University Cancer Center Research Articles

Abstract B020: A blood-based multi-omics test for early evaluation of lymphoma treatment effectiveness

Abstract Introduction: The standard clinical assessment for treatment response of lymphoma currently relies on periodic functional imaging examinations. In this prospective study, we utilized a blood-based multi-omics test, SeekInClarity, to evaluate treatment response and predict patient outcomes in the major types of lymphoma. Methods: 116 patients with various lymphoma subtypes were recruited from two clinical centers: The First Affiliated Hospital of Zhengzhou University and Sun Yat-sen University Cancer Center. Blood samples were collected at pre- treatment (baseline) and after two cycles of treatment (landmark) for SeekInClarity analysis, which integrated shallow whole-genome sequencing (sWGS) data of circulating-free DNA (cfDNA), including copy number aberrations (CNA) and fragment size (FS), with seven protein markers. The molecular tumor burden (MTB) score was calculated with SeekInClarity to assess the therapeutic efficacy of patients. Results: At 95.2% specificity, cancer signals were detected in 74.1% (86/116) of patients at baseline. Higher MTB scores were associated with advanced tumor stages, with MTB+ ratios of 31.8%, 63.6%, 84.6%, and 91.2% for stage I, II, III, and IV, respectively. After two cycles of treatment, patients with MTB+ status exhibited significantly poorer progression-free survival (PFS) (HR: 0.13, 95% CI, 0.05-0.33, P < 0.001) and overall survival (OS) (HR: 0.24, 95% CI, 0.06-0.97, P < 0.05) compared to MTB- patients. These trends were consistent across stages, subtypes, and treatment regimens. Traditional biomarkers, lactate dehydrogenase (LDH) and β2-microglobulin (B2M), showed no OS difference between high and low expression groups. The disease progression (PD) rate was 5.2 times higher in the MTB+ group (41.5%) than in the MTB- group (8.0%, P < 0.001), outperforming LDH (1.1 times, 20.7% vs 18.1%, P = 0.15) and B2M (3.1 times, 43.8% vs 14.0%, P = 0.02). All 116 patients, except four with stable disease, were classified as partial or complete response based on imaging at the landmark analysis. However, 13 patients experienced disease progression within six months after treatment. Notably, six (46.2%) were identified earlier through MTB reduction at the landmark. Greater MTB reduction at landmark associated with better OS (P<0.05). Multivariate Cox regression analysis confirmed MTB reduction at landmark as an independent prognostic indicator for PFS, with low reduction indicating a significant increase in disease progression (HR: 0.11, 95% CI: 0.03-0.42, P < 0.001), while other clinical parameters were not significant. Conclusions: This study confirms the clinical utility of SeekInClarity in evaluating lymphoma treatment responses. Reductions in MTB during treatment are associated with patient survival and can predict therapeutic outcomes. Furthermore, post-treatment MTB status after two cycles is an independent prognostic indicator for both PFS and OS. Citation Format: Mao Mao, Wang Xin hua, Li Zhi ming, Chang Yu, Li Shi yong, Wu Wei, Chang Fang yuan, Chang Yin yin, Zhu Dan dan, Zhang Ming zhi. A blood-based multi-omics test for early evaluation of lymphoma treatment effectiveness [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B020.

Predictive value and model construction of preoperative nutritional indexes for postoperative leakage in gastric cancer

Objective: We aimed to explore the predictive significance of the nutritional indexes in the occurrence of postoperative leakage after gastrectomy, aiming to develop and validate a predictive nomogram for assessing the risk of these complications.Methods: Patients undergoing radical gastrectomy for gastric cancer were studied, using data from The Sixth Affiliated Hospital of Sun Yat-sen University (2019-2022, n=1075) for nomogram development and an external cohort from Sun Yat-sen University Cancer Center (2022, n=286) for validation. The model, focusing on postoperative leakage, was constructed through univariate and backward stepwise regression. The performance of nomogram was assessed using the receiver operating characteristic (ROC) curve, calibration plots, decision curve analysis (DCA), and clinical impact curves (CIC).Results: The incidence rates of postoperative leakage were 6.51% in the training cohort and 6.71% in the external validation cohort, respectively. The nomogram effectively identifies critical factors influencing postoperative leakage risk, including NRS-2002 score, SFMAI, VSR, blood loss, intraoperative time, type of reconstruction, and Lauren type. The areas under the curve (AUC) for the development and external validation cohorts were 0.763 and 0.761, respectively, demonstrating acceptable predictive accuracy. The validation study showed the nomogram's satisfactory calibration, and both DCA and CIC confirmed its significant clinical utility.Conclusions: The nomogram offers an efficient and precise tool for initial screening, effectively identifying individuals at elevated risk for postoperative leakage.

Efficacy and safety of surufatinib in the treatment of patients with neuroendocrine tumor: a real-world study in Chinese population

BackgroundNeuroendocrine tumors (NETs) are rare neoplasms that originate from peptidergic neurons and neuroendocrine cells. Due to their increasing incidence, effective treatment strategies are required. Surufatinib, a novel small-molecule inhibitor with antiangiogenic and immunomodulatory effects, has shown promise in clinical trials for advanced NETs. However, the efficacy and safety of surufatinib are influenced by multiple factors, and there is currently a lack of sufficient real-world studies to explore these potential influencing factors.MethodsWe conducted a retrospective study on 133 patients with NETs who were treated with surufatinib at Sun Yat-sen University Cancer Center. Patients were histologically confirmed to have primary NETs. Statistical analyses, including Cox regression models and Kaplan-Meier curves, were conducted to assess the impact of the primary tumor site on progression-free survival (PFS) and overall survival (OS).ResultsPatients with gastroenteropancreatic NETs (GEP-NETs) exhibited significantly longer PFS and OS compared to extraGEP-NETs patients. Subgroup analyses also revealed variations in survival outcomes among patients with liver metastases depending on the primary tumor site. Adverse events (AEs), including proteinuria and increased bilirubin, were more common in GEP-NETs patients. These findings emphasize the importance of considering primary tumor site in treatment decisions for NETs.ConclusionsPrimary tumor site is a critical factor influencing the efficacy of surufatinib in NETs. Clinicians should consider this factor when determining treatment strategies.

Overall Survival of Young Patients with Hepatocellular Carcinoma in Barcelona Clinic Liver Cancer Stage B in a Retrospective Study Based on a Multicenter Cohort.

Hepatocellular carcinoma (HCC) is usually diagnosed in patients at the age of > 45years. We aimed to determine the prognosis of patients with HCC at the age of 30-44years compared with that of patients at a more senior age. Based on the Sun Yat-sen University Cancer Center database, a total of 1745 patients with HCC were retrospectively enrolled and were assigned to three age groups (30-44, 45-59, and 60-70years). The primary endpoint was overall survival. Among baseline characteristics, five variables including sex, serum albumin level, total bilirubin level, the maximum tumor diameter, and the number of tumor nodules were adjusted using propensity score matching. Patients aged 30-44years presented a worse overall survival, a greater number of HCC nodules, a greater maximum tumor diameter, and higher serum alpha-fetoprotein (AFP) concentration than those aged 45-59years in a crude analysis (p < 0.05). Using propensity score matching, the difference in overall survival between the two cohorts was canceled (p > 0.05). The prognosis of patients with HCC at age 30-44years was equal to that of patients aged 45-59years.

Evolving epidemiological patterns of thyroid cancer and estimates of overdiagnosis in 2013–17 in 63 countries worldwide: a population-based study

The incidence of thyroid cancer has been increasing in many countries, mainly due to overdiagnosis. Given these rapid changes, we aim to assess the specific features of the thyroid cancer diagnosis epidemic and provide estimates of overdiagnosis across countries spanning five continents and identify areas in which coping strategies are needed. Two types of data were retrieved from the International Agency for Research on Cancer (IARC) Global Cancer Observatory database. The long-term annual incidence of thyroid cancer by sex and 5-year age group for all ages from 1980 to 2017 was obtained from continuous population-based registries available in the Cancer Incidence in Five Continents (CI5) plus, with 97 registries from 43 countries selected. Sex-age-specific thyroid cancer cases, overall and by subtype, along with corresponding population counts were retrieved from all registries included in the latest volume of CI5 (CI5-XII), with 385 registries in 63 countries. Annual mortality data from 1980 to 2022 were obtained from WHO, with population counts supplemented by UN population estimates. We estimated age-standardised rates (ASRs) of thyroid cancer incidence and mortality for all ages by sex using direct age standardisation, with the world population as a reference. Long-term annual trends of ASRs were compared between incidence and mortality since 1980. Subtype distribution was calculated for thyroid cancer incidence during 2013-17. We estimated the numbers of thyroid cancer cases and overdiagnosed cases and extrapolated to the whole country using a previously developed and validated method. Thyroid cancer incidence rates rose during 1980-2017 for most countries, with the highest rates seen in South Korea, Cyprus, Ecuador, China, and Türkiye for females and males. An upward trend was seen until the early 2010s, followed by a downward trend in South Korea, the USA, Canada, and Israel and some Western European countries, such as France, Italy, Austria, and Ireland. The difference between the highest and lowest incidence rates ranged from less than 10·0 per 100 000 females in the early 1980s to 101·4 per 100 000 females in 2012. For males, the difference between the highest and lowest incidence rates ranged from 2·7 per 100 000 to 23·5 per 100 000 over the study period. Mortality rates were substantially lower, with a difference between the highest and lowest rates across countries of around 1·0-2·0 per 100 000 for both sexes throughout the study period. During 2013-17, papillary thyroid cancer contributed to the large variation in ASRs of thyroid cancer incidence. The mortality rates of thyroid cancer increased with age for all countries, whereas the observed age-specific incidence rates showed an inverted U-shape in most countries. The magnitude of overdiagnosis varied across countries, ranging from no overdiagnosis (in Uganda, Zimbabwe, and Trinidad and Tobago) to more than 85·0% of thyroid cancer cases being overdiagnosed in females (in Cyprus, China, South Korea, and Türkiye). Overall, 1 736 133 (75·6%) of 2 297 057 cases were attributable to overdiagnosis, including 1 368 181 females and 367 952 males. Although the incidence of thyroid cancer has reached a plateau or decrease in some high-income countries, the magnitude of overdiagnosis is still very large and the expansion of overdiagnosis of thyroid cancer to the transitioning countries has been rapid, which makes it a global public health challenge that needs to be addressed. National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Young Talents Program of Sun Yat-sen University Cancer Center, Italian Association for Cancer Research, and the Italian Ministry of Health (Ricerca Corrente).

Impact of SARS-CoV-2 Pandemic on Diagnosis of Prostate Cancer.

The aim of this study was to prove if the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in a delay in diagnosis and treatment of prostate cancer (PC). A monocentric, retrospective analysis was conducted at a university cancer center. Included were all patients with untreated PC diagnosed between January 2019 and December 2021. The observation covered 22 months of the SARS-CoV-2 pandemic and 14 months preceding it. Nine hundred sixty-nine men prior (T0) and 1,343 during the pandemic (T1) were included. Mean age was 68.0 (SD 8.2). Median initial prostate-specific antigen was 8.1 ng/mL (T0) and 7.9 ng/mL (T1, p = 0.288). Time from biopsy to tumor board (T0: 1.3 months vs. T1: 0.9 months, p = 0.001), to staging (T0: 1.1 months vs. T1: 0.75 months, p = 0.707), and to therapy (T0: 3.0 months vs. T1: 2.0 months, p < 0.001) was shortened during the pandemic. Classified by d'Amico, a significant shift toward higher risk groups was seen (p = 0.024). Local staging showed an insignificant increase in locally advanced PCs. Metastatic diseases decreased from 10.3% to 8.9% (p = 0.433). Pathological staging showed pT3+ in 44.4% versus 44.7% (p = 0.565) and pN+ in 9.9% versus 9.6% (p = 0.899). Regarding the diagnosis and treatment of PC, we could not demonstrate any delays due to the SARS-CoV-2 pandemic.

Comparison of long-term quality of life and their predictors in survivors between paediatric and adult nasopharyngeal carcinoma in the intensity-modulated radiotherapy era

BackgroundTo compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL.MethodsWe enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared.ResultsThe paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults.ConclusionPaediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.

Development and validation of a hierarchical approach for lymphoma classification using immunohistochemical markers.

Accurate lymphoma classification is critical for effective treatment and immunohistochemistry is a cost-effective and time-saving approach. Although several machine learning algorithms showed effective results, they focused on a specific task of classification but not the whole classification workflow, thus impractical to be applied in clinical settings. Thus, we aim to develop an effective and economic machine learning-assisted system that can streamline the lymphoma differential diagnostic workflow using EBER insitu hybridization and immunohistochemical markers. We included pathological reports diagnosed as lymphomas from two cancer centers (Sun Yat-sen University Cancer Center and Peking University Cancer Hospital & Institute). We proposed a hierarchical approach that mimicked the human diagnostic process and employed simplified panels of markers to perform a series of interpretable classification. The diagnostic accuracy for lymphoma pathological subtypes and the markers saving ratio were investigated in both temporal independent population and external medical center. A total of 14,927 patients and corresponding immunohistochemical results from two cancer centers were included. The proposed system had high discriminative ability for differentiating lymphoma pathological subtypes (measured by mean AUC in three validation cohorts, non-Hodgkin and Hodgkin lymphoma: 0.959; non-Hodgkin subtypes: 0.983; B-lymphoma subtypes: 0.868; T-lymphoma subtypes: 0.962; DLBCL subtypes: 0.957). In addition, the system's well selected characteristics can contribute to the development of agreement on panels of markers for differential diagnosis and help minimize cost of immunohistochemical marker techniques (measured by marker saving ratio compared to real clinical settings, internal primary-stage cohort: 16.45% saved, p < 0.001; internal later-stage cohort: 21.73% saved, p < 0.001; external cohort: 3.67% saved, p < 0.001). Machine learning-based hierarchical system using EBER insitu hybridization and IHC markers was developed, which could streamline the workflow by sequentially determining each lymphoma pathological subtype. The proposed system proved to be effective and cost-saving in independent and external validation, thus could be adopted affordably in future clinical practice.

Adding immune checkpoint inhibitors to chemotherapy confers modest survival benefit in patients with small cell lung cancer and brain metastases: a retrospective analysis.

Brain metastases (BM) are highly prevalent and associated with a poor prognosis in patients with small cell lung cancer (SCLC). However, the evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for patients with SCLC and BM remains limited. Therefore, the objective of this study is to evaluate whether the addition of ICIs confers survival benefits for patients with SCLC and BM. This retrospective study enrolled patients with SCLC and BM at the Sun Yat-sen University Cancer Center between January 2018 and December 2022. Clinical characteristics were extracted from medical records. Depending on whether ICIs were added to the first-line treatment, the patients were categorized into the chemotherapy group and the chemoimmunotherapy group. The efficacy of these two treatment approaches was analyzed and compared. A total of 165 patients were enrolled, with 85 in the chemotherapy group and 80 in the chemoimmunotherapy group. The chemoimmunotherapy group showed a tendency towards prolonged intracranial [6.6 vs. 5.9 months, hazard ratio (HR) =0.77; P=0.14] and extracranial (6.9 vs. 6.5 months, HR =0.73; P=0.12) progression-free survival (PFS) and overall survival (OS) (15.6 vs. 14.5 months, HR =0.98; P=0.93) compared to the chemotherapy group. Cox regression analysis identified liver metastases and local treatment for BM as independent prognostic factors for OS in patients. Furthermore, the chemotherapy group and the chemoimmunotherapy group demonstrated similar patterns of initial disease progression. Adding ICIs to chemotherapy confers modest survival benefits in patients with SCLC and BM.

Highly sensitive detection platform-based diagnosis of oesophageal squamous cell carcinoma in China: a multicentre, case–control, diagnostic study

Early detection and screening of oesophageal squamous cell carcinoma rely on upper gastrointestinal endoscopy, which is not feasible for population-wide implementation. Tumour marker-based blood tests offer a potential alternative. However, the sensitivity of current clinical protein detection technologies is inadequate for identifying low-abundance circulating tumour biomarkers, leading to poor discrimination between individuals with and without cancer. We aimed to develop a highly sensitive blood test tool to improve detection of oesophageal squamous cell carcinoma. We designed a detection platform named SENSORS and validated its effectiveness by comparing its performance in detecting the selected serological biomarkers MMP13 and SCC against ELISA and electrochemiluminescence immunoassay (ECLIA). We then developed a SENSORS-based oesophageal squamous cell carcinoma adjunct diagnostic system (with potential applications in screening and triage under clinical supervision) to classify individuals with oesophageal squamous cell carcinoma and healthy controls in a retrospective study including participants (cohort I) from Sun Yat-sen University Cancer Center (SYSUCC; Guangzhou, China), Henan Cancer Hospital (HNCH; Zhengzhou, China), and Cancer Hospital of Shantou University Medical College (CHSUMC; Shantou, China). The inclusion criteria were age 18 years or older, pathologically confirmed primary oesophageal squamous cell carcinoma, and no cancer treatments before serum sample collection. Participants without oesophageal-related diseases were recruited from the health examination department as the control group. The SENSORS-based diagnostic system is based on a multivariable logistic regression model that uses the detection values of SENSORS as the input and outputs a risk score for the predicted likelihood of oesophageal squamous cell carcinoma. We further evaluated the clinical utility of the system in an independent prospective multicentre study with different participants selected from the same three institutions. Patients with newly diagnosed oesophageal-related diseases without previous cancer treatment were enrolled. The inclusion criteria for healthy controls were no obvious abnormalities in routine blood and tumour marker tests, no oesophageal-associated diseases, and no history of cancer. Finally, we assessed whether classification could be improved by integrating machine-learning algorithms with the system, which combined baseline clinical characteristics, epidemiological risk factors, and serological tumour marker concentrations. Retrospective SYSUCC cohort I (randomly assigned [7:3] to a training set and an internal validation set) and three prospective validation sets (SYSUCC cohort II [internal validation], HNCH cohort II [external validation], and CHSUMC cohort II [external validation]) were used in this step. Six machine-learning algorithms were compared (the least absolute shrinkage and selector operator regression, ridge regression, random forest, logistic regression, support vector machine, and neural network), and the best-performing algorithm was chosen as the final prediction model. Performance of SENSORS and the SENSORS-based diagnostic system was primarily assessed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Between Oct 1, 2017, and April 30, 2020, 1051 participants were included in the retrospective study. In the prospective diagnostic study, 924 participants were included from April 2, 2022, to Feb 2, 2023. Compared with ELISA (108·90 pg/mL) and ECLIA (41·79 pg/mL), SENSORS (243·03 fg/mL) showed 448 times and 172 times improvements, respectively. In the three retrospective validation sets, the SENSORS-based diagnostic system achieved AUCs of 0·95 (95% CI 0·90-0·99) in the SYSUCC internal validation set, 0·93 (0·89-0·97) in the HNCH external validation set, and 0·98 (0·97-1·00) in the CHSUMC external validation set, sensitivities of 87·1% (79·3-92·3), 98·6% (94·4-99·8), and 93·5% (88·1-96·7), and specificities of 88·9% (75·2-95·8), 74·6% (61·3-84·6), and 92·1% (81·7-97·0), respectively, successfully distinguishing between patients with oesophageal squamous cell carcinoma and healthy controls. Additionally, in three prospective validation cohorts, it yielded sensitivities of 90·9% (95% CI 86·1-94·2) for SYSUCC, 84·8% (76·1-90·8) for HNCH, and 95·2% (85·6-98·7) for CHSUMC. Of the six machine-learning algorithms compared, the random forest model showed the best performance. A feature selection step identified five features to have the highest performance to predictions (SCC, age, MMP13, CEA, and NSE) and a simplified random forest model using these five features further improved classification, achieving sensitivities of 98·2% (95% CI 93·2-99·7) in the internal validation set from retrospective SYSUCC cohort I, 94·1% (89·9-96·7) in SYSUCC prospective cohort II, 88·6% (80·5-93·7) in HNCH prospective cohort II, and 98·4% (90·2-99·9) in CHSUMC prospective cohort II. The SENSORS system facilitates highly sensitive detection of oesophageal squamous cell carcinoma tumour biomarkers, overcoming the limitations of detecting low-abundance circulating proteins, and could substantially improve oesophageal squamous cell carcinoma diagnostics. This method could act as a minimally invasive screening tool, potentially reducing the need for unnecessary endoscopies. The National Key R&D Program of China, the National Natural Science Foundation of China, and the Enterprises Joint Fund-Key Program of Guangdong Province. For the Chinese translation of the abstract see Supplementary Materials section.

Assessing Barriers and Facilitators to Return to Work for Kidney Cancer Survivors: A 6-Month Longitudinal Study

ObjectivesThis study aimed to investigate the factors that impact the readiness and success of kidney cancer survivors returning to work, providing insights for healthcare professionals, employers, and policymakers. MethodsA prospective longitudinal study was conducted at Sun Yat-sen University Cancer Center from April 2022 to June 2023. The study enrolled 282 kidney cancer survivors aged 18 to 60 who completed three surveys at 1, 3, and 6 months postsurgery. Data collection involved telephone interviews and self-administered questionnaires, capturing sociodemographic information, medical history, and employment status, while follow-up assessments tracked return-to-work readiness. The scales used for analysis included the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire, the Return-to-Work Self-Efficacy Questionnaire, the Perceived Social Support Scale, and the Brief Fatigue Inventory. Generalized Estimation Equations were applied to identify significant factors, with both single-factor and multivariate analyses performed to pinpoint the most critical variables. ResultsReturn-to-work rates at 1, 3, and 6 months postsurgery were 26.9%, 59.9%, and 76.2%, respectively. Higher levels of anxiety, lower self-efficacy, older age, and greater fatigue were associated with reduced return-to-work rates. Physically demanding jobs posed more barriers compared to nonmanual roles. Significant factors identified in multivariate analysis included anxiety, self-efficacy, fatigue, and the nature of the patient's work. ConclusionPsychological, physical, and job-related factors play a crucial role in determining whether kidney cancer survivors can successfully return to work. Tailored support and flexible work arrangements could help kidney cancer survivors reintegrate into the workforce, leading to better long-term outcomes. Implication for Nursing PracticeNursing professionals can play a vital role in assessing and supporting kidney cancer survivors during their recovery process by addressing both psychological and physical factors. Incorporating return-to-work readiness into postoperative care plans, offering mental health support, and liaising with employers to create flexible working conditions could enhance the reintegration of survivors into the workforce.

Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.

Lung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC. Patients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored. One hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3+ cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3+ (P=0.004), CD8+ (P=0.01), and CD68+ (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC. Our study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.

Peripheral NK cell count predicts response and prognosis in breast cancer patients underwent neoadjuvant chemotherapy.

The count of lymphocyte subsets in blood can reflect the immune status of the body which is closely related to the tumor immune microenvironment and the efficacy of NAT. This study aims to explore the relationship between peripheral blood lymphocyte subsets and the efficacy and prognosis of NAT in breast cancer. We retrospectively analyzed clinicopathological information and peripheral blood lymphocyte subpopulation counts of patients receiving NAT from January 2015 to November 2021 at Sun Yat-sen University Cancer Center. Kaplan-Meier curves were used to estimate the survival probability. The independent predictors of NAT response and survival prognosis were respectively analyzed by multivariate logistic regression and Cox regression, and nomograms were constructed accordingly. The prediction efficiency of three nomograms was validated separately in the training cohort and the testing cohort. 230 patients were included in the study, consisting of 161 in the training cohort and 69 in the testing cohort. After a median follow-up of 1238 days, patients with higher NK cell value showed higher pCR rates and higher OS and RFS after NAT (all P < 0.001). Multivariate analyses suggested NK cell count was an independent predictor of NAT response, OS and RFS. We then built nomograms accordingly and validated the prediction performance in the testing cohort (C index for NAT response: 0.786; for OS: 0.877, for RFS: 0.794). Peripheral blood NK cell count is a potential predictive marker for BC patients receiving NAT. Nomograms based on it might help predict NAT response and prognosis in BC.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma.

Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

A log odds of positive lymph nodes-based predictive model effectively forecasts prognosis and guides postoperative adjuvant chemotherapy duration in stage III colon cancer: a multi-center retrospective cohort study

BackgroundThe log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy.MethodA total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan–Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms.ResultsMultivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052–3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084–2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297–2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030).ConclusionThe prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts

BackgroundThis study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China.MethodsFrom February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test.ResultsThe second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature.ConclusionsWe have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial

In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50mg/m2 of paclitaxel and 25mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4Gy in 28 fractions), and toripalimab (240mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR]=13.73, 95% CI 4.43-42.54, P<0.0001) and PFS (HR=32.08, 95% CI 8.57-120.10, P<0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P=0.082) and better PFS (HR=0.43, 95% CI 0.19-0.93, P=0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P=0.036). The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

MMCA-NET: A Multimodal Cross Attention Transformer Network for Nasopharyngeal Carcinoma Tumor Segmentation Based on a Total-Body PET/CT System.

Nasopharyngeal carcinoma (NPC) is a malignant tumor primarily treated by radiotherapy. Accurate delineation of the target tumor is essential for improving the effectiveness of radiotherapy. However, the segmentation performance of current models is unsatisfactory due to poor boundaries, large-scale tumor volume variation, and the labor-intensive nature of manual delineation for radiotherapy. In this paper, MMCA-Net, a novel segmentation network for NPC using PET/CT images that incorporates an innovative multimodal cross attention transformer (MCA-Transformer) and a modified U-Net architecture, is introduced to enhance modal fusion by leveraging cross-attention mechanisms between CT and PET data. Our method, tested against ten algorithms via fivefold cross-validation on samples from Sun Yat-sen University Cancer Center and the public HECKTOR dataset, consistently topped all four evaluation metrics with average Dice similarity coefficients of 0.815 and 0.7944, respectively. Furthermore, ablation experiments were conducted to demonstrate the superiority of our method over multiple baseline and variant techniques. The proposed method has promising potential for application in other tasks.

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.