Objective: Advanced malignant melanoma still poses significant challenges in treatment. Combining nab-paclitaxel, bevacizumab, and immunotherapy has shown promising efficacy across various cancer types. This retrospective study aimed to assess the efficacy and safety of this regimen in patients with advanced melanoma and explore related biomarkers. Methods: Patients with histologically confirmed inoperable stage Ⅲ or Ⅳ melanoma and Eastern Cooperative Oncology Group Performance Status 0-2 were included in this retrospective study conducted from September 2020 to August 2023. Patients received combination therapy with nab-paclitaxel, bevacizumab, and toripalimab (Q3W) at Nanjing Drum Tower Hospital. Maintenance therapy with bevacizumab and toripalimab was given after 6-8 cycles without disease progression or intolerable adverse reactions. Personalized radiotherapy was delivered. The primary endpoint was the confirmed objective response rate (ORR) and disease control rate (DCR). Results: As of January 20, 2024, 28 out of 41 patients showed tumor shrinkage, including 4.9% (n=2) achieving complete response (CR) and 63.4% (n=26) achieving partial response (PR). The confirmed ORR was 63.4% (95% CI: 46.9%-77.9%) and the DCR was 92.7% (95% CI: 80.1%-98.5%). The median PFS was 14.2 months, the 1-year survival rate was 75.5% (95% CI: 62.7%-90.9%), and the 2-year survival rate was 54.6% (95% CI: 38.1%-78.1%). Moreover, patients who received radiotherapy exhibited a longer median progression-free survival (mPFS) (14.3 months vs 7.0 months, HR=0.45 [95% CI: 0.20-1.01]). Grade 3 treatment-related adverse events were leukopenia, neutropenia, AST/ALT elevation, adrenal insufficiency, hypertriglyceridemia and neurotoxicity. No treatment-related deaths were observed. In addition, biomarker analysis showed that liver metastasis, MET mutation, and NF1 mutation were independent predictors of PFS (P=0.006, 0.038, and 0.002, respectively). Conclusions: This study demonstrates that toripalimab, in combination with nab-paclitaxel and bevacizumab, offers a potential therapeutic option for advanced melanoma with acceptable toxicity. Furthermore, this triplet therapy combined with radiotherapy significantly improves PFS. Preliminary biomarker analysis suggests that patients with liver metastasis, MET or NF1 mutations may be less likely to benefit from this treatment regimen.

Objective: To evaluate the efficacy and safety of resectable locally advanced colorectal cancer (LACRC) after neoadjuvant immunotherapy (IT). Methods: A retrospective analysis of the clinicopathological data of 32 patients with locally advanced colorectal cancer who received neoadjuvant immunotherapy followed by radical surgery at the Cancer Hospital Chinese Academy of Medical Sciences, from January 2019 to February 2024. Fisher's exact test was used for univariate analysis, and Logistic regression model was used for multivariate analysis. Results: Of the 32 patients, 23 were male and 9 were female; the median age was 55 years old. Seven patients with microsatellite instable-high (MSI-H) and 1 patient with microsatellite stable (MSS) received neoadjuvant immunotherapy. Eight patients received neoadjuvant immunotherapy, 16 patients (10 MSI-H and 6 MSS) received neoadjuvant chemotherapy combined with IT, and 8 patients (1 MSI-H and 7 MSS) received neoadjuvant chemoradiotherapy combined with IT. Postoperative pathological results showed that 25 patients achieved pathological complete response (pCR) (78.1%), while 7 patients did not achieve pCR (21.9%). The pCR rates were 94.4% (17/18) in MSI-H patients and 57.1% (8/14) in MSS patients, with statistically significant difference between the two groups (P=0.001). Postoperative complications occurred in 8 patients (25.0%), and there were no secondary operations or perioperative deaths. Multivariate analysis results showed that preoperative carcinoembryonic antigen (CEA) level ≥5 ng/ml(OR=0.035,95% CI:0.003～0.260, P=0.003), MSI-H and MSS POLE positive（OR=19.000，95% CI：2.573～399.227，P=0.012）were related to pCR. Conclusions: Neoadjuvant immunotherapy is safe and effective for resectable LACRC. Neoadjuvant immunotherapy alone for resectable MSI-H colorectal cancer (CRC) can achieve satisfactory results, and neoadjuvant immunotherapy in combination with various forms of conventional therapy for patients with resectable MSS CRC could also achieve better short-term effects.

Objective: To investigate the impact of different low density lipoprotein-cholesterol (LDL-C) levels on the risk of gastrointestinal cancer. Methods: A prospective cohort study was used to observe 126 050 in service and retired employees of Kailuan Group who participated in the physical examination for the first time in 2006 or 2008. A total of 122 734 people were finally included in the statistical analysis. The subjects were divided into five groups according to the baseline quintile of low-density lipoprotein cholesterol, namely Q1 group, Q2 group, Q3 group, Q4 group and Q5 group. The impact of different LDL-C groups on the incidence of gastrointestinal tumors was analyzed by Cox proportional hazard model. Results: During follow-up of (12.83±2.43) years, 1 460 cases of gastrointestinal tumors occurred, including 225 cases of esophageal cancer, 431 cases of gastric cancer and 804 cases of colorectal cancer. Cox proportional hazard model analysis found that after adjusting for age, sex, body mass index, high-sensitivity C-reactive protein, education, smoking, alcohol consumption, diabetes, hypertension, physical exercise, excessive salt intake, family history of cancer and taking lipid-lowering drugs, compared with Q5 group, the hazard ratio (HR) values of gastrointestinal tumors in Q1, Q2, Q3 and Q4 groups were 1.28 (95% CI: 1.08, 1.50), 1.07 (95% CI: 0.90, 1.26), 1.31 (95% CI: 1.11, 1.54) and 1.12 (95% CI: 0.94, 1.33), respectively. The HR values of esophageal cancer were 1.21 (95% CI: 0.80, 1.82), 0.82 (95% CI: 0.52, 1.30), 1.47 (95% CI: 1.00, 2.17) and 0.84 (95% CI: 0.54, 1.31), respectively. The HR values of gastric cancer were 1.05 (95% CI: 0.78, 1.41), 0.84 (95% CI: 0.61, 1.16), 1.21 (95% CI: 0.91, 1.63) and 1.04 (95% CI: 0.77, 1.41), respectively. The HR values of colorectal cancer were 1.44 (95% CI: 1.15, 1.80), 1.28 (95% CI: 1.02, 1.62), 1.31 (95% CI: 1.04, 1.65) and 1.26 (95% CI: 1.00, 1.59), respectively. Conclusions: The decrease of baseline LDL-C level may be a risk factor for gastrointestinal malignant tumors, but low LDL-C increases the risk of malignant tumors in a location dependent manner. Although low LDL-C level increases the risk of colorectal cancer, it has no significant correlation with esophageal cancer and gastric cancer.

Objective: To investigate the clinical efficacy, toxicity and prognosis of SOX regimen (Oxaliplatin plus S-1) combined with Pabolizumab in the treatment of patients with metastatic gastric cancer. Methods: The clinical data of 107 patients with advanced metastatic gastric cancer admitted to Wuxi Branch of Ruijin Hospital Shanghai Jiao Tong University School of Medicine from May 2020 to May 2024 were retrospectively collected. According to the treatment methods, the patients in the chemotherapy group (n=56) only received SOX chemotherapy, and the patients in the combined group (n=51) were given SOX chemotherapy combined with Pembrolizumab. The differences of objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), grade Ⅲ-Ⅳ toxicity and quality of life improvement rate between the two groups were analyzed and compared. Results: According to the efficacy evaluation criteria of RECIST1.1, among all subjects, there were 1 case of complete response (CR) and 21 cases of partial response (PR) in chemotherapy group, 2 cases of CR and 31 cases of PR in combination group. The objective response rate (CR+PR%) in combination group was significantly higher than that in chemotherapy group (64.7% vs 39.3%, P=0.015). Stratified analysis showed that in patients with PD-L1 combined positive score (CPS) ≥1, the ORR of the combination group further increased to 75.9% (22/29), with a more significant advantage than the ORR of 38.9% (14/36) in the chemotherapy group (P=0.004). Survival analysis showed that among all enrolled patients, median PFS and median OS in combination group were 9.3 months and 17.4 months respectively, which were significantly longer than 8.4 and 13.1 months in chemotherapy group (PFS: P=0.020; OS: P=0.011). In addition, among patients with PD-L1 CPS ≥1, the median PFS and OS of the combination group showed a more significant advantage in prolonging compared to the chemotherapy group (median PFS: 10.7 months vs 8.2 months, P=0.003; median OS: 19.0 months vs 12.8 months, P=0.005). Among all enrolled patients, 14 cases showed improvement in quality of life in the chemotherapy group and 23 cases in the combination group, and the improvement rate of quality of life in combination group was significantly higher than that in chemotherapy group (45.1% vs 25.0%, P=0.029). There was no statistical difference in the incidence [67.9% (38/56) in chemotherapy group vs 78.4% (40/51) in combination group] of grade Ⅲ-Ⅳ toxicity between the two groups (P=0.219). Conclusion: In patients with PD-L1 CPS ≥1 or all enrolled patients, compared with chemotherapy alone, SOX regimen combined with pembrolizumab in the treatment of metastatic gastric cancer can significantly improve ORR, prolong PFS and OS, improve prognosis and quality of life, while the toxicity has not increased significantly.

Objective: To construct a non-invasive detection platform based on surface enhanced Raman spectroscopy (SERS) combined with machine learning, achieving high-precision recognition of precancerous lesions of gastric cancer. Method: Serum samples were collected from 213 subjects at Jiangdu People's Hospital Affiliated to Yangzhou University from July 6, 2023 to January 1, 2025, including 51 healthy controls and 162 gastric lesion patients (48 cases of high-grade intraepithelial neoplasia [HGIN], 60 cases of early gastric cancer, and 54 cases of advanced gastric cancer). Au Octahedral Nanoparticles (Au OCNPs) substrates was synthesized by seed mediated method, and its morphology was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Serum samples were dropped onto the Au OCNPs array, and SERS spectra were acquired using a confocal micro-Raman spectrometer (excitation wavelength 785 nm, laser power 5 mW, exposure time 10 s). All original spectral data were preprocessed using Origin 2019 software, including spectral band selection, Savitzky-Golay smoothing, airPLS baseline correction, and Min-Max normalization. A principal component analysis-diagonal quadratic discriminant analysis (PCA-DQDA) model was constructed in MATLAB R2023a to evaluate the classification performance for healthy subjects and gastric lesion patients at different stages, and the model's accuracy and area under the curve (AUC) were validated by five-fold cross-validation. Results: The Au OCNPs arrays showed uniform morphology, sharp edges, a lattice spacing of 0.226 nm, and a characteristic absorption peak at 534 nm, with significant SERS enhancement and good reproducibility. The characteristic peak differences in SERS spectra between healthy subjects and gastric lesion patients were mainly concentrated at 625, 728, 1 006, 1 326, 1 446, and 1 584 cm^-1, indicating significant differences in the vibrational modes of biomolecules such as proteins and nucleic acids in serum during the progression of gastric precancerous lesions. For the binary classification of healthy subjects and all gastric lesion patients, the PCA-DQDA model achieved an overall accuracy of 97.2% (207/213). For the multi-class classification of healthy subjects and gastric lesion patients at different stages, the model achieved an overall accuracy of 93.4% (199/213), and an AUC of 0.872. Misclassifications occurred between adjacent subgroups with similar biological characteristics: among 51 healthy subjects, 4 were misclassified as HGIN, with a classification accuracy of 92.2% (47/51); among 48 HGIN samples, 1 was misclassified as healthy and 2 as early gastric cancer, with a classification accuracy of 93.6% (45/48). Conclusion: The serum SERS detection platform based on Au OCNPs arrays and the PCA-DQDA model exhibits advantages of non-invasiveness, high sensitivity, and molecular specificity in identifying gastric precancerous lesions, providing a new strategy for their recognition.

Objective: To analyze the mortality trends of liver cancer in the general population of Qidong City, Jiangsu Province from 1972 to 2024, and to predict the mortality burden from 2025 to 2034, providing a basis for liver cancer prevention and control strategies. Methods: Liver cancer mortality data (1972-2024) were extracted from the Qidong Cancer Registry database. Using corresponding population data, we calculated: crude mortality rate (CR), Chinese age-standardized rate (ASRC, standardized using the 1964 Chinese population), world age-standardized rate (ASRW, standardized using Segi's world population), and median age at death. Joinpoint regression (Joinpoint 4.9.1.0) was employed to estimate annual percent change (APC) and average annual percent change (AAPC) in mortality, The ARIMA model in SAS 9.2 was applied to predict mortality trends over the next decade. Results: A total of 34 773 liver cancer deaths were recorded in Qidong from 1972 to 2024. Compared with 1972-1976, the proportion of liver cancer deaths among all cancer deaths in 2022-2024 decreased from 40.02% to 12.83%. The CR, ASRC, and ASRW declined from 49.33/10⁵, 45.62/10⁵, and 57.23/10⁵ in 1972-1976 to 44.09/10⁵, 8.54/10⁵, and 13.91/10⁵ in 2022-2024, respectively. The male-to-female ratio of ASRW was 3.33:1 from 1972 to 2024. For 2022-2024, the ASRW was 21.16/10⁵ for males and 7.22/10⁵ for females. Age-specific mortality rates showed declining trends in all age groups under 65 years from 1972 to 2024, with greater declines in younger age groups (all P＜0.05). In contrast, the mortality rate in the 75+ years age group showed an increasing trend (AAPC=2.15%, P=0.001). The median age at death from liver cancer in Qidong rose from 49 years in 1972 to 72 years in 2024, and the peak mortality age group shifted gradually from 45-54 years to 75+ years across periods. The time trend analysis revealed that from 1972 to 2024, the AAPCs for ASRW were -2.11%, -2.23%, and -1.89% (all P＜0.001) for both sexes combined, males, and females, respectively, all showing statistically significant downward trends. The CR showed a slow but significant increasing trend for females (AAPC=0.88%, P＜0.001), while the trends for both sexes combined and males were not statistically significant (all P＞0.05). Segmented fitting results showed the most pronounced decline occurred from 2008 to 2024, with an APC of -3.76% for CR and -7.15% for ASRW (both P＜0.001). The overall CR is projected to decline to 40.30/10⁵ in 2034, and the ASRW is projected to decline to 4.40/10⁵. Conclusions: The comprehensive prevention and control efforts implemented over 53 years in the high-incidence area of Qidong have influenced the overall standardized mortality rate and the liver cancer mortality rate among those under 65 years of age, with the most significant decline observed after 2008. Future efforts should focus on strengthening comprehensive prevention and control of liver cancer in the elderly population.

Objective: To analyze the incidence of malignant tumors in children and adolescents (aged 0-19 years) in China in 2022. Methods: Data were sourced from GLOBOCAN 2022 and Cancer Incidence in Five Continents (CI5) Volume Ⅻ. Incidence data by sex and age group for childhood and adolescent cancers from Chinese registries in CI5 Volume XII were extracted to calculate the proportion of each subtype. These proportions were then applied to the overall cancer incidence in children and adolescents in China from GLOBOCAN 2022 to estimate the number of incident cases for different tumor types. World standardized incidence rates (WSR) were calculated using Segi's world standard population. Results: In 2022, there were 32 792 new cases of malignant tumors in children and adolescents (aged 0-19 years) in China, with a WSR of 105.93 per million. Among them, 23 121 new cases occurred in children aged 0-14 years, accounting for 70.51% of all cases in children and adolescents, with a WSR of 100.30 per million. The most common diagnostic types of malignant tumors in Chinese children and adolescents in 2022 were leukemia (11 983 cases, 36.54%), followed by central nervous system tumors (4 485 cases, 13.68%) and lymphoma (2 764 cases, 8.43%), with WSR of 39.78 per million, 14.15 per million and 8.35 per million, respectively. Among different age groups, the highest WSR was observed in the 15-19 years (125.28 per million), followed by the 0-4 years (120.67 per million). Except for the 15-19 years group, the age-specific incidence rate was higher in males than in females. The top three cancer types by incidence in both sexes in 0-14 years group were consistent with those in the 0-19 years group, namely leukemia, central nervous system tumors, and lymphoma. In the 15-19 years group, the top three cancers in males were leukemia, bone tumors, and lymphoma, while in females they were malignant melanomas and other malignant epithelial tumors, leukemia, and malignant gonadal germ cell tumors. Conclusions: The incidence rates and cancer type distribution in children and adolescents vary considerably by sex and age group in China. Targeted prevention and control strategies for childhood and adolescent cancer malignant tumors should be developed accordingly.

Respiratory-correlated four-dimensional (4D) magnetic resonance imaging (4D-MRI) is useful to estimate breathing induced motion for MRI-guided radiotherapy. Based on 4D-MR image sets, a three-dimensional mid-position (MidP) MRI can be generated using deformable image registration (DIR) for radiotherapy planning. However, the desired spatial resolution and image contrast of the MidP MRI may differ from the original 4D-MRI.

This retrospective study validates a high-definition (HD)-MidP MRI approach that combines 4D-MRI motion information with a high-resolution MRI to enhance the spatial resolution of the MidP image.

Computed tomography (CT) and MR image sets of 25 lung cancer patients were eligible, of whom 17 were complete and suitable for analysis. Standard-definition (SD)-MidP images were derived by applying DIR to warp the ten respiratory phases of a 4D-CT or 4D-MRI, whereas the HD-MidP MRI was derived by warping a high-resolution respiratory-triggered MRI to the MidP. The MidP image quality was assessed with a 4-point Likert scale on tumor and organ at risk (OAR) distinctiveness by three readers. Additionally, the gross tumor volume (GTV) was delineated by the readers, from which a consensus contour was derived for each MidP image. Reader contours were evaluated using the Dice similarity coefficient (DSC) and mean distance to agreement (DTA). Anatomical accuracy was evaluated by comparing MidP tumor locations to manually determined tumor displacements, while DIR precision was analyzed using the distance to discordance metric (DDM). Moreover, deformation vector fields (DVFs) from the DIR were used to automatically calculate MidP-based treatment margins.

Eighteen targets were identified in seventeen patients. All HD-MidP MR image sets were delineated, while 98% (53/54) of the SD-MidP CT and 87% (47/54) of the SD-MidP MR image sets were of adequate quality for delineation. The SD-MidP MRI was positively scored in 13 out of 47 assessments for tumor distinctiveness and in 6 out of 47 assessments for OAR distinctiveness. In contrast, the HD-MidP MRI showed a substantial improvement, with positive scores in 45 out of 54 assessments for tumor distinctiveness and 51 out of 54 assessments for OAR distinctiveness. Contour analyses revealed that the HD-MidP MRI achieved the highest average DSC value (0.83) and, simultaneously, the lowest mean DTA value (0.96 mm). Compared to the manually determined tumor displacements, subvoxel differences in MidP tumor location were observed in 96% (52/54) of the registrations. The distribution of DDM values (median: 1.1 mm) for the HD-MidP MRI was found to be significantly higher than the distributions for the SD-MidP CT (median: 0.2 mm) and SD-MidP MRI (median: 0.7 mm), indicating a lower, but still subvoxel, precision for the HD-MidP MRI approach. The DVF variability was higher for the HD-MidP MRI (median: 2.7 mm) than for the SD-MidP MRI (median: 2.3 mm). However, when used to derive treatment margins, these margins were identical.

The presented HD-MidP MRI methodology scored highest on both tumor and OAR distinctiveness, with GTV contours demonstrating the best alignment. Combined with its high anatomical accuracy, these findings support its potential for lung radiotherapy planning.

Esophageal cancer presents significant treatment challenges due to its proximity to critical structures such as the heart, lungs, and spinal cord. While intensity-modulated proton therapy (IMPT) improves dose conformity, it is limited by factors such as the number of beam angles and lateral penumbra. Proton arc therapy (PAT) may overcome these issues by utilizing continuous gantry rotation to enhance conformity and spare organs-at-risk (OARs). This study compared PAT and IMPT in esophageal cancer, focusing on dosimetric outcomes, and dose-averaged linear energy transfer (LET_d) distributions.

A retrospective analysis was conducted on ten esophageal cancer patients with variable tumor characteristics. Treatment plans were created using Monaco v6.1 treatment planning system for both PAT and IMPT, maintaining identical robustness parameters (± 5 mm setup and ± 3.5% range uncertainties). Both modalities were prescribed a total dose of 50.4 Gy(RBE) in 28 fractions, ensuring ≥95% clinical target volume (CTV) coverage in the worst-case scenarios. Key metrics, including conformity index (CI), heterogeneity index (HI), and LET_d, were compared. Robustness evaluations were performed across 21 worst-case scenarios to assess plan quality and OAR sparing.

PAT demonstrated superior dose conformity (CI: 0.67 ± 0.17 vs. 0.54 ± 0.13; p < 0.01) and reduced lung V20 (6.88% vs. 13.44%; p < 0.01) compared to IMPT. Critical structure sparing, including reduced spinal cord doses (max dose of (30.93 ± 10.85) Gy(RBE) vs (23.22 ± 9.55) Gy(RBE), p = 0.02), was achieved without compromising CTV coverage. PAT showed higher LET_d within the CTV and lower LET_d in adjacent organs-at-risk relative to IMPT, without statistically significant differences. While the clinical significance remains uncertain, this pattern may support more refined biological dose shaping.

PAT emerged as a promising modality for esophageal cancer treatment, delivering improved dose conformity and reduced OAR exposure. These advantages suggest PAT's potential to decrease radiation-associated complications and improve therapeutic outcomes, warranting further clinical validation.

Robot-assisted partial nephrectomy (RAPN) is standard for cT1 renal masses, but its feasibility in patients on temporary mechanical circulatory support is poorly documented. We report RAPN performed while a patient was simultaneously supported with venous-arterial extracorporeal membrane oxygenation (VA ECMO) and Impella®, as part of a staged plan for left ventricular assist device (LVAD) implantation and eventual heart transplantation.

A 51-year-old man presented with ST-elevation myocardial infarction complicated by cardiogenic shock requiring percutaneous coronary intervention with stenting, dual antiplatelet therapy, and combined VA ECMO-Impella® support. During workup for cardiac transplant, computed tomography (CT) staging revealed a 16-mm left renal mass suspicious for renal cell carcinoma. A multidisciplinary team prioritized definitive treatment to preserve transplant eligibility and elected RAPN under systemic heparinization alongside aspirin continuation (cangrelor briefly withheld). Therefore, RAPN was performed with 9 min of warm ischemia. The intraoperative course was hemodynamically stable. On postoperative day (POD) 4, late arterial bleeding from the resection bed was controlled by selective angioembolization. On POD 7, a durable LVAD was implanted as a bridge to heart transplantation. Final pathology showed pT1a, G2, R0 clear cell renal cell carcinoma. At 6 months, contrast-enhanced CT showed no recurrence and no major cardiovascular complications.

RAPN during simultaneous ECMO and Impella® support is technically feasible with meticulous anticoagulation management, interventional radiology standby, and coordinated planning. This approach enables oncologic control while preserving a trajectory to transplant candidacy.