDH, 1p/19q, and MGMT predictions on the TCIA set, the gradual fusion model achieves AUCs of 0.87, 0.80, and 0.71, respectively, outperforming both input or output integration models and 2D models. To conclude, our gradual fusion model demonstrated the potential to predict molecular profiles based on pre-treatment MRI. Gradual integration may be a reliable method to design 3D medical imaging models.

TIPS-05 ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY FOLLOWING RADIOTHERAPY IN NEWLY DIAGNOSED LOW-GRADE GLIOMA PATIENT WITH RESIDUE TUMORS: A MULTICENTER, OPEN LABEL, RANDOMIZED TRIAL

Abstract Low-grade glioma (LGG) with infiltrative nature and frequent growth in eloquent area in brain often makes total resection impossible. Although post-radiation adjuvant temozolomide (TMZ) is the standard of care for high-grade gliomas, and radiotherapy and/or TMZ are recommended for the treatment of residue low-grade gliomas, the efficacy of combined radiotherapy with adjuvant TMZ for residue LGG remains to be defined. We have initiated a randomized clinical trial in 2012 to test whether radiotherapy with subsequent TMZ chemotherapy will improve survival of patients with residue LGG compared to radiotherapy alone. This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center, Guangzhou, China (approval No. 5010-2012-03) and was registered with ClinicalTrials.gov (NCT01649830). Inclusion Criteria: Patients age of 18 years to 60 years, with incompletely resected supratentorial WHO grade 2 astrocytoma, oligodendroglioma or oligodendroastrocytoma. Enrolled patients were randomized into: radiation therapy alone (RT) or radiotherapy with subsequent TMZ chemotherapy (RC) group. Start Date: July 2012, Estimated Primary Completion Date:August 2025. Radiation therapy will start within 8 weeks after neurosurgical procedures, with a total dose of 54.0 Gy in 27 - 30 fractions over 6 - 7 weeks. Four weeks after radiotherapy, patients in RC group will receive 6 cycle of TMZ dosed at 200 mg/m2 daily for 5 consecutive days, repeated every 28 days. We have completed enrollment on December 2018 with valid cases of 248 patients. Up to last follow-up date of Feb. 2023, 204 cases were analyzed (see table). There is no significant difference between RT group and RC group on both PFS and OS (5-year PFS 68.9% vs 75.2%, p=0.680; 5-year OS 92.0% vs 86.0%, p=0.400). Longer follow-up and molecular subgroup analysis are currently on the way, which could show benefit in special molecular subgroup.