Cancer Centers In China Research Articles

Delayed gastric emptying risk stratification in patients with pancreatic ductal adenocarcinoma after pancreatoduodenectomy: An international validation cohort study.

Currently, there is still a lack of an accurate predictive model for delayed gastric emptying (DGE) following pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to develop a concise model that could effectively predict the risk of DGE. This retrospective cohort study included a training cohort of 1251 consecutive PDAC patients who underwent PD from the US multicenter ACS-NSQIP database. Additionally, a validation cohort of 934 consecutive PDAC patients who underwent PD was included from the National Cancer Center in China. A total of 46 perioperative indicators were incorporated in the analysis. The DGE risk stratification (DGERS) model was then developed and validated using Lasso-logistic regression. After screening using Lasso-logistic regression, we identified four independent predictors that were significantly correlated with DGE: days to pancreatic drain removal (HR, 1.05; 95% CI, 1.02-1.08; p<0.001), pancreatic fistula (HR, 2.61; 95% CI, 1.65-4.12; p<0.001), sepsis/septic shock (HR, 2.46; 95% CI, 1.52-3.91; p<0.001), and reoperation (HR, 4.16; 95% CI, 2.27-7.57; p<0.001). Based on these factors, we developed a nomogram to predict postoperative DGE. The model demonstrated excellent calibration and optimal performance in the validation cohorts (AUC, 0.73; 95% CI, 0.67-0.73). In the validation cohort, the DGERS exhibited significant risk stratification ability, with AUC values of 0.7, 0.61, and 0.74 for the low-, moderate-, and high-risk groups, respectively. This study identified four factors that independently increased the occurrence of DGE in patients with PDAC after PD, including days to pancreatic drain removal, pancreatic fistula, sepsis/septic shock, and reoperation. Based on these findings, we developed a personalized and straightforward DGERS that enables dynamic and precise prediction of DGE risk, allowing for effective stratification of individuals based on their risk profiles.

Neoadjuvant Immunotherapy Alone for Patients With Locally Advanced and Resectable Metastatic Colorectal Cancer of dMMR/MSI-H Status.

The use of programmed death-1 blockade has a significant therapeutic effect in patients with mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. However, data on preoperative single-agent programmed death-1 blockade are rare. This study aims to evaluate the effectiveness and safety of preoperative programmed death-1 blockade as a conversion strategy in patients with locally advanced and resectable metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancer. This is a retrospective observational study. This study was conducted at a high-volume tertiary referral cancer center in China. Twenty-four patients of consecutive cases since 2020 to 2022 with mismatch repair-deficient/microsatellite instability-high colorectal cancer who received preoperative single-agent programmed death-1 blockade were retrospectively reviewed. These patients had either bulking tumors scheduled for multivisceral resection, a strong desire for organ preservation, or potentially resectable metastatic lesions. Pathological complete response, clinical complete response, toxicity, R0 resection rate, and complications were evaluated. Patients tolerated preoperative immunotherapy well. The R0 resection rate was 95.2%, and the pathological complete response rate was 47.6%. Three patients (12.5%) were evaluated as having a clinical complete response and then underwent "watch and wait." One-half of the patients with cT4b were spared multivisceral resection, whereas 60% (3/5) achieved pathological complete response. All 3 patients with liver metastases obtained complete response of all liver lesions after programmed death-1 blockade treatment. Grade III postoperative complications occurred in 2 patients. The limitations of this study are as follows: retrospective study, small sample size, and short follow-up. Preoperative anti-programmed death-1 therapy alone as a conversion strategy in initially resected difficult mismatch repair-deficient/microsatellite instability-high colorectal cancer can achieve a high tumor complete response. The use of immunopreoperative therapy in patients with T4b colon cancer or low rectal cancer can reduce multivisceral resection and achieve high organ function preservation. See the Video Abstract . ANTECEDENTES:El uso del bloqueo de muerte programada-1 tiene un efecto terapéutico significativo en pacientes con cáncer colorrectal metastásico deficiente en reparación de desajustes/inestabilidad de microsatélites-alta (dMMR/MSI-H). Sin embargo, los datos sobre el bloqueo preoperatorio de muerte programada-1 con un solo agente son escasos.OBJETIVO:Este estudio tiene como objetivo evaluar la eficacia y seguridad del bloqueo preoperatorio de muerte programada-1 como estrategia de conversión en pacientes con cáncer colorrectal localmente avanzado y metastásico resecable con dMMR/MSI-H.DISEÑO:Este es un estudio observacional retrospectivo.ESCENARIO:Este estudio se realizó en un centro oncológico terciario de referencia de gran volumen en China.PACIENTES:Se revisaron retrospectivamente veinticuatro pacientes de casos consecutivos desde 2020-2022 con cáncer colorrectal y dMMR/MSI-H que recibieron bloqueo preoperatorio de muerte programada-1 con un solo agente. Estos pacientes tenían un tumor voluminoso programado para resección multivisceral, un fuerte deseo de preservación del órgano o lesiones metastásicas potencialmente resecables.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la respuesta patológica completa, la respuesta clínica completa, la toxicidad, la tasa de resección R0 y las complicaciones.RESULTADOS:Los pacientes toleraron bien la inmunoterapia preoperatoria. La tasa de resección R0 fue del 95,2% y la tasa de respuesta patológica completa fue del 47,6%. Tres pacientes (12,5%) fueron evaluados como respuesta clínica completa y luego sometidos a "observar y esperar". La mitad de los pacientes cT4b se salvaron de la resección multivisceral, mientras que el 60% (3/5) lograron una respuesta patológica completa. Los tres pacientes con metástasis hepáticas obtuvieron respuesta completa de todas las lesiones hepáticas después del tratamiento de bloqueo de muerte programada-1. En dos pacientes se produjeron complicaciones postoperatorias de grado III.LIMITACIONES:Las limitaciones de este estudio son las siguientes: estudio retrospectivo, tamaño de muestra pequeño y seguimiento corto.CONCLUSIONES:La terapia preoperatoria anti muerte programada-1 sola como estrategia de conversión en el cáncer colorrectal inicialmente difícil de resecar con dMMR/MSI-H puede lograr una alta respuesta completa tumoral. El uso de terapia inmunopreoperatoria en pacientes con cáncer de colon T4b o cáncer de recto bajo puede reducir la resección multivisceral y lograr una alta preservación de la función del órgano. (Traducción-Dr. Felipe Bellolio ).

Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy

ObjectiveTo evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. PatientsWe retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. Main Outcome MeasuresPathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. ResultsThe incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. ConclusionsPreoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.

Adjuvant chemotherapy guided by an integrated mRNA–lncRNA signature in triple-negative breast cancer (BCTOP-T-A01): A randomized, open-label, multicenter phase 3 trial.

525 Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with variable clinical outcomes. We have previously classified patients with TNBC into high- and low-risk groups based on a multigene signature. In this study, we aimed to evaluate the feasibility of utilizing a multigene signature to tailor individualized adjuvant therapy for patients with operable TNBC. Methods: This multicenter, open-label, randomized, phase 3 trial was conducted at 7 cancer centers in China. We included female patients aged 18-70 years with early TNBC after definitive surgery (histologically confirmed axillary lymph node-positive or lymph node-negative with tumor diameter &gt;10 mm). After categorization using the integrated signature, high-risk patients were randomized (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (TEC-GP; arm A), or the standard four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T; arm B). Low-risk patients received the same adjuvant chemotherapy as arm B (arm C). The primary endpoint was disease-free survival (DFS) in the intention-to-treat analysis of arm A versus arm B. Results: Between January 2016 and July 2023, 504 patients (336 high-risk and 168 low-risk; median age, 52 years; 488 with T1-2 tumors; 263 with node-positive disease) were recruited. At a median follow-up of 45.1 months, the 3-year DFS rates were 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28 to 0.95; P = 0.030). Intensive chemotherapy improved DFS relative to standard therapy irrespective of tumor size and nodal status. The 3-year RFS was 92.6% in arm A and 83.2% in arm B (HR, 0.50; 95% CI, 0.25 to 0.98; P = 0.039). The groups did not differ in OS (HR, 0.58; 95% CI, 0.22 to 1.54; P = 0.267; 3-year OS, 98.2% vs 91.3%). Upon receiving the same chemotherapy regimen, patients in arm C had significantly higher DFS (HR, 0.57; 95% CI, 0.33-0.98; P = 0.038; 3-year DFS, 90.1% vs 80.6%), RFS (HR, 0.42; 95% CI, 0.22-0.81; P = 0.007; 3-year RFS, 94.5% vs 83.2%) and OS (HR, 0.14; 95% CI, 0.03-0.61; P = 0.002; 3-year OS, 100% vs 91.3%) compared to patients in arm B. The incidence of grade 3 to 4 treatment-related adverse. events for arms A, B and C, respectively, were thrombocytopenia (14.1%, 2.5%, 1.8%), febrile neutropenia (9.9%, 4.3%, 4.9%), anemia (5.8%, 1.9%, 1.8%), nausea (7.0%, 3.7%, 4.9%), vomiting (8.3%, 4.3%, 4.9%) and myalgia (2.6%, 5.6%, 5.5%). There were no treatment-related deaths. Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable TNBC. Intensive regimens incorporating GP into anthracycline/taxane-based therapy improves survival with manageable toxicity. Clinical trial information: NCT02641847 .

Clinicopathological analysis and management of primary cardiac sarcomas: A retrospective study from two cancer centers in China.

e23544 Background: Primary cardiac sarcomas (PCS) are rare malignant tumors associated with a poor prognosis. The clinical and pathological features of PCS remain elusive. Methods: We retrospectively collected records of patients with PCS at Peking University Cancer Hospital and Zhejiang Cancer Hospital from 2016 to 2023. Clinicopathological data, treatments, and outcomes were included and analyzed. Results: Between January 2016 and October 2023, a total of 26 patients with primary cardiac sarcoma were included, with the majority of patients being female (57.7%). The median age of the patients was 38.5 years (range: 15-82). Tumors were most frequently located in the right (42.3%) and left (26.9%) atria. The predominant histological subtype was angiosarcoma (46.1%), followed by myxoid fibrosarcoma (15.4%) and intimal sarcoma (11.5%). At baseline, the LDH level was elevated in 42.3% of patients. Metastases were observed in 21 (80.8%) patients, predominantly in lung (61.9%), bone (42.9%) and liver (28.6%). Nineteen patients (73.1%) underwent surgery for the primary tumor, with 8 (42.1%) achieving a complete (R0) resection and 11 (57.9%) achieving a microscopically (R1) or macroscopically (R2) incomplete resection. Sixteen patients (61.5%) received anthracycline-based chemotherapy as their first-line palliative treatment. The median overall survival (OS) for all patients was 19.2 months (95% CI: 16.7-31.2). Patients with normal baseline LDH levels had a significantly longer median OS (25.4 months) compared to patients with elevated LDH levels (11.6 months, P= 0.001). The median OS was 25.4 months for patients who underwent R0 resection, compared to 18.7 months for those who underwent R1/R2 resection, and 6.03 months for those who did not undergo surgery. Patients who received anthracycline-based chemotherapy had a moderately better survival than those who received paclitaxel-based chemotherapy (mOS 19.2 vs.14.8 months, P= 0.13). Conclusions: In patients with PCS, angiosarcoma is the predominant histological subtype, and the most common sites of metastasis are the lung, bone, and liver. Elevated LDH is associated with a poorer prognosis. Complete surgical resection of the cardiac sarcoma after diagnosis may benefit long-term survival. [Table: see text]

High versus standard radiation dose of definitive chemoradiotherapy combined with immunotherapy for inoperable esophageal squamous cell carcinoma: A multicenter propensity score matching analysis.

e16118 Background: There is no consensus of the radiation dose for esophageal squamous cell carcinoma (ESCC) in the setting of definitive chemoradiotherapy (dCRT) combined with immunotherapy. This study aimed to compare the efficacy and safety of high-dose (HD) versus standard-dose radiotherapy (SD) for locally inoperable ESCC. Methods: Patients with locally advanced unresectable ESCC or advanced ESCC with supraclavicular lymph node metastases only who received high-dose (≥ 60Gy) or standard-dose (50-50.4Gy) radiation in dCRT combined with anti-PD-1 antibody as the first-line treatment from four academic cancer centers were enrolled. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. Results: Between March 2019 and July 2022, 328 patients were enrolled from four cancer centers in China, with 163 patients in the HD and 165 patients in the SD groups, respectively. The median follow-up time in the HD and SD groups were 28.9 and 25.9 months, respectively. There was no significant difference in overall survival (OS) (median OS: not reached in both, P = 0.080), progression-free survival (PFS) (median PFS: not reached vs. 30.3 months, P = 0.073), locoregional progression-free survival (LRPFS) and distant metastasis survival (DM) between the HD and SD groups. After 1:2 PSM, 156 patients in the HD and 78 patients in the SD groups were selected for further analyses. The results remained consistent and showed that the HD group had no significant benefits in OS (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.50-1.51, P = 0.624), PFS (HR = 0.79, 95%CI = 0.51-1.23, P = 0.300), LRPFS (HR = 0.75, 95%CI = 0.47-1.19, P = 0.228) and DM (HR = 1.05, 95%CI = 0.64-1.73, P = 0.849), compared with the SD group. In terms of failure patterns, the incidences of locoregional failure only (13.5% vs. 16.7%, P = 0.512), distant failure only (10.9% vs. 9.0%, P = 0.648) and synchronous locoregional and distant failure (2.6% vs. 6.4%, P = 0.164) were similar between two groups. No significant difference was found in the incidences of hematological toxicities, esophagitis, pneumonia (12.2% vs. 10.3%, P = 0.664) and fistula (7.1% vs 9.0%, P = 0.603) between the HD and SD groups. Conclusions: Compared with a radiation dose of 50-50.4Gy, the increase in radiation dose (≥60Gy) did not result in survival benefits for inoperable ESCC patients receiving dCRT combined with immunotherapy. Furthermore, similar failure patterns and toxicities were observed between the two treatment groups.

Treatment outcome of elderly patients (≥ 78 years) with head and neck squamous cell carcinoma: A single center experience.

Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.

Abstract PO5-04-01: Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment

Abstract Objective: To explore the efficacy and safety of Inetetamab Combined with Sirolimus and Chemotherapy in the treatment of human epidermal factor receptor 2 (HER2) positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR (PAM) pathway after Trastuzumab treatment. Methods: This prospective multicenter clinical study enrolled HER2 positive metastatic breast cancer patients at the National Cancer Center in China from July 2021 to September 2022 with PAM pathway mutation confirmed by histology or peripheral blood genetic testing. The inclusion criteria included: 1) Recurrent and metastatic breast cancer patients with HER2 positive confirmed histologically; 2) ECOG PS score ≤ 2; 3) Patients who have progressed after previous treatment with Trastuzumab; 4) Patients with PAM pathway mutation confirmed by Genetic testing; 5) Patients' cardiac, pulmonary, liver and bone marrow functions are basically normal; 6) Patients voluntarily sign informed consent forms. The exclusion criteria included: 1) Patients previously treated with mTOR inhibitors or pyrotinib; 2) Patients who have used chronic Corticosteroid for more than 3 months or used Immunosuppressive drug within 4 weeks; 3) Patients with symptomatic central nervous system metastasis; 4) Patients with left ventricular Ejection fraction&amp;lt; 50% or clinical manifestations of obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease; 5)Diagnosed with other malignant tumors within five years. Patients were randomly divided into trial group and control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, and control group received pyrotinib and chemotherapy. RECISTv1.1 standard was used to evaluate the efficacy of patients. Descriptive statistics are used to summarize clinical pathological features. Kaplan Meier method was used to draw survival curves. Log-rank test was used to compare progression free survival (PFS) differences between groups. P&amp;lt; 0.05 was considered statistically significant. Results:A total of 59 HER2 positive metastatic breast cancer patients with abnormal activation of PAM pathway were included, of which 37 patients received the treatment of inetetamab group and 22 patients received the treatment of pyrotinib group. The median follow-up time was 5.33 months. In the intent-to-treat set, the median PFS of patients in the inetetamab group was 4.64 months, which was shorter than 5.69 months in the pyrotinib group. There was no statistically significant difference between the two groups (P=0.51; HR=0.41; 95% CI, 0.12-1.45). The objective response rate (ORR) of the inetetamab group and the pyrotinib group were 28.1% and 29.4%, respectively. In terms of safety, the incidence of adverse events (AE) in the experimental group was (33/37) 89.1%, while (16/21) 76.2% in the control group. The incidence of AE above level 3 in the inetetamab group and pyrotinib group were (13/37) 35.1% and (3/21) 14.3%, respectively. Conclusion:For the metastatic HER2 positive breast cancer patients with abnormal activation of PAM pathway treated with trastuzumab previously, the combination of inetetamab with sirolimus and chemotherapy regimen are equivalent to the combination of pyrotinib and chemotherapy regimen. It demonstrated that combination of inetetamab with sirolimus and chemotherapy could be one of the treatment options for the metastatic HER2 positive breast cancer patients. Citation Format: Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma. Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-01.

Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor: results from three cancer centers in China

BackgroundPembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H.MethodsThis retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS).ResultsThe top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6–21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9–7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events.ConclusionOur study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.

Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy

PurposeThis study assesses the metastasis rate of the key distal lymph nodes (KDLN) that are not routinely dissected in proximal gastrectomy, aiming to explore the oncological safety of proximal gastrectomy for upper gastric cancer who underwent neoadjuvant chemotherapy.MethodsWe analyzed a cohort of 150 patients with proximal locally advanced gastric cancer (cT3/4 before chemotherapy) from two high-volume cancer centers in China who received preoperative neoadjuvant chemotherapy (NAC) and total gastrectomy with lymph node dissection. Metastasis rate of the KDLN (No.5/6/12a) and the risk factors were analyzed.ResultsKey distal lymph node metastasis was detected in 10% (15/150) of patients, with a metastasis rate of 6% (9/150) in No. 5 lymph nodes, 6.7% (10/150) in No. 6 lymph nodes, and 2.7% (2/75) in No. 12a lymph nodes. The therapeutic value index of KDLN as one entity is 5.8. Tumor length showed no correlation with KDLN metastasis, while tumor regression grade (TRG) emerged as an independent risk factor (OR: 1.47; p-value: 0.04). Of those with TRG3 (no response to NAC), 80% (12/15) was found with KDLN metastasis.ConclusionFor cT3/4 proximal locally advanced gastric cancer patients, the risk of KDLN metastasis remains notably high even after NAC. Therefore, proximal gastrectomy is not recommended; instead, total gastrectomy with thorough distal lymphadenectomy is the preferred surgical approach.

Everolimus treatment in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and a predictive model for its efficacy: a multicenter real-world study

Background: Everolimus is beneficial for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). However, some patients developed drug resistance and the well-established predictor for everolimus efficacy was limited. Objectives: The study was designed to evaluate the efficacy of everolimus in different treatment lines and identify several clinicopathological markers to estimate everolimus efficacy in patients with HR+/HER2− ABC. Design: This was a retrospective and multicenter study. Methods: Between 2014 and 2022, more than 2000 patients with tumors who received everolimus were collected from multiple cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital &amp; Institute). A training cohort and two validation cohorts were developed. Results: The training cohort included 338 patients. The median progression-free survival (PFS) for everolimus was 5.6 months, with an objective response rate of 25.1% and a clinical benefit rate of 54.4%. PFS was significantly worse from first-line (1L) to second-line (2L) to third-line (3L), with PFS1L for 13.5 months, PFS2L for 6.1 months, and PFS3L for 4.1 months ( p = 2.9e−6, hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.61–0.82). The clinicopathological characteristics, including post-1L everolimus treatment, Ki67 index of more than 40%, more than two metastatic sites at first recurrence, and receiving adjuvant chemotherapy, were independent risk factors for PFS. A predictive model for everolimus efficacy was established using these four factors. In the low-risk group, patients achieved a median PFS of 12.6 months, significantly longer compared to 2.7 months for those in the high-risk group ( p = 2.4e−64, HR = 9.41, 95% CI = 7.05–12.56). The area under the curve was 0.96, 0.95, and 0.94 for 6-month, 1-year, and 3-year PFS, respectively. Internal validation cohort (PFS 18.4 vs 3.1 months, p = 3.6e−11, HR = 3.78, 95% CI = 2.49–5.74) and external validation cohort (PFS 13.5 vs 3.1 months, p = 2.9e−10, HR = 11.53, 95% CI = 4.68–28.37) confirmed its power for estimating clinical benefits of everolimus. Conclusion: A predictive model was successfully established to predict survival outcomes for everolimus in patients with HR+/HER2− ABC, which may provide references for the management of everolimus in Chinese patients with HR+/HER2− ABC.

The Applicability of the AJCC TNM Staging 8th Edition to Esophageal Small-Cell Carcinoma: A Multicenter Retrospective Trial from China

Small cell carcinoma of the esophagus (SCCE) is a rare type of esophageal cancer, the incidence of it is only 0.1% to 2.4% in all cases of esophageal cancer. However, the optimal disease staging system has not yet been defined. To comprehensively explore the impact of AJCC TNM Staging 8th edition on survival outcome of SCCE. From January 2007 to December 2020, 909 patients with SCCE who had completed TNM staging from 14 cancer centers in China were retrospectively examined. Univariate survival rate analyses were estimated using the Kaplan and Meier method, with comparisons made between groups by the log-rank test. All statistical analyses were conducted using SPSS 25 statistical software. Statistical significance was assumed for a two-tailed p value less than 0.05. TNM stage also was a statistically significant prognostic factor for OS and PFS in SCCE(p<0.001). Increasing clinical T category using the AJCC8 TNM staging system resulted in progressively poorer survival in patients who did not have metastatic (M0) involvement(p<0.01). However, the results of pairwise comparisons showed no significant differences in survival between patients with adjacent phases except for those between T3 versus T2 (p<0.0001). N staging also showed significant influence on OS, and with significant difference between successive stages (p<0.05) except that between the survival rates of N1 and N2 cases (p = 0.00758). Similar to t category, increasing M category was associated with progressively worse survival. The T and N staging confirmed significant influence on PFS in the SCCE patients (p<0.001). AJCC TNM Staging 8th edition criteria for SCCE patients has a high prognostic impact. Therefore, it is applied to clinical practice and future therapeutic trials.

CACA guidelines for holistic integrative management of esophageal carcinoma

Esophageal carcinoma (EC) is a common malignant tumor of the upper digestive tract worldwide. An analysis of the latest data from cancer centers in China showed that the incidence of EC and the number of deaths due to EC in China in 2015 were 266,000 and 188,000, respectively, ranking sixth (6.3%) and fourth (8.0%) among all malignant tumors. The early diagnosis and treatment of EC and standardized diagnosis and treatment are important tasks for EC healthcare professionals in various centers across the country. At present, the 8th edition of the EC staging system jointly released by Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) is the most recent, authoritative and widely used EC staging standard. The EC professional committee of the Chinese Anti-Cancer Association also organizes the "EC Standardization Campaign in China" every year to promote the development of EC diagnostic and treatment norms throughout the country. Since 2011, the EC Committee of the Chinese Anti-Cancer Association has published the Guidelines for Standardized Diagnosis and Treatment of EC. Considering the increasing number of EC clinical studies and the continuous progress in diagnostic and treatment technologies in recent years, the updated Guidelines will include the latest progress in the diagnosis and treatment of EC, with a goal of promoting the forward development of EC diagnosis and treatment in clinical practice.

The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II-III Colorectal Cancer: A Retrospective Multi-Center Cohort Study.

It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy. The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II-III colorectal cancer (CRC). The retrospective cohort analysis was performed on patients with stage II-III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II-III CRC. A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80-2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52-3.70; log-rank P=0.66). Patients over the age of 75 with stage II-III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II-III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.

Tumor senescence leads to poor survival and therapeutic resistance in human breast cancer.

Breast cancer (BRCA) is the most common malignant tumor that seriously threatens the health of women worldwide. Senescence has been suggested as a pivotal player in the onset and progression of tumors as well as the process of treatment resistance. However, the role of senescence in BRCA remains unelucidated. The clinical and transcriptomic data of 2994 patients with BRCA were obtained from The Cancer Genome Atlas and the METABRIC databases. Consensus clustering revealed senescence-associated subtypes of BRCA patients. Functional enrichment analysis explored biological effect of senescence. We then applied weighted gene co-expression network analysis (WGCNA) and LASSO regression to construct a senescence scoring model, Sindex. Survival analysis validated the effectiveness of Sindex to predict the overall survival (OS) of patients with BRCA. A nomogram was constructed by multivariate Cox regression. We used Oncopredict algorithm and real-world data from clinical trials to explore the value of Sindex in predicting response to cancer therapy. We identified two distinct senescence-associated subtypes, noted low senescence CC1 and high senescence CC2. Survival analysis revealed worse OS associated with high senescence, which was also validated with patient samples from the National Cancer Center in China. Further analysis revealed extensively cell division and suppression of extracellular matrix process, along with lower stromal and immune scores in the high senescence CC2. We then constructed a 37 signature gene scoring model, Sindex, with robust predictive capability in patients with BRCA, especially for long time OS beyond 10 years. We demonstrated that the Sene-high subtype was resistant to CDK inhibitors but sensitive to proteosome inhibitors, and there was no significant difference in paclitaxel chemotherapy and immunotherapy between patients with different senescence statuses. We reported senescence as a previously uncharacterized hallmark of BRCA that impacts patient outcomes and therapeutic response. Our analysis demonstrated that the Sindex can be used to identify not only patients at different risk levels for the OS but also patients who would benefit from some cancer therapeutic drugs.

Adjuvant icotinib versus observation in patients with completely resected EGFR-mutated stage IB NSCLC (GASTO1003, CORIN): a randomised, open-label, phase 2 trial.

This phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC). We performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210. A total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3-99.9) than in the observation group (84.0%, 95% CI, 75.1-92.9; P=0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07-0.81; P=0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred. Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile. This study was sponsored by Betta Pharmaceutical Co., Ltd.

A Prospective, Randomized, Placebo-Controlled Study Assessing the Efficacy of Chinese Herbal Medicine (Huangqi Guizhi Wuwu Decoction) in the Treatment of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy.

Objective: This study aimed to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD), which is composed of five crude drugs (Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus), in the treatment of albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) in Chinese patients with breast cancer (BC). Methods: This trial was conducted at the National Cancer Center in China from January 2020 to June 2022. The eligible participants were assigned randomly in a 1:1 ratio to an HGWD group or a control group. The outcome measure was EORTC QLQ-CIPN20 questionnaire. Results: 92 patients diagnosed with BC were enrolled and randomized to either HGWD group (n = 46) or control group (n = 46). There were no significant differences in baseline characteristics between the two groups (p > 0.05). A statistical analysis of the sensory and motor functions of the EORTC QLQ-CIPN20 scores showed that patients in the HGWD group reported a larger decrease in CIPN sensory scores than those in the control group (p < 0.001). The EORTC QLQ-CIPN20 autonomic scores showed no statistical significance between the two groups (p > 0.05). Conclusions: HGWD packs could significantly improve patients’ nab-PTX-induced PN, increase the tolerance for nab-PTX-containing chemotherapy, and further improve the quality of life of patients with BC.

Impact of mature tertiary lymphoid structures on prognosis and therapeutic response of Epstein-Barr virus-associated gastric cancer patients.

Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood. We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively. In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups. Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.

Effect of Surgical Starting Time and Season on Prognosis in Octogenarians with Colorectal Cancer: A Retrospective Study

Aim: To investigate the effect of surgical starting time and season on the prognosis of octogenarians with colorectal cancer. Patients & methods: A total of 291 patients aged 80years or above who received elective colectomy for colorectal cancer between January 2007 and December 2018 in the National Cancer Center in China were included. Results: No significant time- or season-dependent difference in overall survival for all clinical stages was found in the study. Comparing perioperative outcomes, the morning group had a longer operative time than the afternoon group (p=0.03), but no significant difference was found based on the season of colectomy. Conclusion: These findings provide insights into clinical outcomes for colorectal cancer patients aged more than 80years.

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear. To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC. This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021. All patients received chemotherapy alone or CCRT. The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation. Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification. In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.